Morphologic aspects of the cervical (C3-C7) annular epiphysis: a skeletal study.
The annular epiphysis (AE) is a peripheral ring of cortical bone that forms a secondary ossification center in the superior and inferior surfaces of vertebral bodies (VBs). The AE is the last ossification site in the skeleton, typically forming at about the 25th year of life. The AE functions jointly with vertebral endplates to anchor the intervertebral discs to the VBs. To establish accurate data on the sizes of the AE of the cervical spine (C3-C7); to compare the ratios between areas and the ratios of the AE to VBs; to compare the ratios between the superior and inferior VB surface areas; and to compare AE lengths between the posterior and anterior midsagittal areas. Measurement of 424 cervical spines (C3-C7) obtained from the skeletal collection of the Natural History Museum, Cleveland, Ohio (USA). The sample was characterized by sex, age, and ethnic origin. The following measurements were recorded for each vertebra: (1) the surface area of the VBs and the AE, (2) the midsagittal anterior and posterior length of the AE, (3) the ratios between the AE and VB surface areas, and (4) the ratios between the superior and inferior disc surface areas. The study revealed that the AE and VBs in men were larger than in women. With age, the AE and VBs became larger; the ratio between the AE and VB surface was approximately 0.5 throughout the middle to lower cervical spine. The ratio of superior to inferior VBs was approximately 0.8. We found no differences between African Americans versus European Americans or between the anterior versus the posterior midsagittal length of the AE of the superior and inferior VBs. The ratios between the superior and inferior VBs are ≥0.8, and the ratio is the same for the entire middle to lower spine. Thus, the ratio between the superior and inferior VBs to the AE is ≥ 0.5. Men had larger AEs and VBs than women did, with both VBs and AEs becoming larger with age. Knowing these relationships are important so that orthopedic surgeons can best correct these issues in young patients (<25 years old) during spine surgery. The data reported here provide, for the first time, all the relevant sizes of the AE and VB. In future studies, AEs and VBs of living patients can be measured with computed tomography. The ER location and function are clinically significant showing any changes during life that might lead to clinical issues related to intervertebral discs such as intervertebral disc asymmetry, disc herniation, nerve pressure, cervical osteophytes and neck pain.


[Effect of histamine on behavior of the rosette test in patients with pollinosis].
The study comprised of 50 patients with the diagnosis of pollinosis based on characteristic history data, positive results of skin test and positive IgE FAST test with grass pollen allergens. 20 ml of blood was taken from all patients and total E rosette test was carried. Antihistamine was added to rosette test in the concentration of 10(-3) mg/ml in the following doses: 0.1 ml, 0.2 ml, 0.3 ml. Histamine caused stat. sig. (P < 0.001) decrease in the percentage of lymphocytes forming E rosettes. We think that lymphocyte may be injured by histamine under exposition to grass pollens.


FA-Assistant Iodide Coordination in Organic-Inorganic Wide-Bandgap Perovskite with Mixed Halides.
Mixed-halide wide-bandgap perovskites are key components for the development of high-efficiency tandem structured devices. However, mixed-halide perovskites usually suffer from phase-impurity and high defect density issues, where the causes are still unclear. By using in situ photoluminescence (PL) spectroscopy, it is found that in methylammonium (MA+ )-based mixed-halide perovskites, MAPb(I0.6 Br0.4 )3 , the halide composition of the spin-coated perovskite films is preferentially dominated by the bromide ions (Br- ). Additional thermal energy is required to initiate the insertion of iodide ions (I- ) to achieve the stoichiometric balance. Notably, by incorporating a small amount of formamidinium ions (FA+ ) in the precursor solution, it can effectively facilitate the I- coordination in the perovskite framework during the spin-coating and improve the composition homogeneity of the initial small particles. The aggregation of these homogenous small particles is found to be essential to achieve uniform and high-crystallinity perovskite film with high Br- content. As a result, high-quality MA0.9 FA0.1 Pb(I0.6 Br0.4 )3 perovskite film with a bandgap (Eg ) of 1.81 eV is achieved, along with an encouraging power-conversion-efficiency of 17.1% and open-circuit voltage (Voc ) of 1.21 V. This work also demonstrates the in situ PL can provide a direct observation of the dynamic of ion coordination during the perovskite crystallization.


Selection to reduce residual feed intake in pigs produces a correlated response in juvenile insulin-like growth factor-I concentration.
Data from a selection experiment for residual feed intake (RFI) were used to estimate genetic correlations between measures of efficiency and performance traits with juvenile IGF-I, and to demonstrate direct and correlated responses to selection. The heritability of IGF-I was 0.28 +/- 0.06 and genetic correlations of IGF-I with feed intake (0.26 +/- 0.17), backfat (0.52 +/- 0.11), and feed conversion ratio (0.78 +/- 0.14) were moderate to large. The estimated and realized genetic correlations between RFI and IGF-I were 0.63 +/- 0.15 and 0.84. In contrast, genetic correlations between IGF-I and lifetime or test period growth did not differ (P > 0.05) significantly from zero (0.06 +/- 0.14 and -0.19 +/- 0.14). Selection for decreased RFI produced a direct response in RFI, as expected, and was accompanied by downward correlated responses in ADFI, juvenile IGF-I, backfat, and growth traits, listed in order of decreasing relative magnitude, and an increased loin muscle area. The correlated response in IGF-I to selection on RFI demonstrates that this physiological measure is genetically associated with efficiency, and is thus useful as an early information source to estimate genetic merit for efficiency before performance testing. Decreased juvenile IGF-I is associated with leaner, more efficient animals.


Radio Frequency Detection and Characterization of Water-Ethanol Solution through Spiral-Coupled Passive Micro-Resonator Sensor.
We present a microfabricated spiral-coupled passive resonator sensor realized through integrated passive device (IPD) technology for the sensitive detection and characterization of water-ethanol solutions. In order to validate the performance of the proposed device, we explicitly measured and analyzed the radio frequency (RF) characteristics of various water-ethanol solution compositions. The measured results showed a drift in the resonance frequency from 1.16 GHz for deionized (DI) water to 1.68 GHz for the solution containing 50% ethanol, whereas the rejection level given by the reflection coefficient decreased from -29.74 dB to -14.81 dB. The obtained limit of detection was 3.82% volume composition of ethanol in solution. The derived loaded capacitance was 21.76 pF for DI water, which gradually decreased to 8.70 pF for the 50% ethanol solution, and the corresponding relative permittivity of the solution decreased from 80.14 to 47.79. The dissipation factor increased with the concentration of ethanol in the solution. We demonstrated the reproducibility of the proposed sensor through iterative measures of the samples and the study of surface morphology. Successive measurement of different samples had no overlapping and had very minimum bias between RF characteristics for each measured sample. The surface profile for bare sensors was retained after the sample test, resulting a root mean square (RMS) value of 11.416 nm as compared to 10.902 nm for the bare test. The proposed sensor was shown to be a viable alternative to existing sensors for highly sensitive water-ethanol concentration detection.


Thermoanaerobacteriaceae oxidize acetate in methanogenic rice field soil at 50°C.
Rice field soils contain a thermophilic microbial community. Incubation of Italian rice field soil at 50°C resulted in transient accumulation of acetate, but the microorganisms responsible for methane production from acetate are unknown. Without addition of exogenous acetate, the δ(13)C of CH(4) and CO(2) indicated that CH(4) was exclusively produced by hydrogenotrophic methanogenesis. When exogenous acetate was added, acetoclastic methanogenesis apparently also operated. Nevertheless, addition of [2-(13)C]acetate (99% (13)C) resulted in the production not only of (13)C-labelled CH(4) but also of CO(2), which contained up to 27% (13)C, demonstrating that the methyl group of acetate was also oxidized. Part of the (13)C-labelled acetate was also converted to propionate which contained up to 14% (13)C. The microorganisms capable of assimilating acetate at 50°C were targeted by stable isotope probing (SIP) of ribosomal RNA and rRNA genes using [U-(13)C] acetate. Using quantitative PCR, (13)C-labelled bacterial ribosomal RNA and DNA was detected after 21 and 32 days of incubation with [U-(13)C]acetate respectively. In the heavy fractions of the (13)C treatment, terminal restriction fragments (T-RFs) of 140, 120 and 171 bp length predominated. Cloning and sequencing of 16S rRNA showed that these T-RFs were affiliated with the bacterial genera Thermacetogenium and Symbiobacterium and with members of the Thermoanaerobacteriaceae. Similar experiments targeting archaeal RNA and DNA showed that Methanocellales were the dominant methanogens being consistent with the operation of syntrophic bacterial acetate oxidation coupled to hydrogenotrophic methanogenesis. After 17 days, however, Methanosarcinacea increasingly contributed to the synthesis of rRNA from [U-(13)C]acetate indicating that acetoclastic methanogens were also active in methanogenic Italian rice field soil under thermal conditions.


[Cutaneo-reno-colonic fistula in tubercular kidney with staghorn calculus: report of a case].
We report a rare case of colorenocutaneous fistula, in a patient with a stone of the left kidney. The fistula was successfully managed by single stage surgery (nephrectomy, fistulectomy and suture of colon). Histopathological examination revealed renal tuberculosis. Surgery was completed by an anti-tubercular treatment.


IGF IIRα-triggered pathological manifestations in the heart aggravate renal inflammation in STZ-induced type-I diabetes rats.
Pathological manifestations in either heart or kidney impact the function of the other and form the basis for the development of cardiorenal syndrome. However, the mechanism or factors involved in such scenario are not completely elucidated. In our study, to find the correlation between late fetal gene expression in diabetic hearts and their influence on diabetic nephropathy, we created a rat model with cardiac specific overexpression of IGF-IIRα, which is an alternative splicing variant of IGFIIR, expressed in pathological hearts. In this study, transgenic rats over expressing cardiac specific IGF-IIRα and non-transgenic animal models established in SD rats were administered with single dose of streptozotocin (STZ, 55 mg/Kg) to induce Type I diabetes. The correlation between IGF-IIRα and kidney damages were further determined based on their intensity of damage in the kidneys. The results show that cardiac specific overexpression of IGF-IIRα elevates the diabetes associated inflammation and morphological changes in the kidneys. The diabetic transgenic rats showed advancement in the pathological features such a renal tubular damage, collagen accumulation and enhancement in STAT3 associated mechanism of renal fibrosis. The results therefore show that that IGF-IIRα expression in the heart during pathological condition may worsen symptoms of diabetic nephropathy in rats.


