The role of the nose and cranial base in profile assessment: a morphological comparison between native African and Caucasian samples.
The purpose of this research was to evaluate the position of the nose and how it affects clinical judgment of the face in a native African sample. We considered the anatomic location of the nose with respect to the anterior cranial base (ACB) as well as to the maxillary lip, based on guidelines set down by Holdaway but slightly modified for purposes of this research. A comparison of the Shona to a Caucasian sample using selected parameters devised by Holdaway (pronasale to labrale superius) indicated that the Shona had a nose and ACB that were shorter than those of the comparative group of Caucasians. The short anterior cranial base was associated with a short and retro-positioned nose which resulted in deceptively protrusive lips when assessed using Ricketts' profile line. Whilst there was no difference in nose depth between the groups, the nasal angle of the Shona was larger than that of Caucasians, indicating an up-tipped nose. The position of the nose has a bearing on orthodontic treatment planning. Understanding the facial morphology of the Shona led us to conclude that conventional soft tissue measurements may not be applicable to all patients who present for orthodontic treatment, and that it may be necessary to advise the patient to seek other avenues for satisfactory management, which, depending on the chief complaint, may include surgical augmentation of the nose and chin.


Cross-frequency coupling in psychiatric disorders: A systematic review.
Cross-frequency coupling (CFC), an electrophysiologically derived measure of oscillatory coupling in the brain, is believed to play a critical role in neuronal computation, learning and communication. It has received much recent attention in the study of both health and disease. We searched for literature that studied CFC during resting state and task-related activities during electroencephalography and magnetoencephalography in psychiatric disorders. Thirty-eight studies were identified, which included attention-deficit hyperactivity disorder, Alzheimer's dementia, autism spectrum disorder, bipolar disorder, depression, obsessive compulsive disorder, social anxiety disorder and schizophrenia. The systematic review was registered with PROSPERO (ID#CRD42021224188). The current review indicates measurable differences exist between CFC in disease states vs. healthy controls. There was variance in CFC at different regions of the brain within the same psychiatric disorders, perhaps this could be explained by the mechanisms and functionality of CFC. There was heterogeneity in methodologies used, which may lead to spurious CFC analyses. Going forward, standardized methodologies need to be established and utilized in further research to understand the neuropathophysiology associated with psychiatric disorders.


Effect of antifreeze glycoprotein 8 supplementation during vitrification on the developmental competence of bovine oocytes.
The purpose of this study was to investigate the effect of antifreeze glycoprotein 8 (AFGP8) supplementation during vitrification on the survival, fertilization, and embryonic development of bovine oocytes and the underlying molecular mechanism(s). Survival, fertilization, early embryonic development, apoptosis, DNA double-strand breaks, reactive oxygen species levels, meiotic cytoskeleton assembly, chromosome alignment, and energy status of mitochondria were measured in the present experiments. Compared with that in the nonsupplemented group; survival, monospermy, blastocyst formation rates, and blastomere counts were significantly higher in the AFGP8-supplemented animals. Oocytes of the latter group also presented fewer double-strand breaks and lower cathepsin B and caspase activities. Rates of normal spindle organization and chromosome alignment, actin filament impairment, and mitochondrial distribution were significantly higher in the AFGP8-supplemented group. In addition, intracellular reactive oxygen species levels significantly decreased in the AFGP8-supplemented groups, maintaining a higher ΔΨm than that in the nonsupplemented group. Taken together, these results indicated that supplementation with AFGP8 during vitrification has a protective effect on bovine oocytes against chilling injury.


Drop-off in axonal regeneration along the length of a cross-face nerve graft: An experimental study in rats.
The average nerve graft length utilized in cross-face nerve grafting for reconstruction of facial nerve palsy is 20-22 cm. While the graft length is thought to be one of the greatest determinants of muscle strength, the mechanism through which this happens remains unknown. We studied changes in axonal regeneration along the length of a 2 cm cross-face nerve graft in a rat model. The hypothesis was that axon count would decrease along the length of the graft. A 2 cm nerve graft (sciatic nerve) was used as a cross-face nerve graft in 16 adult female, 210-250 g, Sprague Dawley rats. Thirteen weeks later, 5 mm nerve biopsies were taken at four sites: the facial nerve trunk (control), proximal graft, midpoint of graft (1 cm distal to coaptation) and distal graft (2 cm distal to coaptation). Retrograde nerve labeling with FluoroGold was performed at the biopsied nerve site and the facial motor nucleus was taken 1 week later. Microscopic imaging and manual counting of axons and labeled motor nuclei was performed. Retrograde-labeled motor neuron counts were decreased at the midway point of the graft compared to the facial trunk (1517 ± 335 axons, Δ% = 92.5, p = .01) and even further decreased at the distal end of the graft (269 ± 293 axons, Δ% = 175.5, p = .006). Analysis of the nerve biopsies demonstrated no significant differences in myelinated axon count between the nerve trunk and over the length of the nerve graft (range 6207-7179 axons, Δ% = 14.5, p = .07). In a rat model, the number of regenerating motor neurons drops off along the length of the graft and axon count is preserved due to axon sprouting. How this pattern correlates to ultimate muscle strength remains unknown, but this study provides insight into why shorter grafts may afford better outcomes.


Association between essential hypertension and bone mineral density: a systematic review and meta-analysis.
We conducted this systematic review and meta-analysis to evaluate the association between essential hypertension (EH) and bone mineral density (BMD). 17 articles were included in our meta-analysis, with a total of 39,491 patients. Of these, 13,375 were patients with EH and 26,116 were patients without EH. Meta-analysis results showed that EH can reduce the BMD of the lumbar spine (95% CI: -0.08∼0.01, P=0.006), femoral neck (95% CI: -0.09∼-0.02, p = 0.001), ward's triangle (95% CI: -0.45∼-0.25, p=0.000), femoral intertrochanteric (95% CI: -0.90∼-0.64, p = 0.000), calcaneus (95% CI: -0.31∼-0.18, p = 0.000) and distal forearm (95% CI: -0.09∼-0.03, p = 0.000), but EH cannot reduce the BMD of the femur rotor (95% CI: -0.07∼0.24, p = 0.273). Subgroup analysis showed that EH can reduce the BMD of the lumbar spine (95% CI: -0.11∼-0.03, p = 0.000) and femoral neck (95% CI: -0.11∼-0.07, p = 0.000) in Asian populations. In non-Asian populations, EH can reduce the BMD of the femoral neck (95% CI: 0.04∼0.19, p = 0.002), but cannot reduce the BMD of the lumbar spine (95% CI: -0.04∼0.11, p = 0.346). We conducted a systematic review of the published literature on the association of EH and BMD by searching the Cochrane Library, PubMed, EMBASE, CBM, CNKI and VIP databases inception to October 2016. Stata 11.0 software was used for data analysis. Our meta-analysis suggests that EH can reduce the BMD of the human body, and for different parts of the bone, the degree of reduction is different. In addition, for different regions and populations, the reduction level of BMD is inconsistent.


Variation in Sodium Chloride Resistance of Cenococcum geophilum and Suillus granulatus Isolates in Liquid Culture.
We studied the resistance of Cenococcum geophilum and Suillus granulatus isolates to NaCl during growth under axenic culture conditions. C. geophilum isolates displayed variations in NaCl resistance; mycelial growth of most isolates was inhibited above 200mM. All isolates of S. granulatus were tolerant to high NaCl content.


A new operative technique - extra renal ureterocalycostomy for correction of PUJ obstruction in a horseshoe kidney.
The authors describe a novel operative technique in a child with PUJ obstruction in a horseshoe kidney, where a pyeloplasty was clinically indicated but unsafe because of insufficient length of ureter and predicted technical difficulty in transposing large renal vessels coursing to the renal hilum. During the operation, there was a favourably positioned extra renal lower pole calyceal infundibulum identified, of similar dimensions to the spatulated ureter and this was chosen for an end to side tension free anastomosis. As far as the authors are aware this technique of extra renal ureterocalycostomy has not been described before.


Comprehensive clinicopathological and genomic profiling of gallbladder cancer reveals actionable targets in half of patients.
Gallbladder cancer (GBC) is a rare, highly aggressive malignancy with a 5-year survival rate of 5-10% in advanced cases, highlighting the need for more effective therapies. The aim of this study was to identify potentially actionable therapeutic targets for GBC. Specimens and clinicopathological data of 642 GBC patients, diagnosed between 2000 and 2019 were collected using the Dutch Pathology Registry (PALGA) and the Netherlands Cancer Registry. All cases were histologically reviewed and a subset was subjected to a comprehensive next generation sequencing panel. We assessed mutations and gene amplifications in a panel of 54 actionable genes, tumor-mutational burden (TMB), and microsatellite instability (MSI). Additionally, the entire cohort was screened for HER2, PD-L1, pan-TRK, and p53 expression with immunohistochemistry. Histopathological subtypes comprised biliary-type adenocarcinoma (AC, 69.6%), intestinal-type AC (20.1%) and other subtypes (10.3%). The median total TMB was 5.5 mutations/Mb (range: 0-161.1) and 17.7% of evaluable cases had a TMB of >10 mutations/Mb. MSI was observed in two cases. Apart from mutations in TP53 (64%), tumors were molecularly highly heterogeneous. Half of the tumors (50%) carried at least one molecular alteration that is targetable in other tumor types, including alterations in CDKN2A (6.0% biallelically inactivated), ERBB2 (9.3%) and PIK3CA (10%). Immunohistochemistry results correlated well with NGS results for HER2 and p53: Pearson r = 0.82 and 0.83, respectively. As half of GBC patients carry at least one potentially actionable molecular alteration, molecular testing may open the way to explore targeted therapy options for GBC patients.


The influence of maternal exercise on the uteroplacental vascular bed resistance and the fetal heart rate during normal pregnancy.
The effects of maternal exercise were studied in 20 healthy women with uncomplicated pregnancies. A continuous-wave Doppler ultrasound system was used to record arterial flow velocity waveforms from the ascending vasculature downstream from the uterine artery. The fetal heart rate was monitored with a Doppler ultrasound cardiotocograph. No significant change was found in the uterine blood flow velocity waveform post-exercise, as expressed by the pulsatility index, suggesting absence of change in the uterine vascular bed resistance. The fetal heart rate significantly increased after exercise.


