Propensity score-matched comparison of physical activity and quality of life between revision total hip arthroplasty and primary total hip arthroplasty.
Studies on physical activity (PA) after revision total hip arthroplasty (THA) are limited. It is important to assess PA levels as well as improvements in physical function and pain after revision THA. The purpose of the study was to compare accelerometer-measured PA and health-related quality of life (HR-QoL) in patients 1-3 years after revision or primary THA. We also clarified the relationship between measured PA and HR-QoL. This cross-sectional study included 64 patients who underwent revision THA and 188 who underwent primary THA 1-3 years earlier. Outcome measures were accelerometer-measured light PA, moderate-to-vigorous intensity PA, number of steps, questionnaire-based Oxford hip score, SF-8 physical and mental component scores. We conducted propensity-score matching for age, sex, comorbidities, body mass index, and postoperative follow-up duration and compared PA levels and HR-QoL scores between patients after revision THA and primary THA of each 50 patients. Based on propensity scores in the revision THA (68.3 years) and primary THA (67.8 years) groups, light PA, number of steps, and HR-QoL scores 1-3 years after revision THA were significantly lower than those after primary THA (P < 0.05). Moderate-to-vigorous intensity PA did not different between groups (P = 0.204). Measured light PA, moderate-to-vigorous intensity PA, and number of steps after re-THA were moderately correlated with HR-QoL scores. Increasing the time and frequency spent on light PA to the levels after primary THA may lead to an increase in overall PA levels after revision THA. A detailed understanding of PA, including light PA, in daily life and an approach that promotes activity levels are necessary.


A new species of Centruroides (Scorpiones, Buthidae) from Colima, Mexico.
As part of an ongoing survey of scorpion diversity in Colima, Mexico, the isolated mountain Cerro Grande, part of the Biosphere Reserve Sierra de Manantlán, was investigated. Centruroides possanii sp. nov., the fifth species of the genus from the state, was discovered during fieldwork in the massif and is described in the present paper. Physiographical and climatic features of Cerro Grande may restrict the range of this new species; thus, we hypothesized that it may be a microendemic species that requires priority conservation. The new species is not assigned to any Centruroides species group recognized because some of its morphological features do not fit the current diagnosis of any of these groups, and these different groups are non-monophyletic and consequently ill-diagnosed. The new species is profusely illustrated, particularly the hemispermatophore. A distribution map is presented along with the other two more common species distributed in Colima. Because only indirect data on the potency of its venom is available, the medical importance of this new species described here is yet to be known.


Identification of known drugs targeting the endoplasmic reticulum stress response.
The endoplasmic reticulum (ER), a multifunctional organelle, plays a central role in cellular signaling, development, and stress response. Dysregulation of ER homeostasis has been associated with human diseases, such as cancer, inflammation, and diabetes. A broad spectrum of stressful stimuli including hypoxia as well as a variety of pharmacological agents can lead to the ER stress response. In this study, we have developed a stable ER stress reporter cell line that stably expresses a β-lactamase reporter gene under the control of the ER stress response element (ESRE) present in the glucose-regulated protein, 78 kDa (GRP78) gene promoter. This assay has been optimized and miniaturized into a 1536-well plate format. In order to identify clinically used drugs that induce ER stress response, we screened approximately 2800 drugs from the NIH Chemical Genomics Center Pharmaceutical Collection (NPC library) using a quantitative high-throughput screening (qHTS) platform. From this study, we have identified several known ER stress inducers, such as 17-AAG (via HSP90 inhibition), as well as several novel ER stress inducers such as AMI-193 and spiperone. The confirmed drugs were further studied for their effects on the phosphorylation of eukaryotic initiation factor 2α (eIF2α), the X-box-binding protein (XBP1) splicing, and GRP78 gene expression. These results suggest that the ER stress inducers identified from the NPC library using the qHTS approach could shed new lights on the potential therapeutic targets of these drugs.


Arsenite-induced apoptosis of human neuroblastoma cells requires p53 but occurs independently of c-Jun.
Arsenite treatment of human SH-SY5Y neuroblastoma cells leads to an upregulation of caspase-3/7 activity and to the fragmentation of chromatin that is accompanied by elevated p53 and c-Jun levels. Expression of a truncated mutant of p53, p53DD, which interfered with the oligomerization of p53, suppressed the arsenite-induced upregulation of caspase-3/7 activity and the fragmentation of chromatin, indicating that p53 is required for arsenite-induced cell death. These data were corroborated by knockdown experiments of p53 following expression of a p53-specific short hairpin RNA. Likewise, expression of either p53DD or knockdown of p53 prevented caspase-3/7 activation and chromatin fragmentation induced by nutlin-3, a compound that prevents the interaction between p53 and the E3 ubiquitin ligase MDM2. Transcriptional upregulation of a chromatin-embedded p53-responsive reporter gene in either arsenite or nutlin-3 stimulated neuroblastoma cells revealed that the transcriptional activity of p53 was increased under these conditions. Expression of a c-Jun-specific short hairpin RNA failed to impair arsenite-induced caspase-3/7 activation and fragmentation of chromatin. Likewise, inhibition of c-Jun target gene expression by expression of a dominant-negative mutant of c-Jun did not interfere with arsenite-induced caspase-3/7 activation and chromatin fragmentation. However, this approach successfully reduced caspase-3/7 activity induced as a result of forced expression of a constitutively active mutant of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase (MEKK)-1. Together, these data show that the upregulation of p53 is causally linked with arsenite-induced cell death in neuroblastoma cells, whereas the upregulation of c-Jun is not part of this apoptotic signaling cascade.


On an ant - lizard interaction.
The myrmicine ant Crematogaster brevispinosa attacks juveniles and possibly adults of the iguanid lizard, Anolis lineatopus; bitten juveniles usually run away. A juvenile A. lineatopus caged together with 38 C. brevispinosa specimens died within hours due to attacks by these ants. On a study site in Kingston, Jamaica, fewer A. lineatopus were found to inhabit a patch densely occupied by C. brevispinosa than a structurally similar patch where this ant was not present. Similarly, fewer A. lineatopus eggs and anole egg-shells were found in the patch with C. brevispinosa than in that where this species was absent. These findings bear directly on the innate ant avoidance response of juvenile A. lineatopus demonstrated in the laboratory.


Erythrocyte antioxidant activity in human patients with Parkinson's disease.
Three groups have reported defective antioxidant mechanisms in substantia nigra of patients with Parkinson's disease, namely a decreased catalase and peroxidase activity, a reduction of glutathione and, more recently, a diminished nigral glutathione peroxidase activity. We decided to investigate these mechanisms in erythrocytes to determine whether these brain defects represent generalized or genetic aberrations, in which case they should also be present in blood cells. The glutathione cycle has been investigated (reduced and oxidized glutathione, glutathione reductase and peroxidase) plus the activities of catalase and superoxide dismutase. The basal malonaldehyde content of erythrocytes was used as an index of endogenous lipid peroxidation. None of the above-mentioned parameters were found altered in erythrocytes of parkinsonians, suggesting that no genetic or generalized biochemical abnormalities underly the deficiencies detected in substantia nigra.


Effect of erythromycin on the oro-caecal transit time in man.
Erythromycins often cause gastrointestinal side-effects due to an increase in motility or to change in the intestinal bacterial flora. In order to evaluate the effect of erythromycin on gastrointestinal motility. 11 healthy volunteers were given placebo, erythromycin stearate (ES) 1000 mg or a therapeutically equivalent single dose of erythromycin acistrate (EA.2'-acetyl erythromycin stearate) 800 mg in a double-blind trial. The oro-caecal transit time was measured using the hydrogen breath test with lactulose as the substrate. The transit time was estimated from the H2-peak (ppm) in end-expiratory breath by two methods, t1 representing the "front" and t2 the "bulk" of lactulose reaching the colon. t1 was 51 min in the placebo group, 38 min in the EA and 31 min in the ES group (p less than 0.05, ES vs placebo). t2 was 74 min, 64 min, and 46 min, respectively (p less than 0.05, ES vs placebo). The difference between EA and ES was also significant. Six subjects in the ES group but none in the EA group recorded adverse gastrointestinal effects attributable to medication. It was concluded that erythromycin shortens the oro-caecal transit time in man and that EA effects the transit time slightly less than ES.


Quality-of-life assessment in phase III clinical trials of gemcitabine in non-small-cell lung cancer.
Health-related quality-of-life (QOL) endpoints in clinical trials provide decision makers with a more comprehensive picture of a specific treatment than activity-related endpoints alone. Such endpoints are increasingly being reported in cancer clinical trials. We reviewed phase III clinical trials that involved gemcitabine in the treatment of unresectable non-small-cell lung cancer. A systematic literature search was undertaken and 16 phase III clinical trials were found in which gemcitabine therapy was included in a treatment arm and QOL was an endpoint. Twelve of the 16 trials compared a gemcitabine-based treatment with a non-gemcitabine-based treatment. Not all data were reported in the trials, and the findings are mixed. However, a review of these 12 trials generally shows that gemcitabine-containing chemotherapy treatments had either no different or more favourable QOL outcomes than non-gemcitabine-containing chemotherapy treatments. Ten of the 16 trials that were reviewed had a primary endpoint or objective that was not QOL. Of these ten trials, only four concluded that one treatment arm could be therapeutically favoured over another in terms of the non-QOL primary endpoint. Two of the trials reported no difference in QOL and two reported that QOL favoured the arm that was therapeutically favoured. Many more trials will need to be conducted in order to conclude that gemcitabine-containing arms are associated with a more desirable QOL than non-gemcitabine-containing arms and that QOL necessarily favours the therapeutically favoured arm in the treatment of non-small-cell lung cancer.


Percutaneous dilational tracheostomy in neurosurgical patients.
Tracheostomy is often performed in patients requiring long-term mechanical ventilation after severe neurological injury. Percutaneous dilational tracheostomy (PDT) is an alternative to traditional surgical tracheostomy (TST) for creating a tracheostomy. We compared these techniques in neurosurgical patients and assessed the impact on cost and clinical course. We conducted a retrospective chart review of 81 neurosurgical patients treated with either PDT (n = 43) or TST (n = 38). Several clinical endpoints were examined, including days intubated prior to tracheostomy, length of hospital stay, procedural complications, and overall procedure costs. No serious complications occurred with PDT, whereas two minor postoperative complications occurred in the TST group. The time from intubation to tracheostomy was 8 days for the PDT group versus 13 days for the TST group (p < 0.001), and the time from intubation to discharge from the hospital was 20 days for the PDT group compared to 27 days for the TST group (p < 0.005). In our institution, the average cost of PDT was $980.69 less than the cost for TST. PDT appears to have a low incidence of complications in neurosurgical patients and may shorten the length of hospitalization and the overall cost compared with TST.


