Species hybridization between a female blue whale (Balaenoptera musculus) and a male fin whale (B. physalus): molecular and morphological documentation.
In 1986 a large, pregnant, female balaenopterid whale was caught in Icelandic waters. The animal had morphological characteristics of both the blue and the fin whale. Molecular analyses of the whale showed that it was a hybrid between a female blue whale and a male fin whale. The descent of the species hybrid was established without access to either parental specimen. Analysis of the fetus showed that it had a blue whale father. The present report of species hybridization between the two largest cetacean species, the blue and the fin whale, documents the occurrence of cetacean species hybridization in the wild. It is also the first example of any cetacean hybridization giving rise to a fertile offspring.


The impact of preventive measures on controlling Covid-19 pandemic: a statistical analysis study.
The purpose of this paper is to investigate the primary variables associated with the COVID-19 disease and to demonstrate how to evaluate the effect of the earlier consideration of the containment measure and the massive testing policy on controlling the spread of this pandemic. We introduced and analyzed, for the first time to our knowledge, a new variable referred to as the Gap, which was defined as the time between the appearance of the first case and the implementation of the containment measure. A correlation, linear, and nonlinear regression-based statistical analysis was conducted to determine the impact of numerous variables and factors on the spread of this pandemic. 81.3% of the variability of total cases was explained by the variability of total tests, and 72.3% of the variability of total deaths was explained by the variability of total cases. In addition, we have constructed significant nonlinear models that explain 97.8% of the total cases' information and 89.4% of the total deaths' information as a function of the Gap variable. Furthermore, we have found no correlation between the total number of tests and the fatality rate. Consideration of earlier containment is an effective measure that enables the prevention of a catastrophic disease spread scenario. In addition, the massive testing policy has no effect on the fatality rate. However, the performance of tests is highly effective at detecting new cases earlier, before they infect a large number of individuals, and is also an effective method for controlling the spread of this disease. Keywords: COVID-19 disease, preventive measures, containment measure, massive policy of tests, linear and nonlinear models. Copyright: © 2022 The Authors. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/.).


2-azabicyclo[2.2.2]octa-3,5-dione via a nitrile Diels-Alder reaction.
The hetero-Diels-Alder reaction of an electron-deficient nitrile, p-toluenesulfonyl cyanide, with the silyl enol ether of cyclohexenone produced a hydrolytically sensitive [4 + 2] adduct in good yield. Use of Mander's reagent, ethyl cyanoformate, with the same diene, produced an unstable adduct. Hydrolysis of the tosyl cyanide adduct resulted in the isoquinuclidinone 2-aza[2.2.2]octa-3,5-dione as a crystalline compound in excellent yield from the nitrile.


Use of urea by early postpartum Holstein cows.
Thirty-nine lactating Holstein cows were fed high-energy complete rations ad libitum with crude protein: 1) 11.7% (negative control); 2) 13.9% (1% urea); 3) 16.6% (1% urea); or 4) 16.6% (positive control) in a continuous 12-wk study beginning at wk 5 postpartum. Milk production of 27.7, 31.8, 34.0, and 30.4 kg/day showed the use of urea nitrogen by groups 2 and probably 3. Two digestion-nitrogen balance trials with each cow also provided evidence that urea nitrogen was used for milk secretion. Energy digestibility averaged 59.4, 64.2, 65.4, and 65.8; and lower for the negative control diet. Nitrogen solubility in the diets was 28, 36, 32, and 21%, which reflects the objective of selecting ingredients with low nitrogen solubility for use in urea diets. Concentrations of ammonia nitrogen before and after feeding were 1.1, 3.3, 3.5, 4.2, and 2.2, 11.2, 11.9, and 9.3 mg/100 ml of rumen fluid. The prefeeding amounts were probably too low for maximum microbial growth. Urea-nitrogen concentrations in plasma were 8.65, 10.32, 18.00, and 17.03 mg/100 ml. These results lend support to the postulate that lactating cows in early lactation can use urea nitrogen when high-energy complete rations with ingredients of low nitrogen solubility are fed ad libitum.


[Assessing dynamic patterns of forest fragmentation based on a landscape mosaic indicator: a case study of Oregon State, USA].
Effectively assessing landscape pattern characteristics and predicting their dynamics have been a basic prerequisite for more reasonably regulating and managing forest landscape, and maintaining landscape security patterns. In this study, based on three U. S. National Land Cover Databases (1992, 2001 and 2006), the landscape mosaic indicator in combination with the Markov model was adopted to analyze forest fragmentation patterns and changes in the characteristics of spatial interactions between forests and other land use types in Oregon State, USA. The results showed that conversion from the development-dominated type D to the single development type DD in landscape mosaic model had the highest transition probability 0.319, indicating that urbanization has been the major force responsible for the change of regional landscape patterns. In the forest security model, the highest rates of forest loss occurred in agriculture and the developed landscape mosaic type (ad), showing that in the development and agriculture dominated landscapes, encroaching upon forests was at the highest likelihood. The areal percentage of forest over the total study area was less than 50% when reaching a steady-state distribution, with an accelerating rate of forest fragmentation, and the landscape spatial distribution tended to be a mixed landscape pattern. The Kappa coefficient between the simulated values and the observed values from the 2006 landscape mosaic model was estimated at 0.82, indicating this model had a high precision. However, the accuracy of the forest security model was poor, with a Kappa coefficient of 0.21.


Glomerular enlargement in the progression of mesangial proliferative glomerulonephritis.
A close association between glomerular hypertrophy and subsequent sclerosis had been demonstrated in diverse animal and human studies. We investigated the relationship between the glomerular volume and glomerular constituents (mesangial matrix, mesangial cells and capillary lumens) in human mesangial proliferative glomerulonephritis (GN). The data were obtained from glomeruli in the specimens of 23 patients undergoing repeat renal biopsies. Glomerular volume and glomerular constituents of each patient were obtained by averaging those of all glomeruli in each specimen. The interval from the first biopsy to the second was 51.2 +/- 6.8 months and the number of glomeruli included in each specimen was 16 +/- 1. Between glomerular volume and fractional mesangial volume, three patterns were recognized. In 8 of 23 patients glomerular volume and fractional mesangial volume were increased in the second biopsy (Group A). In 12 of 23 patients glomerular volume was decreased and fractional mesangial volume increased in the second biopsy (Group B), and in 3 of 23 patients glomerular volume was increased and fractional mesangial volume decreased in the second biopsy (Group C). One patient who underwent renal biopsy three times shifted from Group A to Group B in the course of mesangial proliferative GN. At the final follow-up, 4 of 12 patients in Group B required hemodialysis in contrast to none of 8 patients in Group A. Between glomerular volume and fractional mesangial volume, a positive and inverse relation existed, and we considered that in the course of mesangial proliferative GN, initially, glomerular size increases and thereafter decreases progressively. With glomerular enlargement, mesangial matrix expansion, glomerular capillary enlargement and relative decrease of the number of capillary lumen profiles and mesangial cells per glomerulus to increased glomerular volume were recognized. We concluded that these histological changes play a role in the progression of mesangial proliferative GN in humans as has been speculated in animal models of renal ablation.


[An introduction to fast and ultrafast sequences in magnetic resonance].
The main limitations of magnetic resonance imaging (MRI) are due to the long acquisition time needed for data sampling. Fast and ultrafast sequences, thanks to progress in hardware and software technology, allow the acquisition times to be dramatically reduced. Such improvements will definitely increase MR capabilities and make MRI a fast and dynamic technique no longer depending on patients' cooperation and limited by patients' conditions--e.g., trauma, pediatric, or claustrophobic patients--or even by the anatomic features of the region of interest. The latest experimental studies are aimed at increasing the clinical applications and the perspectives of clinical MRI and at such ambitious goals as MR-fluoroscopy, interventional MRI, total body examination in less than one minute and functional MRI. In this paper the technical principles and the main indications of this new kind of sequences are reported, with a special emphasis on Gradient-Echo (GE), Turbo Spin-Echo (turbo SE) or Fast Spin-Echo (fast SE), Turbo FLASH and Echo Planar (EP) sequence. A smaller flip angle (FA) and the substitution of the 180 degrees RF pulse with a gradient reversal are the main differences of GE from SE sequences. From GE sequences, several fast sequences are derived, such as angiographic and turbo FLASH sequences. The latter, thanks to 180 degrees preinversion RF pulse, using idoneous inversion times (IT), provide flexible contrast. Turbo SE sequences, which are directly derived from conventional SE sequence, allow the acquisition time to be markedly shortened, by acquiring several Fourier lines of K-space for each TR. The repetition of several 180 degrees pulses following the excitatory 90 degrees RF pulse does the trick through the creation of multiple echoes for a single TR. EP sequences are the fastest ones currently available: with them, an image can be acquired in 30-100 ms. However, the limited availability of the relative hardware and the need of both quality implementation and the definition of clinical indications are major obstacles to the widespread use of these sequences. The SE T2-weighted sequence, the main responsible for the long examination time, will be replaced soon. Further implementation of these sequences will make MRI a fast, flexible and adaptable method to any exam and patient disability.


Cell mediated immunity induced in mice by HPV 16 L1 virus-like particles.
Recombinant human papillomavirus (HPV) type 16 L1 virus-like particles (VLPs) expressed in the baculovirus system were used to investigate the cellular immune response to human papillomavirus type 16. The cell-mediated immune response was evaluated through immunization of mice with HPV 16 L1 virus-like particles using a lymphoproliferation assay and cytokine production and cytometric analysis of lymphocyte subsets. A significant proliferative response was observed which was associated with secretion of both interferon-gamma and interleukin-2. FACS analysis of splenic lymphocytes revealed that CD8+ T-cells were increased in the immunized mice. These results demonstrate that HPV 16 L1 VLPs induce a T-cell response characterized by a Th1 profile and confirm that the HPV 16 VLP is a reasonable candidate for vaccine development.