Interdisciplinary Analyses of Bronze Age Communities from Western Hungary Reveal Complex Population Histories.
In this study, we report 21 ancient shotgun genomes from present-day Western Hungary, from previously understudied Late Copper Age Baden, and Bronze Age Somogyvár-Vinkovci, Kisapostag, and Encrusted Pottery archeological cultures (3,530-1,620 cal Bce). Our results indicate the presence of high steppe ancestry in the Somogyvár-Vinkovci culture. They were then replaced by the Kisapostag group, who exhibit an outstandingly high (up to ∼47%) Mesolithic hunter-gatherer ancestry, despite this component being thought to be highly diluted by the time of the Early Bronze Age. The Kisapostag population contributed the genetic basis for the succeeding community of the Encrusted Pottery culture. We also found an elevated hunter-gatherer component in a local Baden culture-associated individual, but no connections were proven to the Bronze Age individuals. The hunter-gatherer ancestry in Kisapostag is likely derived from two main sources, one from a Funnelbeaker or Globular Amphora culture-related population and one from a previously unrecognized source in Eastern Europe. We show that this ancestry not only appeared in various groups in Bronze Age Central Europe but also made contributions to Baltic populations. The social structure of Kisapostag and Encrusted Pottery cultures is patrilocal, similarly to most contemporaneous groups. Furthermore, we developed new methods and method standards for computational analyses of ancient DNA, implemented to our newly developed and freely available bioinformatic package. By analyzing clinical traits, we found carriers of aneuploidy and inheritable genetic diseases. Finally, based on genetic and anthropological data, we present here the first female facial reconstruction from the Bronze Age Carpathian Basin.


The effects of exposure to air pollution on the development of uterine fibroids.
Air pollution may cause specific genetic or epigenetic abnormalities and lead to the development of uterine fibroids (UFs). However, there have been limited studies evaluating the relationship between air pollutant exposure and the development of UFs. We conducted a 10-year cohort-based case-control study in Taiwan from 2001 to 2010 using National Health Institute Research Database (NHIRD) to assess the association between air pollution and the UFs development among Taiwanese women. The case group consisted of 11,028 women newly diagnosed with UFs during the study period and the control group was 44,112 women aged 25-45 years using density sampling with a 1:4 matching on the date of birth from 224,675 women in 2001-2010. The average age of onset was 36 ± 4.37 years old. Daily concentrations of PM2.5 were estimated by linear mixed-effects model integrating aerosol optical depth (AOD) and meteorological variables; daily concentrations of O3, CO, NO2 and SO2 were calculated by the Inverse Distance Weighting (IDW). The annual cumulative exposure to air pollutants during the study period was calculated corresponding to residential zip codes. In the conditional logistic regression adjusting for confounders, the adjusted odds ratio (aOR) for UFs per 10 μg/m3 increase in PM2.5 was 1.105 (95% confidence interval: 1.069, 1.141), per 10 ppb increase in O3 was 1.075 (95% confidence interval: 1.039, 1.113), respectively. Our study suggests that exposure to PM2.5 and O3 may increase the risk of developing UFs. Further studies are needed to confirm this novel finding.


Impact of TLR5 rs5744174 on stroke risk, gene expression and on inflammatory cytokines, and lipid levels in stroke patients.
Many studies reported that toll-like receptors (TLRs) played an important role in the process of ischemic stroke (IS). However, the impact of TLR5 rs5744174 on stroke risk, gene expression and on inflammatory cytokines, and lipid levels in ischemic stroke patients has not yet been reported and was therefore the subject of this study. In this case-control study, a total of 816 ischemic stroke patients and 816 healthy controls were genotyped using Sequenom MassArray technology. The mRNA expression of TLR5 was detected through quantitative real-time PCR among 52 ischemic stroke patients. The levels of IL-1b, IL-6, IL-8, and TNFα were measured by ELISA among 62 IS patients. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were determined among 816 IS patients using a Hitachi 7600 Automatic Biochemistry Analyzer. Our result showed TLR5 rs5744174 polymorphism was not associated with stroke risk, TLR5 mRNA expression and inflammatory cytokines of IS patients (P > 0.050), but was significantly associated with HDL-C (recessive model: β = - 0.14, 95 % CI: -0.24 to -0.03, P = 0.009). TLR5 rs5744174 polymorphism may have no impact on the stroke risk, gene expression and inflammatory cytokines, but may influence the HDL-C serum level of IS patients in Chinese Han population.


Effects of ganglioside (Cronassial) treatment on MHC Ia antigen expression and allograft survival of pancreatic islets in diabetic rats.
Streptozotocin-diabetic BdII rats were treated daily with 20 mg/kg body weight gangliosides for ten days beginning two days before transplantation. This treatment did not prolong allograft survival of untreated Lewis islets. Culture treatment of isolated Lewis islets with gangliosides (100 micrograms/ml in RPMI 1640) for one day resulted in a significant reduction of MHC Ia antigen positive cells but not of class I antigens within the islets. Transplantation of the ganglioside pretreated islets into non-immunosuppressed BdII recipients prolonged allograft survival to 12 days only in one of five animals.


Patients as actors: the patient's role in detecting, preventing, and recovering from medical errors.
Patients have the most to gain from reducing medical errors; yet, little research has been done to investigate the role they could or already do play in detecting and preventing errors in their own health care. The purpose of this study is to examine patient's role in detecting, preventing, and recovering from medical errors in outpatient oncology. In this paper, we use cognitive work analysis and Rasmussen's taxonomy of human performance to describe five cases of medical errors that occurred in an outpatient, cancer-care setting. We detail the role of the patient in each case, and analyze each role using constructs from previous studies of human behavior and errors. Observational data indicates that patients engage in a range of tasks that identify, prevent, and recover from medical errors in outpatient cancer care. The results of this study point to the importance of considering patients and their work in both the design of patient-care information systems and the structure of clinical-care environments that enable safe and effective health care.


Morphological determination of face-centered-cubic metallic nanoparticles by X-ray diffraction.
X-ray diffraction studies of face-centered-cubic metallic nanoparticles with different morphologies are discussed based on the experimental data and the calculation of the Debye equation with the truncated and perfect strain models. At least four basic morphologies frequently observed in face-centered-cubic metallic nanoparticles, namely sphere, cube, decahedron, and icosahedron, can be clearly distinguished from their characteristic integrated intensity ratios of the first two X-ray diffraction peaks, that is, (200) to (111).


Effects of Met-enkephalin on the mechanical activity and distribution of Met-enkephalin-like immunoreactivity in the cat large intestine.
The effects of Met-enkephalin on the spontaneous and electrically evoked activity were investigated in longitudinal and circular strips isolated from different regions of the large intestine, i.e., proximal colon, distal colon and rectum. Met-enkephalin induced dose-dependent contractile responses which were reversibly blocked by naloxone (10(-6) M). In all longitudinal strips and in the circular strips of the rectum, the effects of Met-enkephalin were prevented by TTX (10(-7) M), demonstrating their neurogenic nature. In the circular strips from the colon, Met-enkephalin induced contractile responses after TTX, proving the existence of smooth muscle opioid receptors. The comparison between the EC50 values of Met-enkephalin showed that the opioid receptors in the different regions have different sensitivity to Met-enkephalin, while the opioid receptors in the longitudinal and circular layers of the same region have equal affinity. Atropine (10(-6) M) and guanethidine (10(-6) M) did not alter significantly the EC50 values, showing that the neurogenic effects of Met-enkephalin on the spontaneous activity involve mainly nonadrenergic, noncholinergic (NANC) neurotransmitter mechanisms. When the preparations were stimulated electrically, Met-enkephalin (10(-9) M) suppressed the cholinergic components of the responses. Met-enkephalin-containing nerve fibers were found in the myenteric plexus of the three intestinal regions. In the colon, where direct smooth muscle effects were observed, fibers containing Met-enkephalin-like immunoreactivity were found to go deep into the circular layer, suggesting that they could supply Met-enkephalin input to the smooth muscle cells.


Puerarin alleviated oxidative stress and ferroptosis during renal fibrosis induced by ischemia/reperfusion injury via TLR4/Nox4 pathway in rats.
To investigate the role of puerarin on renal fibrosis and the underlying mechanism in renal ischemia and reperfusion (I/R) model. Rats were intraperitoneally injected with puerarin (50 or 100 mg/kg) per day for one week before renal I/R. The level of renal collagen deposition and interstitial fibrosis were observed by hematoxylin and eosin and Sirius Red staining, and the expression of α-smooth muscle actin (α-SMA) was examined by immunohistochemical staining. The ferroptosis related factors and TLR4/Nox4-pathway-associated proteins were detected by Western blotting. Puerarin was observed to alleviate renal collagen deposition, interstitial fibrosis and the α-SMA expression induced by I/R. Superoxide dismutase (SOD) activities and glutathione (GSH) level were decreased in I/R and hypoxia/reoxygenation (H/R), whereas malondialdehyde (MDA) and Fe2+ level increased. However, puerarin reversed SOD, MDA, GSH and Fe2+ level changes induced by I/R and H/R. Besides, Western blot indicated that puerarin inhibited the expression of ferroptosis related factors in a dose-dependent manner, which further demonstrated that puerarin had the effect to attenuate ferroptosis. Moreover, the increased expression of TLR/Nox4-pathway-associated proteins were observed in I/R and H/R group, but puerarin alleviated the elevated TLR/Nox4 expression. Our results suggested that puerarin inhibited oxidative stress and ferroptosis induced by I/R and, thus, delayed the progression of renal fibrosis, providing a new target for the treatment of renal fibrosis.


pH and temperature effects on the hydrolysis of three β-lactam antibiotics: ampicillin, cefalotin and cefoxitin.
An understanding of antibiotic hydrolysis rates is important for predicting their environmental persistence. Hydrolysis rates and Arrhenius constants were determined as a function of pH and temperature for three common β-lactam antibiotics, ampicillin, cefalotin, and cefoxitin. Antibiotic hydrolysis rates at pH4-9 at 25 °C, 50 °C, and 60 °C were quantified, and degradation products were identified. The three antibiotics hydrolyzed under ambient conditions (pH7 and 25 °C); half-lives ranged from 5.3 to 27 d. Base-catalyzed hydrolysis rates were significantly greater than acid-catalyzed and neutral pH hydrolysis rates. Hydrolysis rates increased 2.5- to 3.9-fold for a 10 °C increase in temperature. Based on the degradation product masses found, the likely functional groups that underwent hydrolysis were lactam, ester, carbamate, and amide moieties. Many of the proposed products resulting from the hydrolysis of ampicillin, cefalotin, and cefoxitin likely have reduced antimicrobial activity because many products contained a hydrated lactam ring. The results of this research demonstrate that β-lactam antibiotics hydrolyze under ambient pH and temperature conditions. Degradation of β-lactam antibiotics will likely occur over several weeks in most surface waters and over several days in more alkaline systems.


Handgrip exercise does not alter CO2 -mediated cerebrovascular flow-mediated dilation.
Handgrip exercise (HG), a small muscle exercise, improves cognitive function and is expected to provide a useful exercise mode to maintain cerebral health. However, the effect of HG on cerebral blood flow regulation is not fully understood. The present study aimed to examine the effect of acute HG on cerebral endothelial function as one of the essential cerebral blood flow regulatory functions. Thirteen healthy young participants performed interval HG, consisting of 4 sets of 2 min HG at 25% of maximum voluntary contraction with 3 min recovery between each set. Cognitive performance was evaluated before and at 5 and 60 min after interval HG using the Go/No-Go task (reaction time and accuracy). The diameter and blood velocity of the internal carotid artery (ICA) were measured using a duplex Doppler ultrasound system. To assess cerebral endothelial function, hypercapnia (30 s of hypercapnia stimulation, end-tidal partial pressure of CO2 : +9 mmHg)-induced cerebrovascular flow-mediated dilatation (cFMD) was induced, calculated as relative peak dilatation from baseline diameter. The shear rate (SR) was calculated using the diameter and blood velocity of the ICA. As a result, cognitive performance improved only at 5 min after interval HG (reaction time, P = 0.008; accuracy, P = 0.186), whereas ICA SR during interval HG and cFMD after interval HG were unchanged (P = 0.313 and P = 0.440, respectively). These results suggest that enhancement in cerebral endothelial function is not an essential mechanism responsible for acute HG-induced cognitive improvement. NEW FINDINGS: What is the central question of this study? Does handgrip exercise, a small muscle exercise, improve cerebral endothelial function? What is the main finding and its importance? Acute interval isometric handgrip exercise (2 min of exercise at 25% maximum voluntary contraction, followed by 3 min of recovery, repeated for a total of 4 sets) did not improve cerebral endothelial function. Since the cerebrovascular shear rate did not change during exercise, it is possible that acute handgrip exercise is not sufficient stimulation to improve cerebral endothelial function.


Nickel oxide nanoparticles can recruit eosinophils in the lungs of rats by the direct release of intracellular eotaxin.
Instillation of highly soluble nanoparticles (NPs) into the lungs of rodents can cause acute eosinophilia without any previous sensitizations by the role of dissolved ions. However, whether gradually dissolving NPs can cause the same type of eosinophilia remains to be elucidated. We selected nickel oxide (NiO) as a gradually dissolving NP and evaluated the time course pulmonary inflammation pattern as well as its mechanisms. NiO NPs were intratracheally instilled into female Wistar rats at various concentrations (50, 100, and 200 cm(2)/rat) and the lung inflammation was evaluated at various time-points (1, 2, 3, and 4 days). As positive controls, NiCl2 and the ovalbumin-induced allergic airway inflammation model was applied. NiCl2 was instilled at 171.1 μg Ni/rat, which is equivalent nickel concentration of 200 cm(2)/rat of NiO NPs. Cytological analysis and biochemical analysis including lactate dehydrogenase (LDH), total protein, and pro-inflammatory cytokines were measured in bronchoalveolar lavage fluid (BALF). The levels of total immunoglobulin E (IgE) and anaphylatoxins (C3a and C5a) were measured in BALF and serum. The levels of eotaxin were measured in the alveolar macrophages and normal lung tissue before and after addition of cell lysis buffer to evaluate whether the direct lysis of cells can release intracellular eotaxin. NiO NPs produced acute neutrophilic inflammation throughout the study. However, eosinophils were recruited at 3 and 4 days post-instillation of NiO NPs and the magnitude and pattern of inflammation was similar with NiCl2 at 24 h post-instillation. The eosinophil recruitment by NiO NPs was not related with either the levels of total IgE or anaphylatoxins. The lysis of alveolar macrophages and normal lung tissue showed high levels of intracellular eotaxin and the levels of LDH showed positive correlation with the levels of eotaxin. Instillation of NiO NPs produced neutrophilia at 1 and 2 days after instillation, while the mixed type of neutrophilic and eosinophilic inflammation was produced at 3 and 4 days post-instillation, which was consistent with NiCl2. The mechanism of the eosinophilia involves the direct release of intracellular eotaxin due to the rupture of cells by the accumulated solubilized nickel ions in the phagolysosome.


Trace element assessment in Neoechinorhynchus agilis (Rudolphi, 1918) (Acanthocephala: Neoechinorhynchidae) and its fish hosts, Mugil cephalus (Linnaeus, 1758) and Chelon ramada (Risso, 1827) from Ichkeul Lagoon, Tunisia.
Acanthocephalans belonging to the species Neoechinorhynchus agilis were collected from two mullets, Mugil cephalus and Chelon ramada from Ichkeul Lagoon in northern Tunisia. Collected parasites, as well as tissues of their hosts (muscle, liver and intestine), were analysed for trace elements (silver, arsenic, cadmium, cobalt, copper, iron, manganese, nickel (Ni), lead (Pb), selenium, vanadium (V), zinc) using inductively coupled plasma mass spectrometry. Our results showed different accumulation patterns of trace elements in fish tissues and parasites. Among the host tissues, liver accumulated the highest metal amounts. Acanthocephalans showed Ni, Pb and V in significantly higher concentrations compared to their host's tissues. Further, the calculated bioconcentration factors demonstrated a 390-fold higher Pb accumulation in the parasite compared to fish muscle. This study is the first field survey in Tunisia dealing with elements' uptake in parasites and their hosts. Our results corroborate the usefulness of the acanthocephalans for biomonitoring of metal pollution in aquatic ecosystems and promote more research in order to understand host-parasite systems in brackish waters of the Mediterranean area.


COLEC12 regulates apoptosis of osteosarcoma through Toll-like receptor 4-activated inflammation.
To investigate the role of COLEC12 in osteosarcoma and observe the relationship between COLEC12 knockdown and the inflammation of osteosarcoma. Then, further explore whether the process is regulated by TLR4. GEPIA and TCGA systems were used to predict the potential function of COLEC12. Western blot and RT-PCR were used to analyze the protein expression, or mRNA level, of COLEC12 in different tissue or cell lines. The occurrence and development of osteosarcoma were observed by using COLEC12 knockdown lentivirus. The inflammation indexes of osteosarcoma, in vitro and in vivo, were explored. TLR4 knockdown lentivirus was applied to the relationship between COLEC12 and TLR4. COLEC12 expression in SARC tumor tissue was higher than in normal, and a high expression of COLEC12 in SARC patients had a worse prognostic outcome. Pairwise gene correlation analysis revealed a potential relationship between COLEC12 and TLR4. The COLEC12 expression and mRNA level in the tumor or Saos-2 cells were increased. COLEC12 knockdown lentivirus could inhibit osteosarcoma development, in vivo and vitro, through reducing tumor volume and weight, weakening tumor proliferation, migration, and invasion, and enhancing apoptosis. Furthermore, COLEC12 knockdown could increase inflammation of osteosarcoma, in vivo and in vitro, through inducing myeloperoxidase (MPO), TLR4, NF-κB, and C3, and expression of related inflammatory factors. Finally, TLR4 knockdown lentivirus inhibits the progress of inflammation after COLEC12 regulation, in vivo and vitro. COLEC12 may be able to regulate apoptosis and inflammation of osteosarcoma, and TLR4 may be the downstream target factor of COLEC12 in inflammation.


Effect of citrate on serum aluminum concentrations in hemodialysis patients: a prospective study.
Twenty hemodialysis patients were prospectively evaluated to determine if concomitant citrate and aluminum administration enhances the absorption of aluminum, thereby increasing the possibility of toxicity. The four-phase study consisted of phase I, a washout phase; phase II, an aluminum treatment phase; phase III, a treatment phase combining aluminum and soluble calcium citrate; and phase IV, a treatment phase with the patient's original prestudy phosphate binder. Results disclosed a progressive rise in serum aluminum levels (microgram/L) from 47 +/- 8 (phase I) to 62 +/- 12 (phase II) to 74 +/- 13 (phase III) and a drop to 58 +/- 12 (phase IV). The difference in levels between phases I and III was significant. Additionally, and despite the fact that serum calcium concentrations did not change, serum phosphate and immunoreactive parathyroid hormone concentrations were significantly lower when aluminum and citrate were used together. This suggests that citrate enhances the absorption of aluminum and therefore increases the possibility of toxicity in the patient with end-stage renal disease.


Traumatic aortic insufficiency in children: case report and review of the literature.
Aortic valve regurgitation and saccular aneurysm of the ascending aorta developed in a 5-year-old boy following severe compressive injury to the chest. While rare, traumatic aortic valve disruption may lead to serious cardiac dysfunction. Recognition of acute arotic insufficiency and other forms of cardiac damage requires special attention in patients with nonpenetrating chest injury.


Magnetization spoiling in radial FLASH contrast-enhanced MR digital subtraction angiography.
To increase the in-plane spatial resolution and image update rates of 2D magnetic resonance (MR) digital subtraction angiography (DSA) pulse sequences to 0.57 × 0.57 mm and 6 frames/sec, respectively, for intracranial vascular disease applications by developing a radial FLASH protocol and to characterize a new artifact, not previously described in the literature, which arises in the presence of such pulse sequences. The pulse sequence was optimized and artifacts were characterized using simulation and phantom studies. With Institutional Review Board (IRB) approval, the pulse sequence was used to acquire time-resolved images from healthy human volunteers and patients with x-ray DSA-confirmed intracranial vascular disease. Artifacts were shown to derive from inhomogeneous spoiling due to the nature of radial waveforms. Gradient spoiling strategies were proposed to eliminate the observed artifact by balancing gradient moments across TR intervals. The resulting radial 2D MR DSA sequence (2.6 sec temporal footprint, 6 frames/sec with sliding window factor 16, 0.57 × 0.57 mm in-plane) demonstrated small vessel detail and corroborated x-ray DSA findings in intracranial vascular imaging studies. Appropriate gradient spoiling in radial 2D MR DSA pulse sequences improves intracranial vascular depiction by eliminating circular banding artifacts. The proposed pulse sequence may provide a useful addition to clinically applied 2D MR DSA scans.


The association between initial manifestations of childhood-onset systemic lupus erythematosus and the survival.
Childhood-onset systemic lupus erythematosus (cSLE) comprises 15-20% of patients with SLE. Although several studies have reported the outcomes of adult-onset SLE, few investigations have been conducted on cSLE in the Middle East. In a retrospective study, all children with SLE admitted to our tertiary referral center between 1992 and 2011 were recruited. The clinical and laboratory data at the time of onset were recorded and analyzed. Kaplan-Meier analysis was used to calculate the survival rates. Cox regression analysis was applied to assess the predictors of mortality. One hundred and eighty-eight children diagnosed with SLE were enrolled during the study period. Nine patients were censored due to loss to follow-up (6) and incomplete data (3 cases). Mean age of patients at the time of onset was 14.4 (3.05) years. Only 22 (11.8%) children were younger than 10 years at the time of disease onset. In total, 20 patients (11%) died, all after the first decade of life. The most common cause of death was lupus nephritis (10 patients, 50% of deaths) followed by infections (35%), cerebrovascular accidents (10%) and alveolar hemorrhage (5%). Cumulative survival rate after 5, 10, 15 and 20 years was 91, 87, 85, and 79%, respectively. Having hematuria or pleurisy at the time of SLE onset had a negative effect on survival in multivariate analysis. cSLE survival in Iran was comparable to that in other developing countries. Baseline presentation with hematuria predominantly increased the mortality rate in cSLE. Prospective and larger studies in future may unfold other aspects of cSLE.


Degranulated mast cells and TNF-α in oral lichen planus and oral lichenoid reactions diseases.
The objective of this study was to assess mast cells and TNF-α in oral lichen planus (OLP) and oral lichenoid reactions (OLR) patients as diagnostic marker to the differential diagnosis of OLP and OLR diseases. In this cross-sectional study, samples were obtained from 30 OLP and 30 OLR patients, between June 2010 and March 2011 in Dental clinic of the University of Isfahan, Iran. Mast cells in the reticular layer of the lamina propria for samples were evaluated using toluidine blue method and immunohistochemical technique. The clinical relevant data taken into account were: demographical data, total number and degranulated mast cells, ratio of degranulated mast cells and TNF-α positive degranulated mast cells. In OLP and OLR, the total mast cells were 21.2 ± 7.9 and 20.3 ± 6.8, degranulated mast cells were 15.5 ± 6.9 and 19.2 ± 6.9, ratio of degranulated mast cells to total mast cells were 0.716 ± 0.067 and 0.946 ± 0.081, and TNF-α positive degranulated mast cells were 13.6 ± 6.3 and 17.1 ± 6.04, respectively. There was no significant difference for the total mast cells. But degranulated mast cells, ratio of degranulated mast cells and TNF-α positive degranulated mast cells in OLR were significantly higher than OLP patients. Our results showed that the degranulated mast cells, ratio of degranulated mast cells and TNF-α in OLR was significantly more than OLP patients and these may be able to be used as diagnostic markers to the differential diagnosis of OLP and OLR.


Identifying and exploiting grain yield genes in rice.
Improved grain yield has been a major focus of crop breeding programs around the world. With the accomplishments of the Rice Genome Project, genes regulating several agronomically important traits related to grain yield, such as tiller number, grain number, grain size, and plant height, have recently been identified. Although these findings have not been enough to fully characterize the mechanisms that regulate each trait, these genes and knowledge of the molecular mechanisms involved provide a set of tools that can be combined to achieve tailor-made breeding suitable for various programs aimed at higher grain yield.


Notulae seminologicae. 2. The 'short tail' and 'stump' defect in human spermatozoa.
In this note several cases of stunted tails involving the total sperm population in sterile humans are described. Half of the cases are classified as 'short tailed' spermatozoa, the other half as 'stump defect' previously described in bulls. Both defects are referred in details at electron microscopical level.


[Features of crossability, haploidy and polyembryony in hybrid combinations between common barley Hordeum vulgare L. (2n = 14) and wheat-rye substitution lines Triticum aestivum L., cultivar Saratovskaya 29/Secale cereale L., cultivar Onokhoiskaya].
The role of individual chromosomes of rye in the manifestation of crossability and seedling development in hybrid combinations between common barley Hordeum vulgare L., cultivar Nepolegayushchii (2n = 14) and five wheat-rye substitution lines Triticum aestivum L., cultivar Saratovskaya 29/Secale cereale L., cultivar Onokhoiskaya (2n = 40 wheat + 2 rye chromosomes). Crossability, which was measured by two parameters--frequency of set grains and frequency of grains with embryos--was shown to be significantly affected by each of the five rye chromosomes examined: 1R, 2R, 3R, 5R, and 6R; the development of barley haploids was affected by rye chromosomes 1 R, 3R, and 5R. We were the first to demonstrate that polyembryony could be induced by mutual effects of barley cytoplasm and rye chromosome 1R. Possible mechanisms controlling the development of haploids and twins in hybrid combinations H. vulgare x T. aestivum/S. cereale are discussed. The conclusion is drawn that hybrid combinations between common barley and wheat-rye substitution lines can serve as new models for studying incompatibility mechanisms in distant crosses and genetic control of parthenogenesis.


Insights into behavior and mechanism of tetracycline adsorption on virgin and soil-exposed microplastics.
Microplastics (MPs), as vectors of pollutants, have attracted extensive attention because of their environmental effects. However, the adsorption behavior and antibiotic mechanism of environmentally exposed MPs is limited. Here, the adsorption of tetracycline (TC) onto virgin and soil-exposed polylactic acid (PLA), polyvinyl chloride (PVC) and polyethylene (PE) MPs showed that the adsorption capacity of MPs for TC increased after soil exposure, and PLA showed the strongest increase. Soil exposure increased the time to reach equilibrium, and the adsorption rate was controlled by both intraparticle diffusion and membrane diffusion. The isothermal adsorption results of soil-exposed PE and PLA indicated that TC adsorbed on heterogeneous surfaces was affected by the physicochemical adsorption process. The equilibrium absorption capacity of MPs for TC increased by 88% (PLA), 26% (PVC) and 15% (PE) after soil exposure. Soil dissolved organic matter promoted the desorption of TC from MPs, and TC speciation changed with pH. Soil-exposed MPs have the potential to promote TC degradation in solution without the addition of biological inhibitors. Moreover, density functional theory calculations verified that PE and PVC adsorbed TC through physical interactions, while hydrogen bonds were formed on PLA with TC. These results clarified the behavior and mechanisms of TC adsorption on virgin and soil-exposed MPs, which can help in the risk assessment of concomitant pollution of MPs and antibiotics.


Dystrophin-deficient zebrafish feature aspects of the Duchenne muscular dystrophy pathology.
Duchenne muscular dystrophy is caused by mutations in the dystrophin gene. As in humans, zebrafish dystrophin is initially expressed at the peripheral ends of the myofibres adjacent to the myotendinous junction and gradually shifts to non-junctional sites. Dystrophin-deficient zebrafish larvae are characterised by abundant necrotic fibres being replaced by mono-nucleated infiltrates, extensive fibrosis accompanied by inflammation, and a broader variation in muscle fibre cross-sectional areas. Muscle progenitor proliferation cannot compensate for the extensive skeletal muscle loss. Live imaging of dystrophin-deficient zebrafish larvae documents detaching myofibres elicited by muscle contraction. Correspondingly, the progressive phenotype of dystrophin-deficient zebrafish resembles many aspects of the human disease, suggesting that specific advantages of the zebrafish model system, such as the ability to undertake in vivo drug screens and real time analysis of muscle fibre loss, could be used to make novel insights relevant to understanding and treating the pathological basis of dystrophin-deficient muscular dystrophy.


Regional and seasonal variations in ultraviolet B irradiation and vitamin D synthesis in India.
Evaluation of ultraviolet B index (UVBI) and its impact on vitamin D synthesis is important. We observed the maximum UVBI between 11 am and 1 pm. There was no increase in serum 25(OH)D levels following sun exposure during winter as the UVBI was significantly low, emphasizing the need for vitamin D supplementation during these months. The amount of vitamin D3 synthesizing UVB irradiation (290-320 nm) reaching the earth's surface at different altitudes and seasons in different parts of India and it's impact on vitamin D synthesis has not been well studied. The hourly UVB index (UVBI) from 10 am to 3 pm everyday for 12 months was measured by a solar meter in 4 different zones (North, Northeast, West and South) of the country. To study the impact of sun light exposure on vitamin D synthesis during winter, healthy school children aged 10-15 years were exposed to sunlight for a period of 30 min per day, between 11 am to 12 noon with 10 % body surface area, for 4 weeks. The main outcome measures were serum 25(OH)D, PTH, calcium, phosphate, and alkaline phosphatase levels before and after sun exposure. The mean UVBI was highest between 11 am and 1 pm throughout the year in all locations. The highest UVBI was recorded from the North zone (4.5 ± 2.7 μW/Cm(2)), while the least was recorded in the Northeast zone (2.1 ± 1.2 μW/Cm(2)). UVBI readings in the Northeast zone were consistently low throughout the year, while all the other three zones showed significant seasonal fluctuations. Surprisingly, we observed a significant decrease in serum 25(OH)D levels from baseline (6.3 ± 4.6 to 5.1 ± 2.7 ng/mL; p < 0.001) despite sun exposure. The mean UVBI was highest between 11 am and 1 pm throughout the year in all locations. No increase in the serum 25(OH)D levels was observed following sun exposure in winter, emphasizing the need for vitamin D supplementation during these months.


Lactic acid bacteria and yeasts associated with spontaneous fermentations during the production of sour cassava starch in Brazil.
Sour cassava starch is a traditional fermented food used in the preparation of fried foods and baked goods such as traditional cheese breads in Brazil. Thirty samples of sour cassava starch were collected from two factories in the state of Minas Gerais. The samples were examined for the presence of lactic acid bacteria, yeasts, mesophilic microorganisms, Bacillus cereus and faecal coliforms. Lactic acid bacteria and yeasts isolates were identified by biochemical tests, and the identities were confirmed by molecular methods. Lactobacillus plantarum and Lactobacillus fermentum were the prevalent lactic acid bacteria in product from both factories, at numbers between 6.0 and 9.0 log cfu g(-)(1). Lactobacillus perolans and Lactobacillus brevis were minor fractions of the population. Galactomyces geothricum and Issatchenkia sp. were the prevalent yeasts at numbers of 5.0 log cfu g(-)(1). A species similar to Candida ethanolica was frequently isolated from one factory. Mesophilic bacteria and amylolytic microorganisms were recovered in high numbers at all stages of the fermentation. B. cereus was found at low numbers in product at both factories. The spontaneous fermentations associated with the production of sour cassava starch involve a few species of lactic acid bacteria at high numbers and a variety of yeasts at relatively low numbers.


Performance of two clinical fluorescence imaging systems with different targeted and non-targeted near-infrared fluorophores: a cadaveric explorative study.
Near-infrared (NIR) fluorescence-guided surgery is increasingly utilized in humans and pets. As clinical imaging systems are optimized for Indocyanine green (ICG) detection, the usage of targeted dyes necessitates the validation of these systems for each dye. We investigated the impact of skin pigmentation and tissue overlay on the sensitivity of two NIR cameras (IC-FlowTM, VisionsenseTM VS3 Iridum) for the detection of non-targeted (ICG, IRDye800) and targeted (AngiostampTM, FAP-Cyan) NIR fluorophores in an ex vivo big animal model. We quantitatively measured the limit of detection (LOD) and signal-to-background ratio (SBR) and implemented a semi-quantitative visual score to account for subjective interpretation of images by the surgeon. VisionsenseTM VS3 Iridum outperformed IC-FlowTM in terms of LOD and SBR for the detection of all dyes except FAP-Cyan. Median SBR was negatively affected by skin pigmentation and tissue overlay with both camera systems. Level of agreement between quantitative and semi-quantitative visual score and interobserver agreement were better with VisionsenseTM VS3 Iridum. The overlay of different tissue types and skin pigmentation may negatively affect the ability of the two tested camera systems to identify nanomolar concentrations of targeted-fluorescent dyes and should be considered when planning surgical applications.


Evidence of Query Theory as a Tool to Assist Restrained Eaters.
Using theories from decision-making and behavioral economics, we conducted a study to improve understanding of the decisions of Restrained Eaters. We identified Restrained Eaters via the Revised Restraint Questionnaire. One hundred two (N = 102) participants were each randomly assigned to an endowment condition and asked to list their thoughts about 2 products. We found a significant interaction of endowment and thoughts on decisions. Research findings suggest the behavior of Restrained Eaters depends upon both endowment and thoughts, and that they exert self-control beyond food decisions. This work suggests decisions Restrained Eaters make can be manipulated via endowment and how they are instructed to structure their thoughts.


Sarcomere Length Nonuniformity and Force Regulation in Myofibrils and Sarcomeres.
The smallest contractile unit in striated muscles is the sarcomere. Although some of the classic features of contraction assume a uniform behavior of sarcomeres within myofibrils, the occurrence of sarcomere length nonuniformities has been well recognized for years, but it is yet not well understood. In the past years, there has been a great advance in experiments using isolated myofibrils and sarcomeres that has allowed scientists to directly evaluate sarcomere length nonuniformity. This review will focus on studies conducted with these preparations to develop the hypotheses that 1) force production in myofibrils is largely altered and regulated by intersarcomere dynamics and that 2) the mechanical work of one sarcomere in a myofibril is transmitted to other sarcomeres in series. We evaluated studies looking into myofibril activation, relaxation, and force changes produced during activation. We conclude that force production in myofibrils is largely regulated by intersarcomere dynamics, which arises from the cooperative work of the contractile and elastic elements within a myofibril.


Sclerostin antibody increases bone mass by stimulating bone formation and inhibiting bone resorption in a hindlimb-immobilization rat model.
Sclerostin monoclonal antibody (Scl-Ab) has been shown to increase bone mass and bone strength by stimulating bone formation in an ovariectomy-induced bone loss rat model. The purpose of this study was to determine the effects of Scl-Ab in a rat immobilization/disuse model in which there was both a decrease in bone formation and an increase in bone resorption. Ten-month-old female Sprague Dawley rats were divided into normal weight-bearing (normal-loaded, NL) and right hindlimb-immobilization (under-loaded, UL) groups. Both NL and UL rats were treated with vehicle or Scl-Ab at 5 or 25 mg/kg, twice per week for 4 weeks. Trabecular and cortical bone histomorphometric analyses were performed on the proximal tibial metaphysis (PTM) and tibial shaft (TS). Compared to NL controls, UL rats had reduced body and muscle weights, increased bone marrow fat cells in the PTM, increased trabecular bone resorption and periosteal mineral apposition rate (MAR) as well as decreased trabecular MAR and bone formation rate (BFR/BS). In NL bones, treatment with Scl-Ab significantly increased bone formation and decreased bone resorption, resulting in increased trabecular and cortical bone mass. In UL trabecular bone, treatment with Scl-Ab at 5 or 25 mg/kg induced significant and dose-dependent increases in trabecular bone volume and thickness, mineralized surfaces (MS/BS), MAR and BFR/BS, and a significant decrease in eroded surface (Er.S/BS) compared with UL controls. In UL cortical bone, Scl-Ab treatment induced significant increases in cortical width, periosteal and endocortical MS/BS, MAR and BFR/BS, and significant decreases in endocortical Er.S/BS compared with UL controls. Taken together, these findings suggest that antibody-mediated blockade of sclerostin represents a promising new therapeutic approach for the anabolic treatment of immobilization-induced osteopenia.


The performance of the pine beauty moth on water-stressed lodgepole pine plants: a laboratory experiment.
A laboratory experiment was done to see whether artificially induced waterlogging, or water shortage in lodgepole pine (Pinus contorta) would affect the egg laying preference, larval survival and larval growth of Panolis flammea. Female moths showed no egg laying preference between unstressed and stressed plants. Larval survival was greater on unstressed (85%) than on stressed (32%) plants, and the weight of larvae reared on unstressed plants was significantly greater than those reared on stressed plants. These results imply that outbreaks of the pine beauty moth on trees growing in deep unflushed peat are not caused by a stress-induced improvement in the nutritional quality of the host-plant.


[Tumor-infiltrating natural killer and T cells in melanoma].
Melanoma is a highly immunogenic cancer with an increased infiltration of lymphocytes (TIL). TIL are a very heterogeneous population which consists among others of CD8+ T cells, CD4+ T cells, regulatory T cells, B cells, and natural killer (NK) cells and may differ highly between melanoma patients. Distribution, concentration, phenotype, and activation status of the infiltrating lymphocytes vary greatly and impact the prognosis. Different subpopulations of CD8+ T cells, CD4+ T cells, and NK cells have been identified and have been associated with both the course of the disease and the therapeutic response to different therapies. Increased knowledge of the different functions, interactions, activation, and possibilities of actively influencing relevant subgroups may lead to novel, innovative, and promising therapeutic options.


New connections: Getting the good without the bad, opiate edition.
Researchers identify strategies to limit the adverse effects and liabilities of opioid receptor-targeting drugs.


The hepatic interleukin-6 receptor. Down-regulation of the interleukin-6 binding subunit (gp80) by its ligand.
Interleukin-6 (IL6) exerts its action via a cell surface receptor composed of an 80 kDa IL6-binding protein (gp80) and a 130 kDa polypeptide involved in signal transduction (gp130). We studied the role of gp80 in binding, internalization and down-regulation of the hepatic IL6-receptor (IL6R) by its ligand in human hepatoma cells (HepG2). Comparison of transfected HepG2 cells overexpressing gp80 with parental cells indicate that gp80 is responsible for low affinity binding (Kd = 500 pM) of IL6. Furthermore, gp80 is rate-limiting in internalization and degradation of IL6. Internalization resulted in a rapid down-regulation (t1/2 approximately 15-30 min) of IL6-binding sites at the cell surface. More than 80% of the internalized [125I]rhIL6 was degraded. The reappearance of IL6-binding sites at the cell surface required greater than 8 h and was sensitive to cycloheximide, suggesting that gp80 is not recycled after internalization. The down-regulation of the hepatic IL6R by its ligand might play an important role as a protection against overstimulation.


The combination of silver-containing hydroxyapatite coating and vancomycin has a synergistic antibacterial effect on methicillin-resistant Staphylococcus aureus biofilm formation.
Biofilm formation is intrinsic to prosthetic joint infection (PJI). In the current study, we evaluated the effects of silver-containing hydroxyapatite (Ag-HA) coating and vancomycin (VCM) on methicillin-resistant Staphylococcus aureus (MRSA) biofilm formation. Pure titanium discs (Ti discs), Ti discs coated with HA (HA discs), and 3% Ag-HA discs developed using a thermal spraying were inoculated with MRSA suspensions containing a mean in vitro 4.3 (SD 0.8) x 106 or 43.0 (SD 8.4) x 105 colony-forming units (CFUs). Immediately after MRSA inoculation, sterile phosphate-buffered saline or VCM (20 µg/ml) was added, and the discs were incubated for 24 hours at 37°C. Viable cell counting, 3D confocal laser scanning microscopy with Airyscan, and scanning electron microscopy were then performed. HA discs and Ag HA discs were implanted subcutaneously in vivo in the dorsum of rats, and MRSA suspensions containing a mean in vivo 7.2 (SD 0.4) x 106 or 72.0 (SD 4.2) x 105 CFUs were inoculated on the discs. VCM was injected subcutaneously daily every 12 hours followed by viable cell counting. Biofilms that formed on HA discs were thicker and larger than those on Ti discs, whereas those on Ag-HA discs were thinner and smaller than those on Ti discs. Viable bacterial counts in vivo revealed that Ag-HA combined with VCM was the most effective treatment. Ag-HA with VCM has a potential synergistic effect in reducing MRSA biofilm formation and can thus be useful for preventing and treating PJI.Cite this article: Bone Joint Res. 2020;9(5):211-218.


Rapid action on neuroplasticity precedes behavioral activation by testosterone.
Testosterone has been shown to increase the volume of steroid-sensitive brain nuclei in adulthood in several vertebrate species. In male Japanese quail the volume of the male-biased sexually dimorphic medial preoptic nucleus (POM), a key brain area for the control of male sexual behavior, is markedly increased by testosterone. Previous studies assessed this effect after a period of 8-14 days but the exact time course of these effects is unknown. We asked here whether testosterone-dependent POM plasticity could be observed at shorter latencies. Brains from castrated male quail were collected after 1, 2, 7 and 14 days of T treatment (CX+T) and compared to brains of untreated castrates (CX) collected after 1 or 14 days. POM volumes defined either by Nissl staining or by aromatase immunohistochemistry increased in a time-dependent fashion in CX+T subjects and almost doubled after 14 days of treatment with testosterone while no change was observed in CX birds. A significant increase in the average POM volume was detected after only one day of testosterone treatment. The optical density of Nissl and aromatase staining was also increased after one or two days of testosterone treatment. Activation of male copulatory behavior followed these morphological changes with a latency of approximately one day. This rapid neurochemical and neuroanatomical plasticity observed in the quail POM thus seems to limit the activation of male sexual behavior and offers an excellent model to analyze features of steroid-regulated brain structure and function that determine behavior expression.


Octreotide in the treatment of diarrhoea induced by coeliac plexus block.
Prolonged and severe diarrhoea after alcohol celiac plexus block is a rare, but life-threatening, complication if not recognized. This type of diarrhoea may be considered an autonomic neuropathy due to sympathetic denervation. A 65-year-old pancreatic cancer patient developed serious diarrhoea after celiac plexus block which was unresponsive to traditional treatment such as loperamide, dyphenoxylate and opioids. Subcutaneous octreotide, 0.1 mg twice a day, achieved a complete resolution of the symptom. This drug was maintained at the same dosage and was well tolerated for 4 months until death. Octreotide, an analogue of somatostatin, reduces diarrhoea by suppression of intestinal motility and secretion and offers a useful option in the treatment of this complication of celiac plexus block.


A new platform based on IEEE802.15.4 wireless inertial sensors for motion caption and assessment.
Systems for motion caption and assessment in biomechanics are mostly based on photogrammetry. These systems are restricted to the movement analysis lab and moreover, they are very expensive. New advances in MEMs (Microelectromechanical) and wireless technologies enable inertial sensing as an alternatives for motion caption. This paper presents a wireless inertial sensor including 3 linear accelerometers, 3 gyroscopes and 3 magnetometers. The IMU (inertial measurement unit) includes a IEEE802.15.4 compliant transceiver. The platform expands the frontiers of movement analysis for motion caption in real scenarios like sports and wearable robotics since it does not need structurated labs. Besides the advantages, the cost of the platform is much lower comparing actual photogrammetry systems.


