Bonferroni parallel gatekeeping - transparent generalizations, adjusted p -values, and short direct proofs.
In the two-step version (Dmitrienko, Tamhane, Wang and Chen, 2006) of the Bonferroni parallel-gatekeeping multiple-testing procedure (MTP): (a) a family F1 of null hypotheses H is used as a gatekeeper for another family F2 in that no H in F2 can be rejected unless at least one H is rejected in F1; (b) a Bonferroni MTP is used for F1 at local multiple-level alpha in the first step; and (c) Holm's (1979) step-down MTP is used in the second step for F2 at a local multiple level that depends on the rejections made in the first step. It is shown in this article that this two-step procedure can be generalized in that any MTP with multiple-level control and available multiplicity-adjusted p -values can be used instead of Holm's MTP in the second step. A further generalization related to what Dmitrienko, Molenberghs, Chuang-Stein and Offen (2005) called modified Bonferroni parallel gatekeeping is also given where in case all H s in F2 are rejected, additional rejections in F1 can be made in a third step at local multiple-level alpha through any MTP that is more powerful than the initial Bonferroni MTP, e.g. Holm's MTP. The proofs that these two generalized Bonferroni parallel-gatekeeping MTPs have multiple-level alpha are short and direct, without closed-testing arguments. Multiplicity-adjusted p -values can easily be calculated for these MTPs. The extensions to several successive gatekeeper families are straightforward. An illustration is given.


Inhibition of either phosphatidylinositol 3-kinase/Akt or the mitogen/extracellular-regulated kinase, MEK/ERK, signaling pathways suppress growth of breast cancer cell lines, but MEK/ERK signaling is critical for cell survival.
The phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen/extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways are important integrators of growth and survival signals originating from extracellular stimuli. We assessed the importance of these signaling pathways in the growth and survival of 8 breast cell lines (MCF10A, an immortalized line; and 7 cancer cell lines). The cell lines expressed variable levels of both phosphorylated ERK and phosphorylated Akt, but these were unchanged by incubation in serum-free medium. Despite continued activity of these pathways, the cells arrested growth in the absence of serum demonstrating that additional pathways are required for growth. Incubation with the PI3K inhibitor LY294002 suppressed growth of all cell lines, but most remained viable for at least 7-14 days. This long-term survival may be attributable to recovery of phospho-Akt by 24-48 h despite the continued presence of active LY294002, suggesting that alternate pathways may be activating Akt. In contrast, incubation with the MEK inhibitor U0126 not only arrested growth, but also killed all the cell lines within 2-4 days in the absence of serum; the presence of serum only slighted extended viability, except in MCF10A and MDA-MB-468 cells, in which serum provided significantly greater protection. It is likely that these signaling pathways control the level of pro-and anti-apoptotic proteins, yet assessment of Bcl-2 and Bcl-X showed dramatic reduction in level only when large numbers of cells were dead suggesting this may be a consequence rather than cause of death. Overall, the results demonstrate that the MEK/ERK pathway represents the more critical pathway for cell survival of these breast cancer cell lines, and suggest this pathways represents the better target for cancer therapy.


Review of MRI imaging for placenta accreta spectrum: Pathophysiologic insights, imaging signs, and recent developments.
Placenta Accreta Spectrum (PAS) refers to the range of abnormally adhesive and penetrative placental tissue at a uterine scar. PAS is divided into accreta, increta, and percreta based on degree of myometrial invasion. Its incidence has increased, and PAS is now the leading indication for emergency peripartum hysterectomy in the setting of catastrophic hemorrhage from a non-separating placenta. The recent release of the International Federation of Gynecology and Obstetrics (FIGO) guidelines in 2018 coupled with the joint consensus statement from the Society of Abdominal Radiology (SAR) and European Society of Urogenital Radiology (ESUR) in 2020 reflect decades worth of diagnostic and therapeutic advances in this field. Although the increasing role of MRI in PAS diagnosis is evident, the literature on PAS reveals several disparate but conceptually overlapping MRI signs. Identifying and differentiating between placenta increta and percreta on imaging may be quite challenging even with MRI and sometimes even on final pathology. In this review, we aim to (i) provide a clarified understanding of PAS pathophysiology, (ii) comprehensively review and classify MRI signs based on pathophysiologic underpinnings, (iii) highlight shortcomings in the current PAS literature; and (iv) highlight best practice guidelines for imaging diagnosis of PAS.


Preparation, characterization and antibacterial mechanism of the chitosan coatings modified by Ag/ZnO microspheres.
To improve the physicochemical and antibacterial properties of coatings, the chitosan (CS) coatings were respectively prepared by a casting method with zinc oxide (ZnO) and silver (Ag)/ZnO microspheres as modifiers. The chemical structures and micromorphology of ZnO, Ag/ZnO microspheres and CS coatings were characterized by X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy and energy dispersive X-ray spectroscopy. Furthermore, using the dominant spoilage bacteria of aquatic products, Shewanella putrefaciens and Pseudomonas aeruginosa, as objects, the antibacterial activities and mechanism of the CS coatings were investigated. The results show that ZnO and Ag/ZnO microspheres are dispersed homogeneously in the CS coatings. After modified by ZnO and Ag/ZnO microspheres, the mechanical properties and antibacterial abilities of the CS coatings are improved, and that of 0.5% Ag/ZnO-CS coating is the optimal. For pure CS coating, the bacterial cell membrane is damaged slightly because of the electrostatic interaction between NH3+ of CS and the negative charge on bacterial surface. After treated by ZnO-CS composite coating, the bacterial cell membrane is destroyed badly on account of the earlier-mentioned ion interaction and disturbing the synthesis of high molecular weight total protein. With regard to Ag/ZnO-CS composite coating, the bacterial cell membrane is damaged seriously and cell contents are completely released due to ion interaction, disturbing the synthesis of high molecular weight total protein and low molecular weight membrane protein. Hence, Ag/ZnO-CS composite coatings are antimicrobial materials and food preservative materials with great potential application. © 2020 Society of Chemical Industry.


High-performance liquid chromatographic determination of hormonal peptides and their fluorenylmethoxycarbonyl derivatives.
Reference methods for the quantitation of peptide and protein hormones in blood are urgently needed and high-performance liquid chromatography (HPLC) is potentially applicable. Owing to the low concentrations of these substances in body fluids, very low detection limits have to be achieved. This can be done on the one hand by reducing the diameter of the separation column and increasing the number of theoretical plates, and on the other by derivatization. Angiotensin II was chosen as a model compound. Reduction of the inner diameter from 4 to 2 mm increased the peak height by a factor of 3.4 (theoretical value 4.0). The peptide was derivatized with 9-fluorenyl methylchloroformate in lithium carbonate-sodium hydrogencarbonate or sodium borate buffer at different pH values. The precision (coefficient of variation) was 10.4%, the linear range 1:40 (r = 0.998) and the detection limit 500 fmol of derivative on-column. The volume injected was 2 microliter. However, this is not sufficiently sensitive for the quantitation of most peptide hormones using an acceptable maximum specimen volume of 5 ml of serum or plasma.


Porcine intestinal microbiota is shaped by diet composition based on rye or triticale.
The present study aimed to compare the microbiota composition from pigs fed different cereal grain types, either rye or triticale, as sole energy source. Ileal digesta and faeces were sampled from eight pigs of each experiment. Illumina amplicon sequencing of the 16S rRNA gene was used to analyse the microbiota. Concentrations of short-chain fatty acids and ammonia were determined from faecal samples. The grain type revealed significant alterations in the overall microbiota structure. The rye-based diet was associated with an increased abundance of Lactobacillus in ileal digesta and Streptococcus in faeces and significantly higher concentrations of faecal short-chain fatty acids and ammonia compared to triticale. However, triticale significantly promoted the abundance of Streptococcus in ileal digesta and Clostridium sensu stricto in faeces. Diets based on rye or triticale affect varying intestinal microbiota, both of taxonomical and metabolic structure, with rye indicating an enhanced saccharolytic potential and triticale a more cellulolytic potential. Nutrient composition of rye and triticale are attractive for porcine nutrition. Both cereal grains show varying stimuli on the microbiota composition and microbial products of the ileum and faeces.


Deoxynivalenol in pigs: An exclusive effect on the appetite?
A feeding-trial was conducted to determine the effects of a deoxynivalenol (DON)-contaminated diet in growing pigs. DON was added as either the purified toxin or as naturally contaminated wheat. Growth performance, biochemical and hematological parameters and DON-transformation through intestinal bacteria were monitored throughout the study. Epithelial tissues along the gastro-intestinal tract were also examined for pathological changes and selected enzyme activities (oxoglutarat dehydrogenase, alanine-amino-transferase). There were no differences among the dietary treatments in all parameters measured except for feed intake and weight gain in the naturally contaminated diets fed ad libitum. Effectsin vivo could not be explained exclusively by cytotoxicity of DON foundin vitro. These observations may reflect the presence of other unidentified (toxic) compounds in the naturally contaminated grain or the influence of further factors. In future studies synergistic/additive interactions with substances promoting appetite should be taken into consideration.


NMR resonance assignments of the programmed cell death protein 5 (PDCD5) from Toxoplasma gondii.
Toxoplasmosis is a systematic protozoan disease caused by a tiny parasite Toxoplasma gondii. The infection can be dangerous for pregnant woman and people with weak immune systems. The secreted protein named TgPDCD5 (Programmed cell death protein 5 from Toxoplasma gondii) plays an important role in apoptosis-inducing effect on host cells. Here, we report the 1H, 13C, and 15N resonance assignments of TgPDCD5. This work provides the ground for further structural elucidate and biophysical investigation about protein function.


Therapeutic apheresis in pregnancy: General considerations and current practice.
It is widely known that pregnancy does not represent a contraindication to therapeutic apheresis (TA) techniques. In fact, since the first experiences of TA in pregnancy for the prevention of hemolytic disease of the newborn, several diseases are at present treated with TA, mainly within 6 clinical categories: (a) TA is a priority and has no alternative equally effective treatment (e.g., thrombotic thrombocytopenic purpura); (b) TA is a priority but there are alternative therapies not contraindicated in pregnancy (e.g., myasthenia gravis); (c) TA is an effective tool of saving/avoiding drugs contraindicated in pregnancy (e.g., systemic lupus erythematosus); (d) TA is a treatment of specific conditions/complications of pregnancy with maternal and/or fetal risk (e.g., antiphospholipid syndrome); (e) TA is a treatment of specific conditions of pregnancy with exclusive fetal risk (e.g., hemolytic disease of the newborn); (f) TA is a treatment of disease which is strongly indicated and can exceptionally occur during pregnancy (e.g., Goodpasture's syndrome). When dealing with TA pregnant patients, some technical aspects due to the physiological changes of gestation have to be carefully considered, in particular the increase of the circulating blood volume. Moreover a multidisciplinary medical team, including an obstetrician, a clinical consultant, specialist in TA and in transfusion medicine, and a neonatologist stand as a basic requirement for the proper management of some clinical conditions that may be characterized by high maternal and fetal risk.


Schwann cells as drivers of tissue repair and regeneration.
Current evidence suggests that peripheral nerve-associated Schwann cells possess the capacity to promote the repair and regeneration of multiple tissue types, in addition to peripheral nervous system axons. These findings shed light on the nerve-dependent nature of regeneration that has been well documented in various organs. This review outlines recent advances in knowledge surrounding endogenous regenerative functions of Schwann cells across species and tissue types, with a specific focus on the role of Sox2+ dedifferentiated Schwann cells in regulating the proliferation of surrounding tissue-resident mesenchymal precursors.


Relationship of physical fitness to chewing in an 80-year-old population.
Although tooth loss causes a decrease in masticatory ability, which may influence nutritional status, and impair an individual's general health including physical activity, little is known whether a decrease in chewing ability could result in deterioration in physical fitness in a very elderly population. Thus, the present study evaluated the relationship of chewing ability or teeth number with measures of physical fitness in a sample of 80-years-old in Japan. Cross-sectional survey. A total of 1282 people who were 80-years old and resided in the Fukuoka Prefecture were approached. A total of 697 individuals (277 male, 420 female) agreed to participate. Chewing food number and teeth number were related positively with physical fitness measurements of hand grip strength, leg extensor strength, leg extensor power, stepping rate, and one-leg standing time. However, the significant relationship between the number of teeth and physical ability disappeared after adjustment for various confounders, using multiple regression analysis or logistic regression analysis. On the other hand, the relationship of chewing ability with physical fitness measurements of leg extensor strength, one-leg standing time, or isokinetic leg extensor power remained significant even after adjustment for these confounders. There is a relationship between perceived chewing ability (number of foods considered chewable) and physical fitness in this 80-year-old population. Chewing ability may be an independent predictor of physical fitness, thus preventative dental care aimed at preserving chewing ability may be able to enhance activities of daily life and quality of life in very elderly individuals.


Direct control of fractal pattern generation on an optical fractal synthesizer.
We propose a method for direct control of position, rotation, and scaling of fractal patterns generated on an optical fractal synthesizer. In this method we introduce an iterated-function-system mother function to produce control parameters for arbitrary fractal patterns. We implemented the method experimentally and verified the effectiveness of the method.


Colectomy for colon cancer via a 7-cm minilaparotomy.
We herein describe our technique for performing a colectomy to resect colon cancer via a 7-cm minilaparotomy using conventional surgical techniques and instruments. By moving the minilaparotomy wound laterally as well as either caudad or cephalad, the mobilization of the relevant segment of the bowel loop was thus made possible. To ensure an adequate visualization of the operative field during a dissection of the lymph nodes, an Omni-Tract retractor system was used. The division of the colonic mesentery, transection of the affected bowel, and bowel anastomosis were performed extracorporeally or at the level of the incision. This same operation was successfully performed in 102 patients with colon cancer. We conclude that a colectomy for colon cancer via a 7-cm minilaparotomy is an attractive alternative to a conventional full laparotomy in selected patients.


Study on the Mechanisms of Banxia Xiexin Decoction in Treating Diabetic Gastroparesis Based on Network Pharmacology.
In China, Banxia Xiexin decoction (BXD) is applied to treat diabetic gastroparesis (DGP), but its key active ingredients and mechanisms against DGP are unclear. This study is designated to reveal the molecular mechanisms of BXD in treating DGP by adopting a creative approach known as network pharmacology to explore the active ingredients and therapeutic targets of BXD. In our study, 730 differentially expressed genes of DGP were obtained, and 30 potential targets of BXD against DGP were screened out (including ADRB2, DRD1, FOS, MMP9, FOSL1, FOSL2, JUN, MAP2, DRD2, MYC, F3, CDKN1A, IL6, NFKBIA, ICAM1, CCL2, SELE, DUOX2, MGAM, THBD, SERPINE1, ALOX5, CXCL11, CXCL2, CXCL10, RUNX2, CD40LG, C1QB, MCL1, and ADCYAP1). Based on the findings, BXD contains 60 compounds with therapeutic effect on DGP, including the key active ingredients such as quercetin, wogonin, baicalein, beta-sitosterol, and kaempferol. Sixty-eight pathways including TNF signaling pathway, IL-17 signaling pathway, and AGE-RAGE signaling pathway were significantly enriched. In this study, the mechanisms of BXD in treating DGP are affirmed to be a complex network with multi-target and multi-pathway, which provides a reference for future experimental studies.


Energy transfer between Er3+:Sm3+codoped TeO2-Li2O glass.
The energy transfer in Er3+: Sm3+ codoped binary TeO2-Li2O (TLO) glass has been studied using 532 nm laser radiation on the basis of fluorescence intensity and the lifetime measurements. It is observed that the trace of erbium ion can be utilized to sensitize the samarium. The mechanism involved in the present case is found to be dipole-dipole. The energy transfer efficiencies, probabilities of energy transfer and the average donor acceptor distance has been evaluated.


1,4-dioxane-fused 4-anilinoquinazoline as inhibitors of epidermal growth factor receptor kinase.
The 4-anilinoquinazoline PD 153035 (1) is a potential antitumor agent which acts by inhibiting tyrosine kinase activity of epidermal growth factor receptor (EFGR) via competitive binding at the ATP site of enzyme. A series of cyclic analogues of PD 153035 bearing the 1,4-dioxane ring was prepared by reaction of 6-chloro derivative 5 with several aniline nucleophiles. These were evaluated for their ability to inhibit the EGFR kinase and the growth of primary human tumor cell cultures. All of the new 4-anilinoquinazolines exhibited less potency than PD 153035 against EGFR kinase. However, compounds 2b, 2c, 2e, 2g, and 2h showed higher inhibitory activities than PD 153035 against the growth of A431 tumor cell line. The compound 2b containing 3-chloroaniline ring was as potent as PD 153035 against EGFR kinase and showed about 5.4-fold better potency than PD153035 in the inhibition of growth of A431 cell line with good selectivity.


Correlations of evoked potentials with MR imaging and MR spectroscopy in multiple sclerosis.
The current state-of-the-art imaging technique in multiple sclerosis (MS) is magnetic resonance (MR) imaging. With improved imaging technology, MR spectroscopy offers the capacity to identify those chemical changes associated with MS and promises to enhance our ability to understand this disease. Physiologic function in the central nervous system can be measured using evoked potentials. This article analyzes the correlation between these two techniques.


Amyloid arthropathy of the hip joint: MR demonstration of presumed amyloid lesions in 152 patients with long-term hemodialysis.
The aim of this study was to determine the spectrum of MR findings of presumed amyloid arthropathy of the hip joints in patients on long-term hemodialysis. We prospectively performed T1- and T2-weighted spin-echo imaging on 152 consecutive patients on hemodialysis. The duration of hemodialysis ranged from 5 months to 24 years, 2 months (mean: 8 years, 8 months). The frequency, location, and signal intensity of bone lesions were assessed. In 12 cases with contrast-enhanced MR examination, enhancement pattern of bone lesions, synovial lesions, and intra-articular lesions were characterized. Bone lesions presumed to be amyloid deposits were identified in 60 patients (39%). Magnetic resonance imaging revealed that amyloid lesions were more extensive than anticipated by plain radiographs. All bone lesions showed decreased signal intensity on T1-weighted images. On T2-weighted images, bone lesions showed increased signal intensity in 32 patients (54%), decreased signal intensity in 11 patients (18%), and both increased and decreased signal intensity in 17 patients (28%). Following intravenous injection of gadolinium-based contrast, all bone lesions showed moderate enhancement. Synovial thickening could not be identified on T1- and T2-weighted images. However, contrast-enhanced images showed thickened synovial membrane, which could be differentiated from joint fluid. Intra-articular nodules showed decreased or intermediate signal intensity on T1-weighted images and decreased signal intensity on T2-weighted images; the intra-articular nodules were contiguous with subchondral bone lesions. Magnetic resonance imaging is useful for evaluating the distribution and extent of amyloidosis of the hip joints in patients undergoing long-term hemodialysis.


Approaching the bulk limit with finite cluster calculations using local increments: the case of LiH.
Finite-cluster calculations employing high-level wavefunction-based ab initio methods and extended atomic-orbital basis sets are used to determine local energy increments for bulk LiH. It is shown that these increments can be converged with respect to cluster size and point-charge embedding so as to yield bulk cohesive energies with an accuracy of better than 1 mE(h), both at the Hartree-Fock and at correlated levels. Instrumental for the efficiency of the scheme is the introduction of non-orthogonal orbitals, at an intermediate stage.


The influence of road transport on the activities of glutathione reductase, glutathione peroxidase, and glutathione-S-transferase in equine erythrocytes.
Transport of horses may have significant impact on serum biochemical and hematologic analytes and resistance to infection. The aim of our study was to assess the influence of transport stress on selected enzymatic antioxidants in equine blood. The study was conducted on a group of 60 horses of different breeds and ranging in age from 4 to 10 years. Venous blood was collected immediately before loading horses onto trailers for 8 hours of transport (I), immediately after unloading them from the trailer (II), and after subsequent stall rest for 24 hours (III). Hemolysates of blood were prepared, and hemoglobin (Hb) concentration and activities of the enzymatic antioxidants glutathione reductase (GR), glutathione-S-transferase (GST), and glutathione peroxidase (GPx) were measured. Enzyme activities were expressed as units of activity per gram of hemoglobin. There were significant decreases in activities (mean ± SD U/g Hb [minimum-maximum]) of GPx between collection times I (36 ± 14 U/g Hb [9-67 U/g Hb]) and III (30 ± 11 U/g Hb [12-51 U/g Hb]) and of GR between collection times I (54 ± 28 U/g Hb [7-117 U/g Hb]) and II (40 ± 23 U/g Hb [12-145 U/g Hb]). There was no significant difference in activities of GR between collection times I and III (50 ± 27 U/g Hb [9-116 U/g Hb]). There were no differences detected in GST activity among the 3 collection times. Road transport has an impact on activities of the antioxidant enzymes GPx and GR, with recovery of GR activity evident by 24 hours post-transport. Decreased activity of these enzymes may be one mechanism for increased susceptibility to infections that are manifest after shipping; alternatively, decreases may indicate utilization as these enzymes work to neutralize increases in reactive oxygen species.