[Changes in contractility parameters, coronary flow and myocardial oxygen consumption following intravenous diltiazem in patients with coronary heart disease].
In 11 patients (9 men, 2 women) with angiographically confirmed coronary heart disease, hemodynamics, myocardial blood flow, oxygen consumption and lactate extraction were measured at rest before and after administration of 0.3 mg diltiazem per kg body weight. There was a prompt and sustained drop in mean systolic arterial pressure from 141 mm Hg to 127 mm Hg along with a reduction in total peripheral resistance. The filling pressure of the left ventricle remained constant following a post-injection rise lasting up to 5 minutes. A marked sustained drop in heart rate from 82/min to 73/min was registered. Concomitantly, stroke volume index rose from 39 to 49 ml/m2. Due to the decrease in load and frequency, contractility parameters dP/dt and dP/dt/P dropped slightly. Myocardial blood flow did not change. On the other hand, a decrease in the difference between arterial and coronary venous oxygen content indicated a coronary dilatory effect. Fifteen minutes after injection, myocardial oxygen consumption had dropped from 11.6 to 10 ml O2/min and 100 g of tissue. There was no substantial change in lactate extraction. Through a drop in peripheral arterial resistance and heart rate, diltiazem leads to a measurable decrease in myocardial oxygen consumption while the patient is still at rest. At the same time, there are indications of a coronary dilatory effect.


Whole-Genome Analysis of Human Papillomavirus Type 16 Prevalent in Japanese Women with or without Cervical Lesions.
Recent large-scale genomics studies of human papillomaviruses (HPVs) have shown a high level of genomic variability of HPV16, the most prevalent genotype in HPV-associated malignancies, and provided new insights into the biological and clinical relevance of its genetic variations in cervical cancer development. Here, we performed deep sequencing analyses of the viral genome to explore genetic variations of HPV16 that are prevalent in Japan. A total of 100 complete genome sequences of HPV16 were determined from cervical specimens collected from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer, or without cervical malignancies. Phylogenetic analyses revealed the variant distribution in the Japanese HPV16 isolates; overall, lineage A was the most prevalent (94.0%), in which sublineage A4 was dominant (52.0%), followed by sublineage A1 (21.0%). The relative risk of sublineage A4 for cervical cancer development was significantly higher compared to sublineages A1/A2/A3 (odds ratio = 6.72, 95% confidence interval = 1.78-28.9). Interestingly, a novel cluster of variants that branched from A1/A2/A3 was observed for the Japanese HPV16 isolates, indicating that unique HPV16 variants are prevalent among Japanese women.


Development of a wheeled walker braking device using the four-bar mechanism.
The elderly population in many countries has been rising rapidly, and falls are a serious event many elderly people experience. Assistive equipment is actively used to reduce falls among elderly people. Popular types of assistive equipment include canes, electric wheelchairs, and wheeled walkers. Wheeled walkers support the body of elderly people, making their gait comfortable as they age or recover from injuries. Wheeled walkers may be equipped with hand brakes; however, frail older people may experience difficulty using such hand brakes, as they require force to operate. Thus, in the present study, a braking method using a wire connected to a user's belt or clothes was designed and implemented; if the tension of the wire connecting the safety device and the user exceeds a critical value, the wheeled walker brakes, which can prevent the rapid motion of walkers. Two feasibility tests of the wheeled walker with the braking device were conducted: one with 10 healthy adults in their 20s and the other with 10 elderly people over 65 years of age; the tests measured the braking time and speed control using a speed measuring device. The results of the first and second feasibility tests demonstrated that the average braking time of participants was 50.3 ms and 50.7 ms, respectively. All participants in the feasibility tests succeeded in the speed control test. Thus, based on the results, the braking device on the wheeled walker worked properly.


The complete chloroplast genome of Carex laevissima Nakai (Cyperaceae).
Carex laevissima Nakai 1914 (Cyperaceae) is vital for ecological conservation and land virescence, and has high ornamental value. Here the chloroplast genome of Carex laevissima was assembled and systematically analyzed for further genetic research of Carex plants. The chloroplast sequence of Carex laevissima was 188,029 bp in length, including two inverted repeat (IR) regions of 36,699 bp each, a large single-copy (LSC) region of 106,171 bp and a small single-copy region (SSC) of 8460 bp. The overall GC content is 34.0%. It contains 133 genes, including 89 protein-coding, 36 tRNA, and eight rRNA genes. Phylogenetic analysis showed that Carex laevissima is most closely related to Carex neurocarpa.


Collisional Excitation of CF+ by H2: Potential Energy Surface and Rotational Cross Sections.
The CF+ molecule is considered one of the key species for the study of fluorine chemistry in the interstellar medium (ISM). Its recent detection, as well as its potential use as a tracer for atomic fluorine in the ISM, has increased the interest in the study of the physical and chemical properties of this cation. Accurate determination of the CF+ abundance in the ISM requires detailed modeling of its excitation from both radiation and collisions with the most dominant species, which are usually atomic and molecular hydrogen. Here, we report a new highly accurate potential energy surface (PES) describing the interaction between CF+ and the H2 molecule. Exact quantum time-independent calculations of the rotational excitation cross sections for collisions of CF+ with both para- and ortho-H2 are reported. Results obtained for collisions with para-H2 are compared to previous calculations performed using an approximate PES averaged over H2 rotation. Excitation data for collisions with ortho-H2 are provided for the first time.


Determination of Cr(III) and Cr(VI) at sub-ppb levels in water with solid-phase extraction/metal furnace atomic absorption spectrometry.
A simple method using solid-phase extraction combined with metal furnace atomic absorption spectrometry was developed for the determination of Cr(III) and Cr(VI) at sub-ppb levels in water. A 500-ml water sample was adjusted to pH 3 with nitric acid and then passed through an iminodiacetate extraction disk placed on a cation-exchange extraction disk at a flow rate of 20-40 ml min(-1) for concentrating Cr(III). The filtrate was adjusted to pH 10 with aqueous ammonia and then passed through an anion-exchange extraction disk at a flow rate of 2 ml min(-1) for concentrating Cr(VI). The Cr(III) and Cr(VI) collected were eluted with 40 ml of 3 mol l(-1) nitric acid for Cr(III) and 40 ml of 1 g l(-1) diphenylcarbazide solution for Cr(VI). Each eluate was diluted to 50 ml with deionized water and injected into a U-type tungsten board on the metal furnace. The calibration curves of Cr(III) and Cr(VI) showed good linearity in the range of 0.1-0.5 ng. The detection limits corresponding to three times the standard deviation (n = 5) of blank values were 8.1 pg for both Cr(III) and Cr(VI). The analytical value of total Cr (Cr(III) + Cr(VI)) in certified reference material of river water (JSAC 0302-3) was in good agreement with the reference value. The recovery test for 0.50 µg (1.00 µg l(-1)) of Cr(III) and Cr(VI) added to 500 ml of the water samples showed sufficient values (98.1-106%), except for river water sampled downstream due to relatively higher COD(Mn) value. The relative standard deviations (n = 5) were less than 5% for both Cr(III) and Cr(VI).


[Gastric polyps: role of endoscopy].
Elster's classification differentiates epithelial gastric polyps on the basis of cells origin and relative tendency to change into a malignancy. Out of 3.920 endoscopy of upper digestive tract during the last 10 years, we found 41 gastric polyps, 50% asymptomatic. Endoscopic polypectomy were performed in 61% of cases, without any complication. The other 39% were followed-up and/or surgically resected, according to the results of biopsy. Endoscopy is mandatory for detection of lesions often asymptomatic and histological study of surrounding gastric mucosa. Small polyps must be treated by radical endoscopic polypectomy. If they are too big for endoscopic polypectomy, it's well advised and safer to perform periodic biopsy for hyperplastic type and a surgical resection for adenomatous ones. The detection of intestinal metaplastic or malignant changes beyond basal membrane suggests a resection both subtotal or total according to topography of the lesions. In conclusion the role of endoscopy is well defined in order to clarify histological attributes of gastric epithelial polyps and surrounding mucosal areas. More restricted is its role in the treatment of these lesions.


The response to treatment with pituitary growth hormone: the New Zealand experience.
Ninety-four growth hormone deficient New Zealand children were treated with thrice weekly intramuscular injections of human pituitary growth hormone (GH) from 1979 to 1985 and the results from 43 children were analysed in detail. Their height velocity was mean (SD) 4.0 (1.9) cm/yr immediately prior to treatment and 8.5 (3.1) cm/yr in the first year of treatment. In each of the first three years of treatment the height velocity was significantly increased (p less than 0.001), but there was a significant decline in height velocity between the first and second, and second and third years. Nevertheless each year of treatment gave a highly significant gain in relative height. Bone age did not advance more rapidly than chronological age during the first two years of treatment, but did so subsequently. The response to GH, as assessed by the increase in relative height, was negatively correlated with the relative height at the start of treatment and with the maximum pretreatment plasma GH response to insulin hypoglycaemia. There was no correlation with pretreatment relative height velocity or aetiology of GH deficiency. Height velocity improved in five of 14 children treated with thyroxine after starting GH. Discontinuation of GH for one year in 34 children resulted in a highly significant reduction in growth rate from 7.5 (2.4) cm/yr to 2.5 (2.0) cm/yr, however four prepubertal children continued to grow at a rate exceeding 4 cm/yr.


The cytokines interleukin-6 and interferon-α induce distinct microglia phenotypes.
Elevated production of the cytokines interleukin (IL)-6 or interferon (IFN)-α in the central nervous system (CNS) is implicated in the pathogenesis of neurological diseases such as neuromyelitis optica spectrum disorders or cerebral interferonopathies, respectively. Transgenic mice with CNS-targeted chronic production of IL-6 (GFAP-IL6) or IFN-α (GFAP-IFN) recapitulate important clinical and pathological features of these human diseases. The activation of microglia is a prominent manifestation found both in the human diseases and in the transgenic mice, yet little is known about how this contributes to disease pathology. Here, we used a combination of ex vivo and in situ techniques to characterize the molecular, cellular and transcriptomic phenotypes of microglia in GFAP-IL6 versus GFAP-IFN mice. In addition, a transcriptomic meta-analysis was performed to compare the microglia response from GFAP-IL6 and GFAP-IFN mice to the response of microglia in a range of neurodegenerative and neuroinflammatory disorders. We demonstrated that microglia show stimulus-specific responses to IL-6 versus IFN-α in the brain resulting in unique and extensive molecular and cellular adaptations. In GFAP-IL6 mice, microglia proliferated, had shortened, less branched processes and elicited transcriptomic and molecular changes associated with phagocytosis and lipid processing. In comparison, microglia in the brain of GFAP-IFN mice exhibited increased proliferation and apoptosis, had larger, hyper-ramified processes and showed transcriptomic and surface marker changes associated with antigen presentation and antiviral response. Further, a transcriptomic meta-analysis revealed that IL-6 and IFN-α both contribute to the formation of a core microglia response in animal models of neurodegenerative and neuroinflammatory disorders, such as Alzheimer's disease, tauopathy, multiple sclerosis and lipopolysaccharide-induced endotoxemia. Our findings demonstrate that microglia responses to IL-6 and IFN-α are highly stimulus-specific, wide-ranging and give rise to divergent phenotypes that modulate microglia responses in neuroinflammatory and neurodegenerative diseases.