A prospective randomized comparison of single- and double-lumen needles for transvaginal follicular aspiration.
Patients undergoing ultrasound-directed transvaginal follicular aspiration in a large in vitro fertilization (IVF) program were randomized for retrieval with either a single-lumen needle (SLN; N = 22) or a double-lumen needle (DLN; N = 22) to compare recovery rates and the technical aspects of their use. Two hundred ten and two hundred two follicles were aspirated with each needle, respectively. Follicular diameters were measured ultrasonically at the time of aspiration and recorded. One or more washes were performed when using the DLN and the SLN was withdrawn each time to recover the fluid in the dead space of the needle. The distribution of follicular sizes was the same for both needles. Oocyte recovery rates (SLN = 65.7%; DLN = 63.9%) and the incidence of fractured zonae (SLN = 9.1%; DLN = 6.4%) were the same for both needles (alpha greater than 0.50; beta less than 0.01). Although there were no differences between the two needles in the number of oocytes provided for IVF, there were technical differences. The DLN needle was more flexible and frequently deviated from the projected path as observed by ultrasound. The SLN may be preferable because it is technically easier to use; however, there may remain specific indications for the use of the DLN.


Metrical and non-metrical assessment of population affinity from the calcaneus.
To date, there are no metric standards for differentiating between population groups from measurements of the calcaneus in South Africa. Previously, some of the measurements of the calcaneus have been used for sex determination in Americans, Europeans, Italians and South Africans. However, the variations in the number of articular facet present on the superior surface of the calcaneus have been observed in different population groups. This study aims at investigating the potentials of measurements of the calcaneus in diagnosing population affinity and observes population variations of the number of articular facet present on its superior surface in indigenous South Africans and those of European descent. Nine measurements were taken from 180 non-pathological left calcanei in a sample of known sex and population affinity obtained from the Raymond A. Dart Collection of Human Skeletons. Three articular facet types were observed. A significantly higher incidence of type A was observed in South Africans of European descent (SAED) population group while type B predominated in the indigenous South African (ISA) population group. Type C even though rare was found only in ISA group. The metrical data were subjected to discriminant function analyses. The average accuracy in correct classification (81-89%) obtained for the discriminant function equations derived in this study may assist in the determination of population affinity when the calcaneus is present for analysis in forensic cases.


In Vitro Validation of Regional Circumferential Strain Assessment in a Phantom Aortic Model Using Cine Displacement Encoding With Stimulated Echoes MRI.
A novel application of cine Displacement ENcoding with Stimulated Echoes Magnetic Resonance Imaging (DENSE MRI) has recently been described to assess regional heterogeneities in circumferential strain around the aortic wall in vivo; however, validation is first required for successful clinical translation. To validate the quantification of regional circumferential strain around the wall of an aortic phantom using DENSE MRI. In vitro phantom study. Three polyvinyl alcohol aortic phantoms with eight axially oriented nitinol wires embedded evenly around the walls. 3 T; gradient-echo aortic DENSE MRI with spiral cine readout, gradient-echo phase-contrast MRI (PCMR) with Cartesian cine readout. Phantoms were connected to a pulsatile flow loop and peak DENSE-derived regional circumferential Green strains at 16 equally spaced sectors around the wall were assessed according to previously published algorithms. "True" regional circumferential strains were calculated by manually tracking displacements of the nitinol wires by two independent observers. Normalized circumferential strains (NCS) were calculated by dividing regional strains by the mean strain. Finally, DENSE-derived regional strain was corrected by multiplying regional DENSE NCS by the mean strain calculated from the diameter change on the PCMR. One-sample t-test, Paired-sample t-test, and analysis of variance with Bonferroni correction, coefficient of variation (CoV), Bland-Altman analysis; P < 0.05 was considered statistically significant. Aortic DENSE MRI significantly overestimated circumferential strain compared to the wire-tracking method (mean difference and SD 0.030 ± 0.014, CoV 0.31). However, NCS demonstrated good agreement between DENSE and wire-tracking data (mean difference 0.000 ± 0.172, CoV 0.15). After correcting the DENSE-derived regional strain, the mean difference in regional circumferential strain between DENSE and wire-tracking was significantly reduced to 0.006 ± 0.008, and the CoV was reduced to 0.18. For aortic phantoms with mild spatial heterogeneity in circumferential strain, the previously published aortic DENSE MRI technique successfully assessed the regional NCS distribution but overestimated the mean strain. This overestimation is correctable by computing a more accurate mean circumferential strain using a separate cine scan. 2 TECHNICAL EFFICACY: Stage 2.


Interleukin-4 and interleukin-13 enhance CCL26 production in a human keratinocyte cell line, HaCaT cells.
Eotaxin-2/CCL24 and eotaxin-3/CCL26 are CC chemokines and their receptor, CC chemokine receptor 3 is preferentially expressed on eosinophils. It was reported that vascular endothelial cells and dermal fibroblasts produced CCL26. However, the regulation of CCL24 and CCL26 production in keratinocytes has not been well documented. We investigated the expression and production of CCL24 and CCL26 in the human keratinocyte cell line, HaCaT cells. Reverse transcription and polymerase chain reaction was performed using these cells and Enzyme-linked immunosorbent assay was carried out using supernatant of these cells. The production of CCL24 in HaCaT cells was slightly enhanced by IL-4 and that of CCL26 was strongly enhanced by IL-4 and IL-13. Furthermore, TNF-alpha generated a synergistic effect on IL-4 enhanced CCL26 production. Dexamethasone, IFN-gamma and the p38 mitogen-activated protein kinase inhibitor SB202190 inhibited IL-4 enhanced CCL26 production. IL-4 enhanced production of CCL26 was inhibited by leflunomide and JAK inhibitor 1, but not by JAK3 inhibitor, which indicates that it is mediated by JAK1-STAT6-dependent pathway. This result also strongly suggests the involvement of the type 2 IL-4 receptor in IL-4 enhanced production of CCL26. These results suggest that keratinocytes are involved in the migration of CC chemokine receptor 3 positive cells such as eosinophils in a Th2-dominant situation like atopic dermatitis.


The effects of preexisting depression on cerebrovascular health outcomes in geriatric continuing care.
Previous studies have investigated depression as the cause and outcome of vascular deficit in elderly persons. The authors wanted to determine whether baseline depression is predictive of subsequent cardiovascular events in very elderly persons residing in a continuing care retirement community (n = 181). Controlling for demographic factors, both depression and the number of cardiovascular risk factors (CVRFs) at baseline were strongly predictive of stroke, whereas only CVRFs strongly predicted myocardial infarctions. Depression accounted for 12% of the variance in stroke incidence, beyond the contribution of CVRFs. Path analysis indicated that depression was also a partial moderator of the effect of CVRFs. In support of the vascular depression hypothesis, the study findings indicate that, for the oldest old, depression may be a strong predictor of future stroke. The presence of depression in elderly patients should alert physicians to carefully investigate other stroke risk factors and to integrate depression into an overall intervention regimen for reducing patients' risks for stroke.


Endothelial cytoskeletal elements are critical for flow-mediated dilation in human coronary arterioles.
Mitochondrial H2O2 contributes to flow-mediated dilation (FMD) in human coronary arterioles (HCA). We examined the hypothesis that the endothelial cytoskeleton plays a critical role in transducing endothelial wall shear stress into a stimulus for releasing mitochondrial ROS. Phallacidin together with alpha-, beta-tubulin antibodies and Mito-Tracker Red showed the proximity of F-actin, microtubules and mitochondria in endothelial cells. Cytochalasin D (CytoD) and nocodazole (Noc) disrupted endothelial F-actin and microtubules in HCA, respectively, concurrent with a reduction in the generation of cytosolic and H2O2 (hydroethidine and dichlorodihydrofluorescein fluorescence) and mitochondrial superoxide (mitoSox) during flow (control: 3.5 +/- 1.6, Cyto D: 0.51 +/- 0.2, Noc: 0.81 +/- 0.6). FMD, but not the dilation to bradykinin or papaverine, was reduced by Cyto D (26 +/- 10% vs. 56 +/- 3%) or Noc (26 +/- 11% vs. 58 +/- 7%). These results suggest that cytoskeletal elements are a critical component of the signaling mechanism linking endothelial shear stress and mitochondrial release of ROS in the human coronary microcirculation.


Changes within vascular bundles of rodent kidneys caused by different diets.
Morphological effects caused by two different diets (low protein-high water intake, and high protein-restricted water) on the vascular bundles in the outer medullary zone of the kidney were studied in the laboratory white mouse and in the golden spiny mouse (Acomys russatus, Muridae). In both rodents, when on a low protein-high water intake diet, considerable interstitial substance was found between the vasa recta of the bundles. No interstitial substance was found in animals on high protein-low water intake diet; as a result the vasa recta of the vascular bundle adhered closely. The low protein-high water intake diet caused a marked diuresis, low urine osmolality and low urinary urea concentration. It is assumed that the increase in interstitial substance between the vasa recta of the vascular bundle lowers the efficiency of the counter current barrier system for urea in the kidney and, as a consequence, the medullary urea gradient and urine concentrating capacity decreases. In animals on a high protein diet, the closely juxtaposed vasa recta assure an efficient countercurrent exchange, leading to accumulation and maintenance of a large urea gradient in the medulla and maximal urine concentration. It is suggested that the amount of interstitial material between the vasa recta of the vascular bundle might serve as a modulating factor for the urea concentration in the kidney.


Potentiation of CCl4 hepatotoxicity and lethality by chlordecone in female rats.
Female Sprague-Dawley rats (175-200 g) were maintained on a commercial powdered rat chow containing 0 or 10 ppm chlordecone (Kepone; CD). On day 15 of the dietary protocol, a single dose of CCl4 (5-100 microliters/kg) was administered i.p. in corn oil vehicle. Controls received corn oil vehicle only. Twenty-four hours after CCl4 administration, hepatotoxicity was assessed using biochemical, functional, and histopathological parameters. Serum enzymes (GPT, GOT, ICD and OCT) were elevated in a dose related manner in the animals receiving CD-CCl4 combination. CCl4 alone at the doses used had no marked effect. Centrilobular necrosis was observed in the animals receiving CD-CCl4 combination. Biliary excretion of phenolphthalein glucuronide (PG) and the rate of bile flow were decreased in a dose-dependent manner. Forty-eight hour LD50 of CCl4 was decreased 26-fold by CD pretreatment. These results indicate that CD potentiates CCl4 toxicity in female rats as well. Since the hepatic functional status is greatly compromised, the CD potentiated lethality is preceded by hepatic failure. Furthermore, female rats are sensitized to smaller doses of CCl4 in comparison to male rats.


Heat sensitivity and thermal adaptation of photosynthesis in liverwort thalli.
The effect of high temperatures on the photosynthetic apparatus of Preissia quadrata (Scop.) Nees, Conocephalum conicum (L.) Dum. and Marchantia polymorpha L. were investigated. changes in the activities of various photosynthetic reactions were followed by measuring light-dependent oxygen evolution, chlorophyll a fluorescence and light-induced absorbance changes at 518 nm.Mild heat treatment of the thalli led to reversible depression of photosynthesis; the period necessary for complete recovery depended on the extent of heat damage. Irreversible inactivation of photosynthesis after more severe heat stress was caused by damage of photosystem II. On principle, the pattern of reversible and irreversible heat inactivation of photosynthetic reactions in liverwort thalli resembles that observed in leaves of higher plants. However, in contrast to a number of Spermatophyta, exposure of liverwort thalli to high sublethal temperatures did not result in a significant increase in the heat stability of the photosynthetic apparatus indicating that the heat hardening capacity of hygrophytic hepatics is extremely low.


G3BP2: Structure and function.
Ras-GAP SH3 domain binding proteins (G3BPs) are a family of RNA-binding proteins that include G3BP1 and G3BP2 in mammals. The protein structure of G3BP2 allows it to bind with RNA or protein and regulate the nucleoplasmic shuttle, therefore participating in a variety of biological functions such as cell growth, differentiation and migration, and RNA and protein metabolism. G3BP2 is abnormally expressed in many tumors and diseases, such as breast cancer, lung cancer, prostate cancer, cardiac hypertrophy, and atherosclerosis. Many researchers have found that G3BP2 may be a potential therapeutic target. In this review, we examine the structure and expression regulation of G3BP2, and further summarize the function of G3BP2 from three aspects: RNA stabilization, protein subcellular localization, and stress granules assembling to provide a broader understanding of the role of G3BP2.


Comparative genomic and transcriptomic analyses of the Fuzhuan brick tea-fermentation fungus Aspergillus cristatus.
Aspergillus cristatus is the dominant fungus involved in the fermentation of Chinese Fuzhuan brick tea. Aspergillus cristatus is a homothallic fungus that undergoes a sexual stage without asexual conidiation when cultured in hypotonic medium. The asexual stage is induced by a high salt concentration, which completely inhibits sexual development. The taxon is therefore appropriate for investigating the mechanisms of asexual and sexual reproduction in fungi. In this study, de novo genome sequencing and analysis of transcriptomes during culture under high- and low-osmolarity conditions were performed. These analyses facilitated investigation of the evolution of mating-type genes, which determine the mode of sexual reproduction, in A. cristatus, the response of the high-osmolarity glycerol (HOG) pathway to osmotic stimulation, and the detection of mycotoxins and evaluation of the relationship with the location of the encoding genes. The A. cristatus genome comprised 27.9 Mb and included 68 scaffolds, from which 10,136 protein-coding gene models were predicted. A phylogenetic analysis suggested a considerable phylogenetic distance between A. cristatus and A. nidulans. Comparison of the mating-type gene loci among Aspergillus species indicated that the mode in A. cristatus differs from those in other Aspergillus species. The components of the HOG pathway were conserved in the genome of A. cristatus. Differential gene expression analysis in A. cristatus using RNA-Seq demonstrated that the expression of most genes in the HOG pathway was unaffected by osmotic pressure. No gene clusters associated with the production of carcinogens were detected. A model of the mating-type locus in A. cristatus is reported for the first time. Aspergillus cristatus has evolved various mechanisms to cope with high osmotic stress. As a fungus associated with Fuzhuan tea, it is considered to be safe under low- and high-osmolarity conditions.


Characterization of human joint proprioception by means of a threshold hunting paradigm.
A method has been developed to measure the proprioceptive performance of movement detection in human joints, with the threshold hunting paradigm commonly used in other sensory modalities. Methods applied in former studies regarding movement detection were very time consuming (hours), making them not applicable to patients. Using the threshold hunting paradigm, the subject changes the parameter value continuously around the threshold producing a threshold hunting curve, which itself might be valuable for investigation of movement detection performance. The method presented here, is very quick compared to other studies in this field, especially when velocity is hunted and the threshold values are very low. The threshold parameter value is stable since there is a control at any time over the subject's stimulus perception. Furthermore, a Monte Carlo simulation showed that hunting curves can clearly be distinguished from guessing. Also reliability is given. All these points allow to use the method to evaluate the proprioceptive performance of a single individual. Considering the results, the method described may be useful for basic and clinical investigations regarding the proprioceptive performance limits of movement detection aspects.


X-ray interference fringes from a weakly bent plane-parallel crystal with negative strain gradient.
Under the anomalous transmission condition in the Bragg mode, X-ray interference fringes were observed between two beams with different hyperbolic trajectories in a very weakly bent plane-parallel perfect crystal with negative strain gradient. The origin of the fringes was analysed based on the dynamical theory of diffraction for a distorted crystal. In the reflected beam from the entrance surface, the interference fringes were observed between once- and twice-reflected beams from the back surface. In the transmitted beam from the back surface, the interference fringes were observed between the direct beam and once-reflected beam from the entrance surface. In the emitted beam from the lateral surface, the interference fringes were observed between the beams after different numbers of reflections in the crystal. The multiply reflected beams were formed by a combined result of long propagation length along the beam direction with large divergence of the refracted beams when the strain gradient was negative. The period of these interference fringes was sensitive to very weak strain, of the order of 10-7.


Synaptic vesicle pools at the frog neuromuscular junction.
We have characterized the morphological and functional properties of the readily releasable pool (RRP) and the reserve pool of synaptic vesicles in frog motor nerve terminals using fluorescence microscopy, electron microscopy, and electrophysiology. At rest, about 20% of vesicles reside in the RRP, which is depleted in about 10 s by high-frequency nerve stimulation (30 Hz); the RRP refills in about 1 min, and surprisingly, refilling occurs almost entirely by recycling, not mobilization from the reserve pool. The reserve pool is depleted during 30 Hz stimulation with a time constant of about 40 s, and it refills slowly (half-time about 8 min) as nascent vesicles bud from randomly distributed cisternae and surface membrane infoldings and enter vesicle clusters spaced at regular intervals along the terminal. Transmitter output during low-frequency stimulation (2-5 Hz) is maintained entirely by RRP recycling; few if any vesicles are mobilized from the reserve pool.


[Sub-epitrochlear apophysis. A source of median nerve compression. Review of the literature].
The supracondylar process in an osseous spur located above the medial condyle of the humerus. It may be responsible for compression of the median, as well as the ulnar, nerves. Diagnostic must be directed in this direction whenever a deficit is found in the nerve distribution territory of one of these nerves.


Vitamin D Deficiency in Patients with Diabetes in French Guiana: Epidemiology and Relation with Microvascular and Macrovascular Complications.
Vitamin D (VD) insufficiency is common among patients with diabetes in French Guiana. The study aimed to evaluate the prevalence of VD deficiency in the different type of diabetes encountered and to analyze the relationship between VD deficiency and diabetes complications. An observational study was conducted between May 2019 and May 2020 in French Guiana, based on data from the CODIAM study (Diabetes Cohort in French Amazonia), describing the characteristics of patients with diabetes mellitus. Among 600 patients enrolled with diabetes, 361 had an available VD assay. The mean 25(OH)VD (hydroxycalciferol) level was 27.9 ng/mL. The level of VD was inversely proportional to the HbA1c (glycated hemoglobin) level. Patients with angina pectoris had a greater proportion of deficiencies VD < 20 ng/mL than those without angina. By contrast, patients with retinopathy had higher vitamin D concentrations than those without retinopathy. There was no association between vitamin D and arteriopathy, stroke, nephropathy and polyneuropathy. VD deficiency was more frequent in women, and in patients with a high school education. The prevalence of VD deficiency was high in patients with diabetes in French Guiana, emphasizing the importance of VD supplementation.


Prevalence, clinical characteristics and disability of migraine and probable migraine: a nationwide population-based survey in Korea.
Epidemiological data on probable migraine (PM) in Asia have rarely been reported. This study aimed to assess the prevalence, clinical characteristics, and disability of PM in comparison with strict migraine (SM) in Korea. The Korean Headache Survey (KHS) is a nationwide interview survey that investigates the status of headache disorders among adults aged 19-69. We used data from the KHS. In a representative sample of 1507 individuals, the one-year prevalence of SM was 6.0%, and that of PM was 11.5%. Most PM sufferers missed the criterion of typical headache duration (82.0%). Multivariable regression analyses revealed that PM sufferers had an increased odds ratio (OR) for mild headache intensity (OR = 2.08; 95% confidence interval (CI): 1.11-3.90) and decreased ORs for living in a small city (OR = 0.50; 95% CI: 0.26-0.94), living in a rural area (OR = 0.36; 95% CI: 0.14-0.92) and headache frequency five to nine days per month (OR = 0.29; 95% CI: 0.11-0.78) compared to SM sufferers. Some SM and PM sufferers experienced decreased activity (26.4% in SM vs. 18.0% in PM) and missed activity (12.1% in SM vs. 14.4% in PM) due to headache. PM is a prevalent headache disorder in Korea. Some sociodemographic and clinical characteristics of PM are different from those of SM.


Trends in endometrial cancer incidence and mortality in Sweden, 1960-84.
Trends in incidence of and mortality from invasive endometrial cancer in Sweden in 1960-84 were analyzed. The study was based on virtually all 20,371 patients given this diagnosis and 4,887 patients who died of the disease in that period. Only minor changes occurred in age-standardized incidence in pre-menopausal women, in whom the rates declined consistently during the last 15 years, especially in the youngest age groups. Among post-menopausal women, an early increase was followed by stable rates in women over 60 and decreasing rates at ages 50-59 years. In contrast, mortality rates decreased consistently over the study period. Multivariate regression analyses indicated that birth cohort was a more important determinant of incidence and mortality than was time period. The relative risk of developing endometrial cancer increased by about 20 percent in women born around 1900 as compared with 1880, and by an additional 40 percent from the 1910 cohort to the maximum risk attained in those born around 1930. In successively younger birth cohorts, the risk markedly and continuously declined. These strong birth-cohort effects after 1910 may be reasonably explained by the change from the risk-increasing estrogen-only replacement therapy introduced in the 1960s to the less harmful use, starting about 10 years later, of combined estrogen-progestogen regimens; and further, by the protective exposure of a large proportion of pre-menopausal women to oral contraceptives. Mortality, however, decreased steadily in successive cohorts from those born in 1890, indicating that the increase in incidence was referable mainly to non-lethal cancers.


Genotyping and identification of Cryptosporidium spp., Giardia duodenalis and Enterocytozoon bieneusi from free-range Tibetan yellow cattle and cattle-yak in Tibet, China.
To assess the prevalence and molecular characteristics of Cryptosporidium spp., Giardia duodenalis and Enterocytozoon bieneusi in natural grazing local breed cattle, 513 fecal samples from Tibetan yellow cattle and cattle-yaks were tested for these pathogens. Cryptosporidium, G. duodenalis and E. bieneusi in Tibetan yellow cattle prevalence were 0.7% (3/442), 3.8% (17/442) and 2.5% (11/442), respectively. Cryptosporidium bovis (n = 3), G. duodenalis assemblages A (n = 2) and E (n = 15) were identified based on sequence analysis. Among three E. bieneusi genotypes, I (n = 7), EbpC (n = 2) and CHC8 (n = 2) detected, EbpC was classified into Group 1, which has a significant zoonotic importance, whereas genotypes I and CHC8 belonged to Group 2. None of these pathogens was identified in cattle-yaks. The presence of zoonotic C. bovis, assemblage A and EbpC indicates Tibetan yellow cattle may be a potential spread source of intestinal pathogens with a zoonotic transmission risk. The relationships between natural free-range mode and the prevalence or genetic diversity of these pathogens need be confirmed in further studies.


The usefulness of F-18 deoxyglucose whole-body positron emission tomography (PET) for re-staging of renal cell cancer.
The use of whole-body PET for re-staging of renal cell carcinoma has not been investigated. The aim of the current study was to examine the diagnostic accuracy and clinical usefulness of whole-body PET imaging for re-staging of renal cell cancer. Clinical PET was performed for re-staging in 36 patients with advanced renal cell cancer. Written reports of imaging studies (including CT, MRI, US, plain film and bone scan), patient history, and extensive chart notes were used to define the clinical stage before PET (pre-PET stage). The written PET report was used to define the clinical stage after PET (PET stage). Reports were used to determine the accuracy of PET for re-staging renal cell cancer and for defining biopsy proven lesions. Clinical parameters and biopsy proven lesions served as reference for the accuracy of PET for re-staging renal cell cancer. PET classified the clinical stage correctly in 32/36 patients (89%) and was incorrect in 4/36 (11%) (sensitivity and specificity: 87% and 100%). In 20 patients, 25 suspicious lesions were biopsied within 3.2 +/- 6.7 months of the PET study. Of these, 17 were malignant and 8 were benign. PET correctly classified 21/25 (84%) of the biopsied lesions (sensitivity and specificity: 88% and 75%). PET re-stages renal cell cancer with a diagnostic accuracy of 89%. Its diagnostic accuracy for classifying biopsy proven anatomic lesions as malignant or benign was 84%. These findings suggest that PET is useful in characterizing anatomic lesions of unknown significance in patients with renal cell cancer.


High-Throughput Detection of mtDNA Mutations Leading to tRNA Processing Errors.
Some mutations in the tRNA genes of mitochondrial DNA (mtDNA) have been demonstrated to affect the processing of the mitochondrial transcriptome in human patients with mitochondrial disease. A recent analysis of mtDNA mutations in 527 human tumors revealed that approximately a quarter of the somatic mt-tRNA gene mutations lead to aberrant processing of the mitochondrial transcriptome in these tumors. Here, we describe a method, based on mtDNA mutations induced by the mtDNA mutator mouse, to map the sites that lead to transcript processing abnormalities. Mutations in the mtDNA are identified and quantified by amplicon-based mtDNA sequencing, and compared to the allelic ratios observed in matched RNASeq data. Strong deviation in the variant allele frequencies between the amplicon and RNASeq data suggests that such mutations lead to disruptions in mitochondrial transcript processing.


Deletions and single-base mutations within the carboxy-terminal region of the latent membrane protein 1 oncogene in Epstein-Barr virus-related gastric cancers of southern Japan.
The 30-base pair (bp) deletion of the cytoplasmic carboxy-terminal domain of the latent membrane protein 1 (LMP-1) gene was analyzed in 37 frozen tissues from patients with Epstein-Barr virus (EBV)-related gastric cancer and 18 throat washings from healthy adults in southern Japan. The 30-bp deletion was identified in 33 (91.7%) of 36 specimens of EBV-related gastric cancers and in 15 (83.3%) of 18 throat washings from healthy adults. In one case of gastric cancer, an additional 9-bp deletion was identified downstream of the 30-bp deletion. From the last transmembrane domain to the end of the carboxy terminal of LMP-1, mutations were examined in 37 cases of gastric cancers and in three cases of throat washings. Twenty-eight nonsilent mutations were identified in this region of EBV-related gastric cancer and throat washings. Five nonsilent mutations at positions 168,755, 168,746, 168,687, 168,357, and 168,355 were identified in all 30-bp-deleted cases of EBV-related gastric cancers and throat washings. However, these nonsilent mutations were not identified in three patients without the 30-bp deletion. Although the deletion and single-base mutations of the LMP-1 gene in gastric cancers and throat washings were similar to those of nasopharyngeal carcinoma in Taiwan and China, more single-base mutations were found in southern Japan. These data indicate that high prevalence of the 30-bp deletion of the LMP-1 gene in gastric cancers may reflect the prevalence of the deletion variant in the normal population in southern Japan.


Sertraline-induced hyperglycemia: case report.
Empirical studies with humans suggest that selective serotonin reuptake inhibitors (SSRIs) may, through increases in serotonergic activity, increase insulin secretion, increase insulin sensitivity, and lower serum glucose levels. Indeed, the potentially beneficial effects of SSRI treatment in diabetics are documented. However, we describe the case of a female, with diet-controlled, type 2 diabetes, whose glucose levels increased with exposure to sertraline.


The repeatability of 3-dimensional scapular kinematic analysis during bilateral upper extremity movements.
Although three-dimensional electromagnetic systems are widely used to evaluate the 3-dimensional scapular kinematics their reliability when testing bilateral upper extremity tasks is unknown. The purpose of this study was to investigate the repeatability of the scapular kinematic analyses using the Flock of Birds (FOB) system during bilateral upper extremity movements. Twenty-one volunteers without shoulder problems were included (aged 24.8 years; body mass index averaged 21.2 kg/m2) to the study. Scapular internal-external rotation, upward-downward rotation, and anterior-posterior tilt was recorded during bilateral arm elevation on sagittal, scapular and frontal planes. Measurements were repeated at 5-7 days intervals. Intra-session and inter-session repeatability were determined using intraclass correlation coefficients (ICC) scores and standard errors of measurements (SEM). The ICC scores were found to be 0.81 to 0.99 for intra-session measurements and 0.60 to 0.83 for inter-session measurements. The SEM scores were 0.8°-3.4° and 2°-7.2° for the intra and inter-session measurements respectively. The repeatability of the FOB system was excellent for the intra-session measurements, but it was weaker for the inter-session measurements. These results support the use of the FOB system for assessing scapular orientation but the analyses should be conducted more carefully when it is applied to the longitudinal measurements.


Dietary L-arginine and alpha-tocopherol reduce vascular oxidative stress and preserve endothelial function in hypercholesterolemic rabbits via different mechanisms.
Vascular oxidative stress brought about by superoxide radicals and oxidized low-density lipoproteins (oxLDL) is a major factor contributing to decreased NO-dependent vasodilator function in hypercholesterolemia and atherosclerosis. We investigated whether chronic administration of L-arginine (2% in drinking water) or of alpha-tocopherol (300 mg/day) improves endothelium-dependent vasodilator function and systemic NO production, reduces vascular oxidative stress, and reduces the progression of atherosclerosis in cholesterol-fed rabbits with pre-existing hypercholesterolemia. Systemic NO production was assessed as urinary nitrate excretion; oxidative stress was measured by urinary 8-iso-PGF2alpha excretion in vivo, by lucigenin-enhanced chemiluminescence of isolated aortic rings ex vivo, and by copper-mediated LDL oxidation in vitro. Endothelium-dependent relaxation was almost completely abrogated in cholesterol-fed rabbits. Urinary nitrate excretion was reduced by 46+/-10%, and 8-iso-PGF2alpha excretion was increased by 61+/-18% as compared to controls (each P <0.05). Vascular superoxide radical release stimulated by PMA ex vivo was increased by 273+/-93% in this group, and the lag time of LDL oxidation was reduced by 35+/-6% (each P <0.05). Treatment with L-arginine and alpha-tocopherol reduced intimal lesion formation (by 68+/-6 and 4+/-11%, respectively; P <0.05) and improved endothelium-dependent relaxation. Both treatments also normalized urinary 8-iso-PGF2alpha excretion. L-Arginine increased urinary nitrate excretion by 43+/-13% (P <0.05) and reduced superoxide radical release by isolated aortic rings to control levels, which was unaffected by vitamin E treatment. By contrast, vitamin E dramatically increased the resistance of isolated LDL to copper-mediated oxidation in vitro by 178+/-7% (P <0.05), which was only marginally prolonged by L-arginine. Intimal thickening was reduced by both treatments. We conclude that both L-arginine and alpha-tocopherol reduce the progression of atherosclerotic plaques in cholesterol-fed rabbits. However, while L-arginine increases NO formation and reduces superoxide release, alpha-tocopherol antagonizes mainly oxLDL-related events in atherogenesis. Thus, both treatments reduce urinary isoprostane excretion and improve endothelium-dependent vasodilation via different mechanisms.


Synchronous oscillations in the basal secretion of pancreatic-polypeptide and gastric acid. Depression by cholinergic blockade of pancreatic-polypeptide concentrations in plasma.
The effect of cholinergic blockade on the concentrations of pancreatic-polypeptide (PP) in plasma was studied in 19 patients with duodenal ulcer (DU) and 16 control subjects. PP concentrations increased with age both in control subjects and in DU patients. In the DU patients atropine or benzilonium, an antimuscarinic agent with minimal cerebral actions, reduced PP concentrations from 47 (8-220) to 28 (7-53) pmol/liter, n = 18, median and total range. In the control subjects atropine suppressed the PP concentrations from 17 (0-257) to 11 (0-41) pmol/liter, n = 15. Cholinergic blockade had only a minor effect in 1 patient and 1 control, both with high PP concentrations. Both in the DU patients and in the control group the suppression by the cholinergic blockade was most marked in subjects with elevated PP concentrations. Spontaneous acid and PP secretion were measured simultaneously in 25 DU patients. No correlation was found between median acid secretion and median concentrations of PP. However, in the individual patient a positive covariation was found between fluctuations in spontaneous acid secretion and fluctuations in PP concentration. P less than 0.005. We conclude that plasma concentrations of PP in the basal state are suppressible by cholinergic blockade and that PP concentrations fluctuate synchronously with the spontaneous secretion of gastric acid. These results suggest that PP concentrations in plasma before and after cholinergic blockade may possibly serve as indicator of abdominal vagal tone.


The molecular evolution of mammalian spermatogenesis.
The testis is a key male reproductive organ that produces gametes through the process of spermatogenesis. Testis morphologies, sperm phenotypes, and the process of spermatogenesis evolve rapidly in mammals, presumably due to the evolutionary pressure on males to give rise to their own offspring. Here, we review studies illuminating the molecular evolution of the testis, in particular large-scale transcriptomic studies, which were based on bulk tissue samples and, more recently, individual cells. Together with various genomic and epigenomic data, these studies have unveiled the cellular source, molecular mechanisms, and evolutionary forces that underlie the rapid phenotypic evolution of the testis. They also revealed shared (ancestral) and species-specific spermatogenic gene expression programs. The insights and available data that have accumulated also provide a valuable resource for the investigation and treatment of male fertility disorders - a dramatically increasing problem in modern industrial societies.