Future aquatic nutrient limitations.
Nutrient limitation of phytoplankton growth in aquatic systems is moving towards a higher incidence of P and Si limitation as a result of increased nitrogen loading, a N:P fertilizer use of 26:1 (molar basis), population growth, and relatively stable silicate loading. This result will likely alter phytoplankton community composition, and may compromise diatom-->zooplankton-->fish food webs.


Reliability of mycophenolic acid monitoring by an enzyme multiplied immunoassay technique.
For mycophenolic acid (MPA), substantial inter- and intra-individual variability and drug interactions have been observed and therapeutic drug monitoring is now recommended. In this study, a MPA commercial Enzyme Multiplied Immunoassay Technique (EMIT) was evaluated and compared with the HPLC-UV reference method which is easily practicable in a routine laboratory. Plasma samples (n = 117) were collected from adult renal graft patients treated by mycophenolate in combination with either cyclosporin A (CyA) (n = 32) or tacrolimus (n = 85). Considering all samples, correlation was excellent (p < 0.0001). However, significant MPA overestimation was observed with EMIT in the early post-transplant period (30%, n = 32) or when combined with cyclosporin (45%). In the early post-transplant period, or in cases where CyA is used in combination with MPA, the EMIT cannot be recommended. HPLC or LC/MS are here the method of choice.


Instability of the snowshoe hare and woody plant interaction.
We show that Alaskan woody plants respond to browsing in two ways that might destabilize a plantherbivore interaction and account for snowshoe hare population 'cycles'. (1) Browse production of preferred, earliersuccessional woody plants increases in response to moderate levels of browsing. Such yield increases are potentially destabilizing. Later successional woody plants show decreases in yield after moderate browsing, which is consistent with the persistence of snowshoe hares in late successional 'refuge' habitats (Keith 1966, Wolff 1980). (2) Many woody plants are destructively overbrowsed or girdled at the peak of the snowshoe hare cycle. The more palatable and plastic, early to mid successional plants respond by sprouting accompanied by juvenile reversion. Sprouts are markedly less palatable than mature shoots. We show here that sprout palatability and twig biomass are restored in 2-3 years for earlier successional plants, but palatability may not recover for 4-10 years in sprouts of some mid to late successional plants. The decrease in palatability helps to account for the snowshoe hare 'crash' (assuming that damage to more palatable plants is widespread during the 'peak'), and the 2-3 year time lag for recovery of more palatable species could account for (May 1974) the observed 8-11 year period of the hare cycles. Browse yield increases acting during the snowshoe hare population nadir and increase, and sprouting with juvenile reversion acting during the hare peak and decline can in principle account for the oscillatory nature and the observed 8-11 year periodicity of the snowshoe hare cycle.


Effects of hypoxia on noradrenaline release and neuronal reuptake in isolated rabbit thoracic aortic strips.
To clarify the effects of hypoxia on stimulus-evoked noradrenaline release and on neuronal reuptake of the released noradrenaline, we examined the effects of hypoxia on contraction responses of rabbit thoracic aortic strips to transmural electrical stimulation and on the stimulation-evoked overflow of total [3H] and [3H]noradrenaline from the strips prelabelled with [3H]noradrenaline. This was done in the presence or absence of an inhibitor of neuronal uptake (cocaine). In a medium equilibrated with a gas mixture of 95% O2/5% CO2 (control), cocaine doubled the stimulation-evoked overflow of total [3H] and [3H]noradrenaline; there was a concomitant increase (130%) in contractions to electrical stimulation. At 0% O2 (95% N2/5% CO2, hypoxia), cocaine had no significant effects on either the stimulation-evoked overflow of total [3H] and [3H]noradrenaline or contractions. In the absence of the drug, hypoxia decreased the stimulation-evoked overflow of total [3H] and [3H]noradrenaline to 47% and 43%, respectively, of the control values, whereas these values were 31% and 28%, respectively, after exposure to cocaine. The inhibition by hypoxia of contraction responses to electrical stimulation was greater in the presence of cocaine than in its absence. These results show that hypoxia inhibits both noradrenaline release evoked by a given stimulus and neuronal uptake.


Association of chromosome 2 open reading frame 71 in colorectal cancer susceptibility.
Colorectal cancer (CRC) is a serious threat to human physical and mental health. Due to the novelty of the open reading frame (ORF), ORF has shown a wide range of new genetic associations in cancer. The purpose of this study was to explore the association between the C2orf71 SNPs and CRC susceptibility. We recruited 1419 participants to perform an association analysis between C2orf71 SNPs and CRC risk through SNPStats online solftware. Genotyping was completed by the AgenaMassARRAY. In addition, we used false-positive report probability analysis to detect whether the positive findings were noteworthy observations. We also used Haploview 4.2 software and SNPStats online software to conduct the haplotype analysis and analysis of linkage disequilibrium (LD). Finally, the interaction of SNP-SNP in CRC risk was evaluated by multi-factor dimensionality reduction (MDR). The overall analysis showed thatC2orf71-rs17744093, -rs10200693, and -rs13385188 were significantly associated with the CRC susceptibility. C2orf71-rs17744093 was associated with CRC risk under dominant model (OR = 1.25, p = 0.048). -rs10200693 was associated with CRC risk under allele (OR = 1.17, p = 0.041) and log-additive model (OR = 1.16, p = 0.045). -rs13385188 had significant association with CRC risk under multiple genetic models (allele: OR = 1.19, p = 0.023; log-additive: OR = 1.18, p = 0.026). Multiple stratified analyses showed that except for the three candidate SNPS mentioned above, -rs10166913 (age < 60 years and drinking) and -RS17007544 (< 60 years) were associated with increased CRC risk. C2orf71-rs17744093, -rs10200693, -rs10166913, -rs17007544, and -rs13385188 were associated with CRC susceptibility.


Multi-Domains Lifestyle Interventions Reduces Depressive Symptoms among Frail and Pre-Frail Older Persons: Randomized Controlled Trial.
We investigated the effect of multi-domain lifestyle (physical, nutritional, cognitive) interventions among frail and pre-frail community-living older persons on reducing depressive symptoms. Participants aged 65 and above were randomly allocated to 24 weeks duration interventions with nutritional supplementation (N=49), physical training (N=48), cognitive training (N=50), combination intervention (N=49) and usual care control (N=50). Depressive symptoms were assessed by the Geriatric Depression Scale (GDS-15) at baseline (0M), 3 month (3M), 6 month (6M) and 12 month (12M). Mean GDS scores in the control group increased from 0.52 (0M) and 0.54 (3M) to 0.74 (6M), and 0.83 (12M). Compared to the control group, interventions showed significant differences (∆=change) at 6M for cognitive versus control (∆=-0.39, p=0.021, group*time interaction p=0.14); physical versus control (∆ =-0.37, p=0.026, group*time interaction p=0.13), and at 12M for nutrition versus control (∆ =-0.46, p=0.016, group*time interaction p=0.15). The effect for combination versus control was significant at 6M (∆ =-0.43, p=0.020) and 12M (∆ =-0.51, p=0.005, group*time interaction p=0.026). Estimated 12-month cumulative incidence of depressive symptoms (GDS≥2) relative to control were OR=0.38, p=0.037 (nutrition); OR=0.71, p=0.40 (cognitive); OR=0.39, p=0.042 (physical training) and OR=0.38, p=0.037 (combination). Changes in gait speed and energy level were significantly associated with changes in GDS scores over time. Multi-domain interventions that reverse frailty among community-living older persons also reduce depressive symptomatology. Public health education and programmatic measures combining nutritional, physical and cognitive interventions for at-risk frail older people may likely benefit psychological wellbeing.