Geographic and Ethnic Variations in Serum Concentrations of Legacy Persistent Organic Pollutants among Men in the Nenets Autonomous Okrug, Arctic Russia.
The overwhelming majority of Arctic biomonitoring studies in humans include either pregnant or non-pregnant women of reproductive age while little attention is paid to toxic compounds concentrations in men. This study contributes with information of the present amounts of persistent organic pollutants (POPs) in men living in Arctic Russia. We studied the serum concentrations of 11 polychlorinated biphenyl (PCB) congeners and 17 organochlorine pesticides (OCPs) and some of their metabolites in samples collected from 92 adult men (mean age 43 years) from seven different settlements in Nenets Autonomous Okrug (NAO). The median concentrations of individual PCB congeners increased in the order PCB 183, PCB 180, PCB 118, PCB 138, PCB 153. The concentrations of o, p'-DDD, p, p'-DDD, aldrin, mirex and 1,2,3,5-TCB were in most cases below the quantification limit. The observed concentrations of PCBs and chlorinated pesticides were in the same range as those found in similar groups of women of these territories, but lower than of men in other Arctic countries. However, significant geographic differences between the settlements were observed with exceptionally high concentrations of PCBs in the Islands group. The highest serum ∑PCBs and β-HCH levels were observed in adult males aged 60-78 years. We found significant variations in serum concentrations of POPs across settlements and ethnic groups with exceptionally high concentrations of PCBs among the residents of the Arctic islands. At the same time, our findings suggest a considerable decrease in serum concentration of POPs over the last decade.


Evening types demonstrate reduced SSRI treatment efficacy.
Selective serotonin reuptake inhibitors (SSRIs) have a profound effect on the circadian system's response to environmental light, which may impact treatment outcomes for patients depending on their habitual light exposure patterns. Here, we investigated the relationship between time-of-day preference, depressive symptoms and self-reported antidepressant treatment response. Evening types reported having taken a higher number of antidepressant medications in the previous 5 years and lower SSRI efficacy than morning types. While undergoing SSRI treatment, evening types also reported more depressive symptoms and suicidality. It is concluded that time-of-day preference may prove informative in predicting SSRI treatment responses.


Retrospective Analysis of Switching Bimatoprost 0.01% to Bimatoprost 0.03% in Patients with Various Types of Glaucoma and Ocular Hypertension.
Studies comparing the two different formulations of bimatoprost, 0.03% and 0.01%, have shown similar efficacy, but a better adverse effect profile for bimatoprost 0.01% in patients with primary open-angle glaucoma (POAG) and ocular hypertension (OHT). This study assesses the efficacy and tolerability of switching from bimatoprost 0.01% to 0.03% in a patient population with broader spectrum of diagnoses in a real-world clinical setting. Single-centre retrospective observational switch study. Selected patients were on initial topical therapy with bimatoprost 0.01% prior to switching to bimatoprost 0.03%. Intraocular pressure (IOP) was collected from their pre-switch visit, 6- and 12-week after switch. Paired two-sample t-test was performed to compare IOP at different time points versus baseline. Worsening of hyperemia and other adverse events after the switch were identified. Subgroup analysis was performed for POAG and OHT, secondary open-angle glaucoma (SOAG, including pseudoexfoliative and pigmentary glaucoma), normal tension glaucoma (NTG), and angle closure glaucoma (ACG). The study population consisted of 248 eyes (143 patients). There was a significant mean IOP reduction of 1.0 ± 3.7 mmHg (p < 0.001, n = 248) from baseline to week-6 and 1.6 ± 4.0 mmHg (p < 0.001, n = 142) from baseline to week-12 after switch. The IOP reduction was statistically significant in patients with POAG and OHT (6-week: 1.0 ± 3.8 mmHg, n = 76; 12-week: 1.5 ± 4.1 mmHg, n = 49), ACG (6-week: 1.5 ± 4.1 mmHg, n = 72; 12-week: 2.3 ± 4.5 mmHg, n = 46), and NTG (6-week: 0.83 ± 2.5 mmHg, n = 42; 12-week: 1.12 ± 2.1 mmHg, n = 25). Patients with SOAG did not show statistically significant reduction in IOP at 6- or 12-week after switch. Forty-two (29%) of 143 patients experienced adverse events, with the most common being hyperemia (16%). Significant reduction in IOP could be seen after switching from bimatoprost 0.01% to bimatoprost 0.03% in various types of glaucoma except SOAG. Intolerance after switch may be experienced, though not in the majority of cases.


BEL1-LIKE HOMEODOMAIN 11 regulates chloroplast development and chlorophyll synthesis in tomato fruit.
Chloroplast development and chlorophyll(Chl)metabolism in unripe tomato contribute to the growth and quality of the fruit, however these mechanisms are poorly understood. In this study, we initially investigated seven homeobox-containing transcription factors (TFs) with specific ripening-associated expression patterns using virus-induced gene silencing (VIGS) technology and found that inhibiting the expression of one of these TFs, BEL1-LIKE HOMEODOMAIN11 (SlBEL11), significantly increased Chl levels in unripe tomato fruit. This enhanced Chl accumulation was further validated by generating stable RNA interference (RNAi) transgenic lines. RNA sequencing (RNA-seq) of RNAi-SlBEL11 fruit at the mature green (MG) stage showed that 48 genes involved in Chl biosynthesis, photosynthesis and chloroplast development were significantly upregulated compared with the wild type (WT) fruit. Genomic global scanning for Homeobox TF binding sites combined with RNA-seq differential gene expression analysis showed that 22 of these 48 genes were potential target genes of SlBEL11 protein. These genes included Chl biosynthesis-related genes encoding for protochlorophyllide reductase (POR), magnesium chelatase H subunit (CHLH) and chlorophyllide a oxygenase (CAO), and chloroplast development-related genes encoding for chlorophyll a/b binding protein (CAB), homeobox protein knotted 2 (TKN2) and ARABIDOPSIS PSEUDO RESPONSE REGULATOR 2-LIKE (APRR2-like). Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation quantitative polymerase chain reaction (PCR) (ChIP-qPCR) assays were employed to verify that SlBEL11 protein could bind to the promoters for TKN2, CAB and POR. Taken together, our findings demonstrated that SlBEL11 plays an important role in chloroplast development and Chl synthesis in tomato fruit.


Vitamin C deficiency as an unusual cause of pulmonary hypertension and refusal to walk.
Vitamin C deficiency has been a historical disease rarely seen nowadays. We illustrate a case of a boy with autism presenting with severe pulmonary hypertension and refusal to walk secondary to vitamin C deficiency. Initiating treatment with high-dose vitamin C reversed his symptoms and he regained full power of his lower limbs with total normalisation of his pulmonary pressures.


Myelin Measurement Using Quantitative Magnetic Resonance Imaging: A Correlation Study Comparing Various Imaging Techniques in Patients with Multiple Sclerosis.
Evaluation of myelin by magnetic resonance imaging (MRI) is a difficult challenge, but holds promise in demyelinating diseases, such as multiple sclerosis (MS). Although multiple techniques have been developed, no gold standard has been established. This study aims to evaluate the correlation between synthetic MRI myelin volume fraction (SyMRIMVF) and myelin fraction estimated by other techniques, i.e., magnetization transfer saturation (MTsat), T1-weighted images divided by T2-weighted images (T1w/T2w), and radial diffusivity (RD) in patients with MS. We also compared the sensitivities of these techniques for detecting MS-related myelin damage. SyMRIMVF, MTsat, T1w/T2w, and RD were averaged on plaque, periplaque white matter, and normal-appearing white matter (NAWM). Pairwise correlation was calculated using Spearman's correlation analysis. For all segmented regions, strong correlations were found between SyMRIMVF and T1w/T2w (Rho = 0.89), MTsat (Rho = 0.82), or RD (Rho = -0.75). For each technique, the average estimated myelin differed significantly among regions, but the percentage change of NAWM from both periplaque white matter and plaque were highest in SyMRIMVF. SyMRIMVF might be suitable for myelin evaluation in MS patients, with relevant results as compared to other well-studied techniques. Moreover, it presented better sensitivity for the detection of the difference between plaque or periplaque white matter and NAWM.


Lesbian and gay youth in England.
The experience of being gay and young has been seriously neglected in youth culture research and in youth service provision. This stems in part from the pervasiveness of both the heterosexual assumption and the sexual stigma. Since the advent of the gay movement, however, some modest research into gay youth has been conducted and some has been generated through the activity of gay organizations themselves. This paper reviews the experience and problems of being young and gay in Britain as revealed through three research studies. It outlines some key changes that have occurred during the 1980s, especially the emergence of gay youth organizations. It concludes by suggesting the diversity of the gay youth experience in England.


Prognostic factors of neurological sequel in adult patients with tuberculous meningitis.
To evaluate the predictors of neurological sequel in tuberculous meningitis (TBM). This study was carried out at the Department of Clinical Microbiology and Infectious Diseases, Haseki Training and Research Hospital, Istanbul, Turkey, between January 1998 and March 2009. Neurological sequels at 6 months of 160 adult patients with TBM who had been followed up were assessed retrospectively. The prognostic role of various demographic, clinical, laboratory, and radiological findings on admission, in prediction of neurological sequel development, were studied using a multivariate logistic regression. Clinical and therapeutic outcomes at 6 months were determined using a modified Barthel Index. Twenty-seven (17%) patients died and 20 (13%) survivors had neurological sequelae at 6 months. Cranial nerve palsy, presence of tuberculoma, younger age, and basal meningitis were found to be significant predictors of neurological sequelae in univariate analysis, but only younger age (odds ratio [OR] 2.9, 95% confidence intervals [CI] 1.0-8.6, p=0.049), cranial nerve palsy (OR 3.9, 95% CI 1.8-8.8, p=0.001), and presence of tuberculoma (OR 1.9, 95% CI 1.0-4.2, p=0.048) were found to be significant predictors using multivariable logistic regression analysis. Neurological sequelae were more common in patients with tuberculoma and cranial nerve palsy on admission. Development of neurological complications may be seen despite timely and effective anti-tuberculous therapy especially in younger patients.