Male factor infertility trends throughout the last 10 years: Report from a tertiary-referral academic andrology centre.
Trends of male factor causes of couples' infertility over time have been poorly investigated. We investigated trends in the causes of pure male factor infertility (MFI) throughout the last 10 years in a tertiary-referral academic andrology center. Baseline characteristics at first presentation from a cohort of 1647 consecutive male factor infertility patients belonging to primary infertile couples between 2008 and 2018 have been comprehensively collected over time. Seven major causes of male factor infertility were identified: varicocoele; history of cryptorchidism; hypogonadism (primary and secondary); obstructive azoospermia; genetic abnormalities; other causes (large group including the remnant conditions of known causes); and idiopathic infertility. Rates of different male factor infertility causes over the study period were analyzed. Multivariable logistic regression models tested the likelihood of male factor infertility causes over time. Estimated trends were explored graphically. Of all, varicocoele was found in 615 (37.3%), cryptorchidism in 124 (7.5%), genetic abnormalities in 61 (3.7%), hypogonadism in 165 (10%), obstructive conditions in 55 (3.3%), other causes in 129 (7.8%) patients, and idiopathic infertility in 498 (30.3%) patients, respectively. Over time, a reduction in the proportions of cryptorchidism and varicocoele (all P < 0.001) cases was observed, along with an increase in the proportions of hypogonadism, other causes of MFI and idiopathic cases (all P ≤ 0.01). Rates of genetic and obstructive cases remained stable. The observed trends were confirmed at logistic regression models. A decreasing trend in the proportions of varicocoele and cryptorchidism at first presentation was observed over the last 10 years; conversely, the proportions of idiopathic cases, hypogonadal patients, and infertile men presenting with other male factor infertility causes significantly increased over the same time frame at a single tertiary-referral academic andrology center.


Assessment of changes in Streptococcus pyogenes levels using N-acetylgalactosamine-6-sulfatase marker and pharyngeal airway space with appliance therapy in mouth breathers - An ELISA-based study.
The frequency of adenotonsillar hypertrophy in mouth-breathing children when compared to the average found in the general population is considered to be higher. Mouth breathing is considered as one of the causative factors for tonsillitis in children. Through continuous irritation on tonsillar wall, tonsils swell up and inflammation develops. The purpose of the study is to evaluate Streptococcus pyogenes count using colony-forming units (CFUs) and N-acetylgalactosamine-6-sulfatase side chain marker on ELISA (enzyme linked immunosorbent assay) in mouth breathers and to establish its correlation with pharyngeal airway space pre- and post-oral screen appliance therapy. A total number of 24 (n) mouth breathers aged between 5 and 12 years were included in the study and given oral screen appliance therapy. The subjects were evaluated for the various parameters before the delivery of a habit-breaking appliance and then reevaluated for the same parameters (presence of S. pyogenes and its counts, size of tonsils, and pharyngeal airway space dimensions) after 6 months of appliance usage. A statistically significant difference was seen in levels of S. pyogenes using ELISA and CFUs. Furthermore, statistically significant difference was observed in Friedman tonsil scoring and pharyngeal airway space and pre- and post-oral screen appliance therapy. Oral screen appliance therapy reduced the frequency of occurrence of tonsillitis in mouth breathers by decreasing the counts of S. pyogenes bacteria. Upper and lower pharyngeal airway space dimensions were increased after 6 months of appliance therapy in mouth breathers.


Corrigendum: The Extract of Sonneratia apetala Leaves and Branches Ameliorates Hyperuricemia in Mice by Regulating Renal Uric Acid Transporters and Suppressing the Activation of the JAK/STAT Signaling Pathway.
[This corrects the article DOI: 10.3389/fphar.2021.698219.].


Requirements of milk intake and intake of milk components for pre-weaning growth of Pelibuey lambs.
The objective of the present study was to determine the needs of milk intake (MI) and their components (i.e., lactose, fat, protein, and energy) to increase the average daily gain (ADG) of Pelibuey lambs during the pre-weaning period. Data of 62 lambs were used (35 males and 27 females; 32 of single lambing and 30 twins). All lambs were housed in individual pens with their mothers during the first 45 days post-lambing, without access to mother's food. Every 10 d, MI was estimated by the double lamb weighing method, and then, the intake of each milk component was calculated, considering both milk chemical composition and its estimated intake. The ADG was associated with MI and its components through a linear regression analysis. All milk variables were highly (P < 0.05; 0.69 ≤ r ≤ 0.85) correlated with ADG. The ADG explained (P < 0.0001) between 48 and 72% of the variation observed for MI and its components, being lower for fat intake and higher for MI. Given the positive slope parameter (β1), an increase of one kilogram of body weight required intakes of 3.1 kg of milk, 117 g of fat, 203 g of protein, 187 g of lactose, or 16.8 MJ of energy. In conclusion, Pelibuey lambs to gain one kilogram of live weight during the pre-weaning period need to consume 3.1 kg of milk having an adequate amount of protein, fat, lactose, and energy.


Very-nearly-closed-circuit anaesthesia. A computer analysis.
A simple analogue study of inspired oxygen concentrations in a circle absorber system was made. Good agreement with clinical observations and figures reported by others was obtained. The suggested low-flow regime was nitrous oxide 1 litre/min and oxygen 0.6 litre/min, which provides inspired oxygen concentrations between 35-25%, over a range of oxygen consumption from 150-300 ml/min. The use of such low flows is economical and reduces atmospheric pollution in the operating theatre.


Chalcone-benzoxaborole hybrids as novel anticancer agents.
In this study, we report the synthesis of a series of chalcone-benzoxaborole hybrid molecules and the evaluation of their anticancer activity. Their anticancer potency and toxicity were tested on three human cancer cell lines and two normal cell lines. The 4-fluoro compound 15 was found to be the most potent compound with an IC50 value of 1.4μM on SKOV3 cells. The 4-iodo compound 18 and 3-methyloxy-4-amino compound 47 showed good potency on SKOV3 cells while exhibiting low toxicity on normal cells. This work extended the application of benzoxaboroles to the field of anticancer research.


Studies on tryptophan accumulation in brain during methiothepin-induced enhancement of 5-hydroxyindole synthesis.
The elevation of brain tryptophan, 5-hydroxytryptophan and 5-hydroxyindoles (serotonin + 5-hydroxyindole acetic acid) that results from a tryptophan load is potentiated by prior administration of methiothepin, a serotonin receptor antagonist. Co-administration of valine with tryptophan attenuates these effects even in animals receiving methiothepin pretreatment. Administration of methiothepin and tryptophan to rats with widespread reduction of brain 5-hydroxyindole levels resulting from raphe lesions or 5,7-dihydroxytryptamine pretreatment still enabled brain tryptophan levels to rise considerably above the sum of increases found in animals receiving one or the other. Following transection of the spinal cord, the cranial portion still exhibited enhanced uptake of tryptophan and 5-hydroxyindole synthesis following methiothepin plus tryptophan treatment, however, both these events were absent in the caudal segment. Apparently, enhanced tryptophan uptake can proceed in the presence of minimal neuronal activity; however, when nerve impulse flow is eliminated, both 5-hydroxyindole synthesis and tryptophan uptake is impaired.


Teratogenic effects in rabbits of simultaneous exposure to ochratoxin A and aflatoxin B1 with special reference to microscopic effects.
To elucidate the teratogenic effects, ochratoxin A (OTA) and aflatoxin B1 (AFB1) were dissolved in corn oil and administered in combination to New Zealand White rabbits during 6-18 days of gestation orally with the dose levels of OTA+AFB1, 0.05+0.05 and 0.1+0.1mg/kg body weight. To assess pathomorphological features of the anomalies, the fetal serial sections were histologically examined. There was no mortality in any of the treated groups. Body weights and body weight gains of dams in the combined treatment groups were comparable with those of controls and individual treatments. The mean crown to rump lengths in both the combination dose groups and mean fetal weights in high dose combination group were significantly decreased. In the high dose combination, there was increase in the percent of implants resorbed and significant increase in the incidence of visceral anomalies. The combination treatment resulted in various gross, skeletal and visceral anomalies such as wrist drop, scoliosis, bent metacarpals, rudimentary ribs, cardiac defects and microphthalmia. There was a dose-related increase in the percent of litters showing the histopathological changes in the fetal tissues. The incidence of histopathological changes in the tissue sections prepared from fetal liver, kidneys, brain, heart and eyes was found increased in the high dose combination group. The comparative evaluation of the results of combination versus individual treatments revealed that certain anomalies observed in the individual treatment of OTA such as knuckling of fetlock, rudimentary tail or agenesis of tail, wavy ribs, hydrocephalus and agenesis of kidney and AFB1 as enlarged eye sockets and enlarged liver were absent in the combination treatment. However, some new manifestations such as cardiac defects and scoliosis were seen. The results of the present study indicated that in combination, OTA and AFB1 have antagonistic interaction. The presence of subtle lesions histologically due to an interference with normal development suggested that microscopic examination of the fetal tissues could provide additional, useful information to a developmental toxicity study.


Case study: recovery of ancient nuclear DNA from toe pads of the extinct passenger pigeon.
A variety of DNA extraction methods have been employed successfully to extract DNA from museum specimens. Toe pads are a common source of ancient DNA in birds, as they are generally not an informative character and can be removed without significant destruction of precious specimens. However, the DNA in these tissues is often highly degraded, both by natural postmortem decay and due to treatment by preservatives. In this case study chapter, we describe the use of both a commercial DNA extraction method and a silica-based method to extract ancient DNA from desiccated toe pads from the extinct passenger pigeon, Ectopistes migratorius. Successful amplification of nuclear DNA was achieved from both methods, representing the first nuclear DNA sequence recovered from this extinct species. We describe simple modifications to both protocols that we employed during the DNA extraction process.