Gingival enlargement in Niemann-Pick disease: a coincidence or link? Report of a unique case.
A case of a 25-year-old man appearing with generalized gingival enlargement is reported here. Niemann-Pick disease (NPD) was provisionally diagnosed by histopathologic analysis of tissue excised by gingivectomy and later confirmed by quantitative enzyme assay. Correlation between clinical features and histopathologic and biochemical analysis enabled the diagnosis of NPD type C.


Bilateral Thalamic Stroke Arising From an Occlusion of the Artery of Percheron: Barriers to Diagnosis, Management, and Recovery.
A 90-year-old male patient presented with excessive somnolence, right-sided weakness, and left facial droop. CT and MRI scans of the head, taken several days after initial head CT proved to be non-revealing, demonstrated a bilateral thalamic stroke, a rare phenomenon. The infarct arose in the territory of the artery of Percheron, an anatomic variant in which a single artery supplies both sides of the thalamus and midbrain. When this artery becomes occluded, it results in severely dysregulated consciousness and alertness. This type of stroke proved challenging for the medical team, due to poor resolution of initial imaging, as well as the therapy teams, due to the constant need for sleep. This case report outlines how barriers in diagnosis and management make knowledge of the artery of Percheron and its occlusion crucial to patient care and recovery.


Draft Genome Sequence of Psychrotolerant Shewanella sp. Strain VB17, Isolated from Marine Intertidal Sediment near Virginia Beach, Virginia.
We present the draft genome sequence of Shewanella sp. strain VB17, which was isolated from Virginia Beach, Virginia, intertidal sediment. The 5.2-Mb genome sequence of VB17 will be useful for studying the basis for seasonal low-temperature growth and eventual taxonomic classification of the species.


The Long and Winding Road of Atrial Septostomy.
Almost forty years have elapsed since the first description of the use of atrial septostomy in the setting of pulmonary arterial hypertension (PAH) [...].


Artisan fresh cheese from raw cow's milk as a possible route of transmission in a toxoplasmosis outbreak, in Brazil.
The objective of this study was to report an outbreak of human toxoplasmosis occurring in the municipality of Montes Claros de Goiás, Goiás, Brazil, from December 2015 to August 2016. Seven acute cases in June 2016 triggered the subsequent search. A total of 251 individuals were selected through an active search, of which 114 (45.4%) agreed to participate in the research and blood collection. For serological diagnosis were used enzyme-linked immunosorbent assay (ELISA) for IgG and IgM and avidity tests. Of the 114 serum samples evaluated, 12.3% (14/114) showed antibodies against Toxoplasma gondii, with a profile indicative of acute infection. Samples of artisan fresh cheese, public water, vegetables and irrigation water were collected. Toxoplasma gondii DNA fragments were amplified using the polymerase chain reaction from two samples of artisan fresh cheese and a sample of irrigation water from the vegetable garden. A control case study was carried out, and the variable cow's artisan fresh cheese consumption was statistically significant (p = .01). The results showed that cheese analysed and/or irrigated water of vegetable represented an important route of transmission for the disease. This is the first reported outbreak possibly caused by cow's artisan fresh cheese. It is difficult to prove that these routes were the cause of the outbreak; however, the findings allow us to infer that the individuals involved in the outbreak were in contact with these risk factors.


Liveweight gain and copper status of young deer treated or untreated with copper oxide wire particles on ten deer farms in Canterbury.
To measure the liveweight response of young deer to copper supplementation on a range of deer farms in the Canterbury region of the South Island, New Zealand, and relate any response to plasma copper concentration. On each of 10 farms throughout north and mid-Canterbury, young deer (4-7 months old) were allocated by liveweight to two groups of 45-50. The deer in one group each received 5 g copper oxide wire particles (COWP) at the start of the project (March-June 2000) and a further 10 g COWP 3 months later (+Cu group), while the other group received no copper supplementation (-Cu group). Liveweight (+/-1 kg) of all deer was recorded monthly. A 10 ml blood sample was taken from a sub-sample of 10 animals in each group at the beginning of the trial and from the same animals 3 and 6 months later for measurement of plasma copper concentration. There was no significant effect (p=0.96) of treatment with COWP on liveweight gain (overall mean liveweight gain = 169 g/day). This result was consistent for all farms and for both periods. Mean plasma copper concentration declined from 12.5 (SD 3.4) to 10.3 (SD 3.0) micromol/l in +Cu groups, and to a significantly lower level (p<0.001) of 8.6 (SD 3.2) in -Cu groups after 3 months, at which time 38% of -Cu animals were considered hypocupraemic (<8 micromol/l). At the end of the second 3-month period there was no significant treatment effect on plasma copper concentration, which averaged 9.4 (SD 2.3) micromol/l. Of the feed samples submitted (n=46), only 17% had a copper concentration <5.0 mg/kg dry matter (DM), 13% had a molybdenum concentration >1.0 mg/kg, and 21% had a sulphur content >3.5 g/kg. Under the conditions of these trials, no response in liveweight gain to copper supplementation was observed despite evidence of hypocupraemia in 38% of -Cu animals, which gained weight at similar rates to those that had adequate plasma copper levels. The extent of the hypocupraemia was either not sufficiently severe, or not maintained for a long enough period to cause copper deficiency resulting in reduced liveweight gain. No other signs of copper deficiency were evident. There is scope for deer farmers to reassess the need for copper supplementation in young deer.


Assessment of Metabolic Risk Factors and Heart-Healthy Lifestyle in Atherosclerotic Coronary Artery Disease Patients Undergoing Percutaneous Coronary Intervention after a 6-Month Follow-Up.
Mortality due to acute coronary syndrome (ACS) has dramatically diminished because of performing life-saving interventions. This study aims to assess the metabolic risk factors and heart healthy lifestyle following the first episode of ACS under percutaneous coronary intervention (PCI) treatment after the 6-month follow-up. This is a longitudinal study conducted on 40 patients who underwent PCI because of the first episode of ACS. The patients' information including age, weight, abdominal circumference, smoking, functional capacity, patients' metabolic equivalent of task (METS), and laboratory tests including triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), creatinine, fasting blood sugar (FBS), and hemoglobin A1C were recorded before discharge and reassessed after 6-month follow-up. The patients were dominantly male (92.5%) with an average age of 56.8 ± 7.11 years. Physical activity and functional capacity (METS) significantly improved within 6 months (P = 0.019). BMI significantly improved; however, although the abdominal circumference decreased, it was not significant (P = 0.28). The number of smokers (P = 0.12) and the daily number of smoked cigarettes (P = 0.37) nonsignificantly decreased within 6 months. However, HDL-C (P = 0.013) and LDL-C (P = 0.027) changes were not desirable. TG, FBS, and blood pressure did not statistically significant change (P > 0.05). Although BMI, physical activity, and METS remarkably improved, waist circumference decreased nonsignificantly and lipid profile got worse paradoxically. Although this population is limited for generalization, this study shows that we require further schedules to improve ACS secondary prevention practice in our community.


