[The use of ofloxacin in otorhinolaryngology].
Continuing development of antimicrobial resistance highlights the need for new antimicrobial agents. Despite many new molecules there is still a need for effective oral compounds. The fluoroquinolones are a new group of antibiotics with a wide spectrum of antibacterial activity which includes resistant strains and difficult microorganisms as Pseudomonas aeruginosa. Ofloxacin is a fluoroquinolone available for oral use showing good absorption with high blood levels and quite satisfactory tissue, penetration particularly in O.R.L. district. The treatment, consisting of ofloxacin 200 mg twice daily, of several patient (including two cases of rhinitis) was both safe and effective.


DNA sequence and functions of the actVI region of the actinorhodin biosynthetic gene cluster of Streptomyces coelicolor A3(2).
Six open reading frames (ORFs) were identified by DNA sequencing of 5.7 kilobase pairs at the left end of the act cluster (the so-called "actVI region"), in the order: ORFB, ORFA, ORF1, ORF2, ORF3, ORF4. ORF1-4 are transcribed rightward and in the same direction as the ORFs of the actVA region which lies to the right of the actVI region, whereas ORFA and ORFB run in the opposite direction. By complementation of mutants and gene disruption of the wild type strain, the two previously genetically characterized actVI mutations were assigned to ORF1. Although disruption of ORFB and ORF4, using phi C31 derivatives, did not cause any obvious change in actinorhodin production, defects in actinorhodin synthesis were obtained by insertional inactivation of ORFA, ORF1, ORF2, or ORF3. RNA analysis within the ORF1/ORFA intergenic region showed overlapping divergent promoters, at least one of which is under the control of the actII-ORF4 gene product, the transcriptional activator of the act cluster. Data base searches with the deduced products of ORFB and ORF3 failed to show any significant similarities with other known proteins. The deduced product of ORFA strongly resembles those of genes of unknown function from Saccharopolyspora hirsuta and Streptomyces roseofulvus, located within polyketide synthase clusters. The ORF1 product strongly resembles beta-hydroxyacyl-CoA dehydrogenases of bacteria and mammals and the ORF2 and ORF4 products resemble each other and enoyl reductases from bacteria, animals, and plants, with a highly conserved cofactor-binding domain. These findings strongly suggest that the actVI region is involved in catalyzing reduction processes that determine the two stereochemical configurations at C-3/C-15 during actinorhodin biosynthesis. A scheme is proposed for the middle steps of the biosynthesis, that is formation of the pyran ring, leading to the benzoisochromanequinone structure.


The assessment of the ionizing radiation dose received by patients during some diagnostic X-ray examinations carried out on the basis of the working procedures in the health care entities
X-ray examination is a popular and universally used injury and disease diagnostic method. A distinctive X ray examination feature is that it can be done quickly which is extremely important in case of the need for rapid diagnosis of patients in life threatening condition. Another advantage of the X-ray examinations is also relatively low cost of carry. However, X-ray examination involve adverse health effects. During the examination the patient is subjected to ionizing radiation that might have impact on his health. The aim of this study has been to determine and assess the size of the entrance surface doses (ESD) received by patients during selected X-ray examinations performed on the basis of the medical working procedures available in healthcare entities in Masovian Voivodeship in Poland. The examinations were conducted for 71 X-ray units located in the Masovian Voivodeship. Measurements of doses received by the patients were based on our own validated test methods. It was found that the range applied to the high voltage in healthcare entities does not always coincide with the values specified in the standard procedures. It was found in the skull projection radiography AP and LAT that the recorded values were from range 60 to 82 kV (the average value of 74 kV) while in accordance with a standard procedure they should be in the range from 65 to 75 kV. Only in case of cervical spine radiography in the AP projection, the LAT exposure conditions were matching with the standard obligatory procedures in Poland. The consequence of selecting exposure conditions are significant differences in the size of the doses the patient receive during the same medical procedures. The greatest range of ESD doses was found during radiography of the thoracic spine in the projection AP and LAT. The projection LAT measured values were in the range of 523 to 10550 μGy (average value 2175 μGy). It is necessary to update immediately the standard procedures and to develop detailed guidelines for the preparation of working procedures in X-ray rooms.


Effects of atomoxetine on hyper-locomotive activity of the prenatally valproate-exposed rat offspring.
A substantial proportion of patients with autism spectrum disorder (ASD) display hyperactivity as a comorbid symptom. Exposure to valproic acid (VPA) during pregnancy produces ASD-like core behavioral phenotypes as well as hyperactivity in offspring both in human and experimental animals, which makes it a plausible model to study ASD-related neurobiological processes. In this study, we examined the effects of two of currently available attention defecit hyperactivity disorder (ADHD) medications, methylphenidate (MPH) and atomoxetine (ATX) targeting dopamine and norepinephrine transporters (DAT and NET), respectively, on hyperactive behavior of prenatally VPA-exposed rat offspring. In the prefrontal cortex of VPA exposed rat offspring, both mRNA and protein expression of DAT was increased as compared with control. VPA function as a histone deacetylase inhibitor (HDACi) and chromatin immunoprecipitation experiments demonstrated that the acetylation of histone bound to DAT gene promoter was increased in VPA-exposed rat offspring suggesting epigenetic mechanism of DAT regulation. Similarly, the expression of NET was increased, possibly via increased histone acetylation in prefrontal cortex of VPA-exposed rat offspring. When we treated the VPA-exposed rat offspring with ATX, a NET selective inhibitor, hyperactivity was reversed to control level. In contrast, MPH that inhibits both DAT and NET, did not produce inhibitory effects against hyperactivity. The results suggest that NET abnormalities may underlie the hyperactive phenotype in VPA animal model of ASD. Profiling the pharmacological responsiveness as well as investigating underlying mechanism in multiple models of ASD and ADHD may provide more insights into the neurobiological correlates regulating the behavioral abnormalities.


Expression of the 55-kD/64-kD corneal keratins in ocular surface epithelium.
According to the concept of keratin pairing defined by tissue coexpression, a 55-kD/64-kD keratin pair is a marker of "corneal-type" differentiation. Intermediate filament (IF)-enriched preparations from guinea pig and bovine corneal epithelium were analyzed, and a rabbit antiserum was generated against a 55-kD polypeptide enriched in these preparations. This antiserum generated a typical IF-like pattern in cultured bovine corneal epithelial cells. Immunofluorescence microscopic analysis of frozen sections of guinea pig and bovine tissue revealed that the 55-kD antiserum labeled corneal and limbal epithelium. In addition, the antiserum stained a subpopulation of peripheral limbal cells that were distributed in both basal and suprabasal layers of the epithelium. The monoclonal antibody AE5 was used to investigate the distribution of the 64-kD polypeptide in guinea pig and bovine tissue. Immunoblotting analysis revealed that AE5 antibodies recognized a 64-kD polypeptide in guinea pig cornea, but recognized a 66-kD polypeptide in bovine cornea. Immunofluorescence microscopic analysis of guinea pig tissue revealed that AE5 antibodies labeled suprabasal layers of corneal epithelium, in suprabasal layers of limbal epithelium, and in groups of cells in the peripheral limbal epithelium. We discuss the possibility that the ocular epithelial cells recognized by either the 55-kD or the 64-kD antibodies in the peripheral limbus may play a role in the reepithelialization of the cornea after wounding.


A case of NK/T-cell lymphoma complicated by a squamous cell carcinoma of hard palate during combination chemotherapy and radiation therapy.
NK/T-cell lymphoma, which often shows an angiocentric growth pattern, is a distinct clinicopathologic entity highly associated with Epstein-Barr virus. The disease is characterized by a destruction of the upper respiratory tract, particularly the nasal cavity, palate and paranasal sinuses. Interestingly, NK/T-cell lymphoma is closely linked to a variety of complications, such as hemophagocytic syndrome, second primary cancer, sepsis and bleeding. Here we report a case of a 50-year-old man diagnosed initially as NK/T-cell lymphoma of the oropharynx and who developed a second primary carcinoma of the hard palate during combination chemotherapy and radiation therapy.


Yields and Time-of-Flight Spectra of Neutral High-Rydberg Fragments at the K Edges of the CO2 Molecule.
We have studied the production of neutral fragments in high-Rydberg (HR) states at the C 1s and O 1s edges of the CO2 molecule by performing two kinds of experiments. First, the yields of neutral HR fragments were measured indirectly by ionizing such fragments in a static electric field and by collecting resulting singly charged positive ions as a function of the photon energy. Such measurements reveal not only excitations below the core ionization thresholds but also thresholds for single core-hole and shakeup photoionization. Second, we obtained the mass spectra of neutral HR fragments at selected photon energies by exploiting pulsed field ionization; they show atomic fragments C(HR) and O(HR). We discuss dissociation pathways leading to the production of neutral HR fragments in core excitation and ionization of CO2.


10-Hz grazing--incidence pumped Ni-like Mo x-ray laser.
The operation of a Ni-like Mo x-ray laser at 18.9 nm with a repetition rate of 10 Hz has been demonstrated. The laser has been pumped applying the grazing incidence pump arrangement, where a short (picoseconds) pulse irradiates a Mo plasma column generated by a long (a few hundred picoseconds) pulse. The delayed short pulse is incident at a grazing angle on the plasma to heat it efficiently. We used a total energy of less than 450 mJ ( 150 mJ in the long and 250-300 mJ in the short pulse) in a line focus of 7 mm by 50 microm .


Tooth wear in children with Down syndrome.
Several studies have described the impact that dental caries and periodontitis may have on the dentitions of individuals with Down syndrome, but there are few reports about the effects of tooth wear. This investigation aimed to compare the aetiology, prevalence and severity of tooth wear in 49 cytogenetically confirmed Down syndrome children with 49 non-Down syndrome controls. This study involved three aspects: an oral examination, including obtaining dental impressions; a dietary analysis spanning three days; and a questionnaire seeking information about habits, medical problems and medications. Tooth wear severity was scored on a 4-grade scale (none-to-little; moderate; severe; very severe), while aetiology was classified as being due to attrition mainly, erosion mainly, or a combination of both. Double determinations established scoring method reliability and chi-square tests assessed associations between samples. Tooth wear was significantly more frequent (p<0.01) in the Down syndrome than the non-Down syndrome sample (67.4 per cent cf 34.7 per cent), with more of the Down syndrome children showing severe to very severe wear (59.2 per cent cf 8.2 per cent). Significantly more Down syndrome children (p<0.05) displayed a multifactorial aetiology of tooth wear, i.e., both attrition and erosion (46.7 per cent cf 28.6 per cent), although no particular dietary link was established. Gastric reflux and vomiting were reported in over 20 per cent of the Down syndrome sample. Given the potential consequences of high levels of tooth wear, associated with tooth grinding and an acidic oral environment in Down syndrome children, educational programmes aimed at increasing awareness of carers and health professionals are needed urgently.


Use of the articulation index for assessing residual auditory function in listeners with sensorineural hearing impairment.
Two experiments were performed to explore the feasibility of deriving an articulation index (AI) based scheme for quantifying residual auditory function in listeners with sensorineural hearing impairment. In the first experiment the AI procedure was applied to audiograms of normal and sensorineural hearing-impaired individuals in order to predict speech discrimination under various conditions. Good predictions were found for the normal and the less impaired subjects, but not for those with greater impairments. These subjects exhibited a disproportionate loss in speech discrimination compared to that predicted on the basis of the AI procedure. In the second experiment it was investigated whether the AI predictions for presbycusic individuals could be improved by making use of the proficiency factor that is not a function of frequency. The results indicate that the deficit in suprathreshold speech processing is frequency-specific and that, therefore, the proficiency factor is not independent of frequency. It assumes the value of 1 at those frequencies where hearing sensitivity is normal and is substantially reduced for frequencies where hearing threshold is elevated.


Significance of changes in FGF23 levels in childhood primary nephrotic syndrome and children who progress to end‑stage renal disease.
Fibroblast growth factor 23 (FGF23) is an important phosphaturic hormone, yet few studies have focused on FGF23 in children with primary nephrotic syndrome (PNS) and children who progressed to end-stage renal disease (ESRD). This cross-sectional study investigated the significance of changes in FGF23 levels in childhood PNS and children who progressed to ESRD. Of the 41 children included in the study, 17 had PNS with proteinuria and normal renal function (PNS group), 4 had ESRD (ESRD group), and 20 were healthy (control group). Following corticosteroid treatment, patients with PNS and proteinuria entered the remission phase. Serum levels of FGF23, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH-D), and calcium were measured. It was found that FGF23 levels in the PNS and ESRD groups were higher than those in the control group, while serum 25-OH-D levels were lower. Serum PTH levels increased significantly in the ESRD group. In the control group, FGF23 levels were negatively correlated with serum PTH and positively correlated with serum 25-OH-D. FGF23 levels were positively correlated with serum calcium and corrected calcium levels in children with PNS during the remission phase. Increased FGF23 levels in children with PNS, particularly in children who progressed to ESRD. It was also confirmed that serum FGF23 levels begin to rise in children with PNS prior to Stage 1 chronic kidney disease. These findings indicated that increased FGF23 levels may be associated with the progression and severity of nephrosis in children, and that serum FGF23 levels were useful for early detection of abnormal mineral metabolism in children with PNS.


SitePrint: three-dimensional pharmacophore descriptors derived from protein binding sites for family based active site analysis, classification, and drug design.
Integrating biological and chemical information is one key task in drug discovery, and one approach to attaining this goal is via three-dimensional pharmacophore descriptors derived from protein binding sites. The SitePrint program generates, aligns, scores, and classifies three-dimensional pharmacophore descriptors, active site grids, and ligand surfaces. The descriptors are formed from molecular fragments that have been docked, minimized, filtered, and clustered in protein active sites. The descriptors have geometric coordinates derived from the fragment positions, and they capture the shape, electrostatics, locations, and angles of entry into pockets of the recognition sites: they also provide a direct link to databases of organic molecules. The descriptors have been shown to be robust with respect to small changes in protein structure observed when multiple compounds are cocrystallized in a protein. Five aligned thrombin cocrystals with an average core alpha-carbon RMSD of 0.7 A gave three-dimensional pharmacophore descriptors with an average RMSD of 1.1 A. On a larger test set, alignment and scoring of the descriptors using clique-based alignment, and a best first search strategy with an adapted forward-looking Ullmann heuristic was able to select the global minimum three-dimensional alignment in twenty-nine out of thirty cases in less than one CPU second on a workstation. A protein family based analysis was then performed to demonstrate the usefulness of the method in producing a correlation of active site pharmacophore descriptors to protein function. Each protein in a test set of thirty was assigned membership to a family based on computed active site similarity to the following families: kinases, nuclear receptors, the aspartyl, cysteine, serine, and metallo proteases. This method of classifying proteins is complementary to approaches based on sequence or fold homology. The values within protein families for correctly assigning membership of a protein to a family ranged from 25% to 80%.


A(II)GeTeO6 (A = Mn, Cd, Pb): Non-Centrosymmetric Layered Tellurates with PbSb2O6-Related Structure.
A(II)GeTeO6 (A = Mn, Cd, Pb), new non-centrosymmetric (NCS) honeycomb-layered tellurates, were synthesized and characterized. A(II)GeTeO6 (A = Mn, Cd, Pb) crystallize in trigonal space group P312 (No. 149) of edge-sharing Ge4+O6 and Te6+O6 octahedra, which form honeycomb-like-layers in the ab-plane with A(II) (A = Mn, Cd, Pb) cations located between the layers. Their crystal structures are PbSb2O6-related, and the ordering of Ge4+ and Te6+ in octahedral environment breaks the inversion symmetry of the parent PbSb2O6 structure. The size of A(II) cation in six coordination is an important factor to stabilize PbSb2O6-based structure. Temperature-dependent optical second harmonic generation measurements on A(II)GeTeO6 confirmed non-centrosymmetric character in the entire scanned temperature range (0 to 600 °C). The materials exhibit a powder SHG efficiency of ∼0.37 and ∼0.21 times of KH2PO4 for PbGeTeO6 and CdGeTeO6, respectively. Magnetic measurements of MnGeTeO6 indicate anti-ferromagnetic order at TN ≈ 9.4 K with Weiss temperature of -22.47 K.


A novel cuproptosis pattern and tumor immune microenvironment characterization in urothelial carcinoma of the bladder.
Urothelial carcinoma of the bladder (UCB) is the most prevalent malignant tumor of the urinary system worldwide, which has a significant recurrence rate despite multiple treatment options available. As a unique and novel copper-dependent programmed cell death mechanism, the comprehensive impact of cuproptosis on the tumor immune microenvironment, clinicopathological characteristics and the prognosis of patients remains largely unclear. A total of 568 UCB samples were thoroughly examined for cuproptosis patterns using data downloaded from TCGA and GEO, based on 10 cuproptosis-related genes reported previously. Then, the univariate COX regression analysis was performed on the genes that differed across the various patterns. To measure individual cuproptosis pattern, a cuproptosis score system was constructed using a principal component analysis algorithm. To validate the scoring system, immunohistochemical staining was performed on tumor tissues with different pathological grades, and experiments in vitro were conducted about the differentially expressed genes related to prognosis. Finally, the capacity of scoring system to predict the response to immunotherapy was verified by using data from IMvigor 210 cohort. Four unique cuproptosis clusters and two gene clusters were finally found by the investigation. The clinical features and prognosis of patients, as well as the mRNA transcriptome, pathway enrichment, and immune cell infiltration in TME, varied dramatically between various cuproptosis clusters and gene clusters. To identify individual cuproptosis patterns in UCB patients, we also established a cuproptosis scoring system. After validation with multiple methods, it was indicated that the score system could predict the prognosis of UCB patients and was significantly connected to clinical features such TNM category, tumor grade, molecular type and ultimate survival status. The clinical outcomes of UCB patients were predicted effectively according to the tumor mutation burden in conjunction with the scoring system. Furthermore, we found that the cuproptosis score had a significant correlation with the response to immunotherapy and the sensitivity to chemotherapy. This study revealed the potential impact of cuproptosis on the UCB tumor immune microenvironment and clinical pathological characteristics. The cuproptosis score system could effectively predict the prognosis of patients and the response to chemotherapy and immunotherapy.


Shedding light on human cerebral lipofuscin: An explorative study on identification and quantification.
Increased oxidative stress has been associated with several neurodegenerative diseases such as Alzheimer's disease, but also with neurological diseases sharing pathophysiological pathways like epilepsy. Lipofuscin is a nondegradable end-product of oxidative stress; its cerebral presence reflects the cumulative amount of oxidative stress the brain has endured. In this study, we have observed prominent autofluorescent particles in the pial arterial wall and in neocortical parenchyma of young, drug-resistant epilepsy patients (18-28 years old) who underwent resective brain surgery (n = 6), as well as in older control patients (n = 3). With fluorescence spectroscopic imaging, brightfield microscopy, histochemistry and fluorescence lifetime imaging, these autofluorescent particles were identified as the age pigment lipofuscin. An evaluation of these lipofuscin particles using Imaris© software allowed robust quantification, while the 3D properties allowed visualization of the complex configuration. We elaborate on the usefulness of lipofuscin as a marker of cumulative oxidative stress in the brain. Furthermore, we speculate on the observed differences in particle size and density that we found between young patients and older controls, which could imply a role for lipofuscin in the pathophysiology of epilepsy and possibly other neurological diseases.


Outcomes of Patients on the Lung Transplantation Waitlist in Korea: A Korean Network for Organ Sharing Data Analysis.
The demand for lung transplants continues to increase in Korea, and donor shortages and waitlist mortality are critical issues. This study aimed to evaluate the factors that affect waitlist outcomes from the time of registration for lung transplantation in Korea. Data were obtained from the Korean Network for Organ Sharing for lung-only registrations between September 7, 2009, and December 31, 2020. Post-registration outcomes were evaluated according to the lung disease category, blood group, and age. Among the 1,671 registered patients, 49.1% had idiopathic pulmonary fibrosis (group C), 37.0% had acute respiratory distress syndrome and other interstitial lung diseases (group D), 7.2% had chronic obstructive pulmonary disease (group A), and 6.6% had primary pulmonary hypertension (group B). Approximately half of the patients (46.1%) were transplanted within 1 year of registration, while 31.8% died without receiving a lung transplant within 1 year of registration. Data from 1,611 patients were used to analyze 1-year post-registration outcomes, which were classified as transplanted (46.1%, n = 743), still awaiting (21.1%, n = 340), removed (0.9%, n = 15), and death on waitlist (31.8%, n = 513). No significant difference was found in the transplantation rate according to the year of registration. However, significant differences occurred between the waitlist mortality rates (P = 0.008) and the still awaiting rates (P = 0.009). The chance of transplantation after listing varies depending on the disease category, blood type, age, and urgency status. Waitlist mortality within 1 year was significantly associated with non-group A disease (hazard ratio [HR], 2.76, P < 0.001), age ≥ 65 years (HR, 1.48, P < 0.001), and status 0 at registration (HR, 2.10, P < 0.001). Waitlist mortality is still higher in Korea than in other countries. Future revisions to the lung allocation system should take into consideration the high waitlist mortality and donor shortages.


Controlled syntheses, characterization, and reactivity of neutral and anionic lanthanide amides supported by methylene-linked bis(phenolate) ligands.
A series of neutral and anionic bis(phenolate) lanthanide amides were synthesized by general metathesis reactions, and their reactivity was explored. Protolytic ligand exchange reactions of MBMPH2 (MBMP = 2,2'-methylene bis(6-tert-butyl-4-methyl-phenolate)) with [Ln{N(TMS)2}2(mu-Cl)(THF)]2 (TMS = SiMe3) afforded the desired bridged bis(phenolate) lanthanide chlorides [(MBMP)Ln(mu-Cl)(THF)2]2 [Ln = Nd (1), Yb (2)] in high isolated yields. These lanthanide chlorides were found to be useful precursors for the synthesis of the corresponding lanthanide derivatives. Reactions of 1 and 2 with 2 equiv of NaN(TMS)2 in THF produced the expected neutral bis(phenolate) lanthanide amido complexes (MBMP)Ln[N(TMS)2](THF)2 [Ln = Nd (3), Yb (4)] in high yields. Whereas the reactions of 1 and 2 with LiN(TMS)2 in a 1:4 molar ratio gave the anionic bis(phenolate) lanthanide amides as discrete ion-pair complexes [Li(THF)4][(MBMP)Ln{N(TMS)2}2] [Ln = Nd (5), Yb (6)] in high isolated yields. Further study revealed that 5 and 6 can also be conveniently synthesized in high yields by the direct reactions of MBMPH2 with [Ln{N(TMS)2}2(mu-Cl)(THF)]2 in a 2:1 molar ratio, and then with 4 equiv of nBuLi. The reactivity of the neutral and anionic bis(phenolate) lanthanide amides was comparatively investigated. It was found that the insertion reactions of carbodiimide into the Ln-N bond of neutral lanthanide amido complexes 3 and 4 gave the anticipated bis(phenolate) lanthanide guanidinate complexes [(mu-O-MBMP)Nd{(iPrN)2CN(TMS)2}]2 (7) and (MBMP)Yb[(iPrN)2CN(TMS)2] (8), respectively, in high yields, whereas the similar reaction of carbodiimide with anionic amido complex 5 provided the unexpected ligand-redistributed products, and the homoleptic ion-pair bis(phenolate) neodymium complex [Li(DME)2(THF)][(MBMP)2Nd(THF)2] (9) was finally isolated as one of the products. Furthermore, the anionic bis(phenolate) lanthanide amides showed higher catalytic activity for the polymerization of epsilon-caprolactone than the neutral ones. All of the complexes were characterized with elemental analysis and IR spectra, and the definitive molecular structures of 1-3 and 5-9 were provided by single-crystal X-ray analyses.


Reimagining global mental health in Africa.
In 2001, the WHO launched The World Health Report most specifically addressing low-income and middle-income countries (LAMICs). It highlighted the importance of mental health (MH), identifying the severe public health impacts of mental ill health and made 10 recommendations. In 2022, the WHO launched another world MH report and reaffirmed the 10 recommendations, while concluding that 'business as usual for MH will simply not do' without higher infusions of money. This paper suggests the reason for so little change over the last 20 years is due to the importation and imposition of Western MH models and frameworks of training, service development and research on the assumption they are relevant and acceptable to Africans in LAMICs. This ignores the fact that most mental and physical primary care occurs within local non-Western traditions of healthcare that are dismissed and assumed irrelevant by Western frameworks. These trusted local institutions of healthcare that operate in homes and spiritual spaces are in tune with the lives and culture of local people. We propose that Western foundations of MH knowledge are not universal nor are their assumptions of society globally applicable. Real change in the MH of LAMICs requires reimagining. Local idioms of distress and healing, and explanatory models of suffering within particular populations, are needed to guide the development of training curricula, research and services. An integration of Western frameworks into these more successful approaches are more likely to contribute to the betterment of MH for peoples in LAMICs.


Prevalence and time trends of overweight, obesity and severe obesity in 447,925 Swedish adults, 1995-2017.
Aims: The purpose of this research was to describe the current prevalence and historic trends in overweight, obesity and severe obesity in Sweden. Methods: Data on BMI, age, gender, education and geographic region were obtained in n=447,925 Swedish adults through a nationwide screening test (1995-2017). To account for sampling variations, we quantified prevalence estimates and time trends using standardized values (direct method) to all 18-74-year-old Swedes, using nationwide databases. Rates of overweight (BMI ⩾25 kg/m2), obesity (BMI ⩾30 kg/m2) and severe obesity (BMI ⩾35 kg/m2) were calculated across gender, age, education and geographic categories. Years were grouped into two-year sampling periods (except the first period where we used three years) for increased power. We used multivariable logistic regression to quantify independent associations between age, gender, education and region with obesity development and current prevalence rates. Results: In 2016/17 the unstandardized prevalence of overweight, obesity and severe obesity were 55.1%, 16.6% and 4.2%, respectively. Factors associated with a higher obesity prevalence were male gender, older age, lower education and residing in a rural region (all P<0.001). Between 1995 and 2017 the prevalence of severe obesity increased by 153%, compared to obesity (+86%) and overweight (+23%). While there were similar increases in obesity across gender and age groups, people with low education (vs high) and rural areas (vs urban) had a higher prevalence increase (both P<0.001). Conclusions: Rates of overweight, obesity and severe obesity have increased markedly in Swedish adults since 1995. Priority groups for prevention efforts include individuals with low education and those living in rural areas.


The effect of granulocyte and granulocyte-macrophage colony stimulating factors on tumor promotion.
GM-CSF and G-CSF are capable to regulate the maturation of undifferentiated multipotent stem cells into mature granulocytes, macrophages and T cells in the bone marrow. Thereby, clinicians correct neutropenia induced by chemotherapy or radiation routinely with recombinant G- or GM-CSFs in clinical practice. However, relevant studies found that treatment for cancer patients with adjuvant G-/GM-CSF would occasionally enhance the progression of tumors. Besides, constitutive production of G-CSF or GM-CSF by lung cancer cells could stimulate the growth or the invasion of tumor and result in protecting the tumor against unfavorable environment. These findings convinced researchers that G-/GM-CSF overexpression has a positive effect on malignant tumor progression. The purpose of this article was to explore the most recent research and the mechanisms of GM-CSF and G-CSF-induced tumor promotion and their clinical therapeutic applications.


Systemic antibiotics for acne.
Antibiotic therapy for acne is very common. Antibiotics are frequently used in acne, either systemically or topically. Systemic antibiotics are indicated as treatment of moderate and quite severe acne or if acne is considered as very serious by the patient for psychological or social reasons. Results are very often excellent, but failure is possible; in this case using another treatment, especially isotretinoin, is necessary. A few antibiotics are useful: tetracyclines (tetracycline, doxycycline, minocycline, lymecycline), erythromycin, co-trimoxazole and trimethoprim. Their side effects are reviewed. During pregnancy the best antibiotic is erythromycin. For the nursing mother it is generally said that tetracyclines are contraindicated but the risks if they exist are certainly slight. The mechanism of action of systemic antibiotics for acne is not perfectly clear as it is not only antimicrobial: they diminish chemotaxis of polymorphonuclear leukocytes, modify the complement pathways and inhibit the polymorphonuclear leukocyte chemotactic factor and the lipase production in Propionibacterium acnes.


Plant growth-promoting rhizobacteria-mediated induction of phenolics in pea ( Pisum sativum) after infection with Erysiphe pisi.
Qualitative and quantitative estimation of phenolic compounds was done through high performance liquid chromatography (HPLC) in different parts of pea ( Pisum sativum) after treatment with two plant growth-promoting rhizobacteria (PGPR), viz., Pseudomonas fluorescens (strain Pf4) and Pseudomonas aeruginosa (referred to here as Pag) and infection by Erysiphe pisi. The phenolic compounds detected were tannic, gallic, ferulic, and cinnamic acids on the basis of their retention time in HPLC. In all the treated plants, synthesis of phenolic compounds was enhanced. The induction of gallic, ferulic, and cinnamic acids was manyfold more than those in the control. Maximum accumulation of phenolic compounds was observed in plants raised from PGPR-treated seeds and infection with E. pisi. Under pathogenic stress, Pag performed better because a relatively higher amount of phenolics was induced compared with plants treated with Pf4.


ESR spin trapping investigation on peroxynitrite decomposition: no evidence for hydroxyl radical production.
The decomposition of peroxynitrite in the presence of 5,5-dimethyl-1-pyrroline N-oxide (DMPO) generated 5,5-dimethylpyrrolidone-(2)-oxy-(1) (DMPOX) without formation of DMPO/OH. Formate enhanced the peroxynitrite decomposition but did not generate any detectable amount of formate-derived free radicals. Glutathione, cysteine, penicillamine, and ascorbate reacted with peroxynitrite to generate the corresponding thiyl and ascorbyl radicals. The results show that the decomposition of peroxynitrite did not generate any significant amount of OH radicals, and one-electron reduction of peroxynitrite by ascorbate may be one of the important peroxynitrite detoxification pathways.


A study of molecular complex formation between propyl gallate and ascorbic acid in the microemulsion phase of sodium dodecyl sulfate, pentanol and water system.
The association between two water-soluble antioxidants, i.e. ascorbic acid and propyl gallate have been studied by absorption spectroscopy in microemulsion formed in sodium dodecyl sulfate/pentanol/water micellar system. It has been shown that propyl gallate forms 1:1 molecular complex with ascorbic acid in every solution. Evolution of the absorption spectra during the study of molecular complex formation goes through well-defined isosbestic points. The association constants were calculated using curve-fitting procedure. The observed interactions are stronger in the less polar solvents.


Influence of Waist Circumference Measurement Site on Visceral Fat and Metabolic Risk in Youth.
Although the rate of childhood obesity seems to have plateaued in recent years, the prevalence of obesity among children and adolescents remains high. Childhood obesity is a major public health concern as overweight and obese youth suffer from many co-morbid conditions once considered exclusive to adults. It is now well demonstrated that abdominal obesity as measured by waist circumference (WC) is an independent risk factor for cardiovascular disease and metabolic dysfunction in youth. Despite the strong associations between WC and cardiometabolic risk factors, there is no consensus regarding the optimal WC measurement sites to assess abdominal obesity and obesity-related health risk in children and adolescents. Currently, the WC measurement site that provides the best reflections of visceral fat and the best correlations with cardiometabolic risk factors is unclear. The purpose of this review is to explore whether WC measurement sites influence the relationships between WC, visceral fat, and cardiometabolic risk factors in children and adolescents.


Absence of fractionation of mercury isotopes during trophic transfer of methylmercury to freshwater fish in captivity.
We performed two controlled experiments to determine the amount of mass-dependent and mass-independent fractionation (MDF and MIF) of methylmercury (MeHg) during trophic transfer into fish. In experiment 1, juvenile yellow perch (Perca flavescens) were raised in captivity on commercial food pellets and then their diet was either maintained on unamended food pellets (0.1 μg/g MeHg) or was switched to food pellets with 1.0 μg/g or 4.0 μg/g of added MeHg, for a period of 2 months. The difference in δ(202)Hg (MDF) and Δ(199)Hg (MIF) between fish tissues and food pellets with added MeHg was within the analytical uncertainty (δ(202)Hg, 0.07 ‰; Δ(199)Hg, 0.06 ‰), indicating no isotope fractionation. In experiment 2, lake trout (Salvelinus namaycush) were raised in captivity on food pellets and then shifted to a diet of bloater (Coregonus hoyi) for 6 months. The δ(202)Hg and Δ(199)Hg of the lake trout equaled the isotopic composition of the bloater after 6 months, reflecting reequilibration of the Hg isotopic composition of the fish to new food sources and a lack of isotope fractionation during trophic transfer. We suggest that the stable Hg isotope ratios in fish can be used to trace environmental sources of Hg in aquatic ecosystems.


4.6-billion-year-old aragonite and its implications for understanding the geological record of Ca-carbonate.
Owing to its diagenetic instability, aragonite is rare in the geological record and almost entirely absent from pre-carboniferous sedimentary rocks. The former presence of this mineral in older deposits has to be inferred from petrographic, chemical or isotopic proxies. Crystals of aragonite that formed around 4563 million years ago occur in carbonaceous chondrite meteorites, showing that under certain conditions, the orthorhombic polymorph of Ca-carbonate can survive essentially indefinitely. Together with other carbonate minerals, phyllosilicates and sulphides, this aragonite formed by low-temperature water-mediated alteration of anhydrous minerals and glass in the interior of the meteorite's parent asteroid(s). The survival of aragonite for such a long time can be attributed to the loss of free water by its incorporation into phyllosilicates, and to the very low permeability of the fine-grained and organic-rich rock matrix that prevented the ingress of fresh solutions via intergranular flow. By analogy with these meteorites, terrestrial aragonite is likely to survive where it has been similarly isolated from liquid water, particularly in organic-rich mudrocks, and such deposits may provide important new evidence for deducing the original mineralogy of skeletal and non-skeletal carbonates in deep-time.


[Population dynamics and armed violence in Colombia, 1985-2010].
Describe changes in the population structure of Colombia's municipalities in relation to internal displacement in response to armed violence. A descriptive ecological study was carried out. Secondary sources were consulted, taken from the Consolidated Registry of Displaced Population and from the National Administrative Department of Statistics, to calculate expulsion and reception rates for population displaced by violence from 2002 to 2010. Based on these rates, four groups were created of municipalities in the extreme quartile for each rate during the entire period, which were classified as high expulsion, low expulsion, high reception, and low reception. Subsequently, population pyramids and structure indicators were constructed for each group of municipalities for two comparative reference years (1985 and 2010). Municipalities with high expulsion or reception rates experienced a slower epidemiological transition, with lower mean ages and aging indices. The high expulsion group had the least regression, based on the Sundbärg index. In the high reception group, the masculinity ratio decreased the most, especially among the economically active population, and it had the highest population growth. Population dynamics in Colombia have been affected by armed violence and changes in these dynamics are not uniform across the country, leading to important social, economic, and cultural consequences. This study is useful for decision-making and public policy making.


Quality assurance of ambulatory child health care opinions of practicing physicians about proposed criteria.
This paper reports the opinions of a representative sample of 1,329 physicians providing primary care regarding criteria developed by the Joint Committee on Quality Assurance for evaluation of ambulatory child health care. Areas of care were health supervision (in four age ranges), tonsillopharyngitis, bronchial asthma, and urinary infection. The criteria had been previously appraised by 452 "experts"--academicians and practitioners. Physicians rated criteria for relevance to health outcome, and desirability for use in peer review. They also stated whether they usually performed and recorded each item and gave reasons for not recording. Agreement between the pediatricians and other physicians of the sample and the "experts" was close regarding relevance to health outcome, but many fewer criteria were recommended for peer review by the sample. A significant number of respondents said they performed but did not record many of the criteria. Documentation of only abnormal findings was the main reason given for not recording. Criteria dealing with developmental or behavioral assessment or with counseling were rated lower in all categories than more easily measured items.


Predicting respiratory distress by thin-layer chromatography of the newborn gastric aspirate.
The analysis of gastric fluid from newborns for lecithin/sphingomyelin (L/S) ratio evaluation is useful in determining whether respiratory distress will follow an early delivery. Without exception, the L/S ratios obtained on 14 gastric aspirates paralleled and were slightly higher than intrapartum values obtained from corresponding amniotic fluids (5.6 vs 3.7). Of 46 normal infants, only 1 had a gastric aspirate L/S ratio less than 2:1. No false positive results were found. The obstetrician can easily obtain gastric fluid at delivery, and by ordering an L/S ratio determination, the neonatologist can have an estimation of lung surfactant levels within 2 hours after birth. In cases where true respiratory distress syndrome (RDS) must be differentiated from other problems of respiratory distress, this information can assist in the early management of patients with RDS. Even after the development of RDS, the procedure offers a prognostic tool which the clinician can use in discussing the outcome with the parents.


Construction of human corneal endothelial cDNA library and identification of novel active genes.
To describe genes expressed in human corneal endothelial cells and identify novel genes. Sixteen human donor corneas that had no history of corneal disease, infection, or intraocular surgery were used within 7 days of death. Total RNA was extracted from corneal endothelial cells with attached Descemet membranes. A 3'-directed cDNA library was constructed from mRNA by using a pUC19-based primer. These sequences were compared with each other to determine their frequency and were searched against GenBank for identification. To identify novel specific and abundant transcript genes in corneal endothelial cells, the novel genes were compared with an expressed sequence tag database, the expected sequence extended, and 5' rapid amplification of cDNA ends-polymerase chain reaction cloning performed. The human corneal endothelial cDNA library showed that the most abundant transcript was prostaglandin D2 synthase. The remaining transcript genes that were present in abundance consisted of lactate dehydrogenase-A, gene signature (GS) 3582, which is a novel gene without a known function, and matrix Gla protein. The full-length sequence of GS3582 showed similarity to genes obtained in ovary and TESTIS. A human corneal endothelial cDNA library was constructed. An expression profile of corneal endothelium provides probes to monitor physiologic and pathologic conditions of this tissue in terms of gene expression.


Electrocardiographic changes in measles.
Electrocardiograms (ECGs) were recorded in 100 Nigerian children with measles admitted to our paediatric wards or treated on an out-patient basis. The patients were aged 5 months-8 years (mean, 19 months) and the male:female ratio was 1.3:1. Similar recordings were obtained in 100 age- and sex-matched controls. The electrocardiographic changes observed include T wave inversion in 28 patients and prolonged P-R interval in 22. Other changes are prolonged Q-Tc (13 patients), low QRS amplitude (13 patients), abnormal QRS axes in the frontal plane (5 patients) and T wave flattening (4 patients). A statistically significant difference between patients and controls with respect to the above changes was demonstrated in T wave inversion and prolonged P-R interval--the latter in the 5 months-1 year age group. Hence, 35 patients had at least one statistically significant ECG change, giving a prevalence rate of 35%. The implications of the above findings are discussed and the need to intensify efforts aimed at immunizing all children against measles is stressed.


Does feather corticosterone reflect individual quality or external stress in arctic-nesting migratory birds?
The effects of environmental perturbations or stressors on individual states can be carried over to subsequent life stages and ultimately affect survival and reproduction. The concentration of corticosterone (CORT) in feathers is an integrated measure of hypothalamic-pituitary-adrenal activity during the molting period, providing information on the total baseline and stress-induced CORT secreted during the period of feather growth. Common eiders and greater snow geese replace all flight feathers once a year during the pre-basic molt, which occurs following breeding. Thus, CORT contained in feathers of pre-breeding individuals sampled in spring reflects the total CORT secreted during the previous molting event, which may provide insight into the magnitude or extent of stress experienced during this time period. We used data from multiple recaptures to disentangle the contribution of individual quality vs. external factors (i.e., breeding investment or environmental conditions) on feather CORT in arctic-nesting waterfowl. Our results revealed no repeatability of feather CORT within individuals of either species. In common eiders, feather CORT was not affected by prior reproductive investment, nor by pre-breeding (spring) body condition prior to the molting period. Individual feather CORT greatly varied according to the year, and August-September temperatures explained most of the annual variation in feather CORT. Understanding mechanisms that affect energetic costs and stress responses during molting will require further studies either using long-term data or experiments. Although our study period encompassed only five years, it nonetheless provides evidence that CORT measured in feathers likely reflects responses to environmental conditions experienced by birds during molt, and could be used as a metric to study carry-over effects.


Safety and outcome of patients with an acute ST-elevation myocardial infarction transferred for primary coronary intervention: the Neuchâtel experience.
Transferring patients with ST-elevation myocardial infarction (STEMI) for primary percutaneous coronary intervention (PCI) from a community hospital to a PCI centre has been evaluated in randomised trials and shown to be safe and effective. A prolonged transfer time may restrict the benefit of this strategy. We sought to assess 1) safety of transfer from Neuchâtel to Berne, 2) time intervals of patients transferred either directly from on-site or after evaluation in the local emergency room, and 3) clinical long-term outcome. 42 patients with STEMI eligible for reperfusion therapy were prospectively included between January 2003 and June 2004. Twenty patients (48%, group 1) were directly transferred to the PCI centre from on-site. Twenty-two were transferred after initial treatment in the local emergency room: 11 patients (26%, group 2) presented spontaneously at the hospital and 11 patients (26%, group 3) were admitted by the rescue team. No major complication occurred during transport. Median transport time was 33 minutes. Median time from first healthcare contact to balloon consisted of 131 minutes in group 1, 158 minutes in group 2 and 174 minutes in group 3. The overall rate of Major Adverse Cardiac Events (MACE) at 6 months amounted to 9.5%. Transfer for primary PCI of our patients with acute STEMI was safe. Direct transfer from on-site to the PCI centre reduced the time of ischaemia. The overall MACE rate was low.


Adverse drug reactions as a cause for admissions to a department of internal medicine.
To assess the occurrence and pattern of adverse drug reactions as a cause for acute hospital admission. In 681 randomly selected patients, acutely admitted to a clinic of internal medicine at a Swedish university hospital, information was collected from their medical records about current symptoms and use of drugs, previous diseases and the results of medical investigations and tests. In addition, a standardized interview according to a questionnaire was carried out. A group of experts in clinical pharmacology assessed the data obtained from the patients' case records and the results of the interviews, and then, according to WHO criteria, judged the probability that an adverse drug reaction could have caused or contributed to the actual admission to hospital. Out of the 681 cases included, 94 (13.8%) had symptoms and signs that were judged as drug-related and that had caused or contributed to the admission. Eighty-two patients (12.0%) had altogether 99 symptoms that were classified as adverse drug reactions. Of these, 91% were type A reactions. The relationship between the medication and the reaction was judged certain in eight, probable in 17, and possible in 74 cases. The most common adverse drug reactions were cardiovascular (36.3%). Twelve patients (1.8%) had symptoms indicating intoxications. The prevalence of drug-related problems causing or contributing to admission to a clinic of internal medicine is high and is dominated by type A reactions, i.e. reactions in principle predictable and preventable. This implies a possibility to increase drug safety by preventive measures.


Microscopic Authentication of Commercial Herbal Products in the Globalized Market: Potential and Limitations.
Herbal products are marketed and used around the globe for their claimed or expected health benefits, but their increasing demand has resulted in a proportionally increase of their accidental contamination or intentional adulteration, as already confirmed with DNA-based methods. Microscopy is a traditional pharmacopoeial method used for plant identification and we systematically searched for peer-reviewed publications to document its potential and limitations to authenticate herbal medicines and food supplements commercially available on the global market. The overall authenticity of 508 microscopically authenticated herbal products, sold in 13 countries, was 59%, while the rest of 41% were found to be adulterated. This problem was extending over all continents. At the national level, there were conspicuous differences, even between neighboring countries. These microscopically authenticated commercial herbal products confirm that different magnifying instruments can be used to authenticate crude or processed herbal products traded in the global marketplace. The reviewed publications report the successful use of different magnifying instruments, single or in combinations with a second one, with or without a chemical or DNA-based technique. Microscopy is therefore a rapid and cost-efficient method, and can cope with mixtures and impurities. However, it has limited applicability for highly processed samples. Microscopic authentication of commercial herbal products will therefore contribute to raise public awareness for the extent of adulteration and the need to safeguard consumer safety against the challenges of globalization.


Bundles of Brain Microtubules Generate Electrical Oscillations.
Microtubules (MTs) are long cylindrical structures of the cytoskeleton that control cell division, intracellular transport, and the shape of cells. MTs also form bundles, which are particularly prominent in neurons, where they help define axons and dendrites. MTs are bio-electrochemical transistors that form nonlinear electrical transmission lines. However, the electrical properties of most MT structures remain largely unknown. Here we show that bundles of brain MTs spontaneously generate electrical oscillations and bursts of electrical activity similar to action potentials. Under intracellular-like conditions, voltage-clamped MT bundles displayed electrical oscillations with a prominent fundamental frequency at 39 Hz that progressed through various periodic regimes. The electrical oscillations represented, in average, a 258% change in the ionic conductance of the MT structures. Interestingly, voltage-clamped membrane-permeabilized neurites of cultured mouse hippocampal neurons were also capable of both, generating electrical oscillations, and conducting the electrical signals along the length of the structure. Our findings indicate that electrical oscillations are an intrinsic property of brain MT bundles, which may have important implications in the control of various neuronal functions, including the gating and regulation of cytoskeleton-regulated excitable ion channels and electrical activity that may aid and extend to higher brain functions such as memory and consciousness.


There are no in vivo pulsations of mouse blastocysts.
An important event at the onset of the implantation process in mammals is the hatching of the blastocyst from the zona pellucida. Microcinematographic studies of in vitro preimplantation development in mice revealed the pulsatile activity of blastocysts before and during the hatching period. It is generally accepted--up to now--that the in vitro hatching is at least partially the result of repeated contractions and reexpansions of the blastocyst. The presence of pulsatile activity in vivo may confirm this hypothesis. Mouse blastocysts were obtained by a rapid flushing (5-10') from uterine horns on day 4 of pregnancy and the presence or absence of contracted blastocysts was noted. From 410 examined blastocysts only 3% were contracted as compared with the very frequent in vitro pulsations. This result suggests that in mice the in vivo pulsatile activity of blastocysts, practically, does not exist. The in vivo contractions are probably determined by the suboptimal culture conditions.


Dosimetric characterization of a rotating anode x-ray tube for FLASH radiotherapy research.
Most current research toward ultra-high dose rate (FLASH) radiation is conducted with advanced proton and electron accelerators, which are of limited accessibility to basic laboratory research. An economical alternative to charged particle accelerators is to employ high-capacity rotating anode x-ray tubes to produce kilovoltage x-rays at FLASH dose rates at short source-to-surface distances (SSD). This work describes a comprehensive dosimetric evaluation of a rotating anode x-ray tube for potential application in laboratory FLASH study. A commercially available high-capacity fluoroscopy x-ray tube with 75 kW input power was implemented as a potential FLASH irradiator. Radiochromic EBT3 film and thermoluminescent dosimeters (TLDs) were used to investigate the effects of SSD and field size on dose rates and depth-dose characteristics in kV-compatible solid water phantoms. Custom 3D printed accessories were developed to enable reproducible phantom setup at very short SSD. Open and collimated radiation fields were assessed. Despite the lower x-ray energy and short SSD used, FLASH dose rates above 40 Gy/s were achieved for targets up to 10-mm depth in solid water. Maximum surface dose rates of 96 Gy/s were measured in the open field at 47 mm SSD. A non-uniform high-to-low dose gradient was observed in the planar dose distribution, characteristic of anode heel effects. With added collimation, beams up to 10-mm diameter with reasonable uniformity can be produced. Typical 80%-20% penumbra in the collimated x-ray FLASH beams were less than 1 mm at 5-mm depth in phantom. Ramp-up times at the maximum input current were less than 1 ms. Our dosimetric characterization demonstrates that rotating anode x-ray tube technology is capable of producing radiation beams in support of preclinical FLASH radiobiology research.


Morphometric study of emphysema: an hypothesis on the evolution of the anatomic damage of the disease.
Mathematical analysis of morphometric studies on the destruction of pulmonary tissue in cases of centrilobular emphysema has been used to identify degrees and localization of structural damage. From the data, an hypothesis of sequential, cumulative, individual destructive events has been developed to explain the distributive and progressive parenchymal changes in the lungs.


A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain.
Signalling through the receptor protein Notch, which is involved in crucial cell-fate decisions during development, requires ligand-induced cleavage of Notch. This cleavage occurs within the predicted transmembrane domain, releasing the Notch intracellular domain (NICD), and is reminiscent of gamma-secretase-mediated cleavage of beta-amyloid precursor protein (APP), a critical event in the pathogenesis of Alzheimer's disease. A deficiency in presenilin-1 (PS1) inhibits processing of APP by gamma-secretase in mammalian cells, and genetic interactions between Notch and PS1 homologues in Caenorhabditis elegans indicate that the presenilins may modulate the Notch signalling pathway. Here we report that, in mammalian cells, PS1 deficiency also reduces the proteolytic release of NICD from a truncated Notch construct, thus identifying the specific biochemical step of the Notch signalling pathway that is affected by PS1. Moreover, several gamma-secretase inhibitors block this same step in Notch processing, indicating that related protease activities are responsible for cleavage within the predicted transmembrane domains of Notch and APP. Thus the targeting of gamma-secretase for the treatment of Alzheimer's disease may risk toxicity caused by reduced Notch signalling.


Increased right auditory cortex activity in absolute pitch possessors.
We recorded the auditory-evoked magnetic fields from children and adults with absolute pitch during the following tasks: (1) hearing 1000 Hz pure tones inattentively, (2) hearing eight random tones inattentively and (3) listening to eight random tones and identifying each tone. In children with absolute pitch, there was no significant positive correlation between the appearance rate of N100m and the kinds of tasks. In adults with absolute pitch, only the right N100m dipole moments increased significantly in tasks (1) and (2). The present results suggest that the circuit for labeling in the right auditory cortex may lose a function from childhood to adulthood, which reveals neuroplasticity in the development of absolute pitch ability.


De-escalation of High-flow Respiratory Support for Children Admitted with Bronchiolitis: A Quality Improvement Initiative.
Bronchiolitis is the most common cause for hospitalization in the first year of life, with hypoxemia and acute respiratory failure as major determinants leading to hospitalization. In addition, the lack of existing guidelines for weaning and discontinuing supplemental oxygen, including high-flow nasal cannula, may contribute to prolonged hospitalization and increased resource utilization. This single-center quality improvement initiative assessed the effect of implementing a standardized care process for weaning and discontinuing high-flow oxygen for patients hospitalized with bronchiolitis. Patients aged 1-24 months with bronchiolitis admitted to the general wards or ICU step-down unit from February 1, 2018, and January 31, 2020 were included in the study. Primary outcomes included length of stay and time on supplemental oxygen, with time on high-flow oxygen and length of time in ICU step-down unit as secondary outcomes. Balancing measures included transfer rate to Pediatric Intensive Care Unit, intubation rate, 7- and 30-day readmission rates, and 7- and 30-day ED visits after discharge. Following the standardized care process implementation, the mean length of stay decreased from 60.7 hours to 46.7 hours (P < 0.01). In addition, the mean time on any supplemental oxygen decreased by 47% (P < 0.01), the mean time on high-flow oxygen decreased by 45% (P < 0.01), and the mean time in the ICU step-down unit decreased by 27% (P =< 0.01). Balancing measures remained unchanged with no statistically significant differences. Implementing a standardized care process for weaning and discontinuing high-flow oxygen may reduce the length of stay and resource utilization for patients hospitalized with bronchiolitis.


Carotid intima-medial thickness measured on multiple ultrasound frames: evaluation of a DICOM-based software system.
Carotid intima-media thickness (CIMT) measured by B-mode ultrasonography is a marker of atherosclerosis and is commonly used as an outcome in intervention trials. We have developed DICOM-based software that measures CIMT rapidly on multiple end-diastolic image frames. The aims of this study were to compare the performance of our new software with older bitmap-based CIMT measurement software and to determine whether a ten-fold increase in the number of measurements used to calculate mean CIMT would improve reproducibility. Two independent sonographers recorded replicate carotid scans in thirty volunteers and two blinded observers measured CIMT off-line using the new DICOM-based software and older bitmap-based software. A Bland-Altman plot was used to compare CIMT results from the two software programs and t-tests were used to compare analysis times. F-tests were used to compare the co-efficients of variation (CVs) from a standard six-frame measurement protocol with CVs from a sixty-frame measurement protocol. Ordinary least products (OLP) regression was used to test for sonographer and observer biases. The new DICOM-based software was much faster than older bitmap-based software (average measurement time for one scan 3.4 +/- 0.6 minutes versus 8.4 +/- 1.8 minutes, p < 0.0001) but CIMT measurements were larger than those made using the alternative software (+0.02 mm, 95%CI 0.01-0.03 mm). The sixty-frame measurement protocol had worse reproducibility than the six-frame protocol (inter-observer CV 5.1% vs 3.5%, p = 0.004) and inter and intra-observer biases were more pronounced in the sixty-frame than the six-frame results. While the use of DICOM-based software significantly reduced analysis time, a ten-fold increase in the number of measurements used to calculate CIMT did not improve reproducibility. In addition, we found that observer biases caused differences in mean CIMT of a magnitude commonly reported as significant in intervention trials. Our results highlight the importance of good study design with concurrent controls and the need to ensure that no observer drift occurs between baseline and follow-up measurements when CIMT is used to monitor the effect of an intervention.


[Significance of confirming Epstein-Barr virus nuclear antibody as tumor marker].
Study of the association between Epstein-Barr virus (EBV) and the tumors of the nasopharynx renders an opportunity to introduce causal treatment Already have been proven the anti-EBV (anti-Epstein-Barr nucleus antigene) antibodies in the blood serum of the patients infected with EBV, while over 91% of the patients with nasopharyngeal malignant tumors also have a detectable anti-EBV marker. The aim of this research was to determine if there were anti-EBV antibodies in the serum of the patients with the already verified nasopharyngeal malignant tumors, and, if there were, to determine the quantitative ratio to the values in the serum of the healthy controls. The study involved 74 individuals in the period from 1994-2001 divided into four groups: group A counting 11 patients with undifferentiated carcinome of nasopharyngeal type (UCNT); group B counting 25 patients with UCNT X-ray treated at least three years before the onset of the study; group C including 28 healthy subjecets (blood donors), and the group D with 10 patients with planocellular nasopharyngeal carcinoma. Serologic diagnostics of the patients serum was performed using the techniques of Reedman and Klein for the detection of anti-EBV antibodies in the serum. The presence of the statistically significantly higher values of the mean geometric titer (MGT) of the anti-EBNA antibodies was determined in 36 patients with histologically verified UCNT as compared with the control groups including 10 patients with planocellular carcinomas of the nasopharynx and 28 blood donors. Presented were anti-EBNA titers with 95% confidence interval for any participants according to the Hoo clinical classification of nasopharyngeal tumors, as well as according to the fact if they had been radiotreated within the previous three years. The results of this study confirm the conclusions of the recent literature on the possible etiopathogenesis of nasopharyngeal tumors and the use of viral anti-EBNA antibodies as viral markers in the diagnostics of UCNT diseases.


Bioactivities of anastasia black (Russian sweet pepper).
Anastasia Black (Russian sweet pepper) of Capsicum annuum L. var. angulosum Mill. (Solanaceae) was successively extracted with hexane, acetone, methanol and 70% methanol, and the extracts were further separated into a total of twenty-three fractions by silica gel or octadecylsilane (ODS; C18) column chromatography. These extracts and fractions were investigated for their cytotoxicity, anti-human immunodeficiency virus (HIV), anti-Helicobacter pylori (H. pylori), urease inhibition and multidrug resistance (MDR) reversal activity. Some fractions of hexane and acetone extracts showed higher cytotoxic activity against three human oral tumor cell lines (squamous cell carcinoma HSC-2, HSC-3, submandibular gland carcinoma HSG) than against three normal human oral cells (gingival fibroblast HGF, pulp cell HPC, periodontal ligament fibroblast HPLF), suggesting a tumor-specific cytotoxic activity. No fractions displayed anti-HIV activity, but some hydrophobic fractions showed higher anti-H. pylori activity, urease inhibition activity and MDR reversal activity. The higher MDR activity of these fractions against MDR gene-transfected L5178 mouse lymphoma T cells may possibly be due to their higher content of carotene or polyphenol. These data suggest that Anastasia Black should be further investigated as a potent supplement for cancer chemotherapy.


Factors Affecting Long-Term Postoperative Narcotic Use in Discectomy Patients.
Long-term narcotic use has risks and potentially life-threatening opioid-related side effects. Extended narcotic use in patients undergoing discectomy raises concerns of other underlying causes of pain or overprescription and/or abuse. The goal of this study was to determine which factors have an effect on active narcotic prescription >3 months after discectomy. The PearlDiver Database was used in this study. Patients 30-55 years old undergoing discectomy without fusions were queried for active narcotic drug prescription occurring >30 days and >3 months after original surgery. Medical co-diagnoses were independently analyzed for effects on long-term active narcotic prescriptions. Prior narcotic use was defined by use within 4 months before surgery. Of 1321 patients undergoing discectomy, 621 had actively prescribed narcotics >3 months after surgery. Preoperative narcotic use had the largest effect on odds of postoperative prescription (odds ratio [OR] = 3.4). Medical comorbidities increasing odds of long-term narcotic prescriptions included migraines (OR = 1.4), diabetes mellitus (OR = 1.4), depression (OR = 1.6), and smoking (OR = 1.9). Narcotic abuse is a serious problem rooted in overprescription of these drugs, which has ultimately led to much more caution in prescribing among physicians. Because pain management and drug prescription must be balanced, identifying patients who may be susceptible to narcotic overprescription is important. Patients with co-diagnoses increasing odds of long-term narcotic prescriptions would benefit from early and continual postsurgical follow-up to ensure accurate pain management and to determine if narcotic prescriptions are justly warranted in the later postoperative period.


Phase relationship between hippocampal place units and the EEG theta rhythm.
Many complex spike cells in the hippocampus of the freely moving rat have as their primary correlate the animal's location in an environment (place cells). In contrast, the hippocampal electroencephalograph theta pattern of rhythmical waves (7-12 Hz) is better correlated with a class of movements that change the rat's location in an environment. During movement through the place field, the complex spike cells often fire in a bursting pattern with an interburst frequency in the same range as the concurrent electroencephalograph theta. The present study examined the phase of the theta wave at which the place cells fired. It was found that firing consistently began at a particular phase as the rat entered the field but then shifted in a systematic way during traversal of the field, moving progressively forward on each theta cycle. This precession of the phase ranged from 100 degrees to 355 degrees in different cells. The effect appeared to be due to the fact that individual cells had a higher interburst rate than the theta frequency. The phase was highly correlated with spatial location and less well correlated with temporal aspects of behavior, such as the time after place field entry. These results have implications for several aspects of hippocampal function. First, by using the phase relationship as well as the firing rate, place cells can improve the accuracy of place coding. Second, the characteristics of the phase shift constrain the models that define the construction of place fields. Third, the results restrict the temporal and spatial circumstances under which synapses in the hippocampus could be modified.


7,8-Dihydroxyflavone Simultaneously Provides Neuroprotection of Retinal Explants and Proangiogenesis of Human Umbilical Vein Endothelial Cells via the Tropomyosin-Related Kinase Receptor B Signaling Pathway In Vitro.
Purpose: This study aimed to investigate the simultaneous neuroprotective and proangiogenic effects of 7,8-dihydroxyflavone (7,8-DHF) and explore the potential underlying molecular mechanisms. Methods: A coculture system of rat retinal explants and human umbilical vein endothelial cells (HUVECs) was established to determine the optimal concentration of 7,8-DHF, promoting neurite regeneration and HUVEC proliferation. Subsequently, the neuroprotective effect, proangiogenesis properties, and action mechanism of 7,8-DHF at an optimal concentration were investigated. Results: The cell proliferation, survival, migration, tube formation and p-tropomyosin-related kinase receptor B (TrkB)/TrkB levels in HUVECs were significantly promoted by 5 μM 7,8-DHF. The ganglion cell layer neuron survival, neurite regeneration, and p-TrkB/TrkB levels in retinal explants were also significantly promoted by 5 μM 7,8-DHF. All of these pharmacological actions of 7,8-DHF were blocked by N-[2-[(2-oxoazepan-3-yl)carbamoyl]phenyl]-1-benzothiophene-2-carboxamide. Conclusions: 7,8-DHF yields neuroprotection of retinal explants and proangiogenesis of HUVECs through the TrkB signaling pathway in vitro.


The role of apoptosis in the ameliorating effects of a CDR1-based peptide on lupus manifestations in a mouse model.
Experimental systemic lupus erythematosus (SLE) can be induced in mice following immunization with an anti-DNA mAb expressing a major Id, 16/6Id. Treatment with a peptide, designated human CDR1 (hCDR1; Edratide), that is based on the sequence of CDR1 of the 16/6Id ameliorated disease manifestations. In the present study, we investigated the roles of apoptosis and related molecules in BALB/c mice with induced experimental SLE following treatment with hCDR1. A higher state of activation and increased rate of apoptosis were found in lymphocytes of SLE-afflicted mice as compared with healthy controls. The latter effects were associated with up-regulated caspase-8 and caspase-3, and down-regulated Bcl-x(L). The ameliorative effects of hCDR1 were associated with down-regulation of caspase-8 and caspase-3, up-regulation of Bcl-x(L), and a reduced rate of apoptosis. Treatment of diseased mice with an apoptosis-reducing compound that inhibited caspases down-regulated the secretion of the pathogenic cytokine IFN-gamma and lowered the intensity of glomerular immune complex deposits and the levels of proteinuria. Furthermore, coincubation of Bcl-x(L) inhibitors with hCDR1-treated cells abrogated the ability of hCDR1 to reduce the activation state of lymphocytes and to down-regulate the secretion of IL-10 and IFN-gamma. Moreover, the Bcl-x(L)-expressing CD4(+)CD25(+) cells from hCDR1-treated mice induced the expression of Bcl-x(L) in CFSE-labeled CD4(+)CD25(-) cells of the SLE-afflicted mice. Thus, the reduction of apoptosis and the up-regulation of Bcl-x(L), which plays an apparent role in tolerance induction, contribute to at least part of the beneficial effects of hCDR1 on lupus manifestations.


Physician Self-disclosure of Lived Experience Improves Mental Health Attitudes Among Medical Students: A Randomized Study.
Depression and suicidal ideation are common among medical students, a group at higher risk for suicide completion than their age-normed peers. Medical students have health-seeking behaviors that are not commensurate with their mental health needs, a discrepancy likely related to stigma and to limited role-modeling provided by physicians. We surveyed second-year medical students using the Attitudes to Psychiatry (ATP-30) and Attitudes to Mental Illness (AMI) instruments. In addition, we asked questions about role-modeling and help-seeking attitudes at baseline. We then conducted a randomized trial of an intervention consisting of 2 components: (a) a panel of 2 physicians with personal histories of mental illness speaking about their diagnosis, treatment, and recovery to the students, immediately followed by (b) small-group facilitated discussions. We repeated the ATP-30 and AMI after the active/early group was exposed to the panel, but before the control/late group was similarly exposed. Forty-three medical students participated (53% women). The majority of students (91%) agreed that knowing physicians further along in their careers who struggled with mental health issues, got treatment, and were now doing well would make them more likely to access care if they needed it. Students in the active group (n = 22) had more favorable attitudes on ATP-30 (P = .01) and AMI (P = .02) scores, as compared with the control group (n = 21). Medical students can benefit from the availability of, and exposure to physicians with self-disclosed histories of having overcome mental illnesses. Such exposures can favorably improve stigmatized views about psychiatry, or of patients or colleagues affected by psychopathology. This intervention has the potential to enhance medical students' mental health and their health-seeking behaviors.


Alpha-1 Antitrypsin Deficiency Presenting with MPO-ANCA Associated Vasculitis and Aortic Dissection.
The combination of alpha-1 antitrypsin (AAT) deficiency, ANCA-vasculitis, and aortic aneurysm has been rarely described in literature. We report an eventually fatal case in a 70-year-old patient who initially presented with giant cell arteritis and ANCA associated glomerulonephritis. Several years later, he presented with aortic dissection due to large vessel vasculitis, raising the suspicion of AAT deficiency, as two first-line relatives had chronic obstructive pulmonary disease, while they never smoked. This diagnosis was confirmed by AAT electrophoresis and immunohistochemistry on a temporal artery biopsy. Considering AAT deficiency in these cases might lead to a more timely diagnosis.


Airway management with endotracheal tube versus Combitube during parabolic flights.
Training of National Aeronautics and Space Administration space shuttle astronauts revealed difficult airway management with endotracheal tubes (ETTs) under microgravity conditions. The authors performed a randomized comparative study of ETT and Combitube (ETC; Tyco Healthcare, Pleasanton, CA). The aim of the study was to evaluate ease, time of insertion, and success rates during normogravity and parabolic flights using mannequins. After normogravity experiments, four flyers performed intubation on a mannequin during the flights. Sixty-two intubation attempts were performed using the ETC (normogravity, 29; microgravity, 33), and 58 intubation attempts were performed using the ETT (each 29 attempts, both conditions). Time to completion of the intubation procedure, success rate, and ease of insertion were recorded. The ETC performed equally well between normogravity (median, 18 s; range, 17-25 s) and microgravity (median, 18.5 s; range, 17-28 s), whereas the ETT performed significantly slower under microgravity (median, 20 s; range, 17-27 s) as compared with normogravity (median, 18 s; range, 16-22 s; P = 0.019). One hundred nine of 120 (90%) were successful. The ETT and ETC were comparable with respect to successful intubations, under normogravity or microgravity, respectively. Both the ETC and ETT perform comparably well. Slight differences could be found with respect to time of insertion in favor of the ETC. Because this is the first experiment using the ETC on the KC-135, it is shown that there is enough time to perform the insertion procedure. Because the ETC airway requires less training and is easier to insert than an ETT, it is recommended for further study as an alternative airway to what is currently on the shuttle.


Mast cells in type 2 skin inflammation: Maintenance and function.
Mast cells (MCs) are immune cells residing in tissues and playing indispensable roles in maintaining homeostasis and inflammatory states. Skin lesions associated with atopic dermatitis (AD) and type 2 skin inflammation display an increment in MCs, which have both pro- and anti-inflammatory effects. The direct and indirect activations of skin MCs by environmental factors such as Staphylococcus aureus can instigate type 2 skin inflammation in AD with poorly understood mechanisms. Furthermore, both IgE-dependent and -independent degranulation of MCs contribute to pruritus in AD. Conversely, MCs suppress type 2 skin inflammation by promoting Treg expansion through IL-2 secretion in the spleen. Moreover, skin MCs can upregulate gene expression involved in skin barrier function, thus mitigating AD-like inflammation. These functional variances of MCs in AD could stem from differences in experimental systems, their localization, and origins. In this review, we will focus on how MCs are maintained in the skin under homeostatic and inflammatory conditions, and how they are involved in the pathogenesis of type 2 skin inflammation.


Atherosclerotic lesions in humans. In situ immunophenotypic analysis suggesting an immune mediated response.
The immunophenotypical features of the cellular infiltrates in different types of human atherosclerotic lesions, including diffuse intimal thickening as a potential but controversial precursor lesion, have been examined using monoclonal antibodies. Special emphasis is put on monocytes/macrophages, lymphocytes, and their possible interactions. Immuno-double staining techniques have been employed to study these aspects. T lymphocytes and macrophages were detected in diffuse intimal thickening, fatty streaks, and atheromatous plaques. In some lesions a predominance of suppressor/cytotoxic lymphocytes was found, whereas in other lesions mixtures of T suppressor/cytotoxic cells and T helper/inducer cells were found in ratios varying from 1:1 to 4:1. A substantial number of T cells and macrophages was considered to be immunoactivated because of the expression of HLA-DR and, to a lesser extent, of I12 receptor molecules. The activation was particularly evident at sites of close cell-to-cell contact between monocytes/macrophages and lymphocytes. These observations suggest that a specific in situ immune mediated hypersensitivity reaction is associated with the development of atherosclerosis.


A Luminescent Nitrogen-Containing Polycyclic Aromatic Hydrocarbon Synthesized by Photocyclodehydrogenation with Unprecedented Regioselectivity.
We present a nitrogen-containing polycyclic aromatic hydrocarbon (N-PAH), namely 12-methoxy-9-(4-methoxyphenyl)-5,8-diphenyl-4-(pyridin-4-yl)pyreno[1,10,9-h,i,j]isoquinoline (c-TPE-ON), which exhibits high quantum-yield emission both in solution (blue) and in the solid state (yellow). This molecule was unexpectedly obtained by a three-fold, highly regioselective photocyclodehydrogenation of a tetraphenylethylene-derived AIEgen. Based on manifold approaches involving UV/Vis, photoluminescence, and NMR spectroscopy as well as HRMS, we propose a reasonable mechanism for the formation of the disk-like N-PAH that is supported by density functional theory calculations. In contrast to most PAHs that are commonly used, our system does not suffer from entire fluorescence quenching in the solid state due to the peripheral aromatic rings preventing π-π stacking interactions, as evidenced by single-crystal X-ray analysis. Moreover, its rod-like microcrystals exhibit excellent optical waveguide properties. Hence, c-TPE-ON comprises a N-PAH with unprecedented luminescent properties and as such is a promising candidate for fabricating organic optoelectronic devices. Our design and synthetic strategy might lead to a more general approach to the preparation of solution- and solid-state luminescent PAHs.


Opioid Analgesics after Bariatric Surgery: A Scoping Review to Evaluate Physiological Risk Factors for Opioid-Related Harm.
The persisting use of opioids following bariatric surgery has emerged as a prevalent complication, heightening the probability of opioid-related harm (ORM), such as opioid-related fatalities and prescription opioid use disorder (OUD). A comprehensive review of PubMed literature from 1990 to 2023 was conducted to pinpoint physiological influences on postoperative ORM. As a result, we found that patients undertaking bariatric operations often exhibit an inherently higher risk for substance use disorders, likely attributable to genetic predisposition and related neurobiological changes that engender obesity and addiction-like tendencies. Furthermore, chronic pain is a common post-bariatric surgery complaint, and the surgical type impacts opioid needs, with increased long-term opioid use after surgeries. Additionally, the subjective nature of pain perception in patients with obesity can distort pain reporting and the corresponding opioid prescription both before and after surgery. Furthermore, the postoperative alterations to the gastrointestinal structure can affect the microbiome and opioid absorption rates, resulting in fluctuating systemic exposure to orally ingested opioids. The prospect of ORM development post-bariatric surgery appears amplified due to a preexisting susceptibility to addictive habits, surgically induced pain, modified gut-brain interaction and pain management and the changed pharmacokinetics post-surgery. Further research is warranted to clarify these potential risk variables for ORM, specifically OUD, in the bariatric population.


The Role of Oxytocin in Early-Life-Stress-Related Neuropsychiatric Disorders.
Early-life stress during critical periods of brain development can have long-term effects on physical and mental health. Oxytocin is a critical social regulator and anti-inflammatory hormone that modulates stress-related functions and social behaviors and alleviates diseases. Oxytocin-related neural systems show high plasticity in early postpartum and adolescent periods. Early-life stress can influence the oxytocin system long term by altering the expression and signaling of oxytocin receptors. Deficits in social behavior, emotional control, and stress responses may result, thus increasing the risk of anxiety, depression, and other stress-related neuropsychiatric diseases. Oxytocin is regarded as an important target for the treatment of stress-related neuropsychiatric disorders. Here, we describe the history of oxytocin and its role in neural circuits and related behaviors. We then review abnormalities in the oxytocin system in early-life stress and the functions of oxytocin in treating stress-related neuropsychiatric disorders.


Effect of chenodeoxycholic acid and ursodeoxycholic acid administration on acyl-CoA: cholesterol acyltransferase activity in human liver.
In order to investigate the relationship between bile acid pool composition and hepatic cholesterol metabolism in humans, we studied the effect of chronic feeding of chenodeoxycholic (CDCA) or ursodeoxycholic acid (UDCA) on the hepatic activity of acyl-CoA: cholesterol acyltransferase (ACAT) evaluated "in vitro". Twenty-eight gallstone patients were admitted to the study: 15 were untreated subjects, 8 were treated with UDCA (10 mg/kg/day for 15-20 days) and 5 were treated with CDCA (15 mg/kg/day for 15-20 days). A liver specimen and a bile sample were obtained during laparotomy for elective cholecystectomy. Untreated subjects had bile supersaturated with cholesterol (mean saturation index: 1.35 +/- 0.31) whereas subjects treated with either UDCA or CDCA had bile unsaturated with cholesterol (mean saturation index: 0.66 +/- 0.1 and 0.75 +/- 0.06 respectively). In all treated subjects the bile acid administered became predominant in bile. ACAT activity was 14% lower in subjects treated with UDCA and 16% lower in those treated with CDCA compared to controls; the differences did not achieve statistical significance. Microsomal cholesterol content did not differ between the groups (75.4 +/- 7.2 nmol/mg protein in control group; 86.5 +/- 7.0 nmol/mg protein in CDCA treated group; 83.4 +/- 7.0 nmol/mg protein in UDCA treated group). Our data show that the cholesterol esterifying activity of human liver is not affected by changes in bile acid pool composition.


The analysis of survival (mortality) data: fitting Gompertz, Weibull, and logistic functions.
Survival functions are fitted to survival data from several large populations. The Gompertz survival function corresponds to exponential mortality rate increases with time. The Weibull survival function corresponds to mortality rates that increase as a power function of time. A two-parameter, logistic survival function is introduced, and corresponds to mortality rates that increase, and then decrease, with time. A three-parameter logistic-mortality function also is examined. It reflects mortality rates that rise, and then plateau, with age. Data are from published studies of medflies, Drosophila, house flies, flour beetles, and humans. Some survival data are better fit by a logistic survival function than by the more traditionally used Gompertz or Weibull functions. Gompertz, Weibull, or logistic survival functions often fit the survival of 95+% of a population, and the 'tails' of the survival curves usually appear to fall between the values predicted by the three functions. For some populations, such 'tails' appear to be too complex to be fit well by any simple function. Survival data for males and females in some populations are best fit by different functions. Populations of 100 or more are needed to distinguish among the functions. When testing effects of environmental or genetic manipulations on survival, it has been common to determine the changes in parameter values for a given function, such as Gompertz. It may be equally important to determine whether the best-fit function has changed as well.


Immunotherapeutic targeting of established sarcoma in Swiss mice by tumor-derived antigen-pulsed NLGP matured dendritic cells is CD8+ T-cell dependent.
Neem leaf glycoprotein (NLGP) matures human myeloid and mouse bone marrow-derived dendritic cells (DCs). (NLGP) also therapeutically restricts the mouse established sarcoma growth by activating CD8(+) T cells along with increased proportion of tumor residing CD11c(+) DCs. Here, we intended to find out whether CD8(+) T cells become cytotoxic to sarcoma cells after presentation of sarcoma antigen by NLGP-matured DCs to restrict murine sarcoma growth. NLGP was prepared from matured neem(Azadirachta indica) leaves. Solid sarcoma tumor in Swiss mice was developed by subcutaneous inoculation of sarcoma cells. GMCSF-IL-4 generated DCs were matured with NLGP and pulsed with sarcoma antigen for immunotherapy. Status of CD8+CD69+T cells was studied by flow cytometry and secretion of cytokines was measured by ELISA. RT-PCR was used to monitor the status of perforin, granzyme B. NLGP-matured sarcoma antigen-pulsed DCs (DCNLGPTAg) inhibit mouse sarcoma growth. DCNLGPTAg immunization enhances CD8(+) T-cell number within tumor-infiltrating lymphocytes and tumor-draining lymph nodes along with increased perforin and granzyme B expression. Antigen-specific T-cell proliferation and IFN-γ secretion were significantly higher in DCNLGP- and DCNLGPTAg-immunized mice groups. In vivo CD8(+) T-cell depletion abrogated the DCNLGPTAg-mediated tumor growth restriction. DCNLGPTAg restricts CD8(+) T-cell-dependent mouse established sarcoma growth, related to the optimum antigen presentation by DCs to CD8(+) T cells.


Human adenosine A(3) receptor leads to intracellular Ca(2+) mobilization but is insufficient to activate the signaling pathway via phosphoinositide 3-kinase gamma in mice.
Selective antagonists for the adenosine A(3) receptor (A3AR), a member of the G protein-coupled receptors, have been indicated as potential drugs for anti-asthma or anti-inflammation. However, potent antagonists for the rodent A3AR have not been identified. To evaluate the pharmacological effects of human A3AR antagonists in mice, we here generated A3AR-humanized mice, in which the mouse A3AR gene was replaced by its human counterpart. The expression levels of human A3AR in the A3AR-humanized mice were equivalent to those of mouse A3AR in wild-type mice. Elevation of the intracellular Ca(2+) concentration induced by an A3AR agonist was observed in bone marrow-derived mast cells from the A3AR-humanized mice and this Ca(2+) mobilization was completely antagonized by a human A3AR antagonist. However, antigen-dependent degranulation was not potentiated by the A3AR agonist in the mast cells from A3AR-humanized mice. The agonist-stimulated human A3AR did not lead to the phosphorylation of either extracellular signal-regulated kinase 1/2 or protein kinase B in A3AR-humanized mice. The rate of human A3AR internalization in the mast cells was also markedly decreased compared with that of mouse A3AR in the mast cells. These results demonstrate that the human A3AR is insufficient to activate phosphoinositide 3-kinase gamma-dependent signaling pathways in mice, probably due to the uncoupling of member(s) of the G proteins, which are capable of activating phosphoinositide 3-kinase gamma, to the human A3AR, despite the mouse G protein(s) responsible for the Ca(2+) elevation are coupled with the human A3AR.


Embodying disabled liminality: A matter of mal/adjustment to dis/ableism.
This article combines the line of work that links disability and liminality with feminist dis/ability studies to analyse how the 'disabled body-subject' is produced and subjectified during hospitalisation and post-hospitalisation. This analysis is based on six bodily itineraries conducted with three men and three women with a spinal cord injury (five with tetraplegia and one with paraplegia) acquired during their adolescence. First, we interpret hospitalisation as a phase of 'acute liminality' in which the disabled body-subject starts being produced as suspicious, expropriated and de/gendered. Secondly, we illustrate how discharge and the 'return' to the community entail the formation of several bodily assemblages that embody mal/adjustment. This leaves the subject in a state of 'sustained liminality' plagued with paradoxes and ambivalence. We argue that both liminalities lead disabled subjects to do an emotional work consisting of adjusting to situations of affective disablism while also opening up spaces of resistance regarding heterosexist and ableist mandates. We conclude by pointing out the potentialities of a two-way dialogue between medical sociology and dis/ability studies.


A strategy to select suitable physicochemical attributes of amino acids for protein fold recognition.
Assigning a protein into one of its folds is a transitional step for discovering three dimensional protein structure, which is a challenging task in bimolecular (biological) science. The present research focuses on: 1) the development of classifiers, and 2) the development of feature extraction techniques based on syntactic and/or physicochemical properties. Apart from the above two main categories of research, we have shown that the selection of physicochemical attributes of the amino acids is an important step in protein fold recognition and has not been explored adequately. We have presented a multi-dimensional successive feature selection (MD-SFS) approach to systematically select attributes. The proposed method is applied on protein sequence data and an improvement of around 24% in fold recognition has been noted when selecting attributes appropriately. The MD-SFS has been applied successfully in selecting physicochemical attributes of the amino acids. The selected attributes show improved protein fold recognition performance.


Molecular dynamics simulation: a tool for exploration and discovery using simple models.
Emergent phenomena share the fascinating property of not being obvious consequences of the design of the system in which they appear. This characteristic is no less relevant when attempting to simulate such phenomena, given that the outcome is not always a foregone conclusion. The present survey focuses on several simple model systems that exhibit surprisingly rich emergent behavior, all studied by molecular dynamics (MD) simulation.The examples are taken from the disparate fields of fluid dynamics, granular matter and supramolecular self-assembly. In studies of fluids modeled at the detailed microscopic level using discrete particles, the simulations demonstrate that complex hydrodynamic phenomena in rotating and convecting fluids—the Taylor–Couette and Rayleigh–Bénard instabilities—cannot only be observed within the limited length and time scales accessible to MD, but even allow quantitative agreement to be achieved. Simulation of highly counter-intuitive segregation phenomena in granular mixtures, again using MD methods, but now augmented by forces producing damping and friction, leads to results that resemble experimentally observed axial and radial segregation in the case of a rotating cylinder and to a novel form of horizontal segregation in a vertically vibrated layer. Finally, when modeling self-assembly processes analogous to the formation of the polyhedral shells that package spherical viruses, simulation of suitably shaped particles reveals the ability to produce complete, error-free assembly and leads to the important general observation that reversible growth steps contribute to the high yield. While there are limitations to the MD approach, both computational and conceptual, the results offer a tantalizing hint of the kinds of phenomena that can be explored and what might be discovered when sufficient resources are brought to bear on a problem.


Complete Genome Sequence of Burkholderia stabilis FERMP-21014.
Cholesterol esterase (EC 184.108.40.206) was identified in a bacterium, Burkholderia stabilis strain FERMP-21014. Here, we report the complete genome sequence of B. stabilis FERMP-21014, which has been used in the commercial production of cholesterol esterase. The genome sequence information may be useful for improving production levels of cholesterol esterase.