Health risk assessment of eight heavy metals in nine varieties of edible vegetable oils consumed in China.
Eight heavy metals, namely Cu, Zn, Fe, Mn, Cd, Ni, Pb and As, in nine varieties of edible vegetable oils collected from China were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES) and graphite furnace atomic absorption spectrometry (GF-AAS) after microwave digestion. The accuracy of procedure was confirmed by certified reference materials (GBW10018 and GBW08551). The relative standard deviations were found below 10%. The concentrations for copper, zinc, iron, manganese, nickel, lead and arsenic were observed in the range of 0.214-0.875, 0.742-2.56, 16.2-45.3, 0.113-0.556, 0.026-0.075, 0.009-0.018 and 0.009-0.019 μg g(-1), respectively. Cadmium was found to be 2.64-8.43 μg/kg. In general, iron content was higher than other metals in the investigated edible vegetable oils. Comparing with safety intake levels for these heavy metals recommended by Institute of Medicine of the National Academies (IOM), US Environmental Protection Agency (US EPA) and Joint FAO/WHO Expert Committee on Food Additives (JECFA), the dietary intakes of the eight heavy metals from weekly consumption of 175 g of edible vegetable oils or daily consumption 25 g of edible vegetable oils for a 70 kg individual should pose no risk to human health.


Factors Associated with HPV Vaccine Awareness in a Population-Based Sample of Hispanic Women in Puerto Rico.
The objective of this study was to investigate the factors associated with HPV awareness among women aged 16 to 64 years, among underserved minority Hispanic women living in Puerto Rico. A population-based, cross-sectional sample of 566 women, ages 16 to 64 years, living in the San Juan metropolitan area were surveyed regarding sexual behavior, HPV knowledge, and HPV vaccine uptake. Data was analyzed using descriptive statistics and multivariate logistic regression. Overall, 64.8 % of the women in the sample had heard about the HPV vaccine. Among those in the recommended catch-up vaccination age range (16-26 years, n = 86), 4.7 % had received at least one dose of the HPV vaccine. Of those aware of the availability of the HPV vaccine, most had learned about it through the media, whereas, only 39.6 % had learned about it from a physician. Multivariate logistic regression analysis showed that HPV awareness (OR 8.6; 95 % CI 5.0-14.8) and having had an abnormal Pap smear (OR 2.0; 95 % CI 1.2-3.4) were associated with HPV vaccine awareness (p < 0.05). HPV vaccine awareness among Hispanic women in the San Juan metropolitan area of Puerto Rico continues to be low. Strong recommendations from physicians and participation in HPV vaccine educational efforts are essential if the rate of HPV vaccination is to increase in the targeted population. Compared to the USA, and to their US Hispanic counterparts, a health disparity with regard to HPV vaccine awareness and coverage is evident in Puerto Rico; targeted action to deal with this disparity is urgently needed.


Liquid-Flowing Graphene Chip-Based High-Resolution Electron Microscopy.
The recent advances in liquid-phase transmission electron microscopy represent tremendous potential in many different fields and exciting new opportunities. However, achieving both high-resolution imaging and operando capabilities remain a significant challenge. This work suggests a novel in situ imaging platform of liquid-flowing graphene chip TEM (LFGC-TEM) equipped with graphene viewing windows and a liquid exchange system. The LFGCs are robust under high-pressure gradients and rapid liquid circulation in ranges covering the experimental conditions accessible with conventional thick SiNx chips. LFGC-TEM provides atomic resolution for colloidal nanoparticles and molecular-level information limits for unstained wet biomolecules and cells that are comparable to the resolutions achievable with solid-phase and cryogenic TEM, respectively. This imaging platform can provide an opportunity for live imaging of biological phenomena that is not yet achieved using any current methods.


Effects of tumor promoters on the rate and commitment to terminal differentiation of subpopulations of murine keratinocytes.
The effects of skin-tumor-promoting and -nonpromoting agents on the kinetics of terminal differentiation of subpopulations of keratinocytes differing in buoyant density isolated from mice (SENCAR) that are very sensitive to 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion were investigated. Topical pretreatment of dorsal skin with complete (TPA), first-stage (calcium ionophore A23187) and second-stage (mezerein) tumor promoters, but not the hyperplastic agent ethylphenylpropiolate, accelerated the rate of terminal differentiation of keratinocytes with densities less than 1.074 g/cm3, but had little effect on cells with a greater density. Within 8.5 hr of TPA treatment, a period preceding mitosis, a large percentage of the most dense basal-cell keratinocytes (greater than or equal to 1.074 g/cm3) were converted to cells with a lower density, with a reduced plating efficiency and with an increased rate of differentiation, suggesting that TPA induces a subpopulation of basal cells to commit to terminal differentiation, and accelerates the rate of differentiation of committed cells.


Bioprocess development for extraction and purification of cellulases from Aspergillus niger 3ASZ using statistical experimental design techniques.
The amount of cellulosic materials is large and may lead to environmental pollution, so they can be converted into useful materials for use in food or energy. Statistical design (Plackett-Burman and Box-Behnken) was the main topic of this study and was used to optimize the effect of environmental factors on cellulase production by Aspergillus niger. Cellulase production using Plackett-Burman was 6.86-fold higher than the production of cellulase using the basal medium. B0X-Benken showed an increase in the cellulase production equal to 18 times compared to the basal medium, where the cellulase produced had an activity equal to 79.4 U/mL/min. Ammonium sulfate precipitation was applied to the crude enzyme, followed by sequential fractionation with an Amicon system. The Amicon was used to demonstrate the final volume, total enzyme activity, specific activity, purification fold, and yield of cellulase (partially purified enzyme). Numerous cellulolytic enzymes are abundant in Aspergillus species. All of the data showed that Aspergillus sp. might be a reliable source of industrially and economically useful cellulases. By statistically calculating the relevance of a large number of elements in one experiment using a multifactorial statistical design, time may be saved while still maintaining the validity of each component.


Observations on the fumarate reductase system in Haemonchus contortus and their relevance to anthelmintic resistance and to strain variations of energy metabolism.
Fumarate reductase activity in a thiabendazole-resistant strain of Haemonchus contortus was found to be significantly lower than that from a susceptible strain. However, the fumarate reductase activity in a mebendazole-resistant strain did not differ from that in the susceptible strain, even though it was cross-resistant to thiabendazole. Published reports of fumarate reductase activity in strains of H. contortus susceptible or resistant to benzimidazoles were reassessed. A second, unrelated Australian thiabendazole-resistant strain also proved to have significantly diminished fumarate reductase activity, whereas two American strains, one resistant to thiabendazole and one to cambendazole, possess fumarate reductase activities indistinguishable from corresponding susceptible strains. It therefore appears that the phenomenon of benzimidazole resistance cannot be generally correlated with diminished fumarate reductase activity, although in the specific case of the Australian thiabendazole-resistant strains it may be a contributory factor.


MRI demonstration of subarachnoid neurocysticercosis simulating metastatic disease.
We present a patient with neurocysticercosis with spinal subarachnoid spread who presented with lower back pain and progressive numbness and weakness of the left leg. MRI of the spine simulated metastasis. MRI of the brain demonstrated a "bunch of grapes" appearance in the basal cisterns, characteristic of cysticercosis.


Pyloric gland-type tubular adenoma superimposed on intraductal papillary mucinous tumor of the pancreas. Pyloric gland adenoma of the pancreas.
We report a rare case of pyloric gland-type tubular adenoma of the main pancreatic duct. It was a grossly visible polypoid nodule and was composed of closely packed pyloric-type glands. This adenoma was present within an intraductal papillary mucinous adenoma (IPMA). In this IPMA lesion, aggregations of pyloric-type glands were occasionally observed, and most of the cells including ductal lining cells expressed pyloric gland-type mucin. The IPMA of the present case showed more extensive pyloric gland metaplasia or differentiation than commonly noted in IPMAs. We consider this pyloric gland-type tubular adenoma to be derived from a selective growth of IPMA cells showing pyloric gland metaplasia.


Erratum to: An updated genome annotation for the model marine bacterium Ruegeria pomeroyi DSS-3.
[This corrects the article DOI: 10.1186/1944-3277-9-11.].


Study protocol to assess the impact of an integrated nutrition intervention on the growth and development of children under two in rural Bangladesh.
The period from birth to two years is the "critical window" for achieving optimal growth and development. An inadequate quality and quantities of complementary foods, poor child-feeding practices and infection negatively impact the growth of under-twos. Approximately one-third of under-fives in developing countries are stunted; many are also micronutrient deficient. An estimated 6% of mortalities among under-fives can be prevented by ensuring optimal complementary feeding. The objective of the study was to assess the ability of a 12-month integrated nutrition intervention to improve the nutritional status (length-for-age Z-score) of 6 to 12-month-old children in rural Bangladesh. In this community-based randomized controlled trial, the intervention group received a package of interventions that includes, food vouchers; to prepare egg-based nutritious snacks (suji firni for < 1-year-olds, suji halwa for > 1-year-olds), micronutrient powder to fortify children's food at home, child feeding counselling and water, sanitation and hygiene (WASH), behaviour change communication. The control group received routine health messages provided by the government. Baseline and endline surveys were conducted; Data collection was performed monthly on children's growth, food voucher utilization, child feeding and morbidity. In addition, we assessed the cognitive development of the children after 12 months of intervention. This trial aims to explore whether an integrated nutrition intervention can mitigate childhood stunting during the critical window of opportunity in rural Bangladesh. The results may provide robust evidence to improve the linear growth of children in developing countries. The study was retrospectively registered on August 17, 2018 and is available online at ClinicalTrials.gov (ID: NCT02768181).


Reply to: "The partner-an underutilized facilitator to support healthy gestational weight gain".
Facilitators and barriers influencing weight management behaviours were identified in our meta-synthesis of qualitative research entitled "Facilitators and barriers influencing weight management behaviours during pregnancy: a meta-synthesis of qualitative research". This manuscript is in response to the letter submitted by Sparks et al. regarding that work. The authors highlight the importance of including partners into intervention design when addressing weight management behaviours. We agree with the authors that it is important to include partners into intervention design and further research is granted to identify facilitators and barriers affecting their influence over women. As per our findings, the influence of the social context goes beyond the partner and we suggest that future interventions should address other relevant people in women's contexts such as parents, other relatives, and close friends.


Simultaneous approach and avoidance learning in the teleost marine fish Serranus scriba Cuv.
The ability of the fish to discriminate between constant light (the conditional stimulus of food) and flickering light (the conditional stimulus of a painful electric shock) administered in random order during the same experimental sessions was investigated. Approaching the light for food and avoiding the shock by moving away from the light could be tought simultaneously, approach learning being faster.