Prescription of vitamin D was associated with a lower incidence of hip fractures.
Patients with osteoporosis are prone to fragility fractures. Evidence of the effects of active forms of vitamin D on hip fracture prevention is insufficient. We examined the association between vitamin D prescription and incidence of new fractures using the data of osteoporotic patients from the nationwide health insurance claims database of Japan. The follow-up period was 3 years after entry. The untreated patients were never prescribed vitamin D during follow-up (n = 422,454), and the treated patients had a vitamin D medication possession ratio of ≥ 0.5 at all time points (n = 169,774). Propensity score matching was implemented on these groups, yielding 105,041 pairs, and subsequently, the control and treatment groups were established and analyzed. The incidence of new fractures was significantly lower in the treatment group compared with the control group (6.25% vs. 5.69%, hazard ratio 0.936 [95% confidence interval 0.904-0.970], p < 0.001*). By site, hip fractures significantly decreased (0.89% vs. 0.42%, p < 0.001), but not vertebral and radial fractures. Subgroup analysis by vitamin D type showed a significantly lower incidence of total fractures only in alfacalcidol (hazard ratio 0.676 [95% confidence interval 0.628-0.728], p < 0.001*). The results suggest that vitamin D prescription was associated with a reduced incidence of hip fractures.


Navigating through the minefield of read-across tools: A review of in silico tools for grouping.
Read-across is a popular data gap filling technique used within analogue and category approaches for regulatory purposes. In recent years there have been many efforts focused on the challenges involved in read-across development, its scientific justification and documentation. Tools have also been developed to facilitate read-across development and application. Here, we describe a number of publicly available read-across tools in the context of the category/analogue workflow and review their respective capabilities, strengths and weaknesses. No single tool addresses all aspects of the workflow. We highlight how the different tools complement each other and some of the opportunities for their further development to address the continued evolution of read-across.


Bioavailability enhancement of a BCS IV compound via an amorphous combination product containing ritonavir.
To evaluate the effect of ritonavir (RTV) co-administration on the bioavailability of an amorphous dispersion of acetyl-11-keto-beta-boswellic acid (AKBA) and to develop a pharmaceutically acceptable AKBA-RTV combination tablet. A pharmacokinetic (PK) study in rats was conducted to evaluate the influence of RTV co-administration on the oral bioavailability of an AKBA amorphous dispersion. KinetiSol was utilized to enable production of an improved RTV formulation that facilitated the development of an AKBA-RTV combination tablet. Following in-vitro characterization, the PK performance of the tablets was evaluated in male beagles. Co-administration of RTV increased oral absorption of AKBA by about fourfold over the AKBA dispersion alone and approximately 24-fold over the pure compound. The improved RTV amorphous dispersion exhibited similar purity and neutral-phase dissolution to Norvir. The AKBA-RTV combination tablets yielded a substantial increase in AKBA's bioavailability in dogs. Oral absorption of AKBA is substantially limited by intestinal CYP3A activity and poor aqueous solubility. Consequently, AKBA's oral bioavailability is maximized by administration from a supersaturating formulation in conjunction with a CYP3A inhibitor. The AKBA-RTV combination tablet presented herein represents a breakthrough in the oral delivery of the compound facilitating future use as a drug therapy for broad spectrum cancer treatment.


Burden of caregivers for patients with mild cognitive impairment in Japan.
Caregivers of patients with mild cognitive impairment (MCI) already experience a need for increased services comparable to that of individuals caring for Alzheimer's disease patients. However, there have been only a few studies on the MCI caregiver burden. In this study, we examined MCI caregiver burden in a larger number of consecutive outpatients in Japan. One hundred and four consecutive caregivers of people with MCI participated in this study. The caregiver burden was evaluated by the short version of the Japanese version of the Zarit Burden Interview (sZBI). About 20% of the caregivers reported a clinically significant burden. The multiple linear regression analysis showed that the caregiver burden was significantly associated with neurobehavioral symptoms (p < 0.001) and memory problems (p = 0.022) of the patient. The caregiver burden of MCI patients should be given more attention. The management of neurobehavioral symptoms may be important to reduce the burden on caregivers of MCI patients.


Population fluctuations and extinctions of small rodents in coastal southern California.
The population dynamics of three sympatric rodents, Microtus californicus, Mus musculus, and Reithrodontomys megatolis was studied at four sites in coastal southern California. The study was undertaken to determine the extent of local demographic diversity in rodent populations.The populations of all rodent species became extinct on one site, while on another site the populations fluctuated widely and on two other sites the populations remained relatively stable. The most common species, Reithrodontomys, exhibited differences in reproduction, age class structure, recruitment, and survivorship on the two sites which were monitored for relatively long terms. Immigration was the main source of new individuals entering the sites where the Reithrodontomys population was most persistent.On a local scale, some life history characteristics are affected in a density dependent fashion. When viewed on a global scale, the non-equilibrium nature of the rodent populations becomes clear.


Isosorbide dinitrate and exercise performance in patients with congestive heart failure.
Nitrates are widely used for the management of congestive heart failure (CHF), as well as angina pectoris. In both situations, nitrates significantly increase exercise capacity. The mechanism of this beneficial effect is unclear, especially in CHF. Isosorbide dinitrate reduces pulmonary capillary wedge pressure (PCWP) after a first dose. The improvement in exercise capacity is not apparent in the short term but is evident after long-term nitrate administration. Nitrates do not affect hemodynamics at maximal exercise but do reduce PCWP during submaximal exercise in patients with CHF. This observation, in addition to increased oxygen extraction at peak exercise during nitrate administration, suggests a "training like" peripheral effect of nitrates in CHF. Lowering of PCWP by nitrates may be important, since vasodilators that do not reduce PCWP also do not improve exercise capacity in CHF. How PCWP influences exercise performance in CHF is unknown, but the mechanism may relate to effects of PCWP on pulmonary hemodynamics more than on ventilation and blood oxygenation.


The effect of beam slope on the perception of melodic contour.
Musical score reading is a complex task, which involves attending and interpreting multiple visual constituents that are graphically congested. The present investigation examined the 'beam', which although consistently found in music notation, is typically considered as providing no more information than marking metric boundaries (i.e., chunking). However, we provide evidence here that beams enhance visual perception of contour. In Study 1, a Stroop-like paradigm was used in which participants were required to judge the direction of notes or the beam in a compound figure; the two dimensions were either congruent or incongruent. A congruency effect was observed in both tasks, confirming that both notes and beam are processed automatically during score reading. In Study 2, an additional auditory stimulus was presented. The results not only replicated the findings of Study 1, but showed that beams affect both visual and auditory perception. Finally, group differences surfaced: musicians were more affected by the direction of notes than non-musicians when attending to beams, but the effect of beams on judging note direction was comparable in both groups. The implications for understanding musical score reading - specifically issues related to melodic contour - are discussed.


Immunocytochemical localization of hypocalcin in the endocrine cells of the corpuscles of Stannius in three teleost species (trout, flounder and goldfish).
In order to identify the cell-type responsible for the production of hypocalcin (the recently isolated hypocalcemic hormone of teleost fish), the corpuscles of Stannius (CS) of trout, flounder and goldfish, were immunocytochemically stained with antisera raised against trout hypocalcin. The secretory granules of the type-1 cells of the CS, considered to be the hypocalcin-producing cells, showed intense immunoreactivity in all species examined. However, in trout and flounder, the secretory granules produced by the type-2 cells, which have been suggested to represent a functionally different cell-type, also showed an intense immunoreactivity. In goldfish, no type-2 cells were observed. We tentatively conclude that type-1 and type-2 cells represent structurally different forms of the same functional cell-type.