Feeding strategies for the dysphagic patient: a nursing perspective.
The goal of treatment for the dysphagic patient is to maintain safe oral feeding. Achieving this goal requires an individualized care plan using selected feeding strategies. This care plan will need to be altered as changes in the patient's condition occur.


Identification of heavy metal pollutants in wheat by THz spectroscopy and deep support vector machine.
This paper proposes to detect heavy metal pollutants in wheat using terahertz spectroscopy and deep support vector machine (DSVM). Five heavy metal pollutants, arsenic, lead, mercury, chromium, and cadmium, were considered for detection in wheat samples. THz spectral data were pre-processed by wavelet denoising. DSVM was introduced to further enhance the accuracy of the SVM classification model. According to the relationship between the accuracy and the training time with the number of hidden layers ranging from 1 to 4, the model performs the best when the hidden layer network has three layers. Besides, using the back-propagation algorithm to optimize the entire DSVM network. Compared with Deep neural network (DNN) and SVM models, the comprehensive evaluation index of the proposed model optimized by DSVM has the highest accuracy of 91.3 %. It realized the exploration enhanced the classification accuracy of the heavy metal pollutants in wheat.


Copper tolerant yeasts isolated from polluted area of Argentina.
Eleven yeasts were isolated from wastewater sediment samples collected from a copper filter mine plant, located in the province of Tucumán, Argentina, and tested for their heavy metal tolerance. Two isolates were selected based on their multiple tolerance to different heavy metals and their copper biosorption capacity was studied. Analysis of the 26S rDNA D1/D2 domain sequences indicates that isolate RCL-3 showed similarity with Candida sp. and RCL-11 with Rhodotorula mucilaginosa . Growth performance and copper toxicity of both yeasts were evaluated using YNB-glucose medium supplemented with 0.1, 0.2, 0.5 and 1 mM of Cu2+ solutions. Candida sp. RCL-3 was able to grow up to 7 mg ml(-1) biomass in the presence of either 0.1 or 0.2 mM Cu2+, and at 0.5 mM Cu2+ growth reached 5.5 mg ml(-1). R. mucilaginosa RCL-11 reached 8 mg ml(-1) in the presence of 0.1 mM Cu2+, and values of 6.5 and 5.5 mg ml(-1) biomass were obtained at 0.2 and 0.5 mM Cu2+, respectively. Copper accumulation profiles were different: the metal was librated from the intact cells by Candida sp. whereas R. mucilaginosa did not show release from the cells indicating intracellular storage. Specific biosorption of copper by both isolated yeasts showed increase with the initial copper supplied with the medium (up to 11.5 and 8.0 mg Cu g(-1) biomass for Candida sp. and R. mucilaginosa , respectively). However, specific biosorption decreased with time.


Zinc homeostasis and functions of zinc in the brain.
The brain barrier system, i.e., the blood-brain and blood-cerebrospinal fluid barriers, is important for zinc homeostasis in the brain. Zinc is supplied to the brain via both barriers. A large portion of zinc serves as zinc metalloproteins in neurons and glial cells. Approximately 10% of the total zinc in the brain, probably ionic zinc, exists in the synaptic vesicles, and may serve as an endogenous neuromodulator in synaptic neurotransmission. The turnover of zinc in the brain is much slower than in peripheral tissues such as the liver. However, dietary zinc deprivation affects zinc homeostasis in the brain. Vesicular zinc-enriched regions, e.g., the hippocampus, are responsive to dietary zinc deprivation, which causes brain dysfunctions such as learning impairment and olfactory dysfunction. Olfactory recognition is reversibly disturbed by the chelation of zinc released from amygdalar neuron terminals. On the other hand, the susceptibility to epileptic seizures, which may decrease vesicular zinc, is also enhanced by zinc deficiency. Therefore, zinc homeostasis in the brain is closely related to neuronal activity. Even in adult animals and probably adult humans, adequate zinc supply is important for brain functions and prevention of neurological diseases.


Properties of several protein kinases that copurify with rat spinal cord neurofilaments.
Several protein kinases that copurify with neurofilaments (NF) were identified and each kinase was assessed for its ability to phosphorylate NF proteins. NFs were isolated using an axonal flotation procedure and the kinases were extracted from NFs with 0.8 M KCl. NF kinases were incubated with peptide substrates for selected protein kinases, [32P]ATP and protein kinase cofactors and inhibitors to characterize the kinases. Using peptide substrates, three types of kinase were identified, and a fourth was identified using NF protein as substrate. The first three kinases were the catalytic subunit of cAMP-dependent protein kinase, calcium-calmodulin dependent protein kinase II and a cofactor-independent kinase that phosphorylated prepro VIP sequence 156-170 and was inhibited by heparin. Using NF proteins as substrate, a fourth kinase was identified which was cofactor-independent and was not inhibited by heparin. Neither cofactor-independent kinase was casein kinase II. NF proteins were phosphorylated in vitro on serine and threonine, primarily by the two cofactor-independent kinases. Using [alpha-32P]8-N3ATP for affinity labeling, one kinase of 43,800 Da was identified. Thus, in addition to cAMP-dependent protein kinase and calcium-calmodulin dependent protein kinase II, two kinases have been found which are primarily responsible for NF phosphorylation in vitro and are cofactor-independent.


Teaching nursing homes revisited. Survey of affiliations between American medical schools and long-term-care facilities.
A survey of American medical schools was conducted to examine the growth of teaching nursing home programs. Ninety percent (109/121) of schools surveyed reported affiliations with a nursing home(s) for teaching, research, and/or clinical care. Most affiliations occurred in the last six years and were typically with two or more nursing homes. They were usually 120 beds or more in size, and the majority were nonprofit or Veterans Administration units. Eighty-three percent (101/121) of medical schools had teaching programs involving nursing homes. Medical school courses that utilized nursing homes as teaching sites were largely selective or elective and were offered primarily in the senior year. Training programs involving residents were usually mandatory and mainly involved the departments of internal medicine and family practice. Fifty-five percent (66/121) of the schools had research programs involving nursing homes.


Nociceptive thresholds in adult rats of three strains after pain stimulation in the neonatal period.
Nociceptive thresholds in the tail-flick test decreased in adult 2.5-month-old KM, Wag/Rij, and Wistar rats receiving injections of placebo in the neonatal period (days 3-9 of life).


Paediatric Strategy Forum for medicinal product development in mitogen-activated protein kinase pathway inhibitors: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.
As the mitogen-activated protein kinase (MAPK) signalling pathway is activated in many paediatric cancers, it is an important therapeutic target. Currently, a range of targeted MAPK pathway inhibitors are being developed in adults. However, MAPK signals through many cascades and feedback loops and perturbing the MAPK pathway may have substantial influence on other pathways as well as normal development. In view of these issues, the ninth Paediatric Strategy Forum focused on MAPK inhibitors. Development of MAPK pathway inhibitors to date has been predominantly driven by adult indications such as malignant melanoma. However, these inhibitors may also target unmet needs in paediatric low-grade gliomas, high-grade gliomas, Langerhans cell histiocytosis, juvenile myelomonocytic leukaemia and several other paediatric conditions. Although MAPK inhibitors have demonstrated activity in paediatric cancer, the response rates and duration of responses needs improvement and better documentation. The rapid development and evaluation of combination approaches, based on a deep understanding of biology, is required to optimise responses and to avoid paradoxical tumour growth and other unintended consequences including severe toxicity. Better inhibitors with higher central nervous systempenetration for primary brain tumours and cancers with a propensity for central nervous system metastases need to be studied to determine if they are more effective than agents currently being used, and the optimum duration of therapy with MAPK inhibition needs to be determined. Systematic and coordinated clinical investigations to inform future treatment strategies with MAPK inhibitors, rather than use outside of clinical trials, are needed to fully assess the risks and benefits of these single agents and combination strategies in both front-line and in the refractory/relapse settings. Platform trials could address the investigation of multiple similar products and combinations. Accelerating the introduction of MAPK inhibitors into front-line paediatric studies is a priority, as is ensuring that these studies generate data appropriate for scientific and regulatory purposes. Early discussions with regulators are crucial, particularly if external controls are considered as randomised control trials in small patient populations can be challenging. Functional end-points specific to the populations in which they are studied, such as visual acuity, motor and neuro psychological function are important, as these outcomes are often more reflective of benefit for lower grade tumours (such as paediatric low-grade glioma and plexiform neurofibroma) and should be included in initial study designs for paediatric low-grade glioma. Early prospective discussions and agreements with regulators are necessary. Long-term follow-up of patients receiving MAPK inhibitors is crucial in view of their prolonged administration and the important involvement of this pathway in normal development. Further rational development, with a detailed understanding of biology of this class of products, is crucial to ensure they provide optimal benefit while minimising toxicity to children and adolescents with cancer.


The Elusive SLIPPERS Syndrome (Supratentorial Lymphocytic Inflammation with Parenchymal Perivascular Enhancement Responsive to Steroids): A Case Report and Literature Review.
In 2015, the term "SLIPPERS" was created to refer to a rare type of encephalomyelitis called CLIPPERS syndrome that affects the pons and sometimes other nearby structures, but in this case, it primarily affects the supratentorial region. This variation of the condition is responsive to treatment with steroids. We report the case of a patient who presented with seizures and visual field deficit and had typical radiological and histopathological characteristics of SLIPPERS syndrome. Although the literature is inundated with CLIPPERS syndrome, its supratentorial variant is extremely rare. To our knowledge, this is fourth case of SLIPPERS syndrome to be reported in literature and serves to enhance clinicopathological understanding of this elusive entity.


Food labeling; nutrient content claims, definition of sodium levels for the term "healthy." Final rule.
The Food and Drug Administration (FDA) is amending its regulations concerning the maximum sodium levels permitted for foods that bear the implied nutrient content claim "healthy." The agency is retaining the currently effective, less restrictive, "first-tier" sodium level requirements for all food categories, including individual foods (480 milligrams (mg)) and meals and main dishes (600 mg), and is dropping the "second-tier" (more restrictive) sodium level requirements for all food categories. Based on the comments received about technological barriers to reducing sodium in processed foods and poor sales of products that meet the second-tier sodium level, the agency has determined that requiring the more restrictive sodium levels would likely inhibit the development of new "healthy" food products and risk substantially eliminating existing "healthy" products from the marketplace. After reviewing the comments and evaluating the data from various sources, FDA has become convinced that retaining the higher first-tier sodium level requirements for all food products bearing the term "healthy" will encourage the manufacture of a greater number of products that are consistent with dietary guidelines for a variety of nutrients. The agency has also revised the regulatory text of the "healthy" regulation to clarify the scope and meaning of the regulation and to reformat the nutrient content requirements for "healthy" into a more readable set of tables, consistent with the Presidential Memorandum instructing that regulations be written in plain language.


A rare case of choroidal neovascularization following macular hole surgery.
Choroidal neovascularization occurs in a wide spectrum of conditions, including degenerative, inflammatory, traumatic and hereditary conditions, all of which are characterized by breaks in Bruch's membrane. A few cases of choroidal neovascular membrane (CNVM) have been reported in the literature following macular hole surgery. We present a retrospective case study of a single patient who developed CNVM after successful macular hole surgery. The 70-year-old diabetic female underwent macular hole surgery in her right eye. Posterior hyaloid was separated with suction and vitrectomy was performed. Internal limiting membrane (ILM) was stained with trypan blue under air and ILM peeling was performed. Perfluoropropane (C3F8) gas was used as the tamponade. Six weeks post-operation, closure of macular hole was seen. Six months later, she presented with defective vision. Subfoveal classic CNVM was seen in the same eye. About 1%-3% of patients who undergo macular hole surgery develop CNVM. Age-related changes and surgical trauma are considered to be the predisposing factors in reported cases. Injury to the retinal pigment epithelium (RPE) during surgery may be an important factor in our case, since there were no pre-existing age-related changes. CNVM though rare can occur after macular hole surgery, especially in the setting of age-related changes. Injuries to the RPE should be avoided during surgery. We report a case of CNVM after macular hole in which trypan blue was used as a staining agent.


Clustering hybrid regression: a novel computational approach to study and model biohydrogen production through dark fermentation.
Clustering hybrid regression (CHR) approach was developed and evaluated using data from H(2)-producing glucose-based, suspended-cell bioreactor operated for 5 months. The aim was to describe the relationship between metabolic end products and H(2)-production rate. Self-organizing maps (SOM) were used to better visualize the dataset and to detect main metabolic patterns in bioprocess data. SOM detected three distinct metabolic patterns with butyrate, acetate and ethanol as dominant metabolites, respectively. Butyrate dominated metabolism was related to high H(2) production, while acetate and ethanol dominated metabolisms resulted in low H(2) production. CHR models performed well [mean square error (MSE) 0.55 and 0.56] in modeling the H(2)-production rate. The results validate the suitability of the CHR approach in describing the bioprocess behavior and in the modeling of H(2) production rate. The developed model can help in discovering key metabolic interactions and suitable process parameters from complex datasets, and increase the understanding of the bioprocesses occurring in engineered and natural environments.


Antibacterial potential of Thymus linearis essential oil collected from Wasturwan mountain: A combination of experimental and theoretical studies involving in silico molecular docking simulation of the major compounds against Novobiocin-resistant mutant of DNA Gyrase-B.
Antibiotic resistant bacteria are immune to most antibiotics and are therefore very difficult to treat and in most cases lead to death. As such there is a pressing need for alternative and more efficient antibacterial drugs which can target these drug-resistant strains as well. The objective of this research work was to investigate the antibacterial properties of Thymus linearis essential oil (EO) against multiple disease-causing bacterial pathogens. Additionally, the study aimed to examine the molecular docking and molecular dynamic (MD) simulations of the primary components of the EO with the essential bacterial proteins and enzymes. Gas chromatography-mass spectrometry was employed to analyse the chemical composition of Thymus linearis EO. The initial screening for antibacterial properties involved the use of disc diffusion and microdilution techniques. Molecular docking studies were conducted utilising Autodock Vina. The outcomes were subsequently visualised through BIOVIA Discovery Studio. MD simulations were conducted using iMODS, an internet-based platform designed for MD simulations. The essential oil (EO) was found to contain 26 components, with thymol, carvacrol, p-cymene, and γ-terpinene being the primary constituents. The study findings revealed that Thymus linearis EO demonstrated antibacterial effects that were dependent on both the dose and time. The results of molecular docking studies revealed that the primary constituents of the EO, namely thymol, carvacrol, and p-cymene, exhibited robust interactions with the active site of the bacterial DNA gyrase enzyme. This finding provides an explanation for the antibacterial mechanism of the EO. The results indicate that Thymus linearis EO possesses potent antibacterial properties against the MDR microorganisms. Molecular docking analyses revealed that the essential oil's primary components interact with the amino acid residues of the DNA-Gyrase B enzyme, resulting in a favourable docking score.


Sliding resistance with esthetic ligatures: an in-vitro study.
This study was developed to evaluate in vitro the properties related to sliding resistance of esthetic ligatures. Frictional force of 6 ligatures--2 conventional, 2 specially coated elastomeric, Teflon-coated (Dupont, Wilmington, Del) stainless steel, and stainless steel (control) ligatures--were studied by sliding 0.019 x 0.025-in stainless steel wire through the 0.22-in slot of stainless steel bracket. Elastomeric ligatures were tested for frictional and tensile forces under 3 experimental conditions: recent stretching, after 21 days of simulated stretching in artificial saliva, and a demineralizing/remineralizing regimen. Statistical analysis was conducted with ANOVA and Games-Howell tests. There was high correlation between frictional and tensile forces of elastomeric ligatures, with reduction of both after 21 days. The demineralizing/remineralizing regimen reduced the frictional forces of ligatures to the same level as the ligatures in artificial saliva. Teflon-coated and stainless steel ligatures showed the lowest initial frictional forces, but there was no difference in friction of stainless steel and post-stretched elastomeric ligatures. Frictional forces generated by esthetic elastomeric ligatures under simulated oral environments are not stable and are more related to tensile force than to surface characteristics of the ligatures.


Economic effects and spin-offs in a small space economy: the case of Canada.
Canada, through a well-focused space program (telecommunications, earth observation, robotics), has succeeded in developing a space industry largely based on SMEs. The result has been significant economic benefits and technological spin-offs. In this article, the results of two programs, the ESA (European Space Agency) and the STEAR (Strategic Technologies in Automation and Robotics), are compared. The ESA program has generated significant indirect effects and spin-offs for Canadian exports. ESA's reputation and network have enabled SMEs to increase export sales of both space products and other commercial products derived from space technologies. The STEAR program has been highly successful in promoting a new generation of SMEs for space robotics, encouraging both spin-in and spin-offs of technologies. The analysis highlights the complementarity of mission- and diffusion-oriented programs in the technology transfer process.


National trends in oropharyngeal cancer incidence and survival within the Veterans Affairs Health Care System.
Oropharyngeal squamous cell carcinoma (OPSCC) epidemiology has not been examined previously in the nationwide Veterans Affairs (VA) population. Joinpoint regression analysis was applied to OPSCC cases identified from VA administrative data from 2000 to 2012. We identified 12 125 OPSCC cases (incidence: 12.2 of 100 000 persons). OPSCC incidence declined between 2000 and 2006 (annual percent change [APC] = -4.27, P < .05), then increased between 2006 and 2012 (APC = 7.02, P < .05). Significant incidence increases occurred among white (APC = 7.19, P < .05) and African American (APC = 4.87, P < .05) Veterans and across all age cohorts. The percentage of never-smokers increased from 8% in 2000 to 15.7% in 2012 (P < .001), and 2-year overall survival improved from 31.2% (95% confidence interval (CI) [30-33.4]) to 55.7% (95% CI [54.4-57.1]). OPSCC incidence is increasing across all racial and age cohorts in the VA population. Smoking rates remain high among Veterans with OPSCC and gains in survival lag those reported in the general population.


Comparison of herpesviruses isolated from reindeer, goats, and cattle by restriction endonuclease analysis.
A genomic comparison of bovine herpesvirus 1 (BHV-1), caprine herpesvirus (CHV-2) and reindeer herpesvirus (RHV), was performed using 5 restriction endonucleases. Cross neutralization of these three herpesviruses showed that BHV-1 and CHV-2 had a relatively low degree of cross reaction with heterologous viruses. RHV showed a higher degree of such cross reactivity. The restriction endonuclease analyses showed that the migration patterns of the DNA segments were different for the three groups of herpesviruses. The enteric caprine strain could be differentiated from genital strains using BstE II and Hpa I. The genome size of reindeer herpesvirus was estimated to be approximately 86.8 x 10(6) Da (131.8 kbp), and indications of isomerization of this genome were found. It is concluded that reindeer herpesvirus is a distinct species within the family Herpesviridae.


Oxidation of methane and ethylene over Al incorporated N-doped graphene: A comparative mechanistic DFT study.
It is generally recognized that developing effective methods for selective oxidation of hydrocarbons to generate more useful chemicals is a major challenge for the chemical industry. In the present study, density functional theory calculations are conducted to examine the catalytic partial oxidation of methane (CH4) and ethylene (C2H4) by nitrous oxide (N2O) over Al-incorporated porphyrin-like N-doped graphene (AlN4-Gr). Adsorption energies for the most stable configurations of CH4, C2H4, and N2O molecules over the AlN4-Gr catalyst are determined to be -0.25, -0.64, and -0.40 eV, respectively. According to our findings, N2O can be efficiently split into N2 and Oads species with a negligible activation energy on the AlN4-Gr surface. Meanwhile, CH4 and C2H4 molecules compete for reaction with the activated oxygen atom (Oads) that stays on the surface. The energy barriers for partial methane oxidation through the CH4 + Oads → CH3° + HOads and CH3° + HOads → CH3OH reaction steps are 0.16 eV and 0.27 eV, respectively. Furthermore, the produced CH3OH may be overoxidized by Oads to give formaldehyde and water molecules by overcoming a relatively low activation barrier. The activation barriers for C2H4 epoxidation are small and comparable to those for CH4 oxidation, implying that AlN4-Gr is highly active for both reactions. The high energy barrier for the 1,2-hydrogen shift in the OCH2CH2 intermediate, on the other hand, makes the production of acetaldehyde impossible under normal conditions. According to the population analysis, the AlN4-Gr serves as a strong electron donor to aid in the charge transfer between the Al atom and the Oads moiety, which is necessary for the activation of CH4 and C2H4. The findings of the present study may pave the way for a better understanding of the catalytic oxidation the CH4 and C2H4, as well as for the development of highly efficient noble-metal free catalysts for these reactions.


Genetic and pharmacological intervention for treatment/prevention of hearing loss.
Twenty years ago it was first demonstrated that birds could regenerate their cochlear hair cells following noise damage or aminoglycoside treatment. An understanding of how this structural and functional regeneration occurred might lead to the development of therapies for treatment of sensorineural hearing loss in humans. Recent experiments have demonstrated that noise exposure and aminoglycoside treatment lead to apoptosis of the hair cells. In birds, this programmed cell death induces the adjacent supporting cells to undergo regeneration to replace the lost hair cells. Although hair cells in the mammalian cochlea undergo apoptosis in response to noise damage and ototoxic drug treatment, the supporting cells do not possess the ability to undergo regeneration. However, current experiments on genetic manipulation, gene therapy, and stem cell transplantation suggest that regeneration in the mammalian cochlea may eventually be possible and may 1 day provide a therapeutic tool for hearing loss in humans. The reader should be able to: (1) Describe the anatomy of the avian and mammalian cochlea, identify the individual cell types in the organ of Corti, and distinguish major features that participate in hearing function, (2) Demonstrate a knowledge of how sound damage and aminoglycoside poisoning induce apoptosis of hair cells in the cochlea, (3) Define how hair cell loss in the avian cochlea leads to regeneration of new hair cells and distinguish this from the mammalian cochlea where there is no regeneration following damage, and (4) Interpret the potential for new approaches, such as genetic manipulation, gene therapy and stem cell transplantation, could provide a therapeutic approach to hair cell loss in the mammalian cochlea.


Renal tubular acidosis and associated factors in patients with primary Sjögren's syndrome: a registry-based study.
To investigate the clinical features and factors associated with primary Sjögren's syndrome (pSS)-associated renal tubular acidosis (RTA). This case-control study was based on a multicenter pSS registry established by the Chinese Rheumatism Data Center. Patients with pSS, including those with RTA and those without renal involvement, between May 2016 and March 2020 were included in the analysis. Demographic, clinical, and laboratory data were also collected. Univariate and multivariate logistic regression analyses were used to identify factors that were associated with pSS-RTA. This study included 257 pSS patients with RTA and 4222 patients without renal involvement. Significantly younger age at disease onset (40.1 ± 14.1 vs. 46.2 ± 13.1 years, P < 0.001), longer diagnosis interval (15.0 interquartile range [IQR] [1.0, 48.0] vs. 6.0 IQR [0, 34.0] months, P < 0.001), higher EULAR Sjögren's syndrome disease activity index (9 IQR [5, 15] vs. 3 IQR [0, 8], P < 0.001), and a higher prevalence of decreased estimated glomerular filtration rate (25.0% vs. 6.6%, P < 0.001) were observed in pSS patients with RTA than in those without renal involvement. Factors that were independently associated with pSS-RTA included age at disease onset ≤ 35 years (odds ratio [OR] 3.00, 95% confidence interval [CI] 2.27-3.97), thyroid disorders (OR 1.49, 95% CI 1.04-2.14), subjective dry mouth (OR 3.29, 95% CI 1.71-6.35), arthritis (OR 1.57, 95% CI 1.10-2.25), anti-SSB antibody positivity (OR 1.80, 95% CI 1.33-2.45), anemia (OR 1.67, 95% CI 1.26-2.21), elevated alkaline phosphatase level (OR 2.14, 95% CI 1.26-3.65), decreased albumin level (OR 1.61, 95% CI 1.00-2.60), and elevated erythrocyte sedimentation rate (OR 1.78, 95% CI 1.16-2.73). Delayed diagnosis and decreased kidney function are common in pSS patients with RTA. pSS should be considered in patients with RTA, and early recognition and treatment may be useful in slowing the deterioration of renal function in patients with pSS-RTA. Key Points • pSS patients with RTA have earlier disease onset and higher disease activity than pSS patients without RTA, but the diagnosis was frequently delayed. • Decreased kidney function are common in pSS patients with RTA. • Sjögren's syndrome should be considered in young female patients with unexplained RTA, whereas RTA should be screened in pSS patients with early disease onset and elevated ALP level.


Osseointegration of Layer-by-Layer Polyelectrolyte Multilayers Loaded with IGF1 and Coated on Titanium Implant Under Osteoporotic Condition [Retraction].
[This retracts the article DOI: 10.2147/IJN.S148001.].


Exposure to violence in childhood and risk of violence in adult schizophrenia: Results from a multinational study.
This study investigated the connection between childhood violence exposure and violent behavior in adults with schizophrenia spectrum disorders (SSDs). The case-control study included 398 SSD patients: 221 cases with a history of severe interpersonal violence in the past and 177 controls with no history of violence. The findings indicated that cases were significantly more likely to report childhood exposure to all forms of witnessed or personally sustained violence both within and outside the family, with those who had witnessed intra-familial violence being more likely to assault a family member in adulthood. Cases reported exposure to violence before the age of 12 years significantly more frequently than controls, and those with early-life violence exposure were significantly more likely to report that they were in a state of intense anger when they behaved violently. A dose-response relationship was observed, with evidence of an increased risk of later violence when the exposure occurred before the age of 12 and an increased likelihood of intrafamilial violence. The evidence suggests that childhood violence exposure was associated with an increased risk of violent behavior in adult SSD patients, and early exposure was linked to an increased likelihood of physical violence occurring in states of intense anger.


A comparative analysis of kratom exposure cases in Thailand and the United States from 2010-2017.
Background: Interest in the Southeast Asian natural remedy kratom has increased in Western countries recently, along with increasing concern over its potential toxic effects.Objective: To describe and compare demographics, common co-exposure substances, clinical effects, treatments, and medical outcomes of kratom "abuse" exposures in the United States (US) and Thailand.Methods: This is a retrospective analysis of kratom "abuse" exposures, defined as use when attempting to gain a psychotropic effect, reported to the National Poison Data System (NPDS) in the US and the Ramathibodi Poison Center (RPC) in Thailand from 2010 to 2017. Multivariate analysis identified risk factors for severe medical outcomes, defined as both ICU admissions and death.Results: Nine-hundred-twenty-eight cases were included (760 from NPDS and 168 from RPC). A greater proportion of cases involved co-exposures in Thailand (64.8% versus 37.4%; odds ratio [OR] = 3.10, 95% confidence interval [CI] = 2.15-4.47, p < .01). Both countries had a similar prevalence of opioid and benzodiazepine co-ingestions, but the US had more co-ingestions with other sedatives (4.6% versus 0%, OR = 0, 95% CI = 0-0.47, p < .01). Common clinical effects included tachycardia (30.4%), agitation/irritability (26.2%), and drowsiness/lethargy (21.1%). Six deaths occurred, including one single-substance exposure in the US, three multiple-substance exposures in the US, and two multiple-substance exposures in Thailand. Severe medical outcomes were reported more frequently in the US (OR = 18.82, 95% CI = 5.85-60.56, p < .01).Conclusions: Despite lower frequencies of co-ingestants overall, US kratom abuse exposures yielded greater clinical severity. This disparity may be attributable to differences in the products labeled "kratom," greater sedative co-exposures in the US, and/or differences in population genetics or use patterns.


Doppler-guided cannulation of internal jugular vein, subclavian vein and innominate (brachiocephalic) vein--a case-control comparison in patients with reduced and normal intracranial compliance.
A case-control comparison of Doppler guidance on the success rate of central venous cannulation in patients with normal or reduced intracranial compliance. A single operator performed central venous access procedures with continuous wave Doppler guidance. It was used on patients on a ventilator. The position of patients with reduced intracranial compliance (RIC) was not changed for the procedure. Patients with normal intracranial compliance (NIC) were put in the Trendelenburg position. We prospectively evaluated 249 Doppler-guided central venous access procedures performed over a 12-month period at our 10-bed neuro-intensive care unit at a university hospital. The group with RIC included 26 males and 35 females (n=61) aged 16-79 years. In this group 155 Doppler-guided cannulation procedures (62%) were performed. The group with NIC (n=52) comprised 29 males and 23 females aged 34-76 years; 94 Doppler-guided cannulation procedures (38%) were carried out. The veins cannulated in RIC and NIC, respectively, were: right innominate vein: 24/18, left innominate vein 26/12, right subclavian vein 12/7, left subclavian vein 25/14, and right internal jugular vein 33/18 and left internal jugular vein 35/24. The absence of one left internal jugular vein was identified in the NIC group. The success rate of first needle pass in patients with RIC was 92% and in patients with NIC 89%. This study showed that Doppler guidance allows the cannulation of central veins in patients with RIC placed in head-up position. Cannulation can be ensured and first-pass needle placement maximised.


Sleep-related breathing disorder in Duchenne muscular dystrophy: disease spectrum in the paediatric population.
Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease with death usually occurring because of respiratory failure. Signs of early respiratory insufficiency are usually first detectable in sleep. To study the presentation of sleep-related breathing disorder (SRBD) in patients with DMD. A retrospective review of patients with DMD attending a tertiary paediatric sleep disorder clinic over a 5-year period. Symptoms, lung function and polysomnographic indices were reviewed. A total of 34 patients with DMD were referred for respiratory assessment (1-15 years). Twenty-two (64%) reported sleep-related symptomatology. Forced vital capacity (FVC) was between 12 and 107% predicted (n = 29). Thirty-two progressed to have polysomnography of which 15 were normal studies (median age: 10 years) and 10 (31%) were diagnostic of obstructive sleep apnoea (OSA) (median age: 8 years). A total of 11 patients (32%) showed hypoventilation (median age: 13 years) during the 5-year period and non-invasive ventilation (NIV) was offered to them. The median FVC of this group was 27% predicted. There was a significant improvement in the apnoea/hypopnoea index (AHI) (mean difference = 11.31, 95% CI = 5.91-16.70, P = 0.001) following the institution of NIV. The prevalence of SRBD in DMD is significant. There is a bimodal presentation of SRBD, with OSA found in the first decade and hypoventilation more commonly seen at the beginning of the second decade. Polysomnography is recommended in children with symptoms of OSA, or at the stage of becoming wheelchair-bound. In patients with the early stages of respiratory failure, assessment with polysomnography-identified sleep hypoventilation and assisted in initiating NIV.


Assessment of nitrate contamination due to groundwater pollution in north eastern part of Anantapur District, A.P. India.
The north eastern part of Anantapur district is in the state of Andhra Pradesh, India, is significant as it is covered by varied geological formations and has different land use and irrigation practices. Though ground water is the major drinking water source, deterioration in its quality is going unchecked. In such agro-economy based rural areas, the nitrate contamination is rampant and much attention has not been drawn towards this anthropogenic pollution. In the study area ground water samples from different hydrogeological set-up have been collected during the pre and post monsoon seasons and analysed for the major ions such as Ca, Mg, Na, K, CO(3), HCO(3), Cl, SO(4), NO(3) and F. The study revealed that 65% of the samples were found to be unsuitable for drinking purposes in the pre monsoon season and 45% in the post monsoon due to excess nitrate (>45 mg/l) content in the ground water. Among the different seasons and environs, nitrate was in highest concentration in the granitic terrain and canal command areas during pre monsoon season. The nitrate was found to decrease with depth in all the hydrogeological set-ups in both the seasons. Intense agriculture practices, improper sewerage and organic waste disposal methods were observed to contribute nitrate to the shallow and moderately deep aquifers.


Induction of lethal mutations in female mice by 9 generations of gamma-irradiation during foetal development.
Female CBA mice were chronically gamma-irradiated in utero during either of two periods, the 10th to 14th days or the 14th to 18th days of gestation. The doses administered were 34 rad/generation in the earlier group and 160 rad/generation in the latter with dose rates of 0.3 rad/h and 1.7 rad/h, respectively. The doses were given through 9 generations. The effect of the irradiation was expressed as an increased frequency in the rate of recessive lethal equivalents by just above 4%. This corresponds to a mutation rate of 1.5 X 10(-4) mutation/rad/genome in the animals irradiated during the 10th to 14th gestational days and 0.3 X 10(-4) mutation/rad/genome in the 14th to 18th day group. As in earlier investigations, neither dominant mutations nor dominance effects of induced recessive lethal equivalents were found.


Pharmacological action of nicotine in the isolated urinary bladder from rabbit: special reference to the chronic nicotine treatment.
1. A mode of action of nicotine and a change of the responsiveness to nicotine following chronic nicotine treatment in the urinary bladder of rabbit were investigated. 2. Nicotine induced only a contraction in the urinary bladder of rabbit, and the response to nicotine was reduced by hexamethonium, atropine and capsaicin. These findings suggest that the contractile response to nicotine was mediated through an action on the nicotinic receptors and partially due to the release of acetylcholine and tachykinins. 3. Tetrodotoxin did not inhibit the contractile response to nicotine in the rabbit detrusor muscle, suggesting that the nicotine-induced response may be produced mainly through a sodium action potential-independent process. 4. Nicotine-induced contraction was reduced following the chronic nicotine treatment without a change of its pharmacological properties. These findings suggest that chronic nicotine treatment might cause a decrease of the amounts of nicotinic receptors and also receptors for mediators released by nicotine.


Visualization of the thymus with therapeutic doses of radioiodine in patients with thyroid cancer.
Two cases of papillary carcinoma of the thyroid are presented in which whole-body scans following therapeutic doses of iodine-131 revealed intense anterior mediastinal uptake. In both cases, the mediastinal uptake was absent from scans obtained after removal of the entire thymus. Histologically, the resected thymus glands showed hyperplasia and contained neither thyroid tissue nor metastatic foci of thyroid carcinoma. We therefore concluded that anterior mediastinal uptake of radioiodine may be caused by hyperplasia of the thymus.


Discriminative value of serum amyloid A and other acute-phase proteins for coronary heart disease.
We studied the value of serum amyloid A (SAA), a first-class acute-phase protein, as a marker for coronary heart disease (CHD) in a middle-aged male population. In a working population of 16307 men (age, 35-59 years), 446 cases had a history of CHD or prominent Q:QS waves on electrocardiogram. For each case, two matched controls were investigated. SAA, measured by immunonephelometry, was correlated with other acute-phase proteins, cardiovascular risk factors, and infectious serology markers. SAA concentrations were significantly higher in the cases than in controls (P<0.05) and correlated with serum C-reactive protein (CRP) (r=0.61), plasma fibrinogen (r=0.39), serum haptoglobin (r=0.26), and body mass index (r=0.13) (P<0.001). Serum CRP is a better marker for CHD than SAA, which showed discriminative power only in a univariate model comparing highest versus lowest tertile (odds ratio, 1.39; 95% confidence interval, 1.03-1.87). Neither SAA nor other acute-phase proteins correlated with Chlamydia pneumoniae immunoglobulin (Ig)G, Helicobacter pylori IgG and IgA, and cytomegalovirus IgG. In conclusion, although SAA has a discriminative value for CHD, serum CRP is to be preferred as a first-class acute-phase reactant for detection of the disease.


Peroxynitrite mediates high glucose-induced osteoblast apoptosis.
High glucose (HG) state is closely related to diabetic complications, and among these one main pathogenesis involves apoptosis of important functional cells. However, the mechanism of osteoblast (OB) apoptosis induced by HG state is not clear. Peroxynitrite (ONOO-), the strongest oxidant, can mediate apoptosis in various kinds of cells, including OB. Therefore, this study was aimed at investigating whether HG state could induce OB apoptosis through ONOO-. Cultured OB from rat calvariae explanted from E21 fetuses were treated with HG solution. The ratio of OB apoptosis and ONOOcontent was assayed by TUNEL, flow cytometry, and immunohistochemistry. The results showed that HG state could induce ONOO- overformation (p<0.01), and excessive OB apoptosis (p<0.001). However, the HG-induced OB apoptosis could be attenuated by peonol, a potent scavenger of ONOO-. In conclusion, HG state might trigger excessive ONOO- formation, mediating OB apoptosis.


The vascular densities of the macula and optic disc in normal eyes from children by optical coherence tomography angiography.
This study aims to describe the variation and characteristics of vessel density (VD) of the macula and optic disc in the normal eyes of children. This was a retrospective study where subjects aged 5-18 years with normal eyes were enrolled. The macula and optic disc were scanned by optical coherence tomography angiography (OCTA). The influences of age, gender, and axial length (AL) on VD were analyzed. A total of 71 normal eyes from 71 subjects were enrolled. For the macula, the mean VD of fovea, parafovea, and perifovea at superficial retina and deep retina were 20.1%, 50.2%, 49.4%, 36.1%, 53.9%, and 48.1%, respectively. The mean foveal avascular zone (FAZ) was 0.277 mm2. For optic disc, the mean VD of radial peripapillary capillary (RPC) and inside-disc areas were 51.8% and 51.7%, respectively. Significant differences were found between the superior-hemi and inferior-hemi VD of the superficial retinal parafovea, deep retinal perifovea, and perifovea. The fovea VD of the superficial and deep retina and FAZ areas were different between genders. The inside-disc VD was positively correlated with AL, while other VDs had no significant correlation with age and AL. The parafovea VD of the superficial retina, parafovea, and perifovea of the deep retina had superior-hemi VD; boys had a higher fovea VD and smaller FAZ area than those of girls, the macular VD and peripapillary RPC density were steady for 5-18 year-olds. This study provided useful information for furthering the understanding of the development mode of vessel in children and the OCTA clinical applications in children.


Attitudes of elderly Korean patients toward death and dying: an application of Q-methodology.
The aim of this study was to identify the attitudes of elderly Korean patients toward death and dying using Q-methodology to aid in the development of basic strategies for nursing care of elderly Koreans. Thirty participants at a university hospital sorted 40 selected Q-statements on a nine-point scale. Data analysis identified three types of attitudes toward death and dying in elderly patients in Korea: religion-dependent, science-adherent, and sardonic. Religion-dependent elders are highly dependent upon religion as evidenced by their reply that they would like to rely on God and a minister the most. Science-adherent elders have great affection for life and believe in modern medical advancements. The sardonic elders regard death as the dispensation of nature so there is no need to be afraid of death and dying. This study will contribute to the understanding that nurses and other health professionals have of the perceptions of elderly Koreans about death and dying. Also, the findings may provide the basis for the development of more appropriate strategies to improve death and dying education programs of health professionals.


Long-term follow up of clinical outcome of orthodontic tooth movement following extraction of previously auto-transplanted maxillary canines and bone grafting: a case report.
The present case is a 13-year follow up of a patient in which the treatment plan involved removal of unsatisfactory auto-transplanted maxillary canines together with a bone graft to re-establish normal dento-alveolar ridge morphology. Active tooth movement occurred in the graft site. At the time, this was a new approach and there was no information in the literature as to the outcome of this treatment modality. Long-term reports regarding the success of this treatment are lacking. To assess the long-term outcome of active tooth movement into a site that required bone grafting. The upper right canine was non-vital with poor periodontal support on its buccal aspect. Examination revealed a substantial bony defect with a loss of the buccal cortical plate following extraction. To augment the ridge defect bone was taken from the maxillary tuberosity and grafted in the upper right canine extraction site and fixed with a bone screw. Protraction of the first premolar and retraction of the lateral incisor into the graft site was slow and constant. Significant closure of the upper canine extraction space was achieved. There were no significant detrimental bone changes in the interproximal areas of 14 and 12. By employing a bone graft to reestablish alveolar bone prior to tooth movement, excellent bone support, periodontal health and a long-term stable result were obtained.


Primary de novo angiosarcoma of the pleura.
Primary angiosarcoma of the pleura is an extremely rare soft tissue tumor with a poor prognosis. We report a case of primary angiosarcoma of the pleura in which the patient was admitted for dyspnea and massive bilateral recurrent hemothorax with fatal outcome. We also review the literature.


Genetic loss of norepinephrine does not alter adult hippocampal neurogenesis in dopamine beta-hydroxylase deficient mice.
Norepinephrine (NE), and specific adrenoceptors, have been reported to influence distinct aspects of adult hippocampal neurogenesis, including latent stem cell activation, progenitor proliferation, and differentiation. These findings are predominantly based on the use of pharmacological approaches in both in vitro and in vivo systems. Here, we sought to assess the consequences of genetic ablation of NE on adult hippocampal neurogenesis, by examining dopamine β hydroxylase knockout (Dbh -/-) mice, which lack NE from birth. We find that Dbh -/- mice exhibit no difference in adult hippocampal progenitor proliferation and survival. Further, the number of immature newborn neurons, labeled using stage-specific developmental markers within the hippocampal neurogenic niche, was also unaltered in Dbh -/- mice. In contrast, the noradrenergic neurotoxin DSP-4, which had previously been shown to reduce adult hippocampal neurogenesis in rats, also resulted in a decline in hippocampal progenitor proliferation in C57/Bl6N mice. These findings indicate that pharmacological lesioning of noradrenergic afferents in adulthood, but not the complete genetic loss of NE from birth, impairs adult hippocampal neurogenesis in mice.


Mechanism of ventricular tachycardia termination by pacing at left ventricular sites in patients with coronary artery disease.
The mechanism by which pacing terminates ventricular tachycardia (VT) may depend on the location of the pacing site relative to the reentry circuit. The purpose of this study was to compare the mechanisms by which pacing terminates VT at left ventricular (LV) sites with and without concealed entrainment (CE) in patients with prior myocardial infarction. LV mapping was performed in 29 patients (26 men, 3 women, mean age 67 +/- 11 years, ejection fraction 0.28 +/- 0.11) with 55 hemodynamically-tolerated VTs (mean cycle length 478 +/- 92 msec). A total of 408 pacing trains were delivered at 102 sites with CE. Radiofrequency catheter ablation was successful in 41 of 55 VT's. At sites with concealed entrainment, VT was terminated by pacing at 17/41 (41%) successful and at 4/61 (7%) unsuccessful ablation sites (p<0.01). Termination without global ventricular capture was the most frequent termination mode (10/21), followed by termination with orthodromic (4/21) and non-orthodromic capture (7/21). In patients with prior myocardial infarction, pacing at sites of CE during VT usually terminates VT either without global capture or by orthodromic capture. Termination of VT by pacing without global capture or with orthodromic capture at sites of CE suggests that the site is within a critical area of the reentry circuit.


Intraoperative complication rates in cataract surgery performed by ophthalmology resident trainees compared to staff surgeons in a Canadian academic center.
To compare the intraoperative complication rates in cataract surgery performed by resident trainees and staff ophthalmologists. Kensington Eye Institute, University of Toronto, Toronto, Canada. Prospective case series. This study included 8738 consecutive cases of primary phacoemulsification cataract surgery performed by staff surgeons and resident trainees from January to December 2016. There were no exclusion criteria. Data collected included the level of resident training, case complexity, degree of resident involvement, and intraoperative complications. Primary outcome measures included intraoperative complication rates and level of complexity of cataract surgeries performed by resident trainees and staff surgeons. Resident trainees were involved in 44% of surgeries. Of those, 82% were completed in their entirety by a resident and 18% were performed by both the staff surgeon and resident. Staff surgeons performed 56% of all surgeries without resident involvement. Sixty-seven percent of surgeries were simple and 33% were complex, with small pupil or intraoperative floppy-iris syndrome being the most common reason for complex cases. For simple cases, there was no difference in the overall complication rates (1.7% and 2.0%; P = .52), posterior capsule rupture rates (0.9% and 0.8%; P = .76), or vitreous loss rates (0.4% and 0.2%; P = .08) between staff and residents, respectively. There were no differences in complication rates between the two groups.


Statins and Risk of Rheumatoid Arthritis: A Nested Case-Control Study.
Statins have antiinflammatory/immunomodulatory effects that may be useful in preventing rheumatoid arthritis (RA), but previous observational studies about the risk of RA with statin use yielded conflicting results. The aim of this study was to determine whether high-intensity statin treatment is associated with reduced risk of RA. Using data from the UK Clinical Practice Research Datalink, we performed a nested case-control analysis in a population-based cohort of patients who began receiving statins between 1997 and 2009 and were followed up until a first diagnosis of RA, death, end of registration with the physician's practice, or end of January 2011. For each case of RA, 10 age-, sex-, and calendar year-matched controls were randomly selected from risk sets. We estimated the hazard ratio (HR) of incident RA in the highest quintile of duration-weighted average statin intensity compared to the lowest, using conditional logistic regression. Models were adjusted for smoking status, total cholesterol level, obesity, history of cardiovascular disease, coexistent autoimmune disease, hypothyroidism, and persistence with treatment. The cohort included 528,654 new users of statins, with 1,357 new cases of RA occurring during a mean follow-up of 3.3 years, for an incidence rate of 7.9 per 10,000 person-years. Cases were more likely to be smokers, to have other autoimmune diseases, and to have had lower total cholesterol levels at baseline. The incidence of RA was lower in the highest statin intensity quintile (adjusted HR 0.77 [95% confidence interval 0.63-0.95]) in comparison to the lowest quintile. In this large population-based study, high-intensity statin treatment was associated with a reduced risk of RA in comparison to low-intensity statin treatment.


Fibrin Deposit on the Peritoneal Surface Serves as a Niche for Cancer Expansion in Carcinomatosis Patients.
Peritoneal metastasis (PM) is a very serious complication of gastrointestinal and gynecological malignancies which is poorly documented. Modified mesothelial cell layer and their microenvironments can favor fibrin deposition for cancer cell adhesion. Scanning and transmission electron microscopy of peritoneal surface and cancer cell clusters from cancer patients was done. Ascites and its impact on mesothelial cells were assessed by cytokine array. Neprilysin, matrix metalloprotease, epithelial mesenchymal transition (EMT) related molecules (E-cadherin, Snail, Slug, Twist, Vimentin and Fibronectin), tissues factor (TF), endothelial protein C receptors (EPCR) were quantified by q-PCR. Fibrin in the simples were stained using anti fibrin F1E1 antibody. Migration ability was assessed by scratch assay. Cell viability and neprilysin activity were analyzed by bioluminescence. Cancer cells-fibrin interaction was investigated by scanning electron microscopy (SEM) and microcinematography (MCG). Mesothelial cells change their morphology after incubation with carcinomatosis peritoneal fluids in vitro. EMT associated with upregulation of neprilysin, matrix metalloproteinase-2, tissue factor and cytokines secretions such as interleukin-6, and 8, hepatocyte growth factor and granulocyte chemotactic protein-2 mRNA and protein were observed. EPCR expression as a natural anticoagulant was decreased. In parallel, carcinomatosis cell clusters extracted from peritoneal fluids were found to be associated with fibrin. Kinetic analysis of cancer cell-fibrin interaction in vitro studied by MCG showed that fiber filaments generated from clots inhibited cancer cell adhesion on fibrin clots. These results indicated that fibrin deposit on the peritoneal surface serve as niches for cancer expansion in carcinomatosis patients.


Violet Fox: A Clinical View of Vertebral Fractures.
Had Violet's abdominal MR not been performed, or its findings not appreciated, the cause of her clinical event might never have been known because our current concept of osteoporotic vertebral fracture (VF) is substantially predicated on a change in either vertebral height or shape on lateral or sagittal spine imaging. The intention of this commentary is to stimulate a multidisciplinary conversation of osteoporotic VFs from an integrated clinical, physiological, and imaging perspective. For research and epidemiological purposes, osteoporotic VFs have been defined as a reduction in anterior, middle, or posterior vertebral height although the required minimum height reduction (e.g., 15% or 20%) varies among definition schemes. We further classify osteoporotic VFs to be "clinical" when they are accompanied by back pain and "morphometric" when they are not, and we have generally accepted the assertion that most of the osteoporotic VFs are painless, that is, morphometric. This dichotomous VF definition scheme has been the foundation of osteoporosis epidemiology and the primary endpoint in most pivotal osteoporosis pharmaceutical trials. Although, having served the osteoporosis community well, our clinical experience, refined by recent insights into vertebral anatomy and spinal biomechanics, advances in vertebral imaging, and 2 decades of vertebral augmentation suggest that the spectrum of osteoporotic VFs is more complicated than this scheme suggests.


Bone marrow necrosis in bone marrow transplantation: the role of MR imaging.
We describe an ALL patient who developed extensive bone marrow necrosis at the time of relapse 2 months after allogeneic bone marrow transplantation from an HLA-identical sibling. The excruciating and diffuse bone pain, fever and precipitous drop in peripheral blood counts were characteristic. This case illustrates the importance of repeat bone marrow biopsies for the diagnosis of disease relapse and the potential application of MR imaging in the assessment of patients with bone marrow necrosis.


Anti-tumor activity of exopolysaccharide from Rhizopus nigricans Ehrenb on S180 tumor-bearing mice.
In this study, the effect of antitumor and immune activities of extracellular polysaccharides (EPS) from Rhizopus nigricans Ehrenb were investigated using S180 bearing mice. The results revealed that EPS in the concentration range 50-1000 μg/mL can inhibited S180 cell proliferation in a dose dependent manner. EPS at the highest dose of 1000 μg/mL showed significantly antitumor activity against S180 with inhibition rate of 47.53%. However, EPS significantly simulated spleen lymphocytes in the concentration of 500 μg/mL, and the increase proliferation ability showed a dose-dependent effect with EPS at the dose of 50-500 μg/mL. In comparison with the control groups, the weights of tumor were declined and the inhibition rates of tumor were remarkably decreased in the treated groups. Pretreatment with EPS at the dose of 75 mg/kg/day, the inhibition rate was decreased by 44.38% (P<0.05). EPS increased the concentrations of IL-2 and TNF-a. The pathological changes of model control group were very obvious. Meanwhile, the prophylactic administration of EPS could more efficiently inhibit the growth of S180 tumor than direct administration of EPS. EPS could prolong the survival period of S180 tumor bearing mice, and the doses 75 mg/kg/day of EPS and combined with cyclophosphamide (20 mg/kg/day) were 43.36% and 36.28% respectively compared to control groups (P<0.05). The results suggested EPS confirmed in vivo anti-tumor effects observed in vitro, and the mechanism of anti-tumor effect of EPS may be at least in part mediated by increased immune activity in host.


Synthesis and biological profiling of tellimagrandin I and analogues reveals that the medium ring can significantly modulate biological activity.
A novel synthesis of the ellagitannin natural product tellimagrandin I and a series of medium ring analogues is described. These compounds were all subsequently screened for redox activity, ability to precipitate protein and cellular phenotype in HeLa cells. From this we have shown that all properties can be modulated independently by varying ring size and by moving the ester out of conjugation with the biaryl ring system. Increasing ring size increased redox activity and cytotoxicity, leading to the identification of a compound (10) which was significantly more cytotoxic. In addition compounds identified with a redox active scaffold and low cytotoxicity may be employed as a new class of redox probes.


Isolated pulmonary mucormycosis in an apparently normal host: a case report.
Mucormycosis is a rare fungal disease commonly affecting individuals with diabetes mellitus, hematological malignancy, and immune deficiency. Isolated pulmonary mucormycosis is extremely rare. This article reports a case of isolated pulmonary mucormycosis that presented as a solitary cavity infiltrate in a patient with no underlying risk factors.


The effects of butterbur on the histamine and allergen cutaneous response.
Butterbur or Petasites hybridus is an herbal remedy that exhibits antihistamine and antileukotriene activity and has been shown to attenuate the response to adenosine monophosphate challenge in patients with allergic rhinitis and asthma. However, no data are available regarding its effects on the histamine and allergen cutaneous response. To evaluate the effects of butterbur compared with fexofenadine and montelukast on the histamine and allergen wheal and flare cutaneous responses. Atopic patients were randomized into a double-blind, double-dummy, crossover study to receive for 1 week butterbur, 50 mg twice daily (8 AM and 10 PM); fexofenadine, 180 mg once daily (10 PM), and placebo once daily (8 AM); montelukast, 10 mg once daily (10 PM), and placebo once daily (8 AM); or placebo twice daily (8 AM and 10 PM). Patients attended the department at 10 AM and had measurements of the cutaneous wheal and flare responses to histamine, allergen, and saline control at 10-minute intervals for 60 minutes. Twenty patients completed the study. The mean +/- SE histamine wheal and flare responses, respectively, were significantly attenuated (P < .05) by fexofenadine (9.4 +/- 1.8 mm2 and 13.5 +/- 3.2 mm2) compared with placebo (15.5 +/- 3.3 mm2 and 179.8 +/- 74.3 mm2) but not by butterbur (16.4 +/- 2.1 mm2 and 297.7 +/- 121.2 mm2) or montelukast (19 +/- 1.9 mm2 and 240.2 +/- 66.6 mm2). The allergen wheal and flare responses, respectively, were also significantly attenuated (P < .05) by fexofenadine (31.1 +/- 6.3 mm2 and 256.9 +/- 86.5 mm2) compared with placebo (65.4 +/- 15.2 mm2 and 1,014.5 +/- 250.0 mm2) but not by butterbur (50.4 +/- 9.2 mm2 and 1,110.3 +/- 256.1 mm2) or montelukast (58.8 +/- 9.1 mm2 and 1,463.6 +/- 295.6 mm2). Butterbur did not produce any significant effects on the histamine and allergen cutaneous response compared with placebo, whereas mediator antagonism with fexofenadine but not montelukast produced significant attenuation. This finding would suggest that butterbur may not be effective in allergic skin disease.


Comparison of disinfection performance of UVC-LED and conventional upper-room UVGI systems.
We developed a novel, compact upper-room ultraviolet germicidal irradiation system with light-emitting diode sources (UR-UVGI-LED) to enhance the disinfection of bioaerosols in an enclosed room space. Its effectiveness was evaluated and compared with the conventional upper-room ultraviolet germicidal irradiation system with mercury vapor sources (UR-UVGI-MV). Escherichia coli, Serratia marcescens, and Staphylococcus epidermidis were atomized under the well-mixed condition and exposed to UR-UVGI-LED (or UR-UVGI-MV) device. The intensity output of the UR-UVGI-LED was also varied from 0% (no LED), 25%, 50% to 100% to further evaluate the UR-UVGI-LED disinfection effectiveness under different power levels. The decay rates for UR-UVGI-LED ranged from -0.1420 ± 0.04 min-1 to -0.3331 ± 0.07 min-1 for Escherichia coli, -0.1288 ± 0.01 min-1 to -0.3583 ± 0.02 min-1 for Serratia marcescens, and -0.0330 ± 0.01 min-1 to -0.0487 ± 0.01 min-1 for Staphylococcus epidermidis. It was noticed that the intensity level had a non-linear influence on the UR-UVGI-LED's performance. The decay rates achieved by the UR-UVGI-MV system were -0.3867 ± 0.08 min-1 , -0.4745 ± 0.002 min-1 , and -0.1624 ± 0.02 min-1 for Escherichia coli, Serratia marcescens, and Staphylococcus epidermidis, respectively. Hence, the disinfection performance of both UR-UVGI-LED and UR-UVGI-MV systems was comparable for Escherichia coli and Serratia marcescens. These results demonstrate that the UR-UVGI-LED system has a high potential to be used as a safe and effective irradiated light source to disinfect indoor airborne pathogens.


Retention of Hispanics in public sector mental health services.
Hispanic underutilization of mental health facilities extends to lowered retention rates among the chronically mentally ill. A theoretical model of retention was developed with four domains of variables: personal traits, accessibility of social support, treatment characteristics, and facility characteristics. Using data collected from CMHC clinical charts in 1983 and 1984, the model was tested using multiple regression and commonality analysis. The model was tenable (R = .59). However, the commonality analysis suggested that most of the unique variance was contributed by the treatment domain. The social support domain made negligible unique contribution. Implications of the model are discussed.


Multimodal imaging in the diagnosis and management of ophthalmia nodosa.
Ophthalmia nodosa (ON) is a rare but important disease describing ocular inflammation caused by injury from insect hairs ("setae"). Type V ON occurs when there is vitreoretinal involvement. Treatment with systemic steroids are first-line, but vitrectomy is indicated in resistant cases. The purpose of this study was to illustrate how multimodal imaging can facilitate diagnosis and management of ON. This is a single retrospective case report of a patient who presented to Bascom Palmer Eye Institute with Type V ON. Multimodal imaging in a patient with Type V ON was illustrated. A moth seta was localized to the anterior vitreous cavity. Intraocular inflammation responded to 2 weeks of high-dose oral prednisone. Multimodal imaging may guide diagnosis and management of ON by documenting baseline features of ON and facilitating comparison at follow up visits. This allows for safe non-surgical management of Type V ON. Long-term follow up would be necessary to determine whether subsequent surgical intervention was needed in this case.


Right bundle branch block and middle septal fiber block with or without left anterior fascicular block manifested as aberrant conduction in apparent healthy individuals: Electro-vectorcardiographic characterization.
Right bundle branch block (RBBB) evident in the precordial ECG leads may be associated with evidence of left bundle branch involvement in the limb leads. Any of the components of the left bundle can be involved, and this complex interventricular conduction abnormality has previously been described in patients with underlying heart disease. To analyze the electro-vectorcardiographic manifestations of RBBB with left middle septal fiber block (LMSFB), with or without left anterior fascicular block (LAFB) in premature atrial beats of patients without apparent structural heart disease. Twelve patients (8 men/4 women; mean age: 32±8years) with premature atrial contractions with this conduction abnormality were included. Surface 12 simultaneous lead ECG recordings and the corresponding vectorcardiographic loops were analyzed. The QRS complexes with RBBB and also LMSFB persisted for between 150 and 190ms. There were no q waves in lead I. The maximum spatial vector (72-86ms) was directed posteriorly, superiorly, and leftward, and the terminal forces were oriented anteriorly, inferiorly and rightward. In 10 patients, small q waves were apparent in leads V1-V2 and the frontal QRS axis was -60° and -70°, with the 46ms vector located at -50°±5. All of these patients most probably had LAFB in addition to LMSFB. In two patients, the initial electrical forces were directed anteriorly, inferiorly, and leftward, and the 46ms vector axis in the frontal plane was 6° and 11°, respectively, indicating absence of LAFB. The combination of RBBB and LMSFB occurring in patients without apparent structural heart disease may be related to the simultaneous occurrence of block of conduction through these components of the Purkinje network. The anterior fascicle of the left bundle may also be involved.


Influence of rumen bypass fat supplementation during early lactation in tropical crossbred dairy cattle.
The present study investigated the influence of rumen bypass fat-supplemented total mixed ration (TMR) on milk production of tropical crossbred, dairy cows. Twelve stall-fed, tropical crossbred, dairy cows were studied from calving to 15 weeks of lactation. The cows were 397.6 kg in body weight and produced 9.14 L/cow/day milk at the first week of lactation. The experiment was on a complete randomized design with two treatments (i.e., basal diet alone and basal diet with bypass fat supplement) each consisting six (n = 6) replicate cows. During the experimental period, while cows of both treatments were individually fed with respective basal diet (TMR), only the cows allocated for experimental dietary treatment were supplemented with rumen bypass fat (200 g/cow/day) containing calcium salts of long-chain fatty acids. Feed intake, body weight (BW), and milk yield of cows were recorded. Proximate composition of feed, milk composition, and blood metabolic profile of cows were assessed. Dry matter intake and BW of cows were not affected (P > 0.05) by supplementation of rumen bypass fat. The cows supplemented with bypass fat had recorded significantly higher (P < 0.05) milk production compared with cows that did not receive bypass fat supplements until eleventh week of the lactation. As such, bypass fat supplementation resulted 132.38 L/cow higher (P < 0.05) cumulative milk production at 15 weeks compared with their counterparts (1142 vs. 1010 L/cow). But, milk fat, solid non-fat (SNF), protein, and milk urea nitrogen (MUN) contents were not influenced (P < 0.05) by bypass fat supplementation. Bypass fat-supplemented cows had comparatively greater (P < 0.05) serum non-esterified fatty acids (NEFA) level around 6-8 weeks of lactation. However, the serum metabolites' (i.e., NEFA, betahydroxy butyric acid (BHBA), albumin, calcium, and phosphorous) contents of both treatments varied within their respective reference range throughout the experiment. Neither the fat-supplemented cows nor their counterparts experienced negative energy balance (NEB). Benefit cost ratio of bypass fat supplementation confirmed that there is a direct financial benefit of bypass fat supplementation until 12.7th week of lactation. In conclusion, bypass fat supplementation with TMR feeding during early lactation is recommended to increase the milk production of tropical crossbred dairy cows with medium production.


The development of a rapid screening technique to measure antibiotic activity in effluents and surface water samples.
Use of antibiotics in medicine, farming and aquaculture results in a continual supply of these pharmaceuticals and their breakdown products reaching the environment. A method has been developed to use for screening environmental samples to establish whether they contain antibiotics. The assay is based on a commercially available test kit and uses some modifications of the test procedure and SPE techniques to deliver a fast, semi-quantifiable result. Development of the assay and results from spiked and environmental samples are discussed.


Molecular and biochemical mechanisms in teratogenesis involving reactive oxygen species.
Developmental pathologies may result from endogenous or xenobiotic-enhanced formation of reactive oxygen species (ROS), which oxidatively damage cellular macromolecules and/or alter signal transduction. This minireview focuses upon several model drugs (phenytoin, thalidomide, methamphetamine), environmental chemicals (benzo[a]pyrene) and gamma irradiation to examine this hypothesis in vivo and in embryo culture using mouse, rat and rabbit models. Embryonic prostaglandin H synthases (PHSs) and lipoxygenases bioactivate xenobiotics to free radical intermediates that initiate ROS formation, resulting in oxidation of proteins, lipids and DNA. Oxidative DNA damage and embryopathies are reduced in PHS knockout mice, and in mice treated with PHS inhibitors, antioxidative enzymes, antioxidants and free radical trapping agents. Thalidomide causes embryonic DNA oxidation in susceptible (rabbit) but not resistant (mouse) species. Embryopathies are increased in mutant mice deficient in the antioxidative enzyme glucose-6-phosphate dehydrogenase (G6PD), or by glutathione (GSH) depletion, or inhibition of GSH peroxidase or GSH reductase. Inducible nitric oxide synthase knockout mice are partially protected. Inhibition of Ras or NF-kB pathways reduces embryopathies, implicating ROS-mediated signal transduction. Atm and p53 knockout mice deficient in DNA damage response/repair are more susceptible to xenobiotic or radiation embryopathies, suggesting a teratological role for DNA damage, consistent with enhanced susceptibility to methamphetamine in ogg1 knockout mice with deficient repair of oxidative DNA damage. Even endogenous embryonic oxidative stress carries a risk, since untreated G6PD- or ATM-deficient mice have increased embryopathies. Thus, embryonic processes regulating the balance of ROS formation, oxidative DNA damage and repair, and ROS-mediated signal transduction may be important determinants of teratological risk.