Population dynamics in a long-lived seabird: I. Impact of breeding activity on survival and breeding probability in unbanded king penguins.
Understanding the trade-off between current reproductive effort, future survival and future breeding attempts is crucial for demographic analyses and life history studies. We investigated this trade-off in a population of king penguins (Aptenodytes patagonicus) marked individually with transponders using multistate capture-recapture models. This colonial seabird species has a low annual proportion of non-breeders (13%), despite a breeding cycle which lasts over 1 year. To draw inferences about the consequences of non-breeding, we tested for an effect of reproductive activity on survival and on the probability of subsequent breeding. We found that birds non-breeding in year t show the same survival rate as breeders (two-states analysis: breeding and non-breeding). However, breeders had a lower probability of breeding again the following year. This negative phenotypic correlation suggests the existence of reproductive costs affecting future breeding probability, but it might also be strengthened by late arrival for courtship in year t. A three-state analysis including breeding success revealed that failed breeders in year t have a lower probability to reproduce successfully in year t + 1 than non-breeders in year t, providing some evidence for the existence of reproductive costs. Moreover, successful breeders showed higher survival probability. This positive phenotypic correlation between current reproduction and subsequent survival supports the hypothesis of an heterogeneity in individual quality. Males breeding in year t had a lower probability to breed again in year t + 1 than females, suggesting higher reproductive costs for this sex. Such additional costs might be due to higher male parental investment in the final phase of chick-rearing, which also delays the arrival of males in year t + 1, and decreases their breeding probability. Our study is the first to explore the breeding biology and the demography of penguins without the disturbance of flipper-bands.


Porous Hydrogels: Present Challenges and Future Opportunities.
In this feature article, we critically review the physical properties of porous hydrogels and their production methods. Our main focus is nondense hydrogels that have physical pores besides the space available between adjacent cross-links in the polymer network. After reviewing theories on the kinetics of swelling, equilibrium swelling, the structure-stiffness relationship, and solute diffusion in dense hydrogels, we propose future directions to develop models for porous hydrogels. The aim is to show how porous hydrogels can be designed and produced for studies leading to the modeling of physical properties. Additionally, different methods that are used for making hydrogels with physically incorporated pores are briefly reviewed while discussing the potentials, challenges, and future directions for each method. Among kinetic methods, we discuss bubble generation approaches including reactions, gas injection, phase separation, electrospinning, and freeze-drying. Templating approaches discussed are solid-phase, self-assembled amphiphiles, emulsion, and foam methods.


Cervical spine ganglioneuroma and its relationship with neurofibromatosis type 1.
Ganglioneuromas are slow growing tumours arising from tissues of the neural crest, mainly in autonomic nervous system. They are frequently localized in the posterior mediastinum being the intraspinal involvement very uncommon. We present the case of a female patient with bilateral cervical ganglioneuroma, together with a review of the cases published to date, emphasizing in the main characteristics of these tumours and including them as part of neurofibromatosis type 1 spectrum.


Enumeration of viable tubercle bacilli (BCG) by the roll-tube method.
A technique for counting viable BCG particles by the roll-tube method is described.The bacterial suspension is diluted in a 5% solution of bovine albumin (Armour, fraction V) and five drops (0.1 ml) of the appropriate dilution are delivered into each of a number of bottles containing 0.9 ml of Dubos basic medium with 2% agar; the contents of the bottles are maintained in a liquid state at 45 degrees C before inoculation. The inoculation bottles are sealed with rubber stoppers and rolled. The colonies are counted after three to five weeks' incubation at 37 degrees C.Data from a series of counts indicate conformity with a Poisson distribution.The incorporation of oleic acid in the medium is not advisable because it results in low counts and an abnormal dispersion of the numbers obtained with parallel bottles, although the colonies are considerably larger than they are when oleic acid is excluded.


Extracellular peptidase hunting for improvement of protein production in plant cells and roots.
Plant-based recombinant protein production systems have gained an extensive interest over the past few years, because of their reduced cost and relative safety. Although the first products are now reaching the market, progress are still needed to improve plant hosts and strategies for biopharming. Targeting recombinant proteins toward the extracellular space offers several advantages in terms of protein folding and purification, but degradation events are observed, due to endogenous peptidases. This paper focuses on the analysis of extracellular proteolytic activities in two production systems: cell cultures and root-secretion (rhizosecretion), in Arabidopsis thaliana and Nicotiana tabacum. Proteolytic activities of extracellular proteomes (secretomes) were evaluated in vitro against two substrate proteins: bovine serum albumin (BSA) and human serum immunoglobulins G (hIgGs). Both targets were found to be degraded by the secretomes, BSA being more prone to proteolysis than hIgGs. The analysis of the proteolysis pH-dependence showed that target degradation was mainly dependent upon the production system: rhizosecretomes contained more peptidase activity than extracellular medium of cell suspensions, whereas variations due to plant species were smaller. Using class-specific peptidase inhibitors, serine, and metallopeptidases were found to be responsible for degradation of both substrates. An in-depth in silico analysis of genomic and transcriptomic data from Arabidopsis was then performed and led to the identification of a limited number of serine and metallo-peptidases that are consistently expressed in both production systems. These peptidases should be prime candidates for further improvement of plant hosts by targeted silencing.


A Hydrazine-Hydrazone Adamantine Compound Shows Antimycobacterial Activity and Is a Probable Inhibitor of MmpL3.
Tuberculosis remains an important cause of morbidity and mortality throughout the world. Notably, an important number of multi drug resistant cases is an increasing concern. This problem points to an urgent need for novel compounds with antimycobacterial properties and to improve existing therapies. Whole-cell-based screening for compounds with activity against Mycobacterium tuberculosis complex strains in the presence of linezolid was performed in this study. A set of 15 bioactive compounds with antimycobacterial activity in vitro were identified with a minimal inhibitory concentration of less than 2 µg/mL. Among them, compound 1 is a small molecule with a chemical structure consisting of an adamantane moiety and a hydrazide-hydrazone moiety. Whole genome sequencing of spontaneous mutants resistant to the compounds suggested compound 1 to be a new inhibitor of MmpL3. This compound binds to the same pocket as other already published MmpL3 inhibitors, without disturbing the proton motive force of M. bovis BCG and M. smegmatis. Compound 1 showed a strong activity against a panel ofclinical strains of M. tuberculosis in vitro. This compound showed no toxicity against mammalian cells and protected Galleria mellonella larvae against M. bovis BCG infection. These results suggest that compound 1 is a promising anti-TB agent with the potential to improve TB treatment in combination with standard TB therapies.


Design and synthesis of photoresponsive poly(benzyl ester) dendrimers with all-azobenzene repeating units.
A novel class of dendrons and dendrimers containing all-azobenzene units (up to 29 azobenzene groups) was designed and synthesized by the convergent method using a protected orthogonal AB(2) monomer (10) and tetra-functionalized core (11) as building blocks. The preparation of the key monomer (10) involved condensation of a protected nitroso compound (9) and 5-aminoisophthalic acid. These are the first examples of photoresponsive dendrimers with all-azobenzene repeating units. [structure: see text]


Role of Magnetic Coupling in Photoluminescence Kinetics of Mn2+-Doped ZnS Nanoplatelets.
Mn2+-doped semiconductor nanocrystals with tuned location and concentration of Mn2+ ions can yield diverse coupling regimes, which can highly influence their optical properties such as emission wavelength and photoluminescence (PL) lifetime. However, investigation on the relationship between the Mn2+ concentration and the optical properties is still challenging because of the complex interactions of Mn2+ ions and the host and between the Mn2+ ions. Here, atomically flat ZnS nanoplatelets (NPLs) with uniform thickness were chosen as matrixes for Mn2+ doping. Using time-resolved (TR) PL spectroscopy and density functional theory (DFT) calculations, a connection between coupling and PL kinetics of Mn2+ ions was established. Moreover, it is found that the Mn2+ ions residing on the surface of a nanostructure produce emissive states and interfere with the change of properties by Mn2+-Mn2+ coupling. In a configuration with suppressed surface contribution to the optical response, we show the underlying physical reasons for double and triple exponential decay by DFT methods. We believe that the presented doping strategy and simulation methodology of the Mn2+-doped ZnS (ZnS:Mn) system is a universal platform to study dopant location- and concentration-dependent properties also in other semiconductors.


Idiopathic Pulmonary Fibrosis Is a Genetic Disease Involving Mucus and the Peripheral Airways.
Idiopathic pulmonary fibrosis (IPF) is localized to the lung, is characterized by a pattern of heterogeneous, subpleural patches of fibrotic, remodeled lung, and is associated with a median survival of 3-5 years after diagnosis. A common gain-of-function MUC5B promoter variant, rs35705950, is the strongest risk factor (genetic and otherwise), accounting for at least 30% of the total risk of developing IPF. The MUC5B promoter variant can be used to identify individuals in the preclinical phase of this progressive disease, and, in the IPF lung, we have found that MUC5B is specifically overexpressed in bronchoalveolar epithelium. Thus, MUC5B represents a key molecule to understand the mechanisms that appear to initiate the fibroproliferative process in the bronchoalveolar epithelium. Moreover, focusing on MUC5B may provide a unique opportunity to define the early molecular events that lead to, and potentially prevent, the development of IPF.


Heterozygous GLDC and GCSH gene mutations in transient neonatal hyperglycinemia.
Transient neonatal hyperglycinemia is clinically or biochemically indistinguishable from nonketotic hyperglycinemia at onset. In the case of transient neonatal hyperglycinemia, the elevated plasma and cerebrospinal fluid glycine levels are normalized within 2 to 8 weeks. To elucidate the pathogenesis of transient neonatal hyperglycinemia, we studied three patients by screening mutations in the genes that encode three components of the glycine cleavage system. Heterozygous mutations were identified in all of the three patients, suggesting that transient neonatal hyperglycinemia develops in some heterozygous carriers for nonketotic hyperglycinemia.


X-Linked Severe Combined Immunodeficiency and Hepatoblastoma: A Case Report and Review of Literature.
Severe combined immunodeficiency is an inherited disease with profoundly defective T cells, B cells, and natural killer cells. X-linked severe combined immunodeficiency is the most common form. In this report, we describe a 4-month-old male infant who was admitted to our hospital with progressive breathlessness and abdominal mass. He was diagnosed with hepatoblastoma and presented a pneumocystis jirovecii pneumonia at the beginning of chemotherapy. Definitive diagnosis of X-linked severe combined immunodeficiency was established by DNA analysis of the interleukin 2 receptor gamma chain gene. This case is the first report which describes an X-linked severe combined immunodeficiency patient with hepatoblastoma.


Kinetic analysis of receptor-mediated endocytosis of epidermal growth factor by isolated rat hepatocytes.
The interaction of epidermal growth factor (EGF) with cell surface receptors and their subsequent endocytosis in isolated rat hepatocytes were analyzed by measuring changes in the concentrations of cell surface-bound, internalized, and degraded EGF. The kinetic model proposed by Wiley and Cunningham (Cell 25: 433-440, 1981) and Gex-Fabry and Delisi [Am. J. Physiol. 247 (Regulatory Integrative Comp. Physiol. 16): R768-R779, 1984] was basically utilized for the model analysis. The following kinetic parameters were obtained: association and dissociation rate constants for EGF-receptor interaction, internalization rate constant for EGF-receptor complex (kappa e), internalization rate constant for free receptor (kappa t), sequestration rate constant (kappa s) of the complex from shallow (exchangeable) to deep (nonexchangeable) membraneous compartment, intracellular degradation rate constant and initial cell-surface receptor density. The kappa s value, which was obtained by analyzing the time profiles of EGF association with cells, was approximately 5-10 times larger than the kappa e value determined by directly measuring internalized EGF with the acid-washing technique. This suggests the necessary presence of deep (nonexchanging) compartment of the complex in the plasma membrane. The calculated kappa e value is at least several times larger than the kappa t value, yielding the kinetic basis for the occurrence of receptor downregulation induced by excess EGF. We conclude that, in the overall receptor-mediated processing of EGF after bound to the cell surface receptors, the dissociation process is rapid [half-time (t1/2) less than 1 min], the degradation process is much slower (t1/2 approximately equal to 3 h), and the receptor internalization process is intermediate (t1/2 approximately equal to 6-7 min). In addition, two pools for EGF-receptor complex in the plasma membrane seem to be present, although their identification cannot be made.


Understanding culturally safe cancer survivorship care with inuit in an urban community.
Cancer is a leading cause of death among Inuit. A legacy of colonialism, residential schools, and systemic racism has eroded trust among Inuit and many do not receive culturally safe care. This study aimed to explore the meaning of culturally safe cancer survivorship care for Inuit, and barriers and facilitators to receiving it in an urban setting in Ontario Canada. As Inuit and Western researchers, we conducted a descriptive qualitative study. We held two focus groups (n = 27) with cancer survivors and family members, and semi-structured interviews (n = 7) with health providers. Data were analysed using thematic content analysis.Three broad themes emerged as central to culturally safe care: access to traditional ways of life, communication, and family involvement. Family support, patient navigators, and designated spaces were facilitators; lack of support for traditional ways, like country food, was a barrier. Participants were clear what constituted culturally safe care, but major barriers exist. Lack of direction at institutional and governmental levels contributes to the complexity of issues that prevent Inuit from engaging in and receiving culturally safe cancer care. To understand how to transform healthcare to be culturally safe, studies underpinned by Inuit epistemology, values, and principles are required.


Expression of placental glutathione S-transferase in rat tongue mucosa exposed to cigarette smoke.
Glutatione S-transferases (GSTs) are a family of enzymes involved in detoxification of xenobiotics. Placental GST, known as GST-P, has been detected in tissues following exposure to carcinogenic agents being regarded a reliable biomarker of exposure and susceptibility in early phases of carcinogenesis. The aim of this study was to investigate the expressivity of GST-P positive foci in the rat tongue mucosa exposed to cigarette smoke by means of immunohistochemistry. A total of twelve male Wistar rats were distributed into two groups: negative control and experimental group exposed to cigarette smoke during 75 days. After experimental period, no histopathological changes in the tongue mucosa were evidenced in the negative control and the experimental group. However, a total of five GST-P positive foci were detected in two out of six animals exposed to cigarrette smoke. None control animals were noticed GST-P positive foci. These data indicate that expression of GST-P may reflect the carcinogenic effect of cigarette smoke as well as the genetic susceptibility of animals in relation to continuous carcinogens exposure.


Comparisons of the effects of 12-week administration of miglitol and voglibose on the responses of plasma incretins after a mixed meal in Japanese type 2 diabetic patients.
To compare the effects of miglitol [an alpha-glucosidase inhibitor (AGI) absorbed in the intestine] and voglibose (an AGI not absorbed) on plasma glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) levels, 26 and 24 Japanese type 2 diabetic patients were randomly assigned to receive miglitol or voglibose, respectively. After 12-week administration of both drugs, during 2-h meal tolerance test, plasma glucose, serum insulin and total GIP were significantly decreased and active GLP-1 was significantly increased. Miglitol group showed a significantly lower total GIP level than voglibose group. Miglitol, but not voglibose, significantly reduced body weight (BW). In all participants, the relative change in BW was positively correlated with that of insulin significantly and of GIP with a weak tendency, but not of GLP-1. In conclusion, both drugs can enhance postprandial GLP-1 responses and reduce GIP responses. The significant BW reduction by miglitol might be attributable to its strong GIP-reducing efficacy.


Results of a Hepatitis C Virus Screening Program of the 1945-1965 Birth Cohort in a Large Emergency Department in New Jersey.
Persons born between 1945 and 1965 account for an estimated 81% of those infected with hepatitis C virus (HCV) in the United States. However, up to 60% remain undiagnosed. Prior studies have reported HCV screening results from large urban emergency departments. This is a retrospective cohort study of patients in the 1945-1965 birth cohort tested for HCV in a large emergency department (ED) in New Jersey from June 1, 2016, through December 31, 2016. The purpose was to report HCV antibody and viral load results of this testing program located in a small urban/suburban area and to analyze specific characteristics associated with positive results, such as race/ethnicity and insurance status. Descriptive statistics were performed, and, using a multivariate logistic regression model, adjusted odds ratios and 95% confidence intervals were calculated. A total of 3046 patients were screened: 55.8% were white, and 17.9% were black; 52.1% had private insurance, 33.4% Medicare, 3.9% Medicaid. One hundred ninety-two were antibody positive (6.3%). Of 167 with HCV viral load testing results, 43% had a positive viral load. On multivariate analysis, black race and Medicaid were independently associated with a positive HCV viral load. HCV antibody seropositivity was above 6% and twice as high as the Centers for Disease Control and Prevention estimated prevalence in this birth cohort. These results indicate that EDs outside of large urban cities are also important sites for routine HCV screening. Other findings of interest include 43% with chronic HCV infection and the persistent association between black race and positive HCV viral load even when adjusted for insurance status.


Small GTPase Ran: Depicting the nucleotide-specific conformational landscape of the functionally important C-terminus.
The small GTPase Ran is the main regulator of the nucleo-cytoplasmic import and export through the nuclear pore complex. It functions as a molecular switch cycling between the GDP-bound inactive and GTP-bound active state. It consists of a globular (G) domain and a C-terminal region, which is bound to the G-domain in the inactive, GDP-bound states. Crystal structures of the GTP-bound active form complexed with Ran binding proteins (RanBP) show that the C-terminus undergoes a large conformational change, embracing Ran binding domains (RanBD). Whereas in the crystal structures of macromolecular complexes not containing RanBDs the structure of the C-terminal segment remains unresolved, indicating its large conformational flexibility. This movement could not have been followed either by experimental or simulation methods. Here, starting from the crystal structure of Ran in both GDP- and GTP-bound forms we show how rigid the C-terminal region in the inactive structure is during molecular dynamics (MD) simulations. Furthermore, we show how MD simulations of the active form are incapable of mapping the open conformations of the C-terminus. By using the MDeNM (Molecular Dynamics with excited Normal Modes) method, we were able to widely map the conformational surface of the C-terminus of Ran in the active GTP-bound form, which allows us to envisage how it can embrace RanBDs.


Intratumoral Treatment with 5-Androstene-3β, 17α-Diol Reduces Tumor Size and Lung Metastasis in a Triple-Negative Experimental Model of Breast Cancer.
Breast cancer treatment failure is related to low response rates, high costs, and long-term toxicities. Thus, it is necessary to find less toxic, cheaper, and more effective treatments. In situ administration ensures drug delivery to tumor cells and decreases systemic toxic effects. The androstene-3β, 17α-diol (α-AED) reduces breast tumor cell proliferation and is an ideal candidate to treat mammary tumors. This study aims to identify the in vitro and in vivo effects of α-AED on a triple-negative mammary tumor model. An in vitro biphasic steroid effect was observed in mouse and human mammary tumor cells treated with α-AED. In this sense, cells treated with higher doses (100 and 200 μM) showed an antiproliferative effect. The α-AED administrated intratumorally reduced average tumor weight and increased the percentage of natural killer cells (NK), plasmatic, and plasmablast cells in mice tumors. Of note, VEGF levels in all α-AED-treated tumors was lower than in the control and vehicle groups. The tumor in situ increased response was reflected systemically by higher anti-4T1 IgG concentration in serum from α-AED-treated mice, but no other associated systemic changes were detected. The reduction in tumor size for the local injection of α-AED is associated with the anti-proliferative effect of this steroid, and the lower local levels of VEGF may be related to the imperceptible macroscopic metastasis in α-AED-treated mice. The above suggests that α-AED may be used in clinical studies to prove its efficacy as an alternative breast tumor treatment or in conjunction with already established therapies.


First report of Colletotrichum siamense Causing Anthracnose on Crinum asiaticum in Malaysia.
Crinum asiaticum (family Amaryllidaceae), locally known as 'Pokok Bakung', is an ornamental medicinal plant grown in Malaysia. It contains chemical compounds used for antimicrobial, antioxidant, antitumor, antiemetic and wound healing (Patel, 2017). In July 2021, 'Pokok Bakung' leaves with anthracnose symptoms were collected from a park of Universiti Malaysia Sabah in the Sabah province. The disease severity was about 100% with 20% incidence. Red spots were primarily found on the leaf surfaces. Anthracnose developed as the disease progressed, and acervuli were observed in the spots. Small pieces of infected leaves (5 x 5 mm) were excised from spot margins, surface sterilized based on Khoo et al. (2022a), placed on potato dextrose agar (PDA) in Petri dishes, which were incubated for 5 days at 25°C in the dark. The colonies formed on the PDA plates were abundant with gray-white fluffy mycelia after 5 days, and the reverse view revealed brown. UMS01, a representative isolate, was used to morphologically and molecularly characterize the fungus. Conidia were one-celled, cylindrical, hyaline, smooth, and blunt at the ends, measuring 13.8 to 16.5 x 3.6 to 6.7 µm (n = 20). Appressoria ranged in size from 7.6 to 9.3 x 5.5 to 6.9 µm (n= 20) and were ovoid to clavate, spherical to irregular in shape and dark brown in color. Genomic DNA was extracted from fresh mycelia of isolate UMS01 based on Khoo et al. (2021) with the addition of mechanical disruption using a micro pestle before heating at 95°C. PCR amplification was performed based on Khoo et al. (2022a) using ITS1/ITS4, CL1C/CL2C, ACT-512F/ACT-783R, CHS-79F/CHS-354R, and GDF1/GDR1 primer pairs to amplify the internal transcribed spacer (ITS) region, calmodulin (CAL), actin (ACT), chitin synthase (CHS-1), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (Weir et al. 2012). PCR products with positive amplicons were sent to Apical Scientific Sdn. Bhd. for sequencing. The sequences were deposited in GenBank under accession numbers OK458683 (ITS), OL953033 (CAL), OL953030 (ACT), OL953036 (CHS-1), and OL953039 (GAPDH). Before BLAST, the search set were adjusted to exclude model sequences (XM/XP) and the uncultured/environmental sample sequences, and limit to sequences from type material. They were 99-100% similar to the Colletotrichum siamense ITS (JX010171), CAL (JX009714), ACT (FJ907423) and CHS-1 (JX009865), and Colletotrichum changpingense GAPDH (MZ664048) type sequences. The GAPDH marker did not reliably resolve the relationships within the C. gloeosporioides complex (Vieira et al. 2020). Phylogenetic analysis using maximum likelihood based on the combined ITS, CAL, ACT, CHS-1 and GAPDH indicated that the isolate formed a supported clade (100% bootstrap value) to the most related C. siamense. Morphological and molecular characterization matched the description of C. siamense (Huang et al. 2021). Pathogenicity tests were performed to fulfil Koch's postulates by spraying a spore suspension (106 spores/ml) on the leaves of three healthy four-month-old 'Pokok Bakung' plants, while three additional plants were sprayed with water as a control. The inoculated plants were covered with plastics for 48 h at 25°C in the dark. Incubation was performed based on Iftikhar et al. (2022). Symptoms similar to those of the field collection occurred after 6 days post inoculation. No symptoms occurred on the control plants. The experiment was repeated two more times. The reisolated fungal isolates were identical to C. siamense morphologically and molecularly. Previously, C. siamense has been reported to cause anthracnose on Allamanda cathartica (Huang et al. 2021) and avocado (Li et al. 2022) in China, and 'Purple Dream' eggplant in Malaysia (Khoo et al. 2022b). Colletotrichum fructicola has been reported to cause anthracnose on C. asiaticum in China (Qing et al. 2020). To our knowledge, this is the first report of C. siamense causing anthracnose on C. asiaticum in Malaysia. Our findings expand the geographic range of C. siamense and indicate that it could be a potential threat limiting the growth and production of C. asiaticum in Malaysia.


Antipyretic therapy in critically ill patients with established sepsis: a trial sequential analysis.
antipyretic therapy for patients with sepsis has long been debated. The present study aimed to explore the beneficial effect of antipyretic therapy for ICU patients with sepsis. systematic review and trial sequential analysis of randomized controlled trials. Pubmed, Scopus, EBSCO and EMBASE were searched from inception to August 5, 2014. Mortality was dichotomized as binary outcome variable and odds ratio (OR) was chosen to be the summary statistic. Pooled OR was calculated by using DerSimonian and Laird method. Statistical heterogeneity was assessed by using the statistic I2. Trial sequential analysis was performed to account for the small number of trials and patients. A total of 6 randomized controlled trials including 819 patients were included into final analysis. Overall, there was no beneficial effect of antipyretic therapy on mortality risk in patients with established sepsis (OR: 1.02, 95% CI: 0.50-2.05). The required information size (IS) was 2582 and our analysis has not yet reached half of the IS. The Z-curve did not cross the O'Brien-Fleming α-spending boundary or reach the futility, indicating that the non-significant result was probably due to lack of statistical power. our study fails to identify any beneficial effect of antipyretic therapy on ICU patients with established diagnosis of sepsis. Due to limited number of total participants, more studies are needed to make a conclusive and reliable analysis.


Single-centre experience with tunnelled central venous catheters in 150 cancer patients.
Tunnelled venous catheters improve venous access in cancer patients, but are associated with complications. We retrospectively analysed the outcome of Hickman catheter and Port-A-Cath (PAC) insertion in cancer patients from a department of medical oncology and compared these results with the literature. The files of patients in whom insertion of a Hickman or PAC was planned in the period March 1992 to August 1999 were analysed. In total, 150 files were evaluated. In 149 patients, 128 Hickman catheters and 38 PACs were inserted successfully. Complications occurred in 44.6% of the catheters inserted successfully. Infection (24.1%) and thrombosis (7.2%) were observed most frequently. In 66.7% of patients with thrombosis, the catheter tip was positioned incorrectly. Removal for catheter-related complications occurred in 47.7%. Of 146 catheter insertions for which the name of the responsible (resident) surgeon could be traced, 48 different names were identified. In comparison with other studies, we found a high incidence of infections and a high removal rate for catheter-related complications. We confirmed the relationship between thrombosis and an inadequate position of the catheter tip. The level of experience of the (resident) surgeon performing the catheter insertion may have played a role in the high complication rate.


Domestic violence in pregnancy among antenatal attendees at the University of Port Harcourt Teaching Hospital, Port Harcourt.
Domestic violence is common worldwide. When it occurs in pregnancy it is associated with maternal and perinatal morbidity and mortality. It is a human rights violation with medical implication which is under-diagnosed and under-reported. This study sought to determine the prevalence of domestic violence during pregnancy and the factors that promotes domestic violence at the family unit. A cross sectional study of antenatal clients seen at the antenatal booking clinic of the University of Port Harcourt Teaching Hospital from 1st June to 31st December 2007. Five hundred clients selected from a simple random technique completed an interviewer administered structured questionnaire which sought information on domestic violence. Data collected was entered into a spreadsheet and analyzed using the statistical package SPSS 15.00 for Windows. The prevalence of domestic violence during pregnancy in this group was 7.8%. Those who experienced domestic violence were mainly those with low education and low parity. The commonest form of domestic violence was verbal abuse (shouting, cursing) occurring in 43.5% of those who have been abused in the index pregnancy and 1.2% of the victims of domestic violence suffered physical injuries from domestic violence in previous pregnancies. However, less than one third disclosed the incident. Women whose husbands indulge in substance abuse or are without jobs were more likely to experience domestic violence. Abdominal pain and miscarriage were the commonest obstetric complications following domestic violence-in pregnancy in this group. Eight percent of our antenatal mothers suffer domestic violence and many of them are unlikely to report it. Unemployment and substance abuse in the partners are major associated factors. Domestic violence in pregnancy has far-reaching adverse consequence on the mother and her unborn fetus such as miscarriage especially when it occasions bodily harm.


Oriented exchange-coupled L10-FePt/Co core-shell nanoparticles with variable Co thickness.
Exchange-coupled core-shell nanoparticles are expected to be the new generation of permanent magnets, where the orientation of the hard magnetic phase is supposed to play a key role in improving their magnetic performance. In this work, L10-FePt/Co core-shell nanoparticles with Co thickness ranging from 0.6 to 2.2 nm have been synthesized by a seed-mediated growth method. The exchange coupling effect between the hard core and soft shell led to a 60% improvement of the maximum magnetic energy product ((BH)max), compared with the pure L10-FePt core. By tuning the amount of precursor, nanoparticles with different Co shell thicknesses were synthesized. Furthermore, the L10-FePt/Co core-shell nanoparticles were dispersed in epoxy resin and oriented under an external magnetic field. The (BH)max of the anisotropic nanocomposite magnet with a Co thickness of 1 nm is 7.1 MGOe, enhanced by 117% compared with the isotropic L10-FePt magnet, which paves the way for the development of high-performance permanent magnets for energy conversion applications.


Exposure to Organophosphate and Neonicotinoid Insecticides and Its Association with Steroid Hormones among Male Reproductive-Age Farmworkers in Northern Thailand.
Several studies indicated organophosphate (OP) and neonicotinoid (NEO) insecticides are endocrine disruptors; however, data are scarce. This cross-sectional study recruited 143 male farmworkers aged 18-40 years in Fang district, Chiang Mai province, northern Thailand. OP exposure was assessed by measuring urinary dialkylphosphate (DAPs) using a gas-chromatography flame photometric detector. Urinary NEOs, their metabolites (NEO/m) and serum steroid hormones were measured using liquid chromatography-tandem mass spectrometry. Characteristics of participants were determined by face-to-face interviews. DAPs and five NEO/m were detected in more than 60% of samples. The concentration of diethylphosphate was highest among DAP metabolites (geometric mean concentration (GM: 23.9 ng/mL) and the concentration of imidacloprid (IMI) was highest among NEO/m (GM: 17.4 ng/mL). Linear regression models showed that the IMI level was positively associated with testosterone, dehydrocorticosterone (DHC) and dehydroepiandrosterone (DHEA) levels. Imidacloprid-olefin and DHEA levels were positively associated. Thiamethoxam (THX) were inversely associated with DHC and deoxycorticosterone levels. Clothianidin (CLO), THX and N-desmethyl-acetamiprid levels were positively associated with the androstenedione level. CLO and THX levels were inversely associated with the cortisone level. In conclusion, the association between NEO insecticides exposure and adrenal androgens, glucocorticoids and mineralocorticoids, suggest potential steroidogenesis activities. Our findings warrant further investigation.


A serum-free culture method for myeloma progenitors in vitro: proliferative and immunophenotypic characteristics.
Methods for forming multiple myeloma (MM) colonies are difficult because nonproliferative, but viable, plasma cells can survive for several weeks in culture and because MM cells tend to clump readily, forming pseudo-colonies. The present study describes a method for growing pure myeloma colonies in serum-free conditions in which genuine myeloma growth is unequivocally demonstrated. Growth was observed in 17 of 32 MM bone marrow samples. After a delay of 3-5 weeks, during which most cells died, Ig light-chain-restricted colonies emerged, expanded for approximately 3 weeks, and then showed no evidence of further proliferation. Cell doubling time was 8-10 days, and a significant number of cells in all cultures expressed Ki-67, having earlier lacked this nuclear proliferation antigen. In addition, colony formation was abrogated by irradiation, and two of eight cultures were successfully replated in 0.8% methylcellulose. Phenotypic analysis revealed a mixed population of plasma cells (RFD6+) and B-lymphocytes (CD19+, CAL-LA-), and cells were consistently Epstein-Barr virus negative. Culture of myeloma bone marrow by this serum-free method will allow appraisal of the role of various recombinant growth factors.


Impact of fat, protein, and glycemic index on postprandial glucose control in type 1 diabetes: implications for intensive diabetes management in the continuous glucose monitoring era.
Continuous glucose monitoring highlights the complexity of postprandial glucose patterns present in type 1 diabetes and points to the limitations of current approaches to mealtime insulin dosing based primarily on carbohydrate counting. A systematic review of all relevant biomedical databases, including MEDLINE, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials, was conducted to identify research on the effects of dietary fat, protein, and glycemic index (GI) on acute postprandial glucose control in type 1 diabetes and prandial insulin dosing strategies for these dietary factors. All studies examining the effect of fat (n = 7), protein (n = 7), and GI (n = 7) indicated that these dietary factors modify postprandial glycemia. Late postprandial hyperglycemia was the predominant effect of dietary fat; however, in some studies, glucose concentrations were reduced in the first 2-3 h, possibly due to delayed gastric emptying. Ten studies examining insulin bolus dose and delivery patterns required for high-fat and/or high-protein meals were identified. Because of methodological differences and limitations in experimental design, study findings were inconsistent regarding optimal bolus delivery pattern; however, the studies indicated that high-fat/protein meals require more insulin than lower-fat/protein meals with identical carbohydrate content. These studies have important implications for clinical practice and patient education and point to the need for research focused on the development of new insulin dosing algorithms based on meal composition rather than on carbohydrate content alone.


Abdominal dermolipectomy in laparotomy with stoma surgery: case report.
In cases of morbid obesity, excessive soft tissue in the abdomen forms an apron-like deformity called panniculus because of rapid weight loss due to cancer. In laparotomy with stoma aimed at cancer resection, obesity is reported as a major risk factor of stoma complications, one of the most frequent of which is necrosis. In one patient in whom a laparotomy was performed through a midline incision, the authors also carried out an abdominal dermolipectomy aimed at reducing distortion of the abdominal wall in relation to the stoma. This procedure provided two important advantages for stoma surgery, stability, and better postoperative care by the patient.


[Specific and rapid identification of Malassezia species based on the DNA sequences of nuclear ribosomal internal transcribed spacer 1 regions].
Species identification of genus Malassezia is important in epidemiological and etiological studies, however, is difficult by the conventional system. A specific and rapid identification system based on sequences of internal transcribed spacer 1 of ribosomal DNA has therefore been developed. Using this system, we could identify two or more species mixed in the clinical samples.


Primary results of chest wall reconstruction with polydioxanone mesh on animals.
With the development of surgical techniques and biomedical material, increasing synthetic materials are applied to the chest wall reconstruction, such as autologous rib, muscle flap, bovine pericardium and sheet metal. To detect the safety and efficiency of synthetic material Polydioxanone (PDO) in chest wall reconstruction. Healthy adult mongrel dogs operated with PDO, and then some clinical data were collected. Here we showed that PDO mesh could close down the function of chest wall defect, and PDO mesh could be degraded gradually and forms a fibrous layer with the surrounding tissues. Our data further demonstrated PDO mesh leads to slight lung adhesion with a small shrinkage. These findings thus provide the first evidence that the feasibility of PDO mesh in chest wall reconstruction in dogs.


Femoral extraction of transvenous leads and leadless pacemakers-A review of the data, tools, and procedural steps.
Extraction of transvenous leads via the femoral route might be needed when extraction via the implant vein fails or when retained lead fragments exist. The skill set required for this procedure is unique as it relies on the ability to snare and the use of a variety of shelf tools. In this era of leadless pacing, this skill set might be called upon more frequently. In this article, we review the data, tools, and procedural steps of femoral lead extraction and retrieval/extraction of leadless pacemakers.


Anisakis infestation in marine fish and cephalopods from Galician waters: an updated perspective.
A total of 2,673 fresh specimens of cephalopod and fish representing 35 species were obtained from commercial local fisheries in Galician waters (NW Spain). They were examined for anisakid nematodes by digestion of the muscle and elution of the viscera and whole body cavity. All larval nematodes recovered were identified by light microscopy and multilocus electrophoresis as belonging to the species Anisakis simplex sensu stricto and A. pegreffii. Encysted larvae mostly occurred in the viscera but were also found in the flesh of squid and fish. Demographic values for larval nematodes are discussed in relation to host preferences and the ecological niche of both anisakid species at the sampling area. Primary recommendations are also expressed concerning the effects of current fishing and aquaculture practices on the Anisakis problem.


Functional analysis of nonsynonymous single nucleotide polymorphisms of multidrug resistance-associated protein 2 (ABCC2).
Multidrug resistance-associated protein 2 (MRP2; ABCC2) mediates the biliary excretion of glutathione, glucuronide, and sulfate conjugates of endobiotics and xenobiotics. Single nucleotide polymorphisms (SNPs) of MRP2 contribute to interindividual variability in drug disposition and ultimately in drug response. To characterize the transport function of human wild-type (WT) MRP2 and four SNP variants, S789F, A1450T, V417I, and T1477M. The four SNP variants were expressed in Sf9 cells using recombinant baculovirus infection. The kinetic parameters [Km, (μmol/l); V(max), (pmol/mg/min); the Hill coefficient] of ATP-dependent transport of leukotriene C(4) (LTC(4)), estradiol-3-glucuronide (E(2)3G), estradiol-17β-glucuronide (E(2)17G), and tauroursodeoxycholic acid (TUDC) were determined in Sf9-derived plasma membrane vesicles. Transport activity was normalized for expression level. The V(max) for transport activity was decreased for all substrates for S789F, and for all substrates except E(2)17G for A1450T. V417I showed decreased apparent affinity for LTC(4), E(2)3G, and E(2)17G, whereas transport was similar between wild-type (WT) and T1477M, except for a modest increase in TUDC transport. Examination of substrate-stimulated MRP2-dependent ATPase activity of S789F and A1450T, SNPs located in MRP2 nucleotide-binding domains (NBDs), demonstrated significantly decreased ATPase activity and only modestly decreased affinity for ATP compared with WT. SNPs in the NBDs (S789F in the D-loop of NBD1, or A1450T near the ABC signature motif of NBD2) variably decreased the transport of all substrates. V417I in membrane spanning domain 1 selectively decreased the apparent affinity for the glutathione and glucuronide conjugated substrates, whereas the T1477M SNP in the carboxyl terminus altered only TUDC transport.


Matrix-assisted laser desorption/ionisation quadrupole ion trap time-of-flight mass spectrometry of novel shape-persistent macrocycles.
Shape-persistent macrocycles (SPMs) represent innovative molecular building blocks for the development of highly organised supramolecular architectures with application in nanotechnology, chemistry, catalysis and optoelectronics. Systematic mass spectrometric characterisation of SPMs and their collision-activated decay is not available to date. Characterisation of alkoxy-decorated SPMs was performed by matrix-assisted laser desorption/ionisation quadrupole ion trap time-of-flight mass spectrometry (MALDI-QIT-TOFMS) and collision-induced dissociation (CID). Laser excitation of SPMs leads to the formation of stable cation radicals which show characteristic fragmentation patterns. All the product ions formed were identified. Photoelectrons generated during the MALDI process and full-ring conjugation were found to be fundamental for the formation of molecular cation radicals and their stabilisation, respectively. Formation of supramolecular aggregates of SPMs by π-π stacking was proven. SPMs are suitable motifs for the preparation of novel fullerene-based donor-acceptor systems. Alkoxy-decorated SPMs represent promising electron-donating building blocks that can be exploited in electronics and optoelectronics for the development of robust and highly efficient laser-activated supramolecular switches.


The effects of mechanical ventilation on hepato-splanchnic perfusion.
Mechanical ventilation is a cornerstone of ICU treatment. Because of its interaction with blood flow and intra-abdominal pressure, mechanical ventilation has the potential to alter hepato-splanchnic perfusion, abdominal organ function and thereby outcome of the most critically ill patients. Mechanical ventilation can alter hepato-splanchnic perfusion, but the effects are minimal (with moderate inspiratory pressures, tidal volumes, and positive end-expiratory pressure levels) or variable (with high ones). Routine nursing procedures may cause repeated episodes of inadequate hepato-splanchnic perfusion in critically ill patients, but an association between perfusion and multiple organ dysfunction cannot yet be determined. Clinical research continues to be challenging as a result of difficulties in measuring hepato-splanchnic blood flow at the bedside. Mechanical ventilation and attempts to improve oxygenation such as intratracheal suctioning and recruitment maneuvers, may have harmful consequences in patients with already limited cardiovascular reserves or deteriorated intestinal perfusion. Due to difficulties in assessing hepato-splanchnic perfusion, such effects are often not detected.


The complete nucleotide sequence of a rice 17S rRNA gene.
The complete nucleotide sequence of a rice nuclear 17S rRNA gene (rDNA) has been determined. The rice rDNA is 1812 bp long and its G + C content is 51.3%. This nucleotide sequence shows 79%, 80% and 80% homology to those of yeast, Xenopus laevis and rat 18S rDNAs, respectively. Divergency of nucleotide sequences is largely attributed to five blocks of highly variable regions, where eukaryotic specific sequences can be observed.


Limit of validity of Ostwald's rule of stages in a statistical mechanical model of crystallization.
We have only rules of thumb with which to predict how a material will crystallize, chief among which is Ostwald's rule of stages. It states that the first phase to appear upon transformation of a parent phase is the one closest to it in free energy. Although sometimes upheld, the rule is without theoretical foundation and is not universally obeyed, highlighting the need for microscopic understanding of crystallization controls. Here we study in detail the crystallization pathways of a prototypical model of patchy particles. The range of crystallization pathways it exhibits is richer than can be predicted by Ostwald's rule, but a combination of simulation and analytic theory reveals clearly how these pathways are selected by microscopic parameters. Our results suggest strategies for controlling self-assembly pathways in simulation and experiment.


Effect of thermal cycling on microleakage between hard chairside relines and denture base acrylic resins.
Microleakage is a pre-stage of debonding between hard chairside relines and denture base acrylic resins. Therefore, it is important to assess them with regard to the longevity of the relined denture. This study investigated the effect of thermal cycling on the microleakage at the interface of three hard chairside reline resins and three denture base resins. Rectangular bars (12 mm × 3 mm × 3 mm) of Lucitone 550, Acron MC and QC 20 were made and relined with Kooliner, Tokuyama Rebase Fast II and Ufi Gel Hard, Lucitone 550, Acron MC and QC 20 resins. Specimens were divided into one control and two test groups (n=10). In specimens of the control group, the microleakage was performed after the reline procedure. In Test Group 1, the specimens were stored for 24 h in distilled water at room temperature and in Test Group 2; the specimens were thermal cycled from 5 to 55°C for 5000 cycles with a 30-s dwell time. Subsequently, all specimens were immersed in 50% silver nitrate solutions for 24h. All specimens were sectioned longitudinally into three fractions and the lateral sections were examined (n=20). Silver nitrate stain penetration was examined under a stereoscopic lens with ×30 magnification, and the images were captured. Leica Qwin image analysis software was used to determine microleakage at the interface of the materials. Data were analysed using the Kruskal-Wallis test at a 95% level of significance. For all cycles, there were no statistically significant differences between thermal cycled and non-thermal cycled groups (p>0.05). It can be concluded that thermal cycling had no effect on the microleakage.


[Lymphocyte function in patients with anti-D(Rh0) antibodies].
The behaviour of humoral and cellular immunity as well as that of cells bearing Fc receptors was investigated in persons with anti-D antibodies. Peripheral lymphocytes could be identified in 6 of 26 examined test persons particularly sensitized against the stroma of Rh-positive erythrocytes. There was no relation to the anti-D titre. The parameters of humoral immunity showed no correlation to the anti-D titre. In 37 per cent of the persons with anti-D antibodies, which were produced "naturally" or artificially, an increased content of IgE could be proved in the serum. In each case, anti-D formation apparently leads to an increase of cells bearing Fc receptors, which can be recognized by the increased number of EA rosettes. A relation to the anti-D titre did not exist. None of the immunological test methods used is suitable for predicting the success of an artificial immunization for the purpose of gaining high titre anti-D antibodies.


ANCA vasculitis presenting with acute interstitial nephritis without glomerular involvement.
ANCA-associated vasculitis (AAV) with renal involvement typically causes pauci-immune glomerulonephritis. We present a case of acute interstitial nephritis (AIN) as the sole renal lesion without glomerulonephritis with myeloperoxidase (MPO) AAV. A 45-year-old female with history of Crohn's disease, gastroesophageal reflux disease (GERD) with Barrett's esophagus, pulmonary embolism, and polyarthralgias was evaluated in nephrology clinic in 2018. AIN without glomerulonephritis was first diagnosed in 2011 on renal biopsy. p-ANCA was positive with MPO titer of > 100 U/mL. Serum creatinine improved from 2.1 to 0.9 mg/dL with prednisone and azathioprine. Repeat biopsy in 2013 for worsening renal function showed AIN without glomerular involvement. Serum creatinine improved from 1.9 to 1.2 mg/dL with prednisone and cyclosporine. Crohn's disease was diagnosed in 2014. AIN was attributed to Crohn's, and cyclosporine was stopped in 2016. Adalimumab was started in 2016, without improvement in renal function or urine sediment. Attempt was made to switch proton pump inhibitor (PPI) to H2-blocker, but the latter was not tolerated. Repeat biopsy in 2/2018 showed AIN with severe fibrosis and tubular atrophy and glomerulosclerosis but no active glomerular disease. MPO titers remained high at 132 U/mL. Mycophenolic acid and prednisone were started without response, followed by rituximab for AAV-associated AIN. Serum creatinine worsened to 6.0 mg/dL in 9/2018, with plan to start peritoneal dialysis. AAV may present with isolated AIN without glomerular involvement. The rarity of this presentation may contribute to delay in appropriate management. Alternative explanations for AIN, such as Crohn's disease or PPI use should be considered with caution in the setting of high-titer ANCA positivity.


Trends of Underweight and Overweight/Obesity Among Japanese Schoolchildren From 2003 to 2012, Defined by Body Mass Index and Percentage Overweight Cutoffs.
We investigated the prevalence and trends of underweight and overweight/obesity in a population-based sample of Japanese schoolchildren from 2003 to 2012, defined by body mass index (BMI) and percentage overweight (POW). Subjects comprised fourth and seventh graders from the town of Ina, Japan, from 2003 to 2012. The height and weight of each subject were measured. Children were classified as underweight, normal weight, or overweight/obese using two criteria: BMI cutoff points proposed by the International Obesity Task Force and cutoffs based on POW in Japan. Data from 4367 fourth graders and 3724 seventh graders were analyzed. The prevalence of underweight and overweight as defined by POW criteria were lower than those based on BMI criteria. There was a decrease in the prevalence of overweight among fourth-grade boys and girls and seventh-grade girls according to BMI; this decrease was also observed when POW criteria were used for the definition of overweight. The prevalence and trends of both underweight and overweight as defined by POW were underestimated among Japanese schoolchildren compared to those determined using BMI. The results of this study also suggest that trends in underweight and overweight/obesity using POW criteria are similar to those based on BMI criteria among schoolchildren in Japan.


Self-reported oral health, oral hygiene habits and dental service utilization among pregnant women in United Arab Emirates.
The aim of this study was to describe self-reported oral health, oral hygiene habits and frequency of visits to a dentist among pregnant women visiting maternity hospitals in the United Arab Emirates. A cross-sectional study was conducted, with anonymous structured questionnaires distributed to 800 pregnant women who were chosen at random from attendants of three maternity and child health centres from various geographical areas of UAE, during January-March 2010. The response rate was 93.7% (n = 750). Less than quarter of the participated pregnant women were in their first trimester. Almost a quarter (23.5%) of the women believed that they had periodontal problem currently, while 46.3% reported having carious teeth. More than 44% reported having dental pain, and about 40% women felt that her oral health was poor. About 60% reported having heard about the possible connection between pregnancy and the oral health. About 94% of the women were brushing their teeth at least once a day. More than half of the women (58.3%) visited the dentist during their most recent pregnancy, mostly for dental pain. A large proportion of the pregnant women in this study had oral health problems; however, more than 40% of those women had not visited a dentist during their pregnancy, and the majority of those utilized dental services when they had dental pain only. To provide better oral health care, more knowledge needs to be made available to the pregnant women and the medical community.


Nurse practitioner liability and authority.
Nurse practitioners are being held to a higher professional standard. No longer can nurses assume that their practice is protected by physicians and hospitals. Current trends indicate that nurse practitioners are accountable for their actions and are liable for malpractice. Legislation regulating the practice of nurse practitioners varies from state to state; differing opinions among nurses, physicians, and legislators account for some of these variances. The ultimate goal of the health care professions is the delivery of safe, effective, cost-efficient health care. Nurse practitioners are helping to achieve this goal.


Isolation and serial cultivation of rabbit skin epithelial cells.
A method to isolate and to serially cultivate rabbit skin epithelial cells from adult trunk skin has been developed. Using a collagen gel as substrate and trypsin and EDTA to dissociate cells, nonproliferative primary cultures of rabbit cells may be converted to proliferative populations, and at least 3 serial passages achieved. In the presence of large concentrations of methotrexate (up to 1000 microgram/ml), epithelial cells in primary culture show no decrease in their ability to attach, spread, or keratinize. Following conversion to proliferative populations by trypsin and EDTA low concentrations of methotrexate (1 microgram/ml) are strongly cytotoxic. When the incorporation of 32PO4(3-) and 3H-thymidine into DNA of proliferative and nonproliferative cells is compared, the incorporation of 32PO4(3-), but not that of 3H-thymidine, correlates with changes in cell number and DNA content. In both primary and serially cultivated cells, L-serine is required for optimal growth.


Biochemical studies of rat atrial natriuretic factor.
The natriuretic substances were purified from rat atrium (ANF, atrial natriuretic factor) and were shown to be identical with the inhibitor of norepinephrine-induced contraction of smooth muscle. Their four native forms were isolated. Amino acid sequence analyses showed they are peptides with 35, 31, 30 and 25 amino acid residues respectively and contain a ring structure consisting of 17 amino acid residues and a disulfide bridge. The presence of a high molecular weight prohormone was shown. cDNA coding for the precursor was cloned and used to deduce the amino acid sequence of the preprohormone. Genomic DNA for ANF was cloned and the presence of two introns were found. Several ANF peptides were synthesized. Structure-function studies showed that the ring structure is essential for the activity. Antibodies produced against the synthetic 25 amino acid residue ANF were used to develop radioimmunoassay. The presence of ANF in rat plasma was demonstrated as evidence that ANF is a circulating hormone. ANF was also found in the hypothalamus of rats. The quantitative determination of the synthetic ability of ANF has been determined by the application of ANF cDNA for the quantification of ANF messenger RNA. Immunohistochemical methods localized ANF in cardiac atriocytes, gonadotrophs in anterior pituitary and adrenal medulla (chromaffin cells). A strong immuno-reactivity was found in dark cells of the collecting ducts of the kidney. ANF increases cyclic GMP in target cells suggesting that cyclic GMP may be the intracellular mediator of ANF action.


Synthesis of 2-Aminopyridines via a Base-Promoted Cascade Reaction of N-Propargylic β-Enaminones with Formamides.
N-Substituted formamides as nucleophiles react with in situ-generated 1,4-oxazepines from N-propargylic β-enaminones followed by spontaneous N-deformylation to deliver densely substituted 2-aminopyridines in good yields (31-88%). The formyl group is found to be a superior traceless activating group of free amines and would ultimately be removed in situ. This reaction proceeds smoothly at room temperature, in the presence of NaOH as sole additive, without protection from the atmosphere and generates H2O and sodium formate as byproducts.


Cough, expiration and aspiration reflexes: possible anesthetic implications - a brief review.
Systematic study in animals indicated, that in addition to cough there are 2 distinct airway reflexes. The aspiration reflex (AspR) characterized by rapid and strong gasp-like inspiration provoked by stimulation of nasopharynx, nasal phyltrum or auricle of ear. The expiration reflex (ExpR) manifests by prompt expiration, induced by laryngeal stimulation. Both reflexes strongly activate the brainstem inspiratory or expiratory generators, respectively, and inhibit the opposite respiratory and various functional disorders. This paper indicates several functional disorders occurring during manipulation with airways in anaesthesiological practice, which can be influenced positively or negatively by application of these special reflexes (asphyxia, breath-holding, laryngospasm, bronchospasm, sleep apnoea episodes, arrhythmia, collapse, etc.). The AspR, ExpR and CR (cough reflex) have important clinical relevance in anaesthesia and emergency medicine applicable also in domestic therapy and in hardly accessible places particularly by application of ICT (Information & Communication Technologies) using a mobile connection of the patient with the remote hospital centre.


Iii. Sleep assessment methods.
Sleep is a complex phenomenon that could be understood and assessed at many levels. Sleep could be described at the behavioral level (relative lack of movements and awareness and responsiveness) and at the brain level (based on EEG activity). Sleep could be characterized by its duration, by its distribution during the 24-hr day period, and by its quality (e.g., consolidated versus fragmented). Different methods have been developed to assess various aspects of sleep. This chapter covers the most established and common methods used to assess sleep in infants and children. These methods include polysomnography, videosomnography, actigraphy, direct observations, sleep diaries, and questionnaires. The advantages and disadvantages of each method are highlighted.