Nanofat grafting under a split-thickness skin graft for problematic wound management.
Obesity and certain medical disorders make the reconstruction of skin defects challenging. Different kind of procedure can be used for these defect, besides, skin grafting is one of the most common and simplest procedure. Fat grafting and stem cells which are located in the adipose tissue have been commonly used in plastic surgery for regeneration and rejuvenation purposes. To decrease graft failure rate we performed nanofat grafting under an autologous split-thickness skin graft in our patient who had a problematic wound. The case of a 35-year-old female patient with a traumatic skin defect on her left anterior crural region is described herein. After subsequent flap reconstruction, the result was disappointing and the defect size was widened. The defect was treated with combined grafting (nanofat grafting under an autologous split-thickness skin graft). At the 6 months follow-up assessment after combined grafting, the integrity of the skin graft was good with excellent pliability. Combined grafting for problematic wounds seems to be a useful technique for cases requiring reconstruction. The potential existence of stem cells may be responsible for the successful result in our patient.


An effective method for axillary bud culture and RAPD analysis of cloned plants in tetraploid black locust.
An efficient micropropagation technique by axillary bud multiplication was established for cloning tetraploid black locust tree (Robinia pseudoacacia L.). The result showed that the optimal medium for shoot multiplication and elongation was Murashige and Skoog (MS) medium supplemented with 0.5 mg/l 6-benzylaminopurine in combination with 0.5 mg/l kinetin and 0.1 mg/l 1-naphthaleneacetic acid. The best medium for rooting was half-strength MS medium with 0.25 mg/l indole-3-butyric acid. In the present report, we examined the genetic fidelity of the micropropagated plants by the randomly amplified polymorphic DNA (RAPD) method with 25 primers. The cloned plants of tetraploid black locust showed complete stability.


A novel method for the diagnosis of bacterial contamination in the anterior vagina of sows based on measurement of biogenic amines by ion mobility spectrometry: A field trial.
To determine if postpartum subclinical infection occurs in sows, a novel device was used to diagnose such bacterial contamination of the vagina. The device was based on the measurement of biogenic amines by ion mobility spectrometry (IMS). The device is portable and results are obtained within 1 min. Vaginal swabs were taken from 449 sows before first-estrus insemination and 133 (29.6%) had elevated biogenic amines and were considered positives. Sixty-one percent of the sows became pregnant following post-weaning first estrus insemination. Positive scores had no apparent effect on fertility rate which was 64%. Of the sows that became pregnant, 197 (69.1%) were diagnosed as "negative" and 88 (30.9%) were "positive", of which 37 received treatment with antibiotics and were termed "positive treated". The average live-born piglets litter size of the "positives" was 10.02 which was significantly lower (P = 0.031) than the "negative" sows (11.06) while "positive treated" sow average litter size was close to the "negative" (10.56). In conclusion, it was demonstrated that subclinical anterior-vaginal bacterial contamination in lactating sows about 2 wks postpartum is a condition that affects sow litter number and could be determined by the measurement of vaginal biogenic amines with IMS.


Prenatal treatment with retinoic acid activates parathyroid hormone-related protein signaling in the nitrofen-induced hypoplastic lung.
Prenatal treatment with retinoic acid (RA) has been reported to stimulate alveologenesis in hypoplastic lungs (HL) in the nitrofen model of congenital diaphragmatic hernia (CDH). Parathyroid hormone-related protein (PTHrP) promotes alveolar maturation by stimulating surfactant production, regulated by PTHrP receptor (PTHrP-R). PTHrP knockout and PTHrP-R null mice both exhibit pulmonary hypoplasia. We have recently reported that nitrofen inhibits PTHrP signaling in the nitrofen-induced HL. Because both PTHrP and PTHrP-R genes have RA-inducible element, we hypothesized that prenatal administration of RA upregulates pulmonary gene expression of PTHrP and PTHrP-R in the nitrofen-induced HL. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). RA was given on days D18, D19 and D20. Fetal lungs were obtained on D21 and divided into four groups: control, control + RA, nitrofen, nitrofen + RA. RT-PCR and Immunohistochemistry were performed to investigate the pulmonary PTHrP and PTHrP-R gene and protein expression in each group, respectively. The pulmonary gene expression levels of PTHrP and PTHrP-R were significantly increased in nitrofen + RA group compared to nitrofen group (p < 0.05). Immunoreactivity of PTHrP and PTHrP-R was also remarkably increased in nitrofen + RA group compared to nitrofen group. Upregulation of PTHrP and PTHrP-R genes after prenatal treatment with RA in the nitrofen-induced HL suggests that RA may have a therapeutic potential in reverting lung hypoplasia in CDH, by stimulating surfactant production and alveolar maturation.


Physical and anthropogenic drivers shaping the spatial distribution of microplastics in the marine sediments of Chilean fjords.
Several studies have focused on the presence and distribution of microplastics within the water column of coastal waters, but the dynamics of these particles in sediments have received little attention. Here we examine the concentrations and characteristics of microplastics in sediment samples collected from 35 stations within the Inner Sea of Chiloé, Chilean Patagonia. Current velocity, grain size, intensity of salmon farming activities, and human population density were all evaluated as factors potentially explaining concentrations and distribution of microplastic particles within these sediments. Microplastics were detected in all samples, with the highest abundance represented by fibers (88%), fragments (10%) and films (2%). Across the sampled sites, microplastic concentrations averaged 72.2 ± 32.4 (SD) items per kg dw (dry weight) sediment, with the principal polymers identified as polyethylene terephthalate (PET), acrylic, polypropylene (PP) and polyurethane (PUR). Approximately 40% of the variability in distribution and abundance of microplastics was explained by current velocity combined with proximity and intensity of local salmon production activities. SYNOPSIS: Marine currents and aquaculture intensity explain abundance and dynamics of microplastics in marine sediments.


Active lithoautotrophic and methane-oxidizing microbial community in an anoxic, sub-zero, and hypersaline High Arctic spring.
Lost Hammer Spring, located in the High Arctic of Nunavut, Canada, is one of the coldest and saltiest terrestrial springs discovered to date. It perennially discharges anoxic (<1 ppm dissolved oxygen), sub-zero (~-5 °C), and hypersaline (~24% salinity) brines from the subsurface through up to 600 m of permafrost. The sediment is sulfate-rich (1 M) and continually emits gases composed primarily of methane (~50%), making Lost Hammer the coldest known terrestrial methane seep and an analog to extraterrestrial habits on Mars, Europa, and Enceladus. A multi-omics approach utilizing metagenome, metatranscriptome, and single-amplified genome sequencing revealed a rare surface terrestrial habitat supporting a predominantly lithoautotrophic active microbial community driven in part by sulfide-oxidizing Gammaproteobacteria scavenging trace oxygen. Genomes from active anaerobic methane-oxidizing archaea (ANME-1) showed evidence of putative metabolic flexibility and hypersaline and cold adaptations. Evidence of anaerobic heterotrophic and fermentative lifestyles were found in candidate phyla DPANN archaea and CG03 bacteria genomes. Our results demonstrate Mars-relevant metabolisms including sulfide oxidation, sulfate reduction, anaerobic oxidation of methane, and oxidation of trace gases (H2, CO2) detected under anoxic, hypersaline, and sub-zero ambient conditions, providing evidence that similar extant microbial life could potentially survive in similar habitats on Mars.