Mycophenolate Mofetil and Rapamycin Induce Apoptosis in the Human Monocytic U937 Cell Line Through Two Different Pathways.
Transplant vasculopathy may be considered as an accelerated form of atherosclerosis resulting in chronic rejection of vascularized allografts. After organ transplantation, a diffuse intimal thickening is observed, leading to the development of an atherosclerosis plaque due to a significant monocyte infiltration. This results from a chronic inflammatory process induced by the immune response. In this study, we investigated the impact of two immunosuppressive drugs used in therapy initiated after organ transplantation, mycophenolate mofetil, and rapamycin, on the apoptotic response of monocytes induced or not by oxidized LDL. Here we show the pro-apoptotic effect of these two drugs through two distinct signaling pathways and we highlight a synergistic effect of rapamycin on apoptosis induced by oxidized LDL. In conclusion, since immunosuppressive therapy using mycophenolate mofetil or rapamycin can increase the cell death in a monocyte cell line, this treatment could exert similar effects on human monocytes in transplant patients, and thus, prevent transplant vasculopathy, atherosclerosis development, and chronic allograft rejection. J. Cell. Biochem. 118: 3480-3487, 2017. © 2017 Wiley Periodicals, Inc.


Preventing adolescent suicide: a community takes action.
Suicide is the third leading cause of death for adolescents and young people in the United States. The etiology of suicide in this population has eluded policy makers, researchers, and communities. Although many suicide prevention programs have been developed and implemented, few are evidence-based in their effectiveness in decreasing suicide rates. In one northern California community, adolescent suicide has risen above the state's average. Two nurses led an effort to develop and implement an innovative grassroots community suicide prevention project targeted at eliminating any further teen suicide. The project consisted of a Teen Resource Card, a community resource brochure targeted at teens, and education for the public and school officials to raise awareness about this issue. This article describes this project for other communities to use as a model. Risk and protective factors are described, and a comprehensive background of adolescent suicide is provided.


Impact of Serial Intralesional Steroid Injections on Idiopathic Subglottic Stenosis.
Serial intralesional steroid injection (SILSI) has been increasingly used to treat idiopathic subglottic stenosis (iSGS). Prior studies have shown effectiveness, but not in all patients. This multi-institutional study evaluates the effect of SILSI on time to recurrent operation, peak expiratory flow (PEF), and dyspnea. Post-hoc secondary analysis of the North American Airway Collaborative data were performed to evaluate the outcomes of iSGS patients undergoing and not undergoing SILSI. The primary outcome was time to recurrent operation, evaluated using Kaplan-Meier curves and Cox regression analysis. Secondary outcomes were change in PEF and clinical chronic obstructive pulmonary disease questionnaire (CCQ) score. Within patients undergoing SILSI, demographics, time from last procedure, and PEF at initiation of SILSI were evaluated to determine the effect on recurrence. Two hundred and ninety patients were included, 238 undergoing endoscopic dilation alone and 52 undergoing dilation and SILSI. No differences in baseline characteristics were observed. There was no difference in time to recurrence (hazard ratio: 0.64; p = 0.183). There were no differences in PEF or CCQ across the 2.5-year study period. Among 52 patients undergoing SILSI, PEF at the time of starting SILSI did not affect recurrence (χ2 = 0.09, p = 0.77). Patients undergoing and not undergoing SILSI had similar times to recurrence, PEF, and CCQ. Factors predicting recurrence among patients undergoing SILSI were not identified. These results support a randomized controlled trial with a uniform SILSI protocol to quantify the effects of SILSI on objective and subjective outcomes and help determine which iSGS patients benefit most. 3 Laryngoscope, 133:2255-2263, 2023.


Matrix metalloproteinases in destructive pulmonary pathology.
Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that have a number of important physiological roles including remodelling of the extracellular matrix, facilitating cell migration, cleaving cytokines, and activating defensins. However, excess MMP activity may lead to tissue destruction. The biology of MMP and the role of these proteases in normal pulmonary immunity are reviewed, and evidence that implicates excess MMP activity in causing matrix breakdown in chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), sarcoidosis, and tuberculosis is discussed. Evidence from both clinical studies and animal models showing that stromal and inflammatory cell MMP expression leads to immunopathology is examined, and the mechanisms by which excess MMP activity may be targeted to improve clinical outcomes are discussed.


Pharmacological and histopathological characterization of a hyperalgesia model induced by freeze lesion.
Induction of a freeze lesion in human skin is an experimental model of hyperalgesia that allows assessing the antihyperalgesic effects of traditional non-steroidal anti-inflammatory drugs (NSAIDs). We have investigated whether this model is also sensitive to selective cyclooxygenase (COX)-2 inhibitors and have characterized morphological substrates of the generated hyperalgesia in the skin. In eight healthy subjects, a freeze lesion was induced and mechanical pain thresholds (MPT) were tested for 5h following administration of the non-selective COX inhibitor diclofenac (75mg), the COX-2-selective inhibitor parecoxib (40mg) or placebo in a randomized, double-blind cross-over study. In five additional healthy subjects, biopsies were taken from normal skin and the area of freezing injury. Induction of the freeze lesion resulted in hyperalgesia expressed by a decrease of MPT after 24h. Diclofenac and parecoxib, but not placebo, statistically significantly elevated MPT. Histochemical and Western blot analyses of skin biopsies revealed a strong upregulation of COX-2, a slight decrease of COX-1 and activation of nuclear factor kappa B (NF-kappaB) in the area of the freezing injury. These findings indicate that the freeze lesion model is sensitive to NSAIDs including selective COX-2 inhibitors, and that NF-kappaB-dependent COX-2 upregulation contributes to the hyperalgesia in this model.


Capecitabine and tegafur + uracil: new preparations. Metastatic colorectal cancer: two oral fluorouracil precursors, few advantages.
(1) The standard chemotherapy for metastatic colorectal cancer is intravenous fluorouracil combined with calcium folinate. This treatment improves the median survival time by approximately 4-6 months compared with optimal palliative care. (2) Two metabolic precursors of fluorouracil are now available in the European Union for first-line oral treatment of metastatic colorectal cancer, namely capecitabine and tegafur + uracil. According to the licensing terms, only the tegafur-uracil combination must be given with calcium folinate. (3) The evaluation files on each of these two cytotoxic agents contain data from two comparative unblinded trials versus intravenous fluorouracil + calcium folinate (Mayo Clinic protocol). None of these trials showed a difference in survival. (4) Both drugs caused severe diarrhoea in 12% of patients. Severe palmoplantar erythrodysesthesia was more frequent on capecitabine. Longer postmarketing follow-up is available for the tegafur + uracil combination, which has been used in Japan for many years. (5) Patients receiving capecitabine or tegafur + uracil + calcium folinate have to take large numbers of tablets or capsules. (6) In practice, the standard treatment for metastatic colorectal cancer remains the fluorouracil + calcium folinate combination. The tegafur + uracil + calcium folinate combination is only useful for patients who prefer oral administration. Capecitabine has no documented advantage over this latter combination.


Direct oxidative isoperfluoropropylation of terminal alkenes via hexafluoropropylene (HFP) and silver fluoride.
A copper-mediated oxidative isoperfluoropropylation of unactivated terminal alkenes with commercially available hexafluoropropylene (HFP) has been developed. With operational simplicity of the procedure and broad substrate applicability, this strategy provides a general and straightforward way for the construction of C(sp3)-C3F7-i bonds. A variety of allylic isoperfluoropropylated compounds have been efficiently synthesized using this strategy.


Bacterial Recruitment to Carnivorous Pitcher Plant Communities: Identifying Sources Influencing Plant Microbiome Composition and Function.
Processes influencing recruitment of diverse bacteria to plant microbiomes remain poorly understood. In the carnivorous pitcher plant Sarracenia purpurea model system, individual pitchers open to collect rainwater, invertebrates and a diverse microbial community, and this detrital food web is sustained by captured insect prey. This study examined how potential sources of bacteria affect the development of the bacterial community within pitchers, how the host plant tissue affects community development and how established vs. assembling communities differ. In a controlled greenhouse experiment, seven replicate pitchers were allocated to five treatments to exclude specific bacterial sources or host tissue: milliQ water only, milliQ + insect prey, rainwater + prey, established communities + prey, artificial pitchers with milliQ + prey. Community composition and functions were examined over 8-40 weeks using bacterial gene sequencing and functional predictions, measurements of cell abundance, hydrolytic enzyme activity and nutrient transformations. Distinct community composition and functional differences between artificial and real pitchers confirm an important influence of host plant tissue on community development, but also suggest this could be partially related to host nutrient uptake. Significant recruitment of bacteria to pitchers from air was evident from many taxa common to all treatments, overlap in composition between milliQ, milliQ + prey, and rainwater + prey treatments, and few taxa unique to milliQ only pitchers. Community functions measured as hydrolytic enzyme (chitinase, protease) activity suggested a strong influence of insect prey additions and were linked to rapid transformation of insect nutrients into dissolved and inorganic sources. Bacterial taxa found in 6 of 7 replicate pitchers within treatments, the "core microbiome" showed tighter successional trajectories over 8 weeks than all taxa. Established pitcher community composition was more stable over 8 weeks, suggesting a diversity-stability relationship and effect of microinvertebrates on bacteria. This study broadly demonstrates that bacterial composition in host pitcher plants is related to both stochastic and specific bacterial recruitment and host plants influence microbial selection and support microbiomes through capture of insect prey.


Effect of hand sanitizer on the performance of fingermark detection techniques.
Hand sanitizers have seen a rapid increase in popularity amongst the general population and this increased use has led to the belief that hand sanitizers may have an effect on subsequent fingermark detection. Based on this hypothesis, three alcoholic and two non-alcoholic hand sanitizers were evaluated to determine the effect they had on the detection of fingermarks deposited after their use. The following fingermark detection methods were applied: 1,2-indanedione-zinc, ninhydrin, physical developer (porous substrate); and cyanoacrylate, rhodamine 6G, magnetic powder (non-porous substrate). Comparison between hand sanitized fingermarks and non-hand sanitized fingermarks showed that the alcohol-based hand sanitizers did not result in any visible differences in fingermark quality. The non-alcoholic hand sanitizers, however, improved the quality of fingermarks developed with 1,2-indanedione-zinc and ninhydrin, and marginally improved those developed with magnetic powder. Different parameters, including time since hand sanitizer application prior to fingermark deposition and age of deposited mark, were tested to determine the longevity of increased development quality. The non-alcoholic hand sanitized marks showed no decrease in quality when aged for up to two weeks. The time since sanitizer application was determined to be an important factor that affected the quality of non-alcoholic hand sanitized fingermarks. It was hypothesized that the active ingredient in non-alcoholic hand sanitizers, benzalkonium chloride, is responsible for the increase in fingermark development quality observed with amino acid reagents, while the increased moisture content present on the ridges resulted in better powdered fingermarks.


Polymorphic variation of inflammation-related genes and risk of non-Hodgkin lymphoma for Uygur and Han Chinese in Xinjiang.
Polymorphisms of inflammation-related genes have been found to be associated with non-Hodgkin lymphoma (NHL) or some of its subtypes, but only a few relevant data have been reported in China. In this study, the Snapshot method was used to assess genetic variation; a total of 14 single nucleotide polymorphisms (SNPs) for 6 inflammatory factors in 157 NHL cases (64 Uygur ethnic subjects, 93 Han Chinese) and 435 controls (231 Uygur and 204 Han Chinese) were studied from the Xinjiang province of China. Haplotype distribution was estimated using PHASE 2.3 software. Statistical differences in the genotype and haplotype frequencies between case and control groups were also considered and estimated. For the Han population, the geneotype distributions for TNF- αrs1800629, TNF-αrs1800630, IL-6 rs1800795, IL-6 rs1800797, NF-KB1 rs1585215 and TLR-4 rs4986790 showed significant differences between the case and control groups (p<0.05). The TNF-α gene frequencies of ACG and CCA haplotypes in the cases were higher than in the controls (OR=2.45, 95% CI: 1.55-3.89, p=0.0002, OR=2.53, 95% CI: 1.10-5.80, p=0.029, respectively), and the same findings were detected for TNF-β gene CA haplotype (OR=1.87, 95% CI: 1.21-2.90, p=0.0054). However, for the Uygur population, no such significant differences were detected within the gene-type distribution of the 14 SNPs. The TNF-α gene frequency of the CCA haplotype between the two groups (OR=1.98, 95% CI: 1.11-3.51, p=0.021) revealed a statistically significant difference. Our results showed that polymorphic variations of inflammation-related genes could be important to the NHL etiology of the Han population, and that these may only have limited influence on the Uygur population.


Estimating the risk of pressure ulcer development: is it truly evidence based?
The aim of the current method of screening patients is to identify risk factors that are considered to cause, or contribute to, pressure ulcer (PU) development. Yet screening has not resulted in a reduction in pressure ulcer development. The literature was reviewed to identify the level of evidence for the inclusion of risk factors in six published pressure ulcer risk-screening tools. Evidence for each risk factor was ranked according to the National Health and Medical Research Council levels of evidence with a modification. Three of 19 risk factors (mobility, continence and nutrition) included in more than one screening tool have been tested for association with pressure ulcer development. While varying degrees of immobility and decreased serum albumin are reported to significantly increase the risk for PU development, the direction of the relationship, i.e. causal or resultant of PU, is not always clear. No publications reported a significant causal link between incontinence and PU development. Inclusion of risk factors for PU in screening tools must be evidence based. Until other risk factors have been tested for positive predictive value, the Ramstadius approach to screening is the only evidence-based tool.


Endothelial cells, cholesterol, cytokines, and aging.
It has been reported that high levels of cholesterol and triglycerides are associated with increased risk of developing atherosclerosis and shorter life. In fact, vascular endothelial dysfunction occurs during the human aging process. Accumulation of lipids in vascular endothelium activates leukocytes to produce cytokines and chemokines which recruit macrophages. On the other hand, macrophages augment inflammatory response and secrete vascular endothelial growth factor, a key cytokine that mediates angiogenesis and inflammatory response. In addition, hyperlipidaemia is one of the main risk factors for aging, hypertension and diabetes. Here, we review the interrelationship between endothelial cells, high level of cholesterol, and aging.


Authentication Markers for Five Major Panax Species Developed via Comparative Analysis of Complete Chloroplast Genome Sequences.
Ginseng represents a set of high-value medicinal plants of different species: Panax ginseng (Asian ginseng), Panax quinquefolius (American ginseng), Panax notoginseng (Chinese ginseng), Panax japonicus (Bamboo ginseng), and Panax vietnamensis (Vietnamese ginseng). Each species is pharmacologically and economically important, with differences in efficacy and price. Accordingly, an authentication system is needed to combat economically motivated adulteration of Panax products. We conducted comparative analysis of the chloroplast genome sequences of these five species, identifying 34-124 InDels and 141-560 SNPs. Fourteen InDel markers were developed to authenticate the Panax species. Among these, eight were species-unique markers that successfully differentiated one species from the others. We generated at least one species-unique marker for each of the five species, and any of the species can be authenticated by selection among these markers. The markers are reliable, easily detectable, and valuable for applications in the ginseng industry as well as in related research.


Topological analysis of the extrinsic PsbO, PsbP and PsbQ proteins in a green algal PSII complex by cross-linking with a water-soluble carbodiimide.
The close association of the extrinsic PsbO, PsbP and PsbQ proteins with PSII core subunits in oxygen-evolving PSII complexes from a green alga, Chlamydomonas reinhardtii, was examined by cross-linking experiments with a water-soluble carbodiimide, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). The green algal PSII complexes treated with EDC were washed with alkaline Tris to remove the non-cross-linked extrinsic proteins, and then applied to Blue-Native-PAGE to prepare PSII core complexes. The extrinsic proteins cross-linked with PSII core complexes were detected by immunoblotting analysis using antibodies against extrinsic proteins and PSII core subunits. The results showed that the PsbO, PsbP and PsbQ proteins directly associated with CP47, the alpha subunit of cytochrome b559 and a small subunit in PSII core complexes, respectively, through electrostatic interactions. In addition, a cross-linked product between the PsbP and PsbQ proteins was found in alkaline Tris extracts of EDC-treated PSII complexes, and its cross-linked site was examined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI TOF-MS) after digestions with trypsin and endoproteinase Asp-N. The results demonstrated that the positively charged amino group of K176 on the PsbP protein electrostatically interacts with the negatively charged carboxyl group of D28 on the PsbQ protein. These binding properties of the extrinsic proteins in the green algal PSII were compared with those in higher plant PSII.


Total synthesis of the macrocyclic cysteine knot microprotein MCoTI-II.
The first total synthesis of MCoTI-II, a cysteine knot microprotein and potent trypsin inhibitor, is described; a synthetic strategy has been developed that combines efficient backbone construction via optimised solid phase peptide synthesis with one-pot 'thia-zip' native chemical ligation and refolding to yield the natural product.


Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3-L1 adipocyte.
Berberine (BBR), an isoquinoline alkaloid, has a wide range of pharmacological effects, yet its exact mechanism is unknown. In order to understand the anti-adipogenic effect of BBR, we studied the change of expression of several adipogenic enzymes of 3T3-L1 cells by BBR treatment. First, we measured the change of leptin and glycerol in the medium of 3T3-L1 cells treated with 1 micrometer, 5 micrometer and 10 micrometer concentrations of BBR. We also measured the changes of adipogenic and lipolytic factors of 3T3-L1. In 3T3-L1 cells, both leptin and adipogenic factors (SREBP-1c, C/EBP-alpha, PPAR-gamma, fatty acid synthase, acetyl-CoA carboxylase, acyl-CoA synthase and lipoprotein lipase) were reduced by BBR treatment. Glycerol secretion was increased, whereas expression of lipolytic enzymes (hormone-sensitive lipase and perilipin) mRNA was slightly decreased. Next, we measured the change of inflammation markers of 3T3-L1 cells by BBR treatment. This resulted in the down-regulation of mRNA level of inflammation markers such as TNF-alpha, IL-6, C- reactive protein and haptoglobin. Taken together, our data shows that BBR has both anti-adipogenic and anti-inflammatory effects on 3T3-L1 adipocytes, and the anti-adipogenic effect seems to be due to the down-regulation of adipogenic enzymes and transcription factors.


Relationship of cell death to cyclophosphamide-induced ocular malformations.
C57BL/6J mice were used to study the ocular teratogenic effects of cyclophosphamide administered to pregnant females on d 9 of pregnancy at a dose of 5 mg/kg body weight. Nile blue staining demonstrated increased cell death at the base of the optic stalk, in the optic vesicle, and in the perivesicular mesenchyme in treated embryos. Malformations studied at gestational d 11 and 16 by light and scanning electron microscopy included microphthalmos, microphakia, and aphakia and were predictable based upon patterns of increased cell death. These anomalies are similar to those reported with exposure to ethanol or isotretinoin on gestational d 7.


Study on Matrix Damage and Control Methods of Fracturing Fluid on Tight Sandstone Gas Reservoirs.
Hydraulic fracturing is a highly effective method for stimulating the development of gas reservoirs. However, the process of pumping fracturing fluid (FF) into the reservoir unavoidably causes damage to the surrounding matrix, leading to a decrease in the overall stimulation effect. To assess the extent of matrix permeability damage caused by the intrusion of FF, as well as its impact on the pore throat structure, and to propose appropriate measures to control this damage, we conducted a series of experimental studies on tight gas reservoirs. These studies included mercury intrusion, core flow, nitrogen adsorption, linear expansion, and contact angle measurements. The findings revealed that the damage inflicted on matrix permeability by FF was significantly greater than that caused by its gel-breaking counterpart. Surprisingly, the damage rate of the rejecting fluid to the matrix was found to be comparable to that of its gel-breaking counterpart. The fractal dimension (D2) was observed to have a strong correlation with surface area, pore volume, and mean pore size, making it an effective means of characterizing pore structure characteristics. After the rock samples were displaced by the formation water, the D2 value decreased, leading to a decrease in the complexity of the pore throat structure and an increase in matrix permeability. Conversely, the displacement of the FF increased the D2 value, indicating a gradual complication of the pore throat structure and a more uneven distribution of pore sizes. The inclusion of polyamide in antiexpansion FF, as well as its gel-breaking counterpart, proved to be effective in inhibiting the hydration and expansion of clay minerals, thereby reducing water-sensitive damage. Additionally, the use of surfactants with low surface tension enhanced the flowback rate of FF by increasing the contact angle and reducing the work of adhesion. This, in turn, helped to decrease the apparent water film thickness and expand gas flow channels, ultimately improving gas permeability.