Evidence for distinct primase and helicase domains in the 63-kDa gene 4 protein of bacteriophage T7. Characterization of nucleotide binding site mutant.
Gene 4 of bacteriophage T7 encodes two co-linear proteins, the 56- and 63-kDa gene 4 proteins. The 56-kDa protein translocates 5' to 3' on single-stranded DNA using nucleotide hydrolysis for energy and is a helicase. The 63-kDa gene 4 protein catalyzes all of the activities of the 56-kDa gene 4 protein and, in addition, catalyzes the synthesis of oligoribonucleotides on single-stranded DNA. Two conserved residues in a putative nucleotide binding site of the 63-kDa gene 4 protein were mutated by substituting Val and Met for wild-type residues Gly and Lys, at positions 317 and 318, respectively. The mutant 63-kDa gene 4 protein lacks the ability to catalyze the hydrolysis of a nucleoside 5'-triphosphate in a single-stranded DNA-dependent reaction and inhibits nucleotide hydrolysis by wild-type gene 4 proteins. The mutant primase contains 0.4% of the primase activity of the 63-kDa gene 4 protein on M13 single-stranded DNA and 12% of the wild-type primase activity on an oligonucleotide with a single primase recognition site. Addition of wild-type 56-kDa gene 4 protein stimulates the mutant primase activity over 50-fold on M13 single-stranded DNA and 8-fold on oligonucleotides. This increase in primase activity correlates with an increase in the affinity of the mutant primase-wild-type helicase complex for single-stranded DNA template.


Effect of methodological quality measures in spinal surgery research: a metaepidemiological study.
Methodological quality measures of trials in meta-analyses have been shown to influence the pooled effect sizes in several medical fields. However, for spinal surgery, influence of quality measures has not been assessed. The purpose of this study was to analyze the influence of quality measures in studies on effectiveness in spinal surgery. A metaepidemiological study was performed on meta-analyses within spinal surgery. A systematic search was performed in MEDLINE, Cochrane Database, and EMBASE in August 2009. The effect sizes, defined as risk of positive clinical outcome, of trials included in the meta-analyses were assessed. The differences in effect sizes were calculated as risk differences (RDs). Relation of the RDs to potential quality measures such as sponsoring, randomization, allocation concealment, blinding, and study size was assessed with metaregression adjusted for multiple testing. Seven reviews consisting of 118 studies were included. Data provided by the systematic reviews alone were insufficient to analyze the effect of quality measures. Metaregression analysis of 76 of the individual trials reporting clinical outcome, though, showed that sample size, strict randomization, and outcome blinding were significant quality measures influencing study effect. Risk difference of effect from validly randomized studies was higher compared with not validly randomized and comparative observational trials (5.4%; 95% confidence interval [CI], 1.2-9.6; p=.044). Studies with adequate observer blinding showed a 7.2% lower RD (95% CI, 0.8-13.7; p=.049). For each increase of 100 patients, the RD decreased 3.6% (95% CI, 0.5-6.8; p=.098). Contrary to basic methodological assertions, formal and strict randomization appeared to produce a significantly higher RD in spinal surgery research. Sufficient sample size and observer blinding, on the other hand, led to a lower RD as expected. These findings imply that effect of quality measures assessed in metaepidemiological studies should not be too easily translated to research in spinal surgery.


Absence of intramolecular disulfides in the structure and function of native rat glucocorticoid receptors.
The presence of intramolecular disulfides in different functional states of the native glucocorticoid receptor in the absence of added oxidants has been examined on nonreducing SDS-polyacrylamide gels. Possible disulfides were trapped by the reaction of thiols in crude receptor solutions with methyl methanethiolsulfonate or iodoacetamide. The presence of diffuse bands at lower molecular weights than either the fully reduced or the thiol-blocked species for both the intact 98-kDa receptor and the 42-kDa chymotryptic fragment was diagnostic of an intramolecular disulfide(s) that had undergone thiol-disulfide rearrangements. However, both the rearrangements and the formation of intramolecular disulfides were found to occur only with denatured receptors during gel analysis. It appears that the thiols normally complexed with zinc in the zinc fingers may be recruited for disulfide bond formation. Finally, even when a documented intramolecular disulfide was formed in solutions of the native protein, thiol-disulfide rearrangements did not occur. The tertiary structure of the receptor is thus constituted in a manner that not only limits the formation of disulfides but also prevents the usually facile rearrangements of disulfide bond-containing structures to receptor forms that may have greatly reduced activity. Therefore, although intramolecular disulfide bonds may be of transitory importance, the structural or functional changes of native glucocorticoid receptors that are associated with steroid binding, activation, and dissociation of heat shock protein 90 neither involve nor require the formation or reduction of stable intramolecular disulfides.


"Testing Can Be Done Anywhere": A Qualitative Assessment of Targeted Community-Based Point-of-Care Early Infant Diagnosis of HIV in Lusaka, Zambia.
Delayed HIV diagnosis in HIV-exposed infants (HEIs) results in missed opportunities for early antiretroviral therapy (ART), causing significant morbidity and mortality. Early infant diagnosis (EID) depends on the availability of accessible and reliable testing services. We explored the acceptability, appropriateness, and feasibility of deploying a targeted community-based point-of-care (POC) EID testing model (i.e., "community POC model") to reach high-risk mother-infant pairs (MIPs) in Lusaka, Zambia. We conducted in-depth interviews with a purposive sample of health care workers, study staff, and caregivers in high-risk MIPs at 6 health facilities included in a larger implementation research study evaluating the community POC model. We defined "high-risk MIPs" as mothers who did not receive antenatal testing or an attended delivery or infants who missed EID testing milestones. Interviews were audio-recorded, translated, and transcribed verbatim in English. Content and thematic analysis were done using NVivo 10 software. Health care workers (n=20) and study staff (n=12) who implemented the community POC model noted that the portability and on-screen prompts of the POC platform made it mobile and easy to use, but maintenance and supply chain management were key to field operations. Respondents also felt that the community POC model reached more infants who had never had EID testing, allowing them to find infants with HIV infection and immediately initiate them on ART. Caregivers (n=22) found the community POC model acceptable, provided that privacy could be ensured because the service was convenient and delivered close to home. We demonstrate the acceptability, appropriateness, and feasibility of implementing the community POC model in Zambia, while identifying potential challenges related to client privacy and platform field operations. The community POC model may represent a promising strategy to further facilitate active HIV case finding and linkage to ART for children with undiagnosed HIV infection in the community.


Correlates of Blood Pressure Awareness, Treatment, and Control Among Adults 50 Years or Older by HIV Status in Northwestern Tanzania.
The objective of this study was to describe the increasing incidence and risk of cardiovascular disease among persons living with HIV (PLWH) in Sub-Saharan Africa. We also used data to compare hypertension (a common NCD among PLWH) outcomes between PLWH and HIV-uninfected individuals among older adults in Northwestern Tanzania. Hypertension is increasingly common in Sub-Saharan Africa and a leading cause of cardiovascular disease for PLWH. Among those with hypertension, PLWH have a 50% higher risk of incident myocardial infarction compared to the general population. In response to the rising incidence of these non-communicable diseases (NCDs) among PLWH, recently, the Joint United Nations Program on HIV/AIDS supported the integration of NCD care into routine clinical care for HIV. However, data are lacking on levels of awareness of hypertension status, diagnosis, and antihypertensive medication adherence. Given the higher likelihood of elevated blood pressure among PLWH, there is an urgent need to implement interventions to improve blood pressure control in this population. Researchers should evaluate treatment barriers at multiple levels including health system, healthcare providers, and patients' level and tailor evidence-based interventions to increase achievement of blood pressure control for PLWH.


Comparison of magnetic resonance cholangiography and percutaneous transhepatic cholangiography in the evaluation of bile duct strictures after cholecystectomy.
Percutaneous transhepatic cholangiography (PTC) has been the preferred investigation to delineate the anatomy of the biliary tract in a patient with a bile duct stricture after cholecystectomy. Recently magnetic resonance cholangiography (MRC) has been described to evaluate the obstructed biliary tract. This paper reports a comparison of MRC with PTC in evaluating patients with an iatrogenic bile duct stricture. This was a prospective study of 26 patients who had surgery for a bile duct stricture after cholecystectomy. Before operation all patients underwent both MRC and PTC, the results of which were compared with the intraoperative findings. Both PTC and MRC were comparable with regard to image quality, detection of intrahepatic bile duct dilatation, assessment of the level of injury and detection of abnormalities such as intraduct calculi, cholangitic liver abscesses and atrophy of liver lobes. MRC provided additional information in four patients, including detection of associated fluid collections (n = 3) and portal hypertension (n = 1). In eight patients more than one puncture had to be performed during PTC to delineate the complete anatomy. MRC is an accurate and non-invasive imaging procedure for preoperative evaluation of patients with a bile duct injury after cholecystectomy, and is capable of providing additional information which may not be available with PTC.


Awake Craniotomy for Resection of Brain Metastases: A Systematic Review.
Surgery for brain metastases aims to reduce mass effect and achieve local control through maximizing resection. There is increasing recognition that awake craniotomy (AC) is especially relevant for resection of brain metastases in eloquent areas. This study seeks to examine the neurologic outcomes of using AC for brain metastases resection. A systematic search for studies examining the role of AC in patients with brain metastases was conducted via PubMed without limitations on the year of publication, language, or study design, using the following search terms: (cerebral OR brain) and (metastases OR tumor) and (awake OR intraoperative OR eloquent OR supramarginal). Studies were included if patients underwent AC for resection of brain metastases and data on pre- and postoperative neurologic function were available. Seven studies published between 2001 and 2017 with 104 patients who underwent 107 ACs were identified. Gross total resection was achieved in 61% of patients, supramarginal resection was achieved in 32%, and subtotal resection was achieved in 7%. Immediately after operation, 73% of patients experienced no change or improvement in neurologic outcomes, whereas 27% experienced worsening. In the long term, 96% of those with postoperative worsening of function experienced improvements in neurologic function. Most patients experienced improvements in neurologic function immediately after AC, and most patients that experienced short-term worsening of neurologic function after the procedure showed excellent recovery. AC should be considered as a technique to optimize outcomes in brain metastases in eloquent areas.


The great society and health: policies for narrowing the gaps in health status between the poor and the nonpoor.
The "Great Society" may be characterized as a loosely knit program of policies for domestic reform, promulgated by the Johnson Administration in adaptation of the general philosophy and strategies of the New Deal, the Fair Deal, and the New Frontier to certain conditions of the middle 1960s. Among these conditions were demographic, social, political, and economic dimensions, both immediate and long term. The program was marked by some diversity in the strategies of reform and in the particulars of implementing legislation, but also by a general underlying view of the state of American society, the requisites for participation in the benefits of the society, and the appropriate role of the federal government in supporting prosperity and assuring freedom.


Benign uterine mass-discrimination from leiomyosarcoma by a preoperative risk score: a multicenter cohort study.
Discrimination of uterine leiomyosarcoma (LMS) and leiomyoma (LM) prior to surgery by basic preoperative characteristics and development of a preoperative leiomyosarcoma score. A predominantly prospective cohort of 826 patients with LM from a clinical institution and an outpatient center was included in the study. Further a predominantly retrospective cohort of 293 patients with LMS was included from the counseling database of the German Clinical Center of Excellence for Genital Sarcoma and Mixed Tumors (DKSM, University Medicine Greifswald, Germany). We analyzed and compared anamnestic, epidemiological and clinical findings between both cohorts. Tenfold cross-validated logistic regression and random forest was performed on the 80% training set. The preoperative LMS score (pLMS) was developed based on logistic regression and independently evaluated by analyzing the area under the receiver operating characteristic curve (AUC) with the 20% test set. In the LMS cohort, 63.1% had initially surgery for presumed LM and only 39.6% of endometrial biopsies revealed LMS. Key features for LMS discrimination were found to be bleeding symptoms: intermenstrual bleeding [RRc = 2.71, CI = (1.90-3.49), p < 0.001], hypermenorrhea [RRc = 0.28, CI = (0.15-0.50), p < 0.001], dysmenorrhea [RRc = 0.22, CI = (0.10-0.51), p < 0.001], postmenstrual bleeding [RRc = 2.08, CI = (1.30-2.75), p < 0.001], suspicious sonography [RRc = 1.21, CI = (1.19-1.22), p < 0.001] and the tumor diameter (each centimeter difference: β = 0.24, SD = 0.04, p < 0.001). pLMS achieved a mean cross-validated AUC of 0.969 (SD = 0.019) in the training set and an AUC of 0.968 in the test set. The presented score is based on basic clinical characteristics and allows the prediction of LMS prior to a planned surgery of a uterine mass. In case pLMS is between - 3 and + 1, we suggest subsequent diagnostics, such as endometrial biopsy, color Doppler sonography, LDH measurement, MRI and transcervical biopsy.


Current management of reflex sympathetic dystrophy syndrome (complex regional pain syndrome type I).
Although no major advances have occurred in the curative treatment of reflex sympathetic dystrophy syndrome (RSDS), new pathogenic insights may soon lead to innovative approaches, which may also prove effective in alleviating some forms of neuropathic pain. Preventing nerve compression and ischemia-reperfusion injury constitute valuable measures for preventing RSDS. Vitamin C administration can also prevent RSDS, together with clonidine in high-risk patients. Short-term glucocorticoid therapy has been found effective in preventing RSDS after stroke but has not been evaluated in other situations. Beneficial effects of bisphosphonates have been documented in several placebo-controlled trials. Placebo-controlled trials of ketamine and spinal cord stimulation are in order to confirm or refute the promising results obtained in open-label studies. Mirror visual feedback was introduced recently for the rehabilitation of patients with RSDS but needs to be evaluated in randomized controlled trials.


Predictive value of tumor budding in head and neck squamous cell carcinoma: an update.
Head and neck squamous cell carcinoma forms an anatomically and functionally complex group of malignancies. The significant local aggressiveness and frequent regional relapses motivate ongoing research to identify more reliable and sensitive prognostic and predictive biomarkers. One emerging area of cancer biology is the evaluation of tumor budding at the advancing invasive front of various types of epithelial cancers. Recent studies suggest that tumor budding is a relatively common phenomenon in cancer progression and that it may have important prognostic implications for patients due to its potential to provide valuable insights into the biology and clinical behavior of head and neck cancer. In this review, we aim to provide information about tumor budding in head and neck squamous cell carcinoma. Thus, we hope to shed light on the complex biology of these malignancies, as well as aiding diagnostic, classification, and better characterization and thereby, looking for new avenues for improving patient outcomes.


Urban mining of terbium, europium, and yttrium from real fluorescent lamp waste using supercritical fluid extraction: Process development and mechanistic investigation.
There is a significant global push towards recycling of waste electrical and electronic equipment (WEEE) to enable the circular economy. In this study an environmentally sustainable process using supercritical carbon dioxide as the solvent, along with a small volume of tributyl-phosphate-nitric acid (TBP-HNO3) adduct as the chelating agent, is developed to extract rare earth elements (REEs) from fluorescent lamp waste. It is found that mechanical activation using oscillation milling improves extraction efficiency. To elucidate the process mechanism, an in-depth characterization of solids before and after the process using transmission electron microscopy(TEM) and X-ray photoelectron spectroscopy (XPS)is performed. Furthermore, UV visible spectroscopy is performed to determine the coordination chemistry of the rare earths of interest, i.e., yttrium, europium, and terbium during the complexation with TBP-HNO3 adduct. It is found that Al3+ and Ca2+ cations from the aluminium oxide (Al2O3) and hydroxyapatite (Ca5(PO4)3OH) present in the fluorescent lamp waste compete with REEs in reacting with TBP-HNO3 adduct; hence, REE extractions from real fluorescent lamp waste is less than previously reported extractions from synthetic feeds. Not only can management of fluorescent lamp waste help conserve natural resources and protect ecosystems, but it can also facilitate efficient utilization of materials and promote the circular economy.


Mapping and assessment of future changes in the coastal and marine ecosystem services supply in Lithuania.
Assessing and mapping ecosystem services (ES) became an integral part of coastal and marine management practices. Hence, quantitative and validated approaches are lacking, especially to address future conditions. The objective of this study is to apply further existing and develop new methodological frameworks to quantitatively assess and map the current and future supply of 3 ES in the coastal zone of Lithuania: coastal flood protection, nutrient regulation, and maintenance of nursery conditions. For coastal flood ES modelling, 2 time periods (1990 and 2018) and 4 scenarios (A0, A1 A2, A3 - based on future socio-economic changes in Lithuania) were analysed. The coastal flood protection ES model was validated (r2 = 0.30) using tree cover density. The results showed spatial differences among the analysed periods but no statistical differences. High supply areas are located in the southern coastal area, while the central part displays a low supply. For nutrient regulation and maintenance of nursery conditions, 7 time periods were analysed: a historical period and 6 scenarios based on Representative Concentration Pathway 4.5 and 8.5 and 3 Shared Socioeconomic Pathways. The nutrient regulation ES model was validated (r2 = 0.85) using in situ nutrient. Statistical differences were observed for this ES, but a similar spatial distribution of high and low supply areas. A decrease in the supply was observed comparing the historical period and future scenarios. Maintenance of nursery conditions was validated (r2 = 0.72) based on the protection status of the coastal zone. Results show no statistical differences and similar spatial patterns among the periods. Rocky and sandbank areas show a high supply for this ES. Limitations of our work are mainly related to the resolution of the utilised indicators. Nevertheless, the information obtained from our models can support spatial planning and decision-making processes.


Serum total cholesterol, HDL cholesterol and blood pressure levels in 15-year-old adolescents in eastern Finland.
Serum total cholesterol, HDL-cholesterol and blood pressure were studied among 15-year-old school children in Eastern Finland. The mean serum total cholesterol was 4.47 mmol/l in boys and 4.86 mmol/l in girls; mean HDL-cholesterol was 1.29 mmol/l and 1.46 mmol/l, respectively. The mean blood pressure was 135/65 mmHg in boys and 126/67 mmHg in girls. Obese children had higher blood pressure and lower HDL-cholesterol levels than others. Among boys sexual maturation decreased the HDL-cholesterol level. Children whose parents had histories of cardiovascular disease did not have higher cholesterol or higher blood pressure levels than other children. Children at high risk apparently cannot be screened on the basis of parents' history of cardiovascular diseases.


Biomineralization of gold: biofilms on bacterioform gold.
Bacterial biofilms are associated with secondary gold grains from two sites in Australia. 16S ribosomal DNA clones of the genus Ralstonia that bear 99% similarity to the bacterium Ralstonia metallidurans-shown to precipitate gold from aqueous gold(III) tetrachloride-were present on all DNA-positive gold grains but were not detected in the surrounding soils. These results provide evidence for the bacterial contribution to the authigenic formation of secondary bacterioform gold grains and nuggets.


Support for a smoke-free bylaw in parks and on beaches.
In September 2010, Vancouver, Canada enacted a smoke-free bylaw in parks and on beaches. To examine demographic and attitudinal factors associated with the public opinion on Vancouver's outdoor smoke-free bylaw. From 496 randomly selected Vancouver residents, information on demographics, smoking status, and opinions and support for or opposition to the smoke-free bylaw were obtained by telephone surveys. Approximately 84.2% of the sample endorsed the legislation; a greater proportion of non-smokers supported the bylaw than smokers (88.6% vs. 52.0%). In multivariate analysis, demographic variables significantly associated with supporting the smoke-free bylaw were being female, having completed community college/university or Post Graduate work (as compared to high school education or less), and being a nonsmoker. Furthermore, adjusting for demographic variables, all opinions regarding the smoke-free bylaw were significantly associated with its support, with the exception of the belief that the bylaw would increase stigma towards smokers. These findings suggest strong public support in Vancouver for the smoke-free bylaw in parks and on beaches. Jurisdictions considering such legislation should address attitudes which can promote or hinder its adoption. Examination of such policy support on diverse groups within the population may enhance the development of equitable public health policy.


A Reimbursement System Based on a 48-Hour Target Time for Surgery Shortens the Waiting Time for Hip Fracture Fixation in Elderly Patients.
To evaluate whether a pay-for-performance reimbursement system, aimed at expediting surgical fixation of hip fractures in elderly patients, has, in fact, succeeded in shortening the waiting time for surgery. Retrospective analysis of prospectively collected data. Academic Level II trauma center. One hundred fifty patients older than 70 years with femoral neck fractures (OTA/AO 31 A1-A3). Implementation of a reimbursement system which incentivizes meeting a 48-hour target time for surgical fixation of hip fractures in elderly patients. Medical records of 75 consecutive patients operated on 1 year before the implementation of the reimbursement system were compared with records of 75 consecutive patients operated on 1 year after the implementation of the reimbursement system. The collected data included age, sex, American Society of Anesthesiologist score, time from injury to hospital admission, time from admission to surgery, reason for surgical delay beyond 48 hours, perioperative complication rate, and length of postoperative hospitalization. Patients' mean age, sex distribution, American Society of Anesthesiologist score, and time from injury to hospital admission were similar in both groups. The average waiting time for surgery shortened from a mean of 77 hours before implementing the reimbursement system to 28 hours after the implementation (P < 0.001). Before the reimbursement system implementation, 41% of the surgeries were delayed beyond 48 hours due to medical causes, compared with 20% only after the implementation (P < 0.001). Fewer patients developed perioperative complications in the postimplementation group in comparison with the preimplementation group (9% vs. 13%, respectively); however, because the study was not powered to examine differences in complication rate, the significance of this difference remains unclear. A reimbursement system which incentivizes meeting a 48-hour target time for surgery has led to a substantial shortening in the waiting time for surgical fixation of hip fractures in elderly patients in our institution.


The m6A modification-mediated OGDHL exerts a tumor suppressor role in ccRCC by downregulating FASN to inhibit lipid synthesis and ERK signaling.
Metabolic reprogramming is a hallmark of cancer, and the impact of lipid metabolism as a crucial aspect of metabolic reprogramming on clear cell renal cell carcinoma (ccRCC) progression has been established. However, the regulatory mechanisms underlying the relationship between metabolic abnormalities and ccRCC progression remain unclear. Therefore, this study aimed to identify key regulatory factors of metabolic reprogramming in ccRCC and provide potential therapeutic targets for ccRCC patients. Potential metabolic regulatory factors in ccRCC were screened using bioinformatics analysis. Public databases and patient samples were used to investigate the aberrant expression of Oxoglutarate dehydrogenase-like (OGDHL) in ccRCC. The function of OGDHL in ccRCC growth and metastasis was evaluated through in vitro and in vivo functional experiments. Mechanistic insights were obtained through luciferase reporter assays, chromatin immunoprecipitation, RNA methylation immunoprecipitation, and mutagenesis studies. OGDHL mRNA and protein levels were significantly downregulated in ccRCC tissues. Upregulation of OGDHL expression effectively inhibited ccRCC growth and metastasis both in vitro and in vivo. Furthermore, FTO-mediated OGDHL m6A demethylation suppressed its expression in ccRCC. Mechanistically, low levels of OGDHL promoted TFAP2A expression by inhibiting ubiquitination levels, which then bound to the FASN promoter region and transcriptionally activated FASN expression, thereby promoting lipid accumulation and ERK pathway activation. Our findings demonstrate the impact of OGDHL on ccRCC progression and highlight the role of the FTO/OGDHL/TFAP2A/FASN axis in regulating ccRCC lipid metabolism and progression, providing new targets for ccRCC therapy.


Effects of strength training on mobility in adults with cerebral palsy: A systematic review.
Many adults with cerebral palsy report experiencing early-onset decline in mobility and independence. The role of strength training to combat this is not well understood. To examine the effects of strength-training interventions on muscle strength and functional outcomes for adults with CP using the ICF framework. A systematic review was conducted following standardized guidelines and using key words including: adults, cerebral palsy in combination with resistance or strength training, and ambulation and function related key words. Selection criteria included: (a) adults (mean age 18+ years) with CP, (b) strength training intervention, and (c) at least one activity or participation outcome measure. 26 retrieved articles were retained for full review. Data on strength training protocols were extracted and compared to national guidelines. Outcome measures were classified within ICF domains. Six articles met the inclusion criteria. These articles were of high research quality and consistent with recommended training protocols for adults with CP. Positive gains in muscle strength were reported across studies. Changes within the activity ICF dimension were inconsistent, with 2 of the 6 studies observing increases in self-selected walking speed. Findings indicate training benefits for adults with CP. However, a small sample (n = 111 across all included studies) and the absence of extended training regimens and follow-up hindered conclusive results. High consistency in training protocols and outcome measures allowed for critical discussion on key research questions regarding the impact of strength training and subsequent gains in function within ICF domains.


Comparing groups of time dependent data using locally weighted scatterplot smoothing alpha-adjusted serial T-tests.
In statistical analysis of time series researchers often pick key points from curves and run the venerable analysis of variance (ANOVA) to determine if a difference exists between groups. However, this approach fails to compare most of the data across time and thereby may throw out potentially valuable inferences. This study illustrates a novel method termed LOESS alpha-adjusted serial t-testing (LAAST). LAAST employs locally weighted scatterplot smoothing (LOESS) on the data, serial correlation to make alpha adjustments, and point-wise Welch's t-tests to determine regional significance when comparing groups of time dependent data. It was expected that LAAST gives similar results to random field theory (RFT) based inferences while overcoming its shortcomings with respect to longitudinal data analysis. Two data sets were analyzed with LAAST and RFT. The first contained two groups of five simulated random sinusoidal waveforms such that both inline time-series and equivalent time-offset longitudinal conditions were represented. The second data set was comprised of publicly available medial gastrocnemius forces from individuals with (N = 27) and without (N = 16) pain. Results for both data sets indicated similar corrected alpha levels regardless of analysis type, but the applied alpha level corrections were less conservative for LAAST than RFT or Holm-Bonferroni corrections, but often more conservative than Hochberg corrections. Analysis methods employing functional ANOVA and RFT have enabled researchers to effectively run comparisons between groups at all points within the time series and are gaining popularity. However, in some correction methods for multiple comparisons the alpha level correction can in turn lead to inflation of type II error. These results suggest that LAAST is comparable to RFT while also being appropriate for longitudinal type time series data analysis. Additionally, its use of Welch's t-tests improves its validity on non-normally distributed data.


Nutrition and cancer. Recent developments.
Cancer cachexia is a complex syndrome that results in involuntary weight loss, even in the face of adequate nutritional intake. The profound metabolic abnormalities associated with cancer cachexia affect a large percentage of animals with cancer even before any clinical signs are seen. This paraneoplastic syndrome results in alterations in carbohydrate, lipid, and protein metabolism that, if left untreated, decrease the animal's quality of life and lead to a poor response to cancer therapy. An understanding of the metabolic abnormalities associated with cancer cachexia is of paramount importance to the practicing veterinarian to determine an accurate prognosis and to choose the optimal type of intravenous fluids and nutritional therapy for each patient. Although research identifying the optimal diet for cancer-bearing dogs and cats is still underway, some general principles apply. The first is that the patient should receive nutritional elements orally whenever possible. When oral feeding is not possible, nasogastric, gastrostomy, and jejunostomy tube feeding are viable options. When feeding by the gastrointestinal tract is not possible, parenteral feeding is a practical alternative.


Case report: fast reversal of severe osteoporosis after correction of excessive levothyroxine treatment and long-term follow-up.
This case report describes a 38-year-old woman, who presented with bilateral femoral stress fractures and osteoporosis after years of excessive levothyroxine treatment. Her bone health was restored rapidly and long-lasting with the reduction of levothyroxine dosage. No bone-active treatment was warranted. Hyperthyroidism is a known risk factor for osteoporosis and fractures. Recent studies on patients with serum thyrotropin-suppressive therapy have not, however, indicated adverse effects on bone during long-term follow-up. This case report describes long-term follow-up data of a clinically euthyreoid patient, who developed symptomatic osteoporosis due to excessive levothyroxine treatment. After correction of levothyroxine dosage, her bone mineral density (BMD) and previously elevated serum osteocalcin levels normalized rapidly and she remained free from fractures during 23 years of follow-up over menopause. Excessive TSH suppression contributed to the secondary osteoporosis in this patient; BMD normalized after dose reduction of levothyroxine and no fractures occurred during 23 years' follow-up. Some patients develop severe osteoporosis if they are over-substituted with levothyroxine, and decent follow-up of patients with levothyroxine supplementation is mandatory.


Central neurotoxic effects of guanethidine: altered serotonin and enkephalin neurons within the area postrema.
This study reveals that the 5-HT and enkephalin cell body population of the area postrema (AP) is dramatically reduced via exposure to the peripherally circulating neurotoxin guanethidine. Efforts to restore cell body numbers to control levels, with colchicine and monoamine oxidase inhibitors, subsequent to guanethidine treatment are ineffective. However, 5-HT and enkephalin immunostaining of surrounding bulbar nuclei appears normal, implying that the neurotoxic effect of guanethidine is restricted to the AP. In addition, gamma-aminobutyric acid and neurotensin immunostaining within the AP appears normal, subsequent to guanethidine treatment, suggesting that the neurotoxic effect is restricted to specific AP cell populations.


Modeling bacterial immune systems: strategies for expression of toxic - but useful - molecules.
Protection of bacterial cells against virus infection requires expression of molecules that are able to destroy the incoming foreign DNA. However, these molecules can also be toxic for the host cell. In both restriction-modification (R-M), and the recently discovered CRISPR/Cas systems, the toxicity is (in part) avoided through rapid transition of the expression of the toxic molecules from "OFF" to "ON" state. In restriction-modification systems the rapid transition is achieved through a large binding cooperativity, and low translation rate of the control protein. On the other hand, CRISPR array expression in CRISPR/Cas systems involves a mechanism where a small decrease of unprocessed RNAs leads to a rapid increase of processed small RNAs. Surprisingly, this rapid amplification crucially depends on fast non-specific degradation of the unprocessed molecules by an unidentified nuclease, rather than on large cooperativity in protein binding. Furthermore, the major control elements that are responsible for fast transition of R-M and CRISPR/Cas systems from "OFF" to "ON" state, are also directly involved in increased stability of the steady states of these systems. We here discuss mechanisms that allow rapid transition of toxic molecules from the unproductive to the productive state in R-M and CRISPR/Cas systems. The main purpose of this discussion is to put relevant theoretical and experimental work in a perspective that points to general similarities in otherwise mechanistically very different bacterial immune systems.


The release of 5-hydroxytryptamine from rabbit small intestine in vitro.
1. A method is described by which the lumen of intestinal segments may be perfused separately and simultaneously under identical conditions of perfusion pressure and temperature, and the rate of appearance of 5-hydroxytryptamine (5-HT) into the serosal fluid measured.2. 5-HT appeared in the serosal fluid from quiescent segments of rabbit intestine at a rate of about 4.0 ng/cm intestine/hr and about 14.0 ng/cm intestine/hr from segments performing active peristaltic movements.3. For both quiescent and active segments, when the perfusion fluid contained a monoamine oxidase inhibitor, nialamide (Niamid), the rate of appearance of 5-HT was increased and if, in addition, 5-HT was present in the perfusion fluid the rate of appearance of 5-HT in the serosal fluid was even greater.4. The rate of appearance of 5-HT from the intestine of rabbits pretreated with reserpine was about 0.8 ng/cm intestine/hr and Niamid only slightly increased this rate. However, if 5-HT as well as Niamid were present the rate of appearance of 5-HT was about 6.0 ng/cm intestine/hr.5. Possible explanations for these findings are discussed.


Translation and validation of the Korean version of Family Scale.
Familism is an important and complex clinical issue because of its significant impact on family caregiving of elders. The purpose of this study was to examine the psychometric properties of a Korean-translated version of the Family Scale (FS-K) among Korean adults. A descriptive, cross-sectional survey design was used. A panel of experts completed the initial translation into Korean and back-translated the FS. Upon establishment of the content and translation equivalence between English and Korean versions of the FS, psychometric properties were evaluated for reliability and construct validity with a sample of 577 adults. The internal consistency of FS-K was found to be acceptable, and Cronbach's alpha coefficient was .75. For construct validity, the mean scores of the FS-K were significantly different for gender and marital status (p < .05). For the FS-K, six components were extracted, accounting for 53.9% of the variance. Results of this study suggest that the FS-K can be used as a reliable and valid measure of familism among Korean adults. The FS-K will contribute to the understanding of familism for family caregivers caring for elders in both research and clinical practices.


The comparison of steel and titanium dynamic compression plates used for internal fixation of 256 fractures of the tibia.
A consecutive series of 256 fractures of the shaft of the tibia treated by internal fixation with a narrow dynamic compression plate (DCP) is presented. In 123 cases the plates were made of titanium and in 133 cases they were made of stainless-steel. In both groups the age distribution of the patients, the period between operation and the final review and the time of removal of the metal were comparable. All these fractures resulted from skiing accidents. Eighty-six per cent of the 256 fractures were reviewed between 1 and 2 years after the operation. Ninety-one per cent of the titanium group and 93 per cent of the stainless-steel group showed full recovery without any loss of movement in the joints. In both groups there was the same number of refractures, which were chiefly due to subsequent accidents. There were no cases of local wound infection, osteitis or non-union. Furthermore, there was no difference to be seen between the radiological patterns of fracture healing in the two groups. In this series stainless-steel and titanium plates gave the same excellent results.


BMP signalling controls the malignant potential of ascites-derived human epithelial ovarian cancer spheroids via AKT kinase activation.
Epithelial ovarian cancer (EOC) cells have the ability to form multi-cellular aggregates in malignant ascites which dramatically alters cell signalling, survival, and metastatic potential. Herein, we demonstrate that patient ascites-derived EOC cells down-regulate endogenous bone morphogenetic protein (BMP) signalling by decreasing BMP ligand expression when grown in suspension culture to form spheroids. Enforced BMP signalling in these cells via constitutively-active BMP type I ALK3(QD) receptor expression causes the formation of smaller, more loosely-aggregated spheroids. Additionally, ALK3(QD)-expressing spheroids have an increased rate of adhesion and dispersion upon reattachment to substratum. Inhibition of endogenous BMP signalling using recombinant Noggin or small molecule inhibitor LDN-193189, on the other hand, opposed these phenotypic changes. To identify potential targets that impact the phenotype of EOC spheroids due to activated BMP signalling, we performed genome-wide expression analyses using Affymetrix arrays. Using the online Connectivity Map resource, the BMP signalling gene expression signature revealed that the AKT pathway is induced by activated BMP signalling in EOC cells; this finding was further validated by phospho-AKT immuno-blotting. In fact, treatment of EOC spheroids with an AKT inhibitor, Akti-1/2, reduced BMP-stimulated cell dispersion during reattachment as compared to controls. Thus, we have identified AKT as being one important downstream component of activated BMP signalling on EOC spheroid pathobiology, which may have important implications on the metastatic potential of this malignancy.


Factors predisposing to humoral autoimmunity against brain-antigens in health and disease: Analysis of 49 autoantibodies in over 7000 subjects.
Circulating autoantibodies (AB) against brain-antigens, often deemed pathological, receive increasing attention. We assessed predispositions and seroprevalence/characteristics of 49 AB in > 7000 individuals. Exploratory cross-sectional cohort study, investigating deeply phenotyped neuropsychiatric patients and healthy individuals of GRAS Data Collection for presence/characteristics of 49 brain-directed serum-AB. Predispositions were evaluated through GWAS of NMDAR1-AB carriers, analyses of immune check-point genotypes, APOE4 status, neurotrauma. Chi-square, Fisher's exact tests and logistic regression analyses were used. Study of N = 7025 subjects (55.8 % male; 41 ± 16 years) revealed N = 1133 (16.13 %) carriers of any AB against 49 defined brain-antigens. Overall, age dependence of seroprevalence (OR = 1.018/year; 95 % CI [1.015-1.022]) emerged, but no disease association, neither general nor with neuropsychiatric subgroups. Males had higher AB seroprevalence (OR = 1.303; 95 % CI [1.144-1.486]). Immunoglobulin class (N for IgM:462; IgA:487; IgG:477) and titers were similar. Abundant were NMDAR1-AB (7.7 %). Low seroprevalence (1.25 %-0.02 %) was seen for most AB (e.g., amphiphysin, KCNA2, ARHGAP26, GFAP, CASPR2, MOG, Homer-3, KCNA1, GLRA1b, GAD65). Non-detectable were others. GWAS of NMDAR1-AB carriers revealed three genome-wide significant SNPs, two intergenic, one in TENM3, previously autoimmune disease-associated. Targeted analysis of immune check-point genotypes (CTLA4, PD1, PD-L1) uncovered effects on humoral anti-brain autoimmunity (OR = 1.55; 95 % CI [1.058-2.271]) and disease likelihood (OR = 1.43; 95 % CI [1.032-1.985]). APOE4 carriers (∼19 %) had lower seropositivity (OR = 0.766; 95 % CI [0.625-0.933]). Neurotrauma predisposed to NMDAR1-AB seroprevalence (IgM: OR = 1.599; 95 % CI [1.022-2.468]). Humoral autoimmunity against brain-antigens, frequent across health and disease, is predicted by age, gender, genetic predisposition, and brain injury. Seroprevalence, immunoglobulin class, or titers do not predict disease.


Differentiation of fly visual interneurons after laser ablation of their central targets early in development.
To test the differentiation of visual interneurons that had their targets removed before axogenesis, we ablated neuronal precursors in brains of first instar fly larvae by using a laser microsurgery unit. We describe ablations that resulted in the elimination of the third neuropil region (the lobula complex) of the optic lobes. Neural differentiation in the more peripheral second and first neuropil regions (the medulla and the lamina) was thus studied in the absence of the lobula complex. It was found that the medulla neuropil differentiated with normal columnar and layered organization. The neuropil, however, folded along its central surface. The only connection between the medulla and more central neuropil (the midbrain) was via a bundle of axons (the Cuccati bundle) present also in the normal optic lobes. Some types of neurons that normally connect the medulla and the lobula complex could be identified. These appeared to end in a disorganized neuropil mass in the center of the folded medulla. The differentiation of the lamina neuropil also appeared normal in flies with the lobula complex eliminated and the medulla folded. Also, in optic lobes where the medulla was severely disorganized and/or reduced due to laser ablations, the lamina neuropil appeared more or less normal. The results suggest that lamina and medulla nerve cells can differentiate and develop normal neuropil patterns in absence of their appropriate targets.


Distinguished properties of cells isolated from the dentin-pulp interface.
Dental odontoblasts produce dentin mineralized matrix, trigger immune responses and act as sensory cells. The understanding of the mechanisms of these functions has been particularly restricted due to the lack of odontoblasts being cultivable in vitro. Because of the lack of specific markers to identify cells of the odontoblastic lineage, properties of the cells isolated from the dentin-pulp interface were compared to dental pulp cells, periodontal ligament cells, osteoblasts, skin fibroblasts, epithelial cells (A549) and HeLa in the present study. After surgical procedures, the pulp tissue was removed from the tooth crown, and cells were scrapped off the dentin-pulp interface. Explants from teeth of three patients were routinely cultivated, and cells were harvested after several weeks. Cell morphology and ultrastructure was studied by light microscopy (LM), scanning (SEM) or transmission electron microscopy (TEM). Expression of dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP1), TRPV4, and S100 calcium binding protein A4 (S100A4) were analyzed at the protein level by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting using specific antibodies. The differential expression of S100A4 in the various cell lines was further investigated at the gene level by semiquantitative real-time PCR. Mineralization in the various cell types was observed after alizarin red staining after a 28 days incubation period. The immunophenotype of the cells was examined by flow cytometry using monoclonal anti-human antibodies CD90-FITC, CD73-PE, CD105-PE, CD29-PE, CD140a-FITC, CD144-PE, CD45-FITC or CD34-FITC. Differences between median values were statistically analyzed (Mann-Whitney U-test). Cells from the dentin-pulp interface retain the polarity of odontoblast morphology in culture with an elongated, rounded cell body, and an extended cellular process. Ultrastructural analysis of the cells indicates high secretory activity including the extracellular deposition of fibrillar collagen. An extended rough endoplasmic reticulum is lined by a large number of ribosomes, and a vast number of secretory granules merges with the cell membrane. Protein expression of DSPP, DMP1, and TRPV4 as a transient receptor potential cation was detected in all cell lines. S100A4 was found differentially expressed in cultures of cells from tooth tissues. High expression of S100A4 was observed at the protein and gene level in two fractions of cells isolated from the dentin-pulp interface, but was absent or only weakly expressed in pulp cells. S100A4 expression in cells from the dentin-pulp interface and pulp cells is consistent with the intensity of the formation of mineralized nodules detected by alizarin red staining. Immunophenotyping revealed that a high percentage of CD73 (ecto-5-nucleotidase), an enzyme active on the surface of immune-competent cells, was expressed in cells of the dentin-pulp interface. While 72%-78% of positive cells were detected in dentin-pulp interface fractions, only 28-64% of the cells in pulp cell cultures were stained. The present findings obtained with a variety of cells of different origin provide experimental evidence that cells isolated from the dentin-pulp interface express unique properties different from dental pulp cells in particular. The differential expression of S100A4 is a relevant marker candidate for differentiating between dental pulp cells and cells of the odontoblast lineage.


Mechanisms of respiratory innervation during embryonic development.
During embryogenesis, the development of the respiratory tract is closely associated with the formation of an extensive neuronal network. While the topic of respiratory innervation is not new, and similar articles were published previously, recent studies using animal models and genetic tools are breathing new life into the field. In this review, we focus on signaling mechanisms that underlie innervation of the embryonic respiratory tract.


[Cutaneous lymphoid hyperplasia (pseudolymphoma) on the red dye of a tattoo].
Cutaneous lymphoid hyperplasia (pseudolymphoma) on tattoo is rare. The diagnosis is histological. We report a case of cutaneous lymphoid hyperplasia within the red ink of a tattoo found on a 35-year-old man presenting multiple infiltrated nodules confined to the red areas of his tattoo, which he had done 2 months ago. The pathological examination showed a diffuse lympho-histiocytic dermo-hypodermal infiltrate, associated with a lichenoid reaction. Immunohistochemistry displayed T-cell infiltration (CD3+, CD5+, CD8+). The treatment is difficult, knowing that the spontaneous regression seems possible, and the progression into a lymphoma is exceptional in the case of a chronic evolution over a number of years.


The attachments of the anteromedial and posterolateral fibre bundles of the anterior cruciate ligament. Part 2: femoral attachment.
The aim of this study was to describe the anatomical locations of the femoral attachments of the anteromedial (AM) and posterolateral (PL) bundles of the anterior cruciate ligament (ACL). Twenty-two human cadaver knees with intact ACLs were used. The femoral attachments of the two bundles were identified, marked and photographed. They were measured and described in terms of the o'clock positions parallel to the femoral long axis and parallel to the roof of the intercondylar notch. The centres of the bundles were also measured in a high-low and a superficial-deep manner referencing from the centre of the posterior femoral condyle, and with respect to their positions within a measurement grid defined in this study. The bulk of the AM bundle was attached between the 9.30 and 11.30 o'clock positions and the PL bundle between the 8.30 and 10 o'clock positions. The AM and PL bundles were consistently found in specific zones of the measurement grid. Using the posterior condyle reference method, the centre of the AM bundle was at 68 +/- 7% (range 57-78) in a shallow-deep direction and 55 +/- 5% (44-62) in a high-low direction. The PL bundle was found at 56 +/- 8% (40-73) in a shallow-deep direction, and 62 +/- 7.0% (40-70) in a high-low direction. The attachment was oriented at 37 degrees to the femoral long axis. The results from this study could be used to guide ACL reconstruction techniques.


Development of a microfluidic approach for the real-time analysis of extrinsic TGF-β signalling.
Autocrine and paracrine signalling are traditionally difficult to study due to the sub-micromolar concentrations involved. This has proven to be especially limiting in the study of embryonic stem cells that rely on such signalling for viability, self-renewal, and proliferation. Microfluidics allows to achieve local concentrations of ligands representative of the in vivo stem cell niche, gaining more precise control over the cell microenvironment, as well as to manipulate ligands availability with high temporal resolution and minimal amount of reagents. Here we developed a microfluidics-based system for monitoring the dynamics of TGF-β pathway activity by means of a SMAD2/3-dependent luciferase reporter. We first validated our system by showing dose-dependent transcriptional activation. We then tested the effects of pulsatile stimulation and delayed inhibition of TGF-β activity on signalling dynamics. Finally, we show that our microfluidic system, unlike conventional culture systems, can detect TGF-β ligands secreted in the conditioned medium from hESCs.


Inflammatory biomarkers in overweight and obese Iranian women are associated with polyphenol intake.
The evidence shows that obesity is associated with chronic inflammation in obese subjects. Polyphenols are a complex group of plant secondary metabolites that may play a role in reducing the risk of obesity and obesity-related diseases. Given the scarcity of evidence on the association between inflammatory markers and dietary polyphenols intake in overweight/obese Iranian women, the current study aims to investigate this link. The present cross-sectional study was conducted on 391 overweight and obese Iranian women aged 18-48 years (body mass index (BMI) ≥ 25 kg/m2). A 147-item food frequency questionnaire (FFQ) was used to assess dietary intake, as well as anthropometric indices including weight, height, waist circumference (WC), and hip circumference (HC) and biochemistry parameters including triglyceride (TG), total cholesterol (Chole), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), serum glutamic pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT), galactin-3 (Gal-3), monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta (TGF-β), interleukin-1 beta (IL_1β), plasminogen activator inhibitor-1 (PA-I), serum leptin concentrations, and C-reactive protein of high sensitivity (hs-CRP) in all participants. The inflammatory markers were assessed using the enzyme-linked immunosorbent assay (ELISA). The findings revealed a significant negative association between flavonoids intake and MCP-1 (P = 0.024), lignans intake and MCP-1 (P = 0.017), and Gal-3 (P = 0.032). These significant associations were observed between other polyphenols intake and IL_1β (P = 0.014). There was also a significant positive association between other polyphenol intake and TGF-β (P = 0.008) and between phenolic acid intake and TGF-β (P = 0.014). Our findings suggest that a high polyphenol intake may help individuals to reduce systemic inflammation. Further large studies involving participants of different ages and genders are highly warranted.


Clinical considerations in Parkinson's disease cell therapy.
Cell replacement therapy is an area of increasing interest for treating Parkinson's disease (PD). However, to become a clinically practical option for PD patients, it must first overcome significant barriers, including establishment of safe and standardized surgical procedures, determination of appropriate perioperative medication regimens, demonstration of long-term graft survival and incorporation, and standardized, clinically meaningful follow-up measures. In this review, we will describe the current status of cell therapy for PD with special attention to these critical requirements, to define guideposts on the road to bring the benefit of this therapy to the Parkinson's clinic.


Comparative distribution of neuropeptide Y Y1 and Y5 receptors in the rat brain by using immunohistochemistry.
Neuropeptide Y (NPY) Y1 and Y5 receptor subtypes mediate many of NPY's diverse actions in the central nervous system. The present studies use polyclonal antibodies directed against the Y1 and Y5 receptors to map and compare the relative distribution of these NPY receptor subtypes within the rat brain. Antibody specificity was assessed by using Western analysis, preadsorption of the antibody with peptide, and preimmune serum controls. Immunostaining for the Y1 and Y5 receptor subtypes was present throughout the rostral-caudal aspect of the brain with many regions expressing both subtypes: cerebral cortex, hippocampus, hypothalamus, thalamus, amygdala, and brainstem. Further studies using double-label immunocytochemistry indicate that Y1R immunoreactivity (-ir) and Y5R-ir are colocalized in the cerebral cortex and caudate putamen. Y1 receptor ir was evident in the central amygdala, whereas both Y1- and Y5-immunoreactive cells and fibers were present in the basolateral amygdala. Corresponding with the physiology of NPY in the hypothalamus, both Y1R- and Y5R-ir was present within the paraventricular (PVN), supraoptic, arcuate nuclei, and lateral hypothalamus. In the PVN, Y5R-ir and Y1R-ir were detected in cells and fibers of the parvo- and magnocellular divisions. Intense immunostaining for these receptors was observed within the locus coeruleus, A1-5 and C1-3 nuclei, subnuclei of the trigeminal nerve and nucleus tractus solitarius. These data provide a detailed and comparative mapping of Y1 and Y5 receptor subtypes within cell bodies and nerve fibers in the brain which, together with physiological and electrophysiological studies, provide a better understanding of NPY neural circuitries.


[Morphological changes in the liver in acute galactosamine poisoning with different protein levels in the diet].
Changes in hepatocyte ultrastructure after galactosamine administration to rats adapted to diets with different protein content have been studied. Typical galactosamine effects on hepatocytes were manifested earlier in animals on low and high protein diets. At the same time a considerable decrease in protein synthesis led to insufficient expression of the reparative processes in all the observed groups of animals.


Non-traumatic chylothorax: diagnostic and therapeutic strategies.
Non-traumatic chylothorax refers to accumulation of chyle in the pleural space in the absence of any traumatic disruption to the thoracic duct. Chyle originates from the intestines and is transported via the thoracic duct into systemic circulation. The anatomical course of the thoracic duct is complex with considerable variation; therefore, development of chylothorax is dependent on the site and level of the thoracic duct defect. Non-traumatic chylothorax is associated with a wide range of medical disorders, but malignancy accounts for three-quarters of cases. In up to 9% of cases, the aetiology remains unknown (termed idiopathic chylothorax). Gross appearance of pleural fluid is neither sensitive nor specific enough to diagnose chylothorax; therefore, biochemical analysis of the pleural fluid is required. Pleural fluid triglyceride level >1.24 mmol·L-1 (110 mg·dL-1) with a cholesterol level <5.18 mmol·L-1 (200 mg·dL-1) is diagnostic of chylothorax. In borderline cases, lipoprotein electrophoresis can help confirm the diagnosis by detecting chylomicrons in the pleural fluid. Once the diagnosis of chylothorax is confirmed, the next step is to find the cause and identify the leakage point, for which various lymphatic specific radiological investigations may have an important role. There is paucity of data on the most suitable approach to manage non-traumatic chylothoraces and treatment often depends on the underlying cause. In general, conservative treatment is tried first, usually for a limited time, before considering more invasive measures. A multidisciplinary approach is recommended with close liaison among the respiratory physicians, thoracic surgeons, oncologists, interventional radiologists, dietitians and pharmacists. To review the pathophysiology, aetiology, and epidemiology of non-traumatic chylothorax.To discuss diagnostic and therapeutic strategies in the management of non-traumatic chylothorax.


Endodontic management in a patient with vitamin D-resistant Rickets.
Hypophosphatemic vitamin D-resistant rickets (VDRRs) is a metabolic bone disease caused by abnormalities in the vitamin D receptive system or in phosphate and calcium metabolism. This condition occurs in growing skeleton affecting bone and dentin mineralization, resulting in systemic and oral manifestations. A 15-year-old boy was referred to the private clinic for endodontic treatment in #9. His medical history revealed VDRR disease. The dental findings were multiple periapical lesions in several teeth without obvious reason such as caries or trauma. The radiographic examination showed short roots, enlarged pulp chambers with longer pulp horns, thin dentin and enamel, missing or poorly defined lamina dura, and abnormalities in the cementoenamel junction, all pathognomonic features of the disorder. Conservative endodontic treatment was completed in all teeth with pulp necrosis and rarefactions. A 6-month, 1-year, and 2-year follow-up radiographic examination revealed progressive improvement with bone reconstruction without any clinical symptoms. Early diagnosis, conventional treatment, and continuous radiographic examination are important factors in improving dental alterations in patients with VDRRs.