Imaging biomarker with T1ρ and T2 mappings in osteoarthritis - in vivo human articular cartilage study.
Osteoarthritis (OA) of the knee is a common and disabling disease worldwide. Its prevalence is increasing in view of the aging population. Changes in collagen content, its orientation and GAG content in the articular cartilage with age are the major features in knee osteoarthritis. These changes in collagen and GAG contents show no manifestation in plain radiography and conventional magnetic resonance imaging (MRI). Nevertheless, early diagnosis of the knee osteoarthritis is of paramount importance clinically in view of the evolution of putative interventions in its early stage. The aim of this project is to identify the relationships between the two imaging biomarkers (i.e. T1ρ and T2 mappings) and the GAG concentration in living human symptomatic cartilage. 28 patients with clinical diagnosis of knee osteoarthritis were enrolled. 7 males and 16 females were recruited and their mean age was 68.1 (ranges from 53 to 84). Conventional PD sequence, T1ρ and T2 mappings were performed for each subject within 1 week before total knee arthroplasty. Articular cartilage from the lateral tibial plateau was harvested and the GAG content in cartilage was determined by using dimethylmethylene blue method. T1ρ mean and T2 values were calculated and correlate with GAG concentration statistically. The mean value T1ρ was 40.3±13.5ms, ranging from 15.3 to 69.3ms and the mean value T2 was 31.0±10.5ms, ranging from 16.1 to 46.9ms. The mean value of GAG content was 80.1±33.3mg, ranging from 24.9 to 166.0mg while the mean value of GAG concentration was 267.4±165.9mg/cm(3), ranging from 91.3 to 760.5mg/cm(3). T2 values were inversely correlated with GAG concentration with R(2)=0.375, p=0.001 while T1ρ values were also inversely correlated with GAG concentration with R(2)=0.200, p=0.025. This in vivo study confirmed that T1ρ and T2 values correlate with the GAG concentration in living human knee cartilages which corroborate with the previous works. The later (T2 values) is found more reliable in our study and less controversial in literatures. We postulate that T2 values can serve as a non-invasive imaging biomarker in the progress of knee osteoarthritis in terms of both disease diagnosis and treatment response monitoring.


[Current studies of energy expenditure and the quantitative and qualitative adequacy of nutrition of female textile workers].
The study was designed to analyze nutrition and daily energy losses of textile workers. Energy intake constituted in general 2600 kcal for female weavers and 2300 kcal for spinning workers. Weavers' nutrition is redundant in caloric content but deficient in polyunsaturated fat acids, Vitamins A, B, C and calcium salts.


Identification of changes in volatile compounds in dry-cured fish during storage using HS-GC-IMS.
Changes in the volatile components of dry-cured fish during storage at 4 ℃ and 25 ℃ were investigated by HS-GC-IMS fingerprinting combined with principal component analysis (PCA). Topographic plots were used to establish the fingerprints of flavor substances, and 32 signal peaks were identified that corresponded to 22 compounds, mainly aldehydes, ketones, alcohols and esters. During storage at 4 ℃, 3-methylbutanal, dimethyl ketone and hexanal were the main volatile components, while hexanal, 1-octen-3-ol and 3-methylbutanal were the main compounds of dry-cured fish stored at 25 ℃; butyl methyl ketone was only observed at 25 °C. In the early stage of storage, significant changes in octanal, 3-methylbutanal and ethyl acetate were found in dry-cured fish at both temperatures (P < 0.05) while heptanal, pentanal and butanal changed significantly in the late stage (P < 0.05). PCA clearly distinguished the samples in relation to their storage temperature and time. In addition, heat map clustering analysis further revealed the differences and similarities among different samples, and those results were in accordance with the PCA results.


Service user involvement in risk assessment and management: the Transition Inventory.
Drawing on self-prediction theory and the positive benefits of increasing health service user participation in risk assessments, the Transition Inventory (TI) was developed. It is an aid to the assessment of areas that people anticipate will be of difficulty in the next stage of transition, for example from open hospital to the community. The aim of this paper is to determine reliability and convergent/discriminant validity data for the TI and its subscales, including behavioral impulsivity, social pressure, substance misuse, financial/employment, leisure, negative affect, interpersonal and family concerns and social alienation. Eighty-eight male offenders coming towards the end of a period of imprisonment were asked to complete the TI. Their results were compared with the staff-rated Measures of Criminal Attitudes and Associates (MCAA) scale, alcohol blame and causation of crime items. Comparisons with the MCAA's antisocial intent scale, which is a future-orientated scale, and the associates scale allowed for convergent/discriminant validity to be examined with TI scales. With a community offender sample, TI results were used to predict researcher ratings. The TI scales demonstrated adequate internal consistency. Overall, the MCAA's antisocial intent scale had higher correlations with the TI than with a nonfuture-orientated scale. TI scales also demonstrated convergent validity with other measures and preliminary predictive validity with researcher ratings. The TI provides a way to increase service user involvement in the assessments that determine when and how they transfer to settings where they will have more independence.


The nursing process: A supportive model for nursing students' learning during clinical education - A qualitative study.
The aim of this study was to increase understanding of nursing students' learning during clinical education in relation to the nursing process. Nursing students' learning during clinical education is of great importance in creating meaning for theory and development of core competencies. As a theoretical model, the nursing process is challenging to apply in practice for both students and registered nurses, although use of the model has benefits for patient care. This is a descriptive qualitative study with an abductive approach. Twelve semi-structured interviews with nursing students in education from six universities in Sweden were conducted in 2021-2022. Data were examined using qualitative content analysis. The results revealed that the nursing process supported learning when theory and practice 'spoke the same language'. This allows for the opportunity to perform in a consistent way with the theory, while obtaining awareness of an invisible process. Furthermore, the nursing process supported learning by incorporating a thought structure for the student´s professional role through developing independence to conduct a holistic assessment and increasing an understanding of the nurse´s area of responsibility. The results revealed that when theory and practice were aligned, the nursing process became a meaningful structure to develop a sustainable, safe way of thinking for one's future professional role. It is important to use supportive pedagogical models for students and supervisors that facilitate the integration of concepts of the nursing process in practice.


Prevalence of musculoskeletal disorders and associated risk factors in canadian university students.
Musculoskeletal disorders (MSKDs) present a significant burden to health care systems worldwide. Evidence suggests that university students may have unique risk factors for developing MSKDs; however, research on the corresponding prevalence and risk factors of MSKDs in Canadian students is limited. Using a multi-year cross-sectional survey, we aimed to understand the prevalence and risk factors of MSKDs in students at McMaster University. A survey on the prevalence of MSKD as well as potential risk factors was conducted online in the years 2018-2022. Our outcomes were the prevalence of MSKDs over the last 7 days and the last 12 months, as well as presence of lower body, upper body, and spine MSKDs. We investigated risk factors using negative binomial regression analysis, including a sex-stratified analysis. There were a total of 289 respondents in 2018 with a decrease in the number of participants in the subsequent years (n2019 = 173, n2020 = 131, n2021 = 76). Participants reported a median of 2-3 pain sites in the last year and 1-2 pain sites in the last week in all four years. The most prevalent sources of self-reported pain were the lower back and neck. Depending on the year and outcome studied, 59-67% of participants reported neck/lower back pain in the last year, and 43-49% reported it in the last week. Although risk factors were different depending on the year and sex, overall, poorer mental health, being in health care studies, regular sports participation (males only), older age, and less hours of sleep were significantly associated with higher prevalence of MSKDs. This study identified that MSKDs are a prevalent source of pain in university students. While some risk factors, such as mental health, are known to play a role in developing MSKDs, sports activity and academic pressure are risk factors that are unique to students. Our study also suggests that there may be differences in risk factors between sexes.