Clinical, echocardiographic and echophonocardiographic characteristics of the atrial myxomas in 22 years period.
Atrial myxomas are the most frequent benign tumors of the heart. Left atrial myxomas are about 3-4 times more frequent then right. Clinical findings reveal atrioventricular obstruction symptoms and signs, symptoms and signs of peripheral arteries or pulmonary artery embolisation and/or nonspecific symptoms. Review of atrial myxomas diagnosed at the Clinic of Cardiology in 20 years period and analysis of clinical characteristics, transthoracic echocardiographic (TTE), transesophageal echocardiographic (TEE), and M-mod echophonographic findings. TTE is performed in all, but TEE in 16 patients. Simultaneous M-mod echophonocardiographic examination were performed in 11 patients, when optional equipment was applicable. We found 24 atrial myxomas: 19 (79.2%) in left and 5 (20.810%) in right atrium. 21(87.5%) patients had some of the symptoms, but 3 (12.5%) were asymptomatic. TTE was performed in all patients, but we found 1 (2.4%) false negative result. TEE was performed in 14 (58.3%) patients. Echophonocardiographic recordings showed early diastolic tumor "plop" in 10 patients and unusual late diastolic tumor "plop" in one right atrial myxoma, which has not yet been described. TTE is a reliable method in diagnosis of atrial myxomas, but not in all cases, while TEE has been found as always reliable. Echophonocardiographic recording is useful for confirmation and understanding of auscultatory finding when applicable.


Treatment-related toxicity and symptom-related bother following postoperative radiotherapy for prostate cancer.
Patients have reported late effects and symptom-related bother following postoperative radiotherapy for prostate cancer. Patients treated with postoperative radiotherapy were surveyed at a median 56 months after radiotherapy using the Prostate Cancer Radiation Therapy instrument. A retrospective review was undertaken to obtain Radiation Therapy Oncology Group-Late Effects Normal Tissue (RTOG-LENT) toxicity scores at baseline and during follow-up. Survey response was 64.5%. Median prostate bed radiation dose was 66 Gy given at a median 14 months after surgery. Adjuvant hormone therapy was given for 2 to 3 years to 40 patients; 22 received salvage therapy. PCRT impairment subscales were reported as mild for gastrointestinal dysfunction, moderate for genitourinary dysfunction and marked for sexual dysfunction. The use of one or more incontinence pads daily was reported by 25.6% and was similar to 23% use reported at baseline. Frequent or worse urinary frequency or hematuria was reported by 4.8%, and by 8.4% of respondents for bowel dysfunction. Moderate to severe disruption from bowel and bladder dysfunction was reported by up to 5.4% and 2.4% of respondents, respectively. Erectile function was described as poor to none in 88.3% of respondents, and dissatisfaction with sexual functioning was reported by 42.7%. Counselling or treatment was offered to 59% of those followed. Combined surgery and postoperative radiotherapy are associated with low and moderate rates of bowel and bladder dysfunction respectively, with low reported bother. High levels of sexual dysfunction and bother are seen following combined therapy. More effective pre- and post-treatment counselling are required, along with research into more effective prevention and treatment strategies.


Influence of Cobalt Source, Folic Acid, and Rumen-Protected Methionine on Performance, Metabolism, and Liver Tissue One-Carbon Metabolism Biomarkers in Peripartal Holstein Cows.
Vitamin B12 plays a role in the remethylation of homocysteine to Met, which then serves as a substrate for Met adenosyltransferase (MAT) to synthesize S-adenosylmethionine (SAM). We investigated effects of feeding two cobalt sources [Co-glucoheptonate (CoPro) or CoPectin, Zinpro Corp.], an experimental ruminally-available source of folic acid (FOA), and rumen-protected Met (RPM) on performance and hepatic one-carbon metabolism in peripartal Holstein cows. From -30 to 30 d around calving, 72 multiparous cows were randomly allocated to: CoPro, CoPro + FOA, CoPectin + FOA, or CoPectin + FOA + RPM. The Co treatments delivered 1 mg Co/kg of DM (CoPro or CoPectin), each FOA group received 50 mg/d FOA, and RPM was fed at 0.09% of DM intake (DMI). Milk yield and DMI were not affected. Compared with other groups, the percentage of milk protein was greater after the second week of lactation in CoPectin + FOA + RPM. Compared with CoPro or CoPro + FOA, feeding CoPectin + FOA or CoPectin + FOA + RPM led to a greater activity of MAT at 7 to 15 d postcalving. For betaine-homocysteine S-methyltransferase, CoPro together with CoPectin + FOA + RPM cows had greater activity at 7 and 15 d than CoPro + FOA. Overall, supplying FOA with CoPectin or CoPectin plus RPM may enhance S-adenosylmethionine synthesis via MAT in the liver after parturition. As such, these nutrients may impact methylation reactions and liver function.


Celastrol inhibits colorectal cancer cell proliferation and migration through suppression of MMP3 and MMP7 by the PI3K/AKT signaling pathway.
Colorectal cancer (CRC) is one of the most frequent malignant tumors. Signaling by the PI3K/AKT pathway is crucial for CRC development and progression, including proliferation and migration. Celastrol has an anticancer effect, but its mechanism needs to be determined. Here, we showed that celastrol suppressed CRC cell proliferation and migration. Celastrol treatment also decreased the PI3K/AKT pathway components, and MMP3 and MMP7 expression levels. In addition, knockdown of AKT, not mTOR, inhibited MMP3 and MMP7 expression levels and AKT silencing promoted the celastrol-induced effects on CRC cell proliferation and migration. Taken together, these findings indicated that the celastrol-induced antitumor effects were mediated through MMP3 and MMP7 by the PI3K/AKT signaling pathway.


Lung specific stealth liposomes as antitubercular drug carriers in guinea pigs.
The problem of patient non-compliance in the management of tuberculosis (TB) can be overcome by reducing the dosing frequency of antitubercular drugs (ATD) employing drug carriers. This study reports on the intravenous (iv) administration of lung specific stealth liposomes encapsulating ATD (rifampicin and isoniazid in combination) to guinea pigs and the detailed pharmacokinetic/chemotherapeutic studies. Following a single iv administration of liposomal drugs, the latter were found to exhibit sustained therapeutic levels in plasma for 96-168 hr with half-lives of 24-70 hr, mean residence time (MRT) of 35-81 hr and organ drug levels up to day 7. The relative bioavailability (as compared to oral free drugs) was increased by 5.4-8.9 folds, whereas the absolute bioavailability (as compared to iv free drugs) was increased by 2.9-4.2 folds. Weekly therapy with liposomal ATD for 6 weeks produced equivalent clearance of Mycobacterium tuberculosis from organs as did daily therapy with oral free drugs. Hence, intravenous liposomal ATD offer the therapeutic advantage of reducing the dosing frequency and improving the patient compliance in the management of TB.


Synthesis of CuInSe2 nanocrystals with tunable size by reverse microemulsion method.
Copper Indium diselenide (CIS) nanocrystals were synthesized by a new room-temperature reverse microemuslion route. By changing the water to surfactant ratio, the size of the particles can be readily adjusted while the composition of the particles can be tuned by changing the precursor ratio. The UV-visible absorption and photoluminescence spectra show blue shift for CIS particles with smaller size. The corresponding band gaps of the as-prepared CIS particles are approximately 2 eV, which is larger than that of bulk CIS.


MRI Findings After Surgery for Chiari Malformation Type I.
Surgery plays an important role in the management of Chiari I malformation. The purpose of this article is to review expected and unexpected MRI findings after the various types of surgery performed during the treatment of Chiari I malformation and associated abnormalities. Familiarity with optimal MRI techniques and findings is important when evaluating postoperative changes after treatment of Chiari I malformation.


Lactate in the brain: an update on its relevance to brain energy, neurons, glia and panic disorder.
Lactate is considered an important metabolite in the human body, but there has been considerable debate about its roles in brain function. Research in recent years has suggested that lactate from astrocytes may be crucial for supporting axonal function, especially during times of high metabolic demands or hypoglycemia. The astrocyte-neuron lactate transfer shuttle system serves a protective function to ensure a supply of substrates for brain metabolism, and oligodendrocytes appear to also influence availability of lactate. There is increasing evidence for lactate acting as a signaling molecule in the brain to link metabolism, substrate availability, blood flow and neuronal activity. This review will attempt to connect evidence to the relationship lactate has to panic disorder (PD), which suggests that its transporters, receptors or metabolism warrant investigation as potential therapeutic targets in PD.


Effects of Moringa oleifera silage on milk yield, nutrient digestibility and serum biochemical indexes of lactating dairy cows.
This study investigated the effects of Moringa oleifera (MO) as a partial substitute of alfalfa hay on milk yield, nutrient apparent digestibility and serum biochemical indexes of dairy cows. MO was harvested at 120 days post-seeding. Fresh MO was cut, mixed with chopped oat hay (425:575 on a DM basis), ensiled and stored for 60 days. Sixty healthy Holstein dairy cows were allocated to one of three groups: NM (no MO or control), LM (low MO; 25% alfalfa hay and 50% maize silage were replaced by MO silage) or HM (high MO; 50% alfalfa hay and 100% maize silage were replaced by MO silage). The feeding trial lasted 35 days. The LM and HM diets did not affect dry matter (DM) intake, milk yield or milk composition (lactose, milk fat, milk protein and somatic cell count). The apparent digestibility of DM and NDF was lower for HM group than NM group. Additionally, there were no significant differences in serum biochemical indexes between the LM and NM groups. The HM group had lower serum concentrations of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol and higher serum concentrations of urea than the NM group. The partial replacement of alfalfa hay (≤50%) and maize silage with MO silage had no negative effects on milk yield, in vivo nutrient apparent digestibility or serum biochemical indexes of lactating cows.


[Functional maturation of the somatosensory neocortex S1 in the rat. Electrophysiological and histochemical study (author's transl)].
The functional maturation of the somatosensory neocortex has been studied using the projection areas of the whiskers. Natural stimulation of the whiskers evokes global potentials and unitary responses from the 4th postnatal day on. From the 2nd postnatal week the characteristics of the unit responses approximate in latency, topographic organisation of the projections, coding of the directions and temporal characteristics of the stimulation those of the adult. The histochemical activity of succinyl dehydrogenase is demonstrated in layer IV a little before the first electrophysiological response but the typical massed organisation is only seen from the 5th postnatal day. During maturation optical densitometry shows a rapid rise in enzyme activity untill the 7th postnatal day then a slower rise up to the 21st day after which it stabilises.


Synthesis and preliminary evaluation of [18F]FEtP4A, a promising PET tracer for mapping acetylcholinesterase in vivo.
N-[18F]Fluoroethyl-4-piperidyl acetate ([18F]FEtP4A), an analog of [11C]MP4A for mapping brain acetylcholineseterase (AchE) activity, was prepared by reacting 4-piperidyl acetate (P4A) with [18F]fluoroethyl bromide ([18F]FEtBr) using a newly developed automated system. Preliminary evaluation showed that the initial uptake of [18F]FEtP4A in the mouse brain was > 8% injected dose/g tissue. The distribution pattern of [18F]FEtP4A in the brain was striatum>cerebral cortex>cerebellum within 10-120 min post-injection, which reflected the distribution rank pattern of AchE activity in the brain. Moreover, chemical analysis of in vivo radioactive metabolites in the mouse brain indicated that 83% of [18F]FEtP4A was hydrolyzed to N-[18F]fluoroethyl-4-piperidinol ([18F]FEtP4OH) after 1 min intravenous injection. From these results, [18F]FEtP4A may become a promising PET tracer for mapping the AchE in vivo.


[Effects of omega-3 polyunsaturated fatty acids on the state of insulin resistance, the content of some pro- and antiinflammatory factors in patients with type 2 diabetes mellitus and cardiovascular autonomic neuropathy].
We have investigated the influence of the long-chain ω-3 polyunsaturated fatty acids (ω-3 PUFA) administration on the insulin resistance parameters, levels of high sensitivity C-reactive protein (hsCRP), some pro- and anti-inflammatory cytokines in patients with type 2 diabetes mellitus (T2 DM) and cardiovascular autonomic neuropathy (CAN). The study involved 12 patients with T2 DM without verified cardiovascular diseases (CVD), 36 patients with T2 DM and functional stage of CAN, of median age 50–59 years, disease duration 1–6 years and HbA1c levels – 7.1±0.6%. 15 healthy subjects were control group. Screening for CAN, that included five standard cardiovascular tests, was performed. The levels of blood glucose, HbA1c, immunoreactive insulin (IRI), hsCRP, tumor necrosis factor α (TNFα), interleukin (IL)-6, IL-8 and IL-10 were measured. The index of insulin resistance (HOMA-IR) and TNFα/IL-10 ratio were calculated. Patients with T2 DM and CAN were divided into 2 groups: patients of the 1st group (group of comparison, n=15) received standard glucose-lowering therapy; patients of the 2nd group (n=21) received one capsule/day of the ω-3 PUFA (∼90% ethyl ester of PUFA (1000 mg), in particular eicosapentaenoic – 460 mg, docosahexaenoic acid – 380 mg and 4 mg α-tocopherol acetate) in addition to the standard therapy. The duration of the study was 3 months. Obtained results showed, that development of CAN in patients with T2 DM is accompanied by increase of the IRI (26.6±1.73 mcIU/ml, p<0.001 – compared to the control; p1<0.001 – compared to T2 DM patients without CVD); hsCRP (2.77±0.24 mg/l, p<0.001, p1<0,001); TNFα (5.75±0.24 pg/ml, p<0.001, p1<0.001); IL-6 (5.88±0.38 pg/ml, p<0.001, p1<0.001); IL-8 (6.65±0.3 pg/ml, p<0.001, p1>0.05); IL-10 (15.86±1.4 pg/ml, p<0.05, p1>0.05) levels; TNFα/IL-10 (44.2±3.57%, p<0.01, p1<0.05) and HOMA-IR. After 3 months of treatment no statistically significant changes (p>0.05) of investigated parameters, in particular levels of IRI (-6.8±2.0%); hsCRP (-7.2±1.63%); TNFα (-6.1±1.0%); IL-6 (-5.8±1.77%); IL-8 (-3.9±1.57%); IL-10 (-3.7±2.34%); TNFα/IL-10 (-0.5±2.3%) in patients from the group of comparison were found. The administration of ω-3 PUFA to patients with T2 DM and CAN promoted to the statistically significant decrease in hsCRP (-14.8±2.91%, p<0.05), TNFα (-14.1±2.15%, p<0.01), IL-6 (-13.5±2.7%, p<0.05), IL-8 (-9.8±2.13%, p<0.05), TNFα/IL-10 ratio (-34.6±1.93%, p<0.05); a slighty decrease in the content of the IRI (-10.3±1.1%, p>0.05), IL-10 (+7.9 ±6.42%, p>0.05), HOMA-IR was observed. Obtained results could witness, that prescription of ω-3 PUFA leads to decrease of the proinflammatory immune response activity and allows to consider ω-3 PUFA as a promising medicine in treatment and/or prevention of CAN in patients with DM 2.


Conformational influence on the type of stabilization of sulfur radical cations in cyclic peptides.
The free-radical chemistry of two oxidized cyclic dipeptides is investigated using time-resolved optical and conductivity detection. Two cyclic dipeptides, cyclo-Gly-L-Met and cyclo-D-Met-L-Met, are synthesized and irradiated with nanosecond pulses of electrons, which initiate the oxidation of the methionine side chains with hydroxyl radicals from the radiolysis of water. The cyclic peptides are taken to be models for the interior of proteins where there are no terminal groups. This opens up the possibility that neighboring-group effects can be studied directly between the initially formed sulfur radical cations and the heteroatoms associated with the peptide bonds. Such complexation of the sulfur radical cations is observed with the amide nitrogen atoms. In addition, intermolecular stabilization with the unoxidized sulfur atoms on separate cyclic dipeptide molecules is observed. Little or no intramolecular stabilization by the unoxidized sulfur in the neighboring methionine occurs in cyclo-D-Met-L-Met, in contrast to the previously observed intramolecular sulfur stabilization of the sulfur radical cation in the isomer cyclo-L-Met-L-Met. This contrasting behavior is rationalized by conformational differences in the two isomers as seen through molecular-modeling simulations. The implications for the oxidation of the protein calmodulin, which contains multiple residues of methionine, are discussed as having analogous determining factors.


Pregnant woman with primary membranous nephropathy - case report.
Membranous nephropathy is a common form of glomerulonephritis typically presenting between 30 to 50 years of age with nephrotic range proteinuria, with one third of patients undergoing spontaneous remission, one third experiencing non-progressive CKD (Chronic Kidney Disease) while the remaining third progressing to ESRD (end stage renal disease). A 21-year old pregnant female developed massive proteinuria and hypoalbuminemia during first weeks of pregnancy and required intensive nephrological evaluation and treatment. Renal biopsy was performed, microscopic examination was consistent with Membranous Nephropathy and as anti-PLA2R antibodies tested positive, active disease was confirmed. The patient received an immunosuppressive treatment consisting of prednizone and cyclosporine A, enoxaparine was also implemented. In the follow up proteinuria and hypoalbuminemia decreased significantly, stable eGFR and anti-PLA2R (M-type phospholipaseA2 receptor) depletion were observed. C-section was performed at 31 weeks of gestational age due to premature rupture of membranes. The baby developed correctly, showed no signs of nephrotic syndrome. After delivery the mother's immunosuppressive treatment was continued. Diagnostic algorithm of adult patients with nephrotic syndrome suggests that in cases positive for anti PLA2R antibodies one can diagnose idiopathic membranous nephritis (IMN) based on serological testing and desist kidney biopsy. An early immunosupressive treatment applied in described case confirms proper procedure.


Matrix factorisation methods applied in microarray data analysis.
Numerous methods have been applied to microarray data to group genes into clusters that show similar expression patterns. These methods assign each gene to a single group, which does not reflect the widely held view among biologists that most, if not all, genes in eukaryotes are involved in multiple biological processes and therefore will be multiply regulated. Here, we review several methods of matrix factorisation that identify patterns of behaviour in transcriptional response and assign genes to multiple patterns. We focus on these methods rather than traditional clustering methods applied to microarray data, which assign one gene to one cluster.


[Obstructed defecation].
Adequate therapy of obstructed defecation (pelvic outlet obstruction) is often challenging, as the etiology and clinical symptoms include a wide range of disorders. Standardized diagnostic assessment has to differentiate between obstructed defecation caused by either pelvic outlet obstruction or slow transit constipation. Additionally, morphologic changes of colon, rectum, or the pelvic floor have to be separated from functional disorders. Providing defecography or dynamic MR of the pelvic floor, common causes of outlet obstruction such as sigmoidoceles, in which surgery is indicated, and rectal prolapse can be diagnosed with high accuracy. However, the diagnosis and therapeutic options in symptomatic rectocele and intussusception are controversial. Patients with functional disorders such as rectoanal dyssynergia are candidates for conservative treatment (biofeedback). To identify patients who will benefit from surgery for obstructed defecation, careful patient selection remains the crucial issue in diagnostic assessment.


Rasterstereographic measurement of scoliotic deformity.
Back surface topography has gained acceptance in recent decades. At the same time, the motivation to use this technique has increased. From the view of the patient, the cosmetic aspect has played and still plays a major role as it provides a comprehensive documentation of cosmetic impairment. From the view of the medical practitioner, the aspect of reducing X-ray exposures in diagnosis and follow-up has been dominant and still prevails. Meanwhile, new aspects have emerged: due to the consequent three-dimensional view of the scoliotic condition, treatment success can be visualized convincingly. Clinical diagnosis is supported by information otherwise not supplied by X-rays, such as when functional examinations and diagnostic tests are recorded. Like rasterstereography, most techniques of actual back surface measurement refer to photogrammetry and the triangulation method. However, with respect to the particular clinical application, a wide spectrum of implementations exists. Applications in a clinic require high accuracy of measurement in a short time and comprehensive analysis providing data to be used to supplement and compare with radiographic data. This is exemplified by rasterstereography; the procedures of surface analysis and localization of landmarks using curvatures and the reconstruction of the spinal midline will be described. Based on rasterstereographic analysis, different geometrical measures that characterize the back surface are given and underlying skeletal structures described. Furthermore, in analogy to radiological projection, a 3-D reconstruction of the spinal midline is visualized by a frontal and lateral projection, allowing comparison with pertinent X-rays. Surface topography and, in particular, rasterstereography provide reliable and consistent results that may be used to reduce X-ray exposure. Unfortunately, the correlation of shape parameters with the radiological Cobb angle is poor. However, the wealth of additional applications substantially enhances the spectrum of clinical value.


[Chapter 3. Governing the research on embryos].
The bioethics laws since their first adoption in 1994 until the latest proposals, have been widely commented and analyzed, regarding the provisions related to the legal qualification and the legal status of the embryo and of the embryonic stem cells. The legal issues raised by these hesitations imply instability for both researchers and health professionals about what they can and cannot do when it comes to the embryo and its cells. Thus, while the protection of the embryo was the subject of a consensus until the end of the 2000s, it now appears as the object of a political will, from researchers and state agencies, to support this research. The legal frameworks have been modified step by step leading to an administrative police that reconciles freedom of research and ethical issues whose legal enforcement remains weak and uncertain. It will therefore be important to highlight the legal and institutional milestones that led to the acceptance of embryo research and to the liberalization of the legal framework. Some doubts will then be expressed about the benefits of this liberalization notably because cases law on the patentability of inventions resulting from this research are a bit of a threat to encourage development perspectives and because embryonic stem cells could remain marginal because of the economic and scientific contexts.


Neutralizing antibody response in dogs and cats inoculated with commercial inactivated rabies vaccines.
In Japan, the import quarantine regulation against rabies has required from 2005 that dogs and cats should be inoculated with the rabies vaccine and that the neutralizing antibody titer should be confirmed to be at least 0.5 international units (IU)/ml. The fluorescent antibody virus neutralization (FAVN) test is used as an international standard method for serological testing for rabies. To achieve proper immunization of dogs and cats at the time of import and export, changes in the neutralizing antibody titer after inoculation of the rabies vaccine should be understood in detail. However, few reports have provided this information. In this study, we aimed to determine evaluated, such changes by using sera from experimental dogs and cats inoculated with the rabies vaccine, and we tested samples using the routine FAVN test. In both dogs and cats, proper, regular vaccination enabled the necessary titer of neutralizing antibodies to be maintained in the long term. However, inappropriate timing of blood sampling after vaccination could result in insufficient detected levels of neutralizing antibodies.


Membrane metallo-endopeptidase mediates cellular senescence induced by oncogenic PIK3CAH1047R accompanied with pro-tumorigenic secretome.
The hotspot mutation H1047R in the oncogenic PIK3CA gene is frequently detected in breast cancer and enhances the enzymatic activity of PI3K to activate AKT/mTOR signaling cascade. Aberrant elevated PI3K activation has been reported to promote the tumorigenesis of breast cancer, but the mechanisms underlying are still needed to be elucidated. Here, we found that continuously activating PIK3CAH1047R conferred human mammary epithelial MCF-10A cells to cellular senescence upon serum-starvation. Similarly, breast cancer T47D and HCC1954 cells harboring H1047R mutation were senescent when cells were deprived of serum. PI3K/AKT/mTOR axis but not p53 or RB might be required for the induction of senescence. Notably, membrane metallo-endopeptidase (MME) was identified as a downstream effector of PI3K to mediate the induction of senescence, which might be associated with its glycosylation. Senescent cells elicited a distinct secretome dependent on PI3K and MME. Specifically, IL-6 promoted the proliferation of normal cells and CCL2 induced the M2-like polarization of macrophages, which might create an immunosuppressive microenvironment during the initiation and/or development of breast cancer. This study shed new light on the tumorigenesis induced by hyper-activated PI3K and might provide new clues for the prevention and therapy of breast cancer.


[A comparative evaluation of parenteral and oral preparations of gold and D-penicillamine in the treatment of rheumatoid nephropathy].
Analysis is made of the results of the treatment with parenteral (crysanol and myochrysine) and oral (ridaura) gold drugs as well as with small doses of D-penicillamine (DP) of patients suffering from rheumatoid arthritis with the signs of nephropathy. The latter ones were identified, respectively, in 18 out of 80 patients who began receiving treatment, in 17 out of 72, and in 16 out of 61 patients. The clinical, laboratory, instrumental and morphological manifestations of nephropathy are described and analysis of their dynamics under the treatment impact is provided. It is noted that these types of basic therapy produce a beneficial effect on the manifestations of rheumatoid nephropathy. That referred to a greater measure to the gold drugs than to the small doses of DP. The degree of counteracting the symptoms of renal pathology agreed well with a good clinical effect in respect to the articular syndrome and inflammatory responses of blood. Among patients receiving crysanol, iatrogenic nephropathy was recorded in 8.75% of cases, among those on ridaura, in 2.8%, and those on DP, in 8.2% of cases. The authors provide evidence for the use of gold drugs and DP in patients suffering from rheumatoid nephropathy.


Review of Current Advances in Serologic Testing for COVID-19.
To examine and summarize the current literature on serologic methods for the detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A literature review was performed using searches in databases including PubMed, medRxiv, and bioRxiv. Thirty-two peer-reviewed papers and 23 preprints were examined. The studies included lateral flow immunoassay, enzyme-linked immunosorbent assay, chemiluminescence immunoassay, and neutralizing antibody assays. The use of all major SARS-CoV-2 antigens was demonstrated to have diagnostic value. Assays measuring total antibody reactivity had the highest sensitivity. In addition, all the methods provided opportunities to characterize the humoral immune response by isotype. The combined use of IgM and IgG detection resulted in a higher sensitivity than that observed when detecting either isotype alone. Although IgA was rarely studied, it was also demonstrated to be a sensitive marker of infection, and levels correlated with disease severity and neutralizing activity. The use of serologic testing, in conjunction with reverse transcription polymerase chain reaction testing, was demonstrated to significantly increase the sensitivity of detection of patients infected with SARS-CoV-2. There was conflicting evidence regarding whether antibody titers correlated with clinical severity. However, preliminary investigations indicated some immunoassays may be a surrogate for the prediction of neutralizing antibody titers and the selection of recovered patients for convalescent serum donation.


Validation of serum progesterone <35nmol/L as a predictor of miscarriage among women with threatened miscarriage.
Our recent paper, based on a pilot cohort of 119 women, showed that serum progesterone <35 nmol/L was prognostic of spontaneous miscarriage by 16 weeks in women with threatened miscarriage in early pregnancy. Using a larger cohort of women from the same setting (validation cohort), we aim to assess the validity of serum progesterone <35 nmol/L with the outcome of spontaneous miscarriage by 16 weeks. In a prospective cohort study, 360 pregnant women presenting with threatened miscarriage between gestation weeks 6-10 at a tertiary hospital emergency unit for women in Singapore were recruited for this study. The main outcome measure measured is spontaneous miscarriage prior to week 16 of gestation. Area under the ROC curve (AUC) and test characteristics (sensitivity, specificity, positive and negative predictive value) at a serum progesterone cutpoint of <35 nmol/L for predicting high and low risk of spontaneous miscarriage by 16 weeks were compared between the Pilot and Validation cohorts. Test characteristics and AUC values using serum progesterone <35 nmol/L in the validation cohort were not significantly different from those in the Pilot cohort, demonstrating excellent accuracy and reproducibility of the proposed serum progesterone cut-off level. The cut-off value for serum progesterone (35 nmol/L) demonstrated clinical relevance and allow clinicians to stratify patients into high and low risk groups for spontaneous miscarriage.


Localized Arm Volume Index: A New Method for Body Type-Corrected Evaluation of Localized Arm Lymphedematous Volume Change.
Volume measurement is a common evaluation for upper extremity lymphedema. However, volume comparison between different patients with different body types may be inappropriate, and it is difficult to evaluate localized limb volume change using arm volume. Localized arm volumes (Vk, k = 1-5) and localized arm volume indices (LAVIk) at 5 points (1, upper arm; 2, elbow; 3, forearm; 4, wrist; 5, hand) of 106 arms of 53 examinees with no arm edema were calculated based on physical measurements (arm circumferences and lengths and body mass index [BMI]). Interrater and intrarater reliabilities of LAVIk were assessed, and Vk and LAVIk were compared between lower BMI (BMI, <22 kg/m) group and higher BMI (BMI, ≥22 kg/m) group. Interrater and intrarater reliabilities of LAVIk were all high (all, r > 0.98). Between lower and higher BMI groups, significant differences were observed in all Vk (V1 [P = 6.8 × 10], V2 [P = 3.1 × 10], V3 [P = 1.1 × 10], V4 [P = 8.3 × 10], and V5 [P = 3.0 × 10]). Regarding localized arm volume index (LAVI) between groups, significant differences were seen in LAVI1 (P = 9.7 × 10) and LAVI5 (P = 1.2 × 10); there was no significant difference in LAVI2 (P = 0.60), LAVI3 (P = 0.61), or LAVI4 (P = 0.22). Localized arm volume index is a convenient and highly reproducible method for evaluation of localized arm volume change, which is less affected by body physique compared with arm volumetry.


[Cardiac lesions in Takayasu's disease. A case with initial pericarditis and tamponade].
The authors report the case of 21-year old female patient with a particular form of Takayasu's disease remarkable for its initial presentation and its cardiac and coronary lesions. The disease began with miscarriage at the 5th months of pregnancy, followed by acute pericarditis with tamponade. Subsequently, lesions of the aortic and mitral valves developed, while the myocardium became involved with left ventricular dilatation and hypokinesia confirmed by echocardiography and cineangiography. Coronary arteriography revealed large coronary aneurysms which are exceptional in this disease. This case prompted the authors to discuss the various cardiac lesions and the relationship of Takayasu's disease with pregnancy.


Two cases of unilateral limbal Vernal keratoconjunctivitis in the same family: first case report.
This case report describes two cases of unilateral limbal Vernal keratoconjunctivitis (VKC) in the same family. To our knowledge, these are the first two reported cases of unilateral limbal VKC. VKC is a chronic inflammatory disease that typically affects both eyes, with unilateral cases being rare and previously only reported in the tarsal form. Our first case involved a 12-year-old girl with a history of allergic asthma, who had been experiencing conjunctivitis in her right eye since the age of 7. Upon examination, she was diagnosed with unilateral limbal VKC and treated with 1% cyclosporine eye drops with a significant improvement observed at the one and three-month follow-ups. Her 7-year-old brother was also examined and found to have unilateral limbal VKC in his right eye, although it was milder and not associated with allergic pathogenesis. Therefore, in this case, a treatment with hydrocortisone eye drops was started leading to an immediate reduction of the itching. In both cases an IgE-mediated mechanism is less likely because of the monolateral eye involvement, the complete absence of nasal symptoms, the lack of correlation between symptoms and any pollen season, and the negative prick skin test in one of the two siblings. Both cases suggest that unilateral VKC may occur even in the limbal form and that genetic mechanisms may contribute to the inflammatory reaction in VKC. This report highlights the need for further studies to explain the occurrence of unilateral VKC cases and reminds clinicians to consider the possibility of unilateral limbal VKC in pediatric patients.


Two-state model for bacterial chemoreceptor proteins. The role of multiple methylation.
To help understand the bacterial chemotactic response of excitation and adaptation, we propose a simple two-state model for receptor proteins (methyl-accepting chemotaxis proteins), in the light of evidence that they undergo multiple methylation in a preferred order. The model includes the following assumptions. (1) The receptor protein is in rapid equilibrium between two conformations, S and T, and the equilibrium shifts towards the T form as the number of methyl groups increases. (2) Attractants bind to the S form of the receptor, repellents bind to the T form, and both classes of ligand shift the S/T equilibrium according to the mass-action law. (3) The S form of the receptor accepts methyl groups one by one in a definite order, while the T form releases the methyl groups in the reverse order. Methylation and demethylation are slow reactions, and changes in the total number of methyl groups lag behind shifts in the S/T equilibrium. (4) The pattern of bacterial swimming at any moment is determined by the partition of the receptor between the two conformations, with tumbling frequency being a monotonically increasing function of the total T fraction of the receptor. This model shows that, if the receptor satisfies two sets of relationships imposed on its equilibrium and kinetic constants, it can maintain the steady-state total T fraction essentially constant over a broad range of ligand concentration, enabling cells to adapt to large changes in chemical environment. A stepwise change in ligand concentration leads to a rapid change in the total T fraction (excitation), followed by a slow relaxation process (adaptation). Computer simulations have been made of the whole response process, employing a receptor with six methylation sites per molecule and assuming simple sets of parameters. The results are in general agreement with published data on receptor methylation, as well as with a variety of observations of bacterial chemoresponse. Multiple methylation of the receptor proves to be necessary for the cells to respond sensitively to environmental changes.


Routine nasogastric tubes are not required following cystectomy with urinary diversion: a comparative analysis of 430 patients.
Postoperative nasogastric tube (NGT) use has been shown to increase postoperative morbidity in patients undergoing nonurological abdominal surgery. We examine the omission of NGTs as a method of decreasing postoperative gastrointestinal complications and hospital stay in patients undergoing cystectomy with urinary diversion. Between January 1983 and December 2001, 430 patients underwent cystectomy with urinary diversion at our institution. We retrospectively compared patients who received postoperative NGTs with those who did not with regard to gastrointestinal recovery time, gastrointestinal complications and hospital stay. After correcting for confounding factors using ANCOVA the time to first bowel sounds, time to first flatus and the duration of hospitalization were shorter in patients not receiving NGTs (p = 0.006, 0.001 and 0.032, respectively). Omitting NGTs did not increase the risk of ileus, bowel obstruction, wound dehiscence, anastomotic leakage or aspiration pneumonia and it did not result in more frequent postoperative NGT placement. The results of the current study suggest that gastric decompression with NGTs following cystectomy with urinary diversion may prolong gastrointestinal recovery, which may be a factor leading to increased duration of hospitalization. We propose that postoperative NGTs should not be used routinely in the management of cystectomy cases.


Vascular malformation of hand: cavernous lymphangioma.
A case of congenital cavernous lymphangioma of the hand presenting in a newborn is presented. The mass on the dorsum of the hand was removed with the overlying skin and underlying paratenon at three years of age. Re-surfacing was performed with a free flap transfer. There were no post-operative complications during one year of follow-up.


"Hard to crack": experiences of community integration among first- and second-generation Asian MSM in Canada.
Asians are the largest racial minority in Canada making up 11% of the population and represented over 60% of new immigrants between 2001 and 2006. We examined the experiences of community integration for first-generation (n = 27) and second-generation (n = 22) Asian Canadian men who have sex with men (MSM) in their ethnic and gay communities. Through focus group interviews, we explored their level of connectedness and the level of discrimination they experienced in the two communities. Findings indicate that Asian MSM in general perceived their ethnic community as homophobic, stemming from a combination of seeing sex as taboo, stereotypes about being gay, and the affiliation with religion. Although the literature indicates that immigrants rely on the support of their ethnic communities, our finding suggest that this is not the case for Asian immigrant MSM, who in our sample reported feeling less connected compared to their second-generation counterparts. For the gay community, our sample reported mixed experiences as some regarded it as welcoming, whereas others described it as racist. However, these experiences did not differ by generational status. Many were aware of explicit messages stating "No Asians" in dating contexts, while at the same time being aware that some older White men were interested in dating Asians exclusively. Barriers to integration in both communities may contribute to feelings of isolation. Theoretical implications are discussed.


Factors influencing function and recovery following hip repair surgery.
Despite advances in surgical techniques and rehabilitation, many patients or individuals fail to regain their prior functional ability following hip repair surgery. The purpose of this study was to evaluate the most commonly cited predictors of successful recovery: age, balance, gender, fatigue, fall efficacy, pain, comorbidity, complications following surgery, cognitive ability, depression, and functional status prior to surgical intervention. Seventy-three persons following hip repair surgery were evaluated in an inpatient rehabilitation program and 3 months following discharge. This is a secondary analysis of data used in a previous study. The data analyzed in this study were from a study evaluating the impact of post surgical video-based education. Balance and cognitive ability were the best predictors of functional ability 3 months following discharge from a rehabilitation setting. As to return to functional ability following discharge, balance, cognitive status, and prior functional ability were the best predictors. Men reported higher functional levels 3 months following discharge and were more likely to return to their presurgical functional level. DISCUSSION/RECOMMENDATIONS: The significant influence of balance and fatigue on functional ability highlights the need for interventions aimed at improving balance and reducing fatigue as persons recover following hip repair surgery.


Recurrent Membranoproliferative Glomerulonephritis After Kidney Transplantation: Risk Factors and Impact on Graft Survival.
BACKGROUND Membranoproliferative glomerulonephritis (MPGN) is an uncommon cause of end-stage renal disease (ESRD). Recurrence rates after transplantation range from 11.8% to 18.9% after 5 and 15 years, respectively. This study aimed to assess the risk factors of MPGN recurrence after kidney transplantation and its impact on graft survival. MATERIAL AND METHODS This was a single-center retrospective cohort, including renal transplant recipients older than 18 years, with a diagnosis of MPGN in native kidneys. Data were obtained from medical records during the first 5-year post-transplant follow-up. Primary endpoints were graft function and survival. Secondary endpoints were MPGN recurrence risk factors and these cases' clinical, laboratory, and histological features. RESULTS Twenty-eight patients were included; the majority male (60.7%), with a mean age of 24.0±9.4 years. At MPGN native diagnosis, all patients presented proteinuria, with C3 consumption in 42.9%. Histological analysis showed 13 (42.9%) MPGN type I and 5 (17.9%) type II, with no cases of type III. MPGN recurrence occurred in 7 (25.0%) patients; 85.7% were male, 57.1% were recipients from a living donor, all presenting nephrotic syndrome and hematuria, with C3 consumption in 71.4%. The graft function was similar between the groups. Two (28.6%) patients progressed to graft failure in the recurrence group, and 1 died with a functioning graft. CONCLUSIONS The MPGN recurrence rate was 25%, most of them recipients of kidneys from living donors. Nephrotic syndrome and C3 consumption were frequent at recurrence. The graft function was similar between the groups, and the 5-year graft survival rate in the recurrence group was higher than in other studies.


Histological and micro Computed Tomography analysis of a femoral stress fracture associated with prolonged bisphosphonate use.
The origin of atypical femoral fractures (AFF) associated with bisphosphonate therapy remains to be elucidated. In this study, a biopsy of an AFF site is analyzed to determine whether microdamage and/or morphological changes are present in the area of the AFF. Cortical bone from an AFF region was obtained during a preventive stabilization in a patient with a symptomatic AFF. This bone was scanned using microCT (resolution=0.01 mm), stained with basic fuchsin and analyzed histologically. The diameter of the Haversian canals was higher in the vicinity of the AFF compared to the bone further away from the AFF. The bone mineral density within the cortex ranged from 1020 to 1080 mg HA/cm3. We observed penetration of basic fuchsin into the matrix, which is a tell-tale sign of diffuse damage. The higher diameter of haversian canals is likely to result in higher local stresses and consequently increased microdamage. The diffuse microdamage in the biopsy may furthermore be directly related to bisphosphonate use, preventing repair of microdamage, and consequently the development of the AFF. Increased porosity of the cortex and accumulation of microdamage might have lead to a stress fracture and ultimately a complete AFF.


Engineered cell differentiation and sexual reproduction in probiotic and mating yeasts.
G protein-coupled receptors (GPCRs) enable cells to sense environmental cues and are indispensable for coordinating vital processes including quorum sensing, proliferation, and sexual reproduction. GPCRs comprise the largest class of cell surface receptors in eukaryotes, and for more than three decades the pheromone-induced mating pathway in baker's yeast Saccharomyces cerevisiae has served as a model for studying heterologous GPCRs (hGPCRs). Here we report transcriptome profiles following mating pathway activation in native and hGPCR-signaling yeast and use a model-guided approach to correlate gene expression to morphological changes. From this we demonstrate mating between haploid cells armed with hGPCRs and endogenous biosynthesis of their cognate ligands. Furthermore, we devise a ligand-free screening strategy for hGPCR compatibility with the yeast mating pathway and enable hGPCR-signaling in the probiotic yeast Saccharomyces boulardii. Combined, our findings enable new means to study mating, hGPCR-signaling, and cell-cell communication in a model eukaryote and yeast probiotics.


Natural Steroids and Androgen Antagonists used as Neuroprotection in Common Neurological Disorders.
Multiple classes of natural products, such as antiandrogens or steroids have been used as antioxidants and anti-inflammatory treatments in neurodegenerative diseases. This paper aims to review current knowledge on these substances and their possible relationship with free radicals as an alternative therapy and prevention of common neurological disorders. An exhaustive review of the neurochemical mechanisms of these substances in the central nervous system of humans and animal models is yet to be undertaken in the literature, particularly regarding their importance and increasing use. Androgen receptor antagonists act in a different way that may underlie the benefits of natural products, with the expectation that in adults, neurological disorders would respond to natural antiandrogens. We hope that this work would provide valuable insight into the protective and therapeutic roles for natural antiandrogens and steroids in common neurological disorders.


Safety and Efficacy of Adding Fixed-Combination Brinzolamide/Timolol Maleate to Prostaglandin Therapy for Treatment of Ocular Hypertension or Glaucoma.
Purpose. To evaluate the safety and efficacy of adding brinzolamide 1%/timolol maleate 0.5% fixed combination (BTFC) to a prostaglandin analog (PGA). Methods. This was a 12-week, open-label, single-arm study of patients with open-angle glaucoma or ocular hypertension with intraocular pressure (IOP) not sufficiently controlled after ≥4 weeks of PGA monotherapy. The primary outcome was mean IOP change from baseline at week 12. Other outcomes included IOP change from baseline at week 4, percentage of patients achieving IOP ≤18 mmHg at week 12, and patient experience survey responses at week 12. Results. Forty-seven patients were enrolled and received treatment. The most commonly used PGAs were latanoprost (47%) and travoprost (32%). Mean ± SD IOP was decreased at week 12 (17.2 ± 4.1 mmHg) compared with baseline (23.1 ± 3.0 mmHg; P < 0.001, paired t-test); IOP at week 4 was 17.2 ± 3.3 mmHg. At week 12, 70% of patients achieved IOP ≤18 mmHg. Patient-reported symptoms (e.g., pain and redness) were mostly unchanged from baseline. Twenty-eight adverse events (AEs) were reported; the most frequently reported AE was headache (3 events in 2 patients). Conclusion. Adjunctive BTFC + PGA therapy was effective and well tolerated. IOP decreased by 6 mmHg at weeks 4 and 12.


Spinal injuries after ejection seat evacuation in fighter aircraft of the German Armed Forces between 1975 and 2021.
The ejection seat is one of the most important rescue tools for military aircrews. However, the high ejection speeds place high loads on the pilots, which is mainly absorbed by the pilot's spine. The differentiated evaluation of spinal injuries is of particular importance because this has a decisive influence on the further personal life and career of the affected aircrew members. Factors influencing the occurrence of a fracture as well as the impact of a spinal injury on military flight certification have not been addressed sufficiently to date. The authors conducted a retrospective evaluation of ejection seat evacuations in German Armed Forces combat aircraft accidents between 1975 and 2021. The total number of aviation accidents with ejection seat initiations and the survived ejections were collected. Accident-specific data and pilot-specific data were collected. In addition, it was evaluated whether aircrew members were recertified for military flight after the accident. The type of spinal injury and the location of the injury were evaluated. In addition to the descriptive statistics, two logistic regression models were developed to assess prediction values of accident- and pilot-specific factors for spine injuries. A total of 103 aircrew members were included in this retrospective analysis. The overall prevalence of spine injuries was 56.3%, and the overall prevalence of spine fractures was 33.0%. In the first regression model analysis, there was no association with pilot flight experience, age, height, weight, BMI, and being diagnosed with a spine fracture. Similarly, aircraft type, altitude, and airspeed were not associated with the occurrence of spine fractures. In the regression model analysis for predictors of rejection in military flight recertification after ejection seat evacuation, lumbar spine fractures were associated with higher odds of being rejected for recertification. Military aircraft crew members have a high risk of suffering from a spine injury after emergency evacuation using an ejection seat. In the subsequent medical workup, special attention should be paid to the spine, and ideally a consultation with a spine surgeon should be performed. Lumbar spine fractures may have major consequences for military flight certification, and therefore special attention should be paid to successful rehabilitation.


Dietary Supplementation of Selenium-Enriched Probiotics Enhances Meat Quality of Broiler Chickens (Gallus gallus domesticus) Raised Under High Ambient Temperature.
We investigated the effects of selenium-enriched probiotics (SP) on broiler meat quality under high ambient temperature and explore their underlying mechanisms. A total of 200 1-day-old male broiler chicks (Ross 308) were randomly allotted to four treatment groups, each with five replicates, in groups of ten birds. These birds were fed a corn-soybean basal diet (C), a basal diet plus probiotics supplementation (P), a basal diet plus Se supplementation in the form of sodium selenite (SS, 0.30 mg Se/kg), and a basal diet with the addition of selenium-enriched probiotics (SP, 0.30 mg Se/kg). The experiment lasted for 42 days. The birds were sacrificed by cervical dislocation, and the breast muscles were removed for further process. Our results showed that SP diet significantly increased (p < 0.05) the physical (pH, colors, water holding capacity, drip loss, shear force) and sensory characteristics of breast meat. All P, SS, and SP supplementation enhanced the antioxidant system by increasing (p < 0.05) the Se concentrations, glutathione (GSH) levels, activities of glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) whereas decreasing (p < 0.05) malondialdehyde (MDA) levels, with SP being higher than P and SS. Moreover, SP diet significantly upregulated (p < 0.05) the mRNA levels of glutathione peroxidase genes (GPx1, GPx4) while it downregulated heat stress biomarkers such as heat shock protein (HSP) 70 as compared to C, P, and SS diets. In conclusion, our findings suggest that SP may function as beneficial nutritive supplement that is capable of improving meat quality during the summer season.


Assessing Hospital Performance After Percutaneous Coronary Intervention Using Big Data.
Although risk adjustment remains a cornerstone for comparing outcomes across hospitals, optimal strategies continue to evolve in the presence of many confounders. We compared conventional regression-based model to approaches particularly suited to leveraging big data. We assessed hospital all-cause 30-day excess mortality risk among 8952 adults undergoing percutaneous coronary intervention between October 1, 2011, and September 30, 2012, in 24 Massachusetts hospitals using clinical registry data linked with billing data. We compared conventional logistic regression models with augmented inverse probability weighted estimators and targeted maximum likelihood estimators to generate more efficient and unbiased estimates of hospital effects. We also compared a clinically informed and a machine-learning approach to confounder selection, using elastic net penalized regression in the latter case. Hospital excess risk estimates range from -1.4% to 2.0% across methods and confounder sets. Some hospitals were consistently classified as low or as high excess mortality outliers; others changed classification depending on the method and confounder set used. Switching from the clinically selected list of 11 confounders to a full set of 225 confounders increased the estimation uncertainty by an average of 62% across methods as measured by confidence interval length. Agreement among methods ranged from fair, with a κ statistic of 0.39 (SE: 0.16), to perfect, with a κ of 1 (SE: 0.0). Modern causal inference techniques should be more frequently adopted to leverage big data while minimizing bias in hospital performance assessments.


A Call for Reform: Variability and Insufficiency in Radiation Oncology Resident Didactics-a Brief Report and National Survey of Program Directors.
An informal needs assessment and lack of a national standardized curriculum suggest that there is tremendous variability in the formal teaching of radiation oncology resident throughout the USA. The goal of this study was to characterize formal radiation oncology resident education, in order to identify knowledge gaps and areas for improvement. We developed a 14-item survey consisting of the following domains: program characteristics, teaching faculty, formal teaching time, instructional approaches for formal teaching, curricular topics, and satisfaction with didactics. All 91 accredited US-based radiation oncology program directors received an invitation to complete the survey anonymously by email. Twenty-four (26% response rate) program directors responded. Programs used a variety of instructional methods; all programs reported using lecture-based teaching and only a minority using simulation (38%) or flipped classroom techniques (17%). Other than PowerPoint, the most common electronic resource utilized was quizzing/polling (67%), webinar (33%), and econtour.org (13%). The lack of a national, standardized, radiation oncology residency didactic curriculum promotes variability and insufficiency in resident training. Themes for improvement were diversity in didactic topics, incorporation of evidence-based teaching practices, increased faculty involvement, and sharing of resources across programs. Development of a national curriculum and increased electronic resource sharing may help address some of these areas of improvement.


A new technique to identify hybrid myotubes in vitro without culture fixation.
Fluorescent latex microspheres (FLMs) were used to label myoblasts and to permit the observation of hybrid myotubes before culture fixation. This type of labeling did not affect survival, development, or fusion of these cells. The FLMs were retained for several weeks. Labeled mouse myoblasts were co-cultured with unlabeled rat myoblasts to verify whether the marker was released and spread from labeled to unlabeled cells. The nuclear stain Hoechst 33258 was used to distinguish the myoblasts from both species and permitted the demonstration that there was virtually no re-uptake. Hybrid myotubes were also obtained by co-culturing mouse myoblasts containing rhodamine FLMs and rat myoblasts containing green FLMs. These mixed cultures were observed repeatedly with a fluorescent microscope without any cytotoxic effect. Several myotubes were observed before fixation of the cultures to contain both types of fluorescent labels. Subsequent fixation and staining with Hoechst dye confirmed that these myotubes were hybrids.


Gluteal perforator flaps for coverage of pressure sores at various locations.
Flap coverage is essential for successful treatment of pressure sores, and musculocutaneous flaps have been preferred universally. Development of perforator flaps supplied by musculocutaneous perforators has allowed reconstructive surgeons to harvest flaps without including muscles. Perforator flaps have enhanced the possibility of donor sites because a flap can be supplied by any musculocutaneous perforator, and donor-site morbidity is also reduced. Between November of 1998 and June of 2002, the authors used 35 gluteal perforator flaps in 32 consecutive patients for coverage of pressure sores located at sacral (n = 22), ischial (n = 7), and trochanteric (n = 6) regions. The mean age of the patients was 53.1 years (range, 5 to 87 years), and there were 16 male and 16 female patients. All flaps in this series were supplied by musculocutaneous arteries arising from gluteal muscles. Patients were followed up for a mean period of 13.6 months. Wound dehiscence was observed in two patients and treated by secondary closure. Three patients died during the follow-up period. All flaps survived except one that had undergone total necrosis, and only one recurrence was noted during the follow-up period. Gluteal perforator flaps are safe and reliable options for coverage of pressure sores located at different locations. Freedom in flap design and low donor-site morbidity make gluteal perforator flaps an excellent choice for pressure sore coverage.


Emerging waterborne infections: contributing factors, agents, and detection tools.
Because microorganisms are easily dispersed, display physiological diversity, and tolerate extreme conditions, they are ubiquitous and may contaminate and grow in water. The presence of waterborne enteric pathogens (bacteria, viruses, and protozoa) in domestic water supplies represents a potentially significant human health risk. Even though major outbreaks of waterborne disease are comparatively rare, there is substantial evidence that human enteric pathogens that are frequently present in domestic water supplies are responsible for low-level incidence of waterborne microbial disease. Although these diseases are rarely debilitating to healthy adults for more than a few hours to a few days, enteric pathogens can cause severe illness, even death, for young children, the elderly, or those with compromised immune systems. As the epidemiology of waterborne diseases is changing, there is a growing global public health concern about new and reemerging infectious diseases that are occurring through a complex interaction of social, economic, evolutionary, and ecological factors. New microbial pathogens have emerged, and some have spread worldwide. Alternative testing strategies for waterborne diseases should significantly improve the ability to detect and control the causative pathogenic agents. In this article, we provide an overview of the current state of knowledge of waterborne microbial pathogens, their detection, and the future of new methods in controlling these infectious agents.