Knockdown of Rice microRNA166 by Short Tandem Target Mimic (STTM).
Small RNAs, including microRNAs (miRNAs), are abundant in plants and play key roles in controlling plant development and physiology. miRNAs regulate the expression of the target genes involved in key plant processes. Due to functional redundancy among miRNA family members in plants, an ideal approach to silence the expression of all members simultaneously, for their functional characterization, is desirable. Target mimic (TM) was the first approach to achieve this goal. Short tandem target mimic (STTM) is a potent approach complementing TM for silencing miRNAs in plants. STTMs have been successfully used in dicots to block miRNA functions. Here, we describe in detail the protocol for designing STTM construct to block miRNA functions in rice. Such approach can be applied to silence miRNAs in other monocots as well.


Two novel monoclonal antibodies to VWFA3 inhibit VWF-collagen and VWF-platelet interactions.
The interaction of collagen-von Willebrand factor (VWF)-GPIb is essential for platelet adhesion, especially under high shear conditions. VWF, which acts as a bridge between platelets and exposed subendothelium, interacts with collagen through its A3 domain, which is a new target for the antithrombotic agent. To develop functional blockers that specifically inhibit VWF-dependent adhesion of platelets to collagen under high shear stress. To develop murine antihuman VWF A3 monoclonal antibodies (mAbs) by standard hybridoma technology, and characterize their abilities to block interactions between VWF A3 and collagen as well as platelet function. Thirty anti-VWF-A3 mAbs were obtained. Among them, two mAbs, designated as SZ-123 and SZ-125, were found to inhibit VWF-collagen type III interaction. SZ-123 and SZ-125 inhibited the binding of purified human VWF (1.5 or 3 mug mL(-1)) to human placenta collagen type III (IC(50) = 0.07 +/- 0.02 and 0.15 +/- 0.03 mug mL(-1), respectively) or to calf skin collagen type III (IC(50) = 0.48 +/- 0.06 and 0.51 +/- 0.07 mug mL(-1), respectively) coated on plates. Under flow shear condition (1000 s(-1)), SZ-123 and SZ-125 inhibited platelet adhesion on human placenta collagen- or calf skin collagen-coated surfaces. Both mAbs also inhibited platelet aggregation induced by ristocetin, botrocetin or bovine plasma. SZ-123 and SZ-125 inhibited VWF-collagen and VWF-platelet interactions.


Fluorination in the design of membrane protein assemblies.
Protein design approaches based on the binary patterning of nonpolar and polar amino acids have been successful in generating native-like protein structures of amphiphilic α-helices or idealized amphiphilic β-strands in aqueous solution. Such patterning is not possible in the nonpolar environment of biological membranes, precluding the application of conventional approaches to the design of membrane proteins that assemble into discrete aggregates. This review surveys a promising, new strategy for membrane protein design that exploits the unique properties of fluorocarbons-in particular, their ability to phase separate from both water (due to their hydrophobicity) and hydrocarbons (due to their lipophobicity)-to generate membrane protein assemblies. The ability to design such discrete assemblies should enable the disruption of protein-protein interactions and provide templates for novel biomaterials and therapeutics.


Thyroid cartilage invasion in laryngeal and hypopharyngeal squamous cell carcinoma treated with total laryngectomy.
The objective of this study is to analyze the accuracy of computed tomography in detecting malignant thyroid cartilage invasion. In a retrospective chart review, 120 patients with carcinoma of the larynx and hypopharynx underwent computed tomography before total laryngectomy. These data were compared with the histological specimens. Multidetector computed tomography (MDCT) scan had a positive predictive value (PPV) of 76 % and a negative predictive value (NPV) of 69 %. The specificity of MDCT was 89 % and sensitivity was 46 %. Comparison between radiologic suspected cartilage invasion and histologic results showed a significant correlation (p < 0.02). We found no significant impact of cartilage invasion concerning survival rates (5-year overall survival p = 0.683; 5-year disease-free survival p = 0.711). Preoperative CT scan is an important instrument in detecting neoplastic cartilage invasion.


A Golgi study of the lateral reticular nucleus in the rat.
The organization of the lateral reticular nucleus (LRN) of the rat was investigated by using the Golgi technique. Golgi-Cox preparations revealed neurons with shapes similar to those observed in Nissl-stained preparations. Fusiform cells possess rectilinear dendrites with secondary dendrites which are longer than the parent stem. The remaining cell types have short dendrites which branch for three or four generations and follow a tortuous course. These two types of neurons are similar to the isodendritic and allodendritic neurons which have been reported in the reticular formation. The neurons throughout the LRN form cell clusters. In Golgi preparations five to ten cells are seen in each cluster but counterstaining reveals that the clusters are made up of many more cells than the Golgi preparations suggest. Many cells lie in close apposition and the dendrites of the cells in each cluster intertwine to form dendritic plexuses. Dendritic input from both neighbouring and distant cell clusters also contributes to the plexus formations within each cell cluster. Under high magnification, the dendrites show irregularities in their contours, including warty excrescenses, bumps and an array of spines, some of which are pedunculated. The appendages are confined primarily to distal portions of the dendrites, with few spines observed on the somata and proximal dendrites. Varicosed dendrites are also in common occurrence throughout the nucleus.


Activated thrombin activatable fibrinolysis inhibitor (TAFIa) is associated with inflammatory markers in inflammatory bowel diseases TAFIa level in patients with IBD.
Thrombin activatable fibrinolysis inhibitor (TAFI) has been reported to be involved in the pathogenesis and progression of inflammatory bowel disease (IBD). Activated TAFI (TAFIa) attenuates fibrinolysis by cleaving C-terminal lysine residues thus down-regulating plasminogen activation. To date, no reports on TAFIa in IBD have been published. Plasma levels of TAFIa were measured using a functional assay in 55 consecutive patients with ulcerative colitis (UC) and 50 with Crohn's disease (CD). Associations of TAFIa with disease activity, hemostatic variables and inflammatory markers were assessed. Plasma TAFIa was higher in CD patients than in those with UC. The disease activity correlated positively with TAFIa levels in the UC group, but not in the CD group. In UC patients, there were positive correlations of TAFIa with white blood cells, C-reactive protein and fibrinogen and an inverse correlation with albumin. In the CD group, a positive correlation was shown for C-reactive protein, fibrinogen and platelet count, while a negative correlation was noted for albumin. This study is the first to show that TAFIa is increased in CD patients compared with UC and its levels are associated with inflammatory markers in both forms of IBD. These findings fit in the hypothesis that TAFIa may be a marker of active IBD, and in particular of active UC.


Microbiological diagnostic procedures for respiratory cystic fibrosis samples in Spain: towards standard of care practices.
The microbiological procedures for cystic fibrosis (CF) samples of 17 participating Spanish centers were examined to verify their compliance with current international and national guidelines and to implement the best standards of care for microbiology practices. A 47-item questionnaire covering different CF microbiology aspects was sent to participant laboratories. Telephone interviews were performed when necessary. Data about samples processing for bacteria, mycobacteria and fungi were collected. Gene sequencing (71%), MALDI-TOF (59%) or both (94%) were available for most laboratories. Susceptibility testing was performed by automated microdilution systems (94%) and manual diffusion methods (59%). However, a low use of selective media for Staphylococcus aureus (59%) and Burkholderia cepacia complex (71%), and of epidemiological typing methods (41%) was reported. Most Spanish laboratories are in agreement with consensus guidelines for the processing of CF respiratory samples, but need to improve in the use of specific selective media and typing methods for epidemiologic studies.


Pathogenesis of Escherichia coli cystitis and pyelonephritis: apparent lack of significance of bacterial motility and chemotaxis towards human urine.
All 45 microscopically motile urinary isolates tested here (37 Escherichia coli, two Enterobacter cloacae, two Citrobacter freundii, three Proteus mirabilis and one Proteus morganii) were strongly attracted to fresh human urine in a capillary chemotaxis assay. This observation suggested that urine taxis of gram-negative bacteria promotes their invasion of the human lower urinary tract and their ascension to the kidney(s). However, the incidence of motile isolates and their activity in urine taxis assays were similar for fecal E. coli isolates, for isolates from patients with recurrent cystitis and from patients with presumed pyelonephritis (E. coli blood isolates with concomitant E. coli bacteriuria). Thus, the present study of E. coli did not support the hypothesis that bacterial motility is a virulence factor in urinary tract infection.


Real-life burden of hospitalisations due to COPD exacerbations in Spain.
Patients with chronic obstructive pulmonary disease (COPD) often suffer episodes of exacerbation of symptoms (ECOPD) that may eventually require hospitalisation due to several, often overlapping, causes. We aimed to analyse the characteristics of patients hospitalised because of ECOPD in a real-life setting using a "big data" approach. The study population included all patients over 40 years old with a diagnosis of COPD (n=69 359; prevalence 3.72%) registered from 1 January 2011 to 1 March 2020 in the database of the public healthcare service (SESCAM) of Castilla-La Mancha (Spain) (n=1 863 759 subjects). We used natural language processing (Savana Manager version 3.0) to identify those who were hospitalised during this period for any cause, including ECOPD. During the study 26 453 COPD patients (38.1%) were hospitalised (at least once). Main diagnoses at discharge were respiratory infection (51%), heart failure (38%) or pneumonia (19%). ECOPD was the main diagnosis at discharge (or hospital death) in 8331 patients (12.0% of the entire COPD population and 31.5% of those hospitalised). In-hospital ECOPD-related mortality rate was 3.11%. These patients were hospitalised 2.36 times per patient, with a mean hospital stay of 6.1 days. Heart failure was the most frequent comorbidity in patients hospitalised because of ECOPD (52.6%). This analysis shows that, in a real-life setting, ECOPD hospitalisations are prevalent, complex (particularly in relation to heart failure), repetitive and associated with significant in-hospital mortality.


PDK1 protein phosphorylation at Thr354 by murine protein serine-threonine kinase 38 contributes to negative regulation of PDK1 protein activity.
Murine protein serine-threonine kinase 38 (MPK38) is a member of the AMP-activated protein kinase-related serine/threonine kinase family, which acts as cellular energy sensors. In this study, MPK38-induced PDK1 phosphorylation was examined to elucidate the biochemical mechanisms underlying phosphorylation-dependent regulation of 3-phosphoinositide-dependent protein kinase-1 (PDK1) activity. The results showed that MPK38 interacted with and inhibited PDK1 activity via Thr(354) phosphorylation. MPK38-PDK1 complex formation was mediated by the amino-terminal catalytic kinase domain of MPK38 and the pleckstrin homology domain of PDK1. This activity was dependent on insulin, a PI3K/PDK1 stimulator, as well as various apoptotic stimuli, including TNF-α, H(2)O(2), thapsigargin, and ionomycin. MPK38 inhibited PDK1 activity in a kinase-dependent manner and alleviated PDK1-mediated suppression of TGF-β (or ASK1) signaling, probably via the phosphorylation of PDK1 at Thr(354). In addition, MPK38-mediated inhibition of PDK1 activity was accompanied by the modulation of PDK1 binding to its positive and negative regulators, serine/threonine kinase receptor-associated protein and 14-3-3, respectively. Together, these findings suggest an important role for MPK38-mediated phosphorylation of PDK1 in the negative regulation of PDK1 activity.


The efficiency of prostaglandin E2 vaginal suppositories versus intracervical prostaglandin gel for induction of labor in patients with unfavorable inducibility prospects.
Two different applications of prostaglandin E2 for induction of labor were randomly used in 113 women with an unripe cervix; 57 women were given prostaglandin suppositories each containing 2.5 mg PGE2 in a basis of Witepsol S55 (Dynamit Nobel), another 56 women were treated with intracervical gel containing 1 mg PGE2 in 5 g hydroxypropylmethyl cellulose. The treatment was repeated after 4 h if the cervix was still unripe, and the procedure was repeated the following day if the cervix was still unfavorable. Cesarean sections was performed within 48 h after the start of induction and before the second stage of labor in 8 women in the suppository group and 7 women in the intracervical gel group. Of the remaining 98 women, 73% (34/48 women) in the suppository group and 36% (18/50 women) in the cervical gel group had delivered within 24 h (p less than 0.01). After 48 h, 88% (42/48 women) in the suppository group and 74% of the women (37/50 women) in the cervical gel group had delivered (p greater than 0.05). The induction-delivery interval in the suppository group was half that found in the cervical gel group. There was no significant difference between the two groups in the use of instrumental vaginal deliveries and cesarean sections nor was there any difference with regard to fetal distress. The post-delivery condition of the newborn was similar in the two groups. No side-effects were reported in either of the two groups.


Decrease of collagen biosynthesis ability of rat kidney fibroblasts transformed with SV--40 virus.
Rat kidney fibroblasts transformed with SV-40 produce "in vitro" a significantly lower amount of hydroxyproline-containing material which is collagenase sensitive as compared to normal cells. In contrast to normal fibroblast cultures, no collagenous material was found by histochemical methods in intercellular spaces of transformed cultures.


HLA-A, B, C, DR, MT, and MB antigens in recurrent aphthous stomatitis.
In this report we have investigated the frequencies of HLA-A, B, C, DR, MT, and MB markers in 26 Sicilian subjects affected by recurrent aphthous stomatitis (RAS) and in 84 healthy controls. Our data show that the frequency of HLA-DR7 antigen is significantly increased in RAS-affected persons (61.5% versus 21.4%; pc less than 0.0025), whereas the B5 antigen frequency is decreased significantly (absent in patients versus 27.3% in controls; pc = 0.04). Thus, present results suggest that HLA-linked genetic factors may play a role in the development of RAS.


[Experiments in vitro with Litomosoides carinii (Nematoda: Filarioidea). I. Maintenance of adult females and microfilariae as well as release of microfilariae in different culture media (author's transl)].
Embryos of L. carinii continue intrauterine development to microfilariae and are totally released into the medium within 5--6 days when the latter (Tc 199) is changed daily and air is used as the gas phase. Oogenesis or further fertilization of eggs, however, does not occur in vitro in any of the media examined by us. One female releases 140 X 10(3) microfilaria/day on an average in vitro within 5--6 days. Mean initial numbers of 300 X 10(3) Mf/female/day are observed. Addition of equine serum inhibits microfilarial release in vitro; normal cotton rat serum prolongs survival of females while total numbers of released microfilariae or retained embryonic stages are not increased. The serum of post-patent animals does not influence the numbers of released microfilariae or their viability or survival of females. Microfilariae released in vitro in Tc 199 + 33% normal cotton rat serum survive for more than 8 days, when air is used as the gas phase and the medium is changed daily. Microfilariae isolated from the blood of patent animals survive for at most 6 days, at a 48-hourly change of medium survival does not even exceed 4 days.


[Micromethod of estimation of total bilirubin using a single stable reagent (author's transl)].
The authors propose a method of estimation of total bilirubin characterised by the use of a single stable reagent, excellent reproducibility and a particularly narrow correlation (r = 0.993) with Michaelsson's method. They study the influence of protein, reduced glutathion and hemoglobin on the reaction.


Modulating the Nordic Hamstring Exercise From "Zero to Hero": A Stepwise Progression Explored in a High-Performance Athlete.
The Nordic hamstring exercise (NHE) is commonly implemented to selectively improve eccentric knee-flexor strength. However, the standard version of the exercise (leveled shanks, extended hip joint) is too strenuous for most individuals, whose muscle activity rapidly decreases at extended knee angles. Hitherto, a gradual approach to the exercise has been missing. In this exploratory case study, we investigated elite performance to introduce a stepwise progression to the NHE. To determine the extent to which exercise modifications (shank inclination, additional load, hip flexion) altered NHE mechanics. One male long jumper (age = 33 years, height = 171 cm, mass = 69 kg) with high-level expertise in the NHE performed 20 exercise variations. The corresponding kinematics, kinetics, and electromyographic activity of the biceps femoris long head (BFlh) and semitendinosus (ST) muscles were evaluated. Exercise variations demonstrated gradually increased peak moments from 69% (zigzag pose) to 154% (inclined bent single-legged version) versus a standard NHE. Shank inclination and additional load elicited small to moderate effects on peak moments, BFlh, and ST (0.24 ≤ d ≤ 0.72), whereas hip flexion largely affected all tested variables (2.80 ≤ d ≤ 6.66), especially muscle activity (BFlh = -63%; ST = -55% of maximal voluntary isometric contraction). These insights will help practitioners and scientists design multifaceted stepwise NHE progressions by creating differentiated stimuli that best match the strength capacities of individuals and address their specific needs.


The reliability and validity of pain interference measures in persons with cerebral palsy.
To evaluate the reliability and validity of 2 measures of pain interference in persons with cerebral palsy (CP). Standardized interviews to assess pain and impact of pain on activities. University medical center. Fifty adults with CP. Patients asked to rate pain's intensity, interference with general activities, and depression levels. Pain interference scales: Chronic Pain Grade (CPG) and Brief Pain Inventory (BPI); rating of disability: Craig Handicap Assessment and Reporting Technique (CHART); rating of depression: Center for Epidemiologic Studies Depression (CES-D) Scale. Mean interference of pain on 3 CPG items (pain interference with daily activities, social activities, work) were 1.74 +/- 2.45, 1.06 +/- 2.05, and.89 +/- 1.84 (out of 10), respectively. Mean interference on 10 modified BPI interference items ranged from 2.28 +/- 3.01 to 3.67 +/- 3.15 (out of 10). The composite CPG interference score did not correlate significantly with pain intensity. However, the composite BPI interference score did correlate significantly with pain intensity (r = .66, P < .01). There was no significant association shown between average pain and the CHART score (r = -.21, NS). Pain showed a significant association with CES-D score (r = .45, P < .05). Internal consistency of the 3 CPG items was inadequately low (Cronbach alpha = .59), whereas that of the 10 BPI items was excellent (.89). The pain interference items of the BPI serve as a reliable and valid measure of pain's impact on persons with CP-related pain.


Multi-platforms medical computer systems integration.
Presently, software architects face the challenge of integrating and linking different application software packages built on different computer platforms. Often they inherit various systems, ranging from mainframe to PDA-based applications. The first stage before programming different interfaces is to identify the means of communications most suitable for particular systems. The experience of the Mount Sinai Medical Center in New York, which combines a hospital, a healthcare network, a research center and a medical school, illustrates common problems faced by a number of medical institutions. This paper will discuss the various options, including the Internet, software architects have, and how they can use them during the development of an infrastructure for health care systems.


Precise and rapid isotopomic analysis by (1)H-(13)C 2D NMR: Application to triacylglycerol matrices.
An optimized HSQC sequence was tested and applied to triacylglycerol matrices to determine their isotopic and metabolomic profiles. Spectral aliasing and non-uniform sampling approaches were used to decrease the experimental time and to improve the resolution, respectively. An excellent long-term repeatability of signal integrals was achieved enabling to perform isotopic measurements. Thirty-two commercial vegetable oils were analyzed by this methodology. The results show that this method can be used to classify oil samples according to their geographical and botanical origins.


Pregnancy and progression of diabetic nephropathy.
Pregnancy could damage kidney function in diabetic nephropathy. We investigated the long-term impact of pregnancy on the progression of diabetic nephropathy. Our observational follow-up study included all women patients with Type I (insulin-dependent) diabetes mellitus who developed diabetic nephropathy between 1970 and 1989 at Steno Diabetes Center (n = 93). Follow-up lasted 16 years (range 3-28) from the onset of diabetic nephropathy until death or the year 2000. A total of 26 women became pregnant after the onset of diabetic nephropathy (group A). The remaining 67 served as control subjects (group B). All patients received aggressive antihypertensive treatment (blood pressure goal < 140/90 mmHg). The two groups were comparable at onset of diabetic nephropathy regarding blood pressure, albuminuria, s-cholesterol, smoking, retinopathy and s-creatinine (mean 79(SD 23) micromol/l). The slopes of 1/s-creatinine (1000.l.micromol(-1).year(-1)) during the whole observation period were -0.39(0.40) compared with -0.41(0.70) (group A vs B-NS). The slopes of 1/s-creatinine before and after pregnancy were similar. Decline in creatinine clearance (ml/min/yr) was 3.2 (3.4) compared with 3.2 (5.1) (group A vs B -NS). At the end of follow-up, 35 % (95 %-CI:17-53) of the pregnant women had died and 19 % (7-39) had reached end stage renal disease compared to 34 % (23-45) and 24 %(14-34) of the control subjects, respectively(NS). Group A and B had similar blood pressure levels during the whole observation period: 136(13)/83(7) vs 139 (14)/85(7) mmHg (NS). Pregnancy has no adverse long-term impact on kidney function and survival in Type I diabetic patients with well-preserved kidney function (normal serum creatinine) suffering from diabetic nephropathy.


Interpretation of IgG subclass values: a comparison of two assays.
Because we have noted discordant results in the measurement of IgG subclass concentrations by means of a widely available commercial radial immunodiffusion (RID) kit in comparison with an enzyme-linked immunosorbent assay (ELISA) developed at the Centers for Disease Control (CDC), we conducted in a blinded manner a comparison of the two assays, using sera from 48 healthy children. The correlation coefficients between the assays were 0.92, 0.82, 0.93, and 0.86 for the IgG1, IgG2, IgG3, and IgG4 assays, respectively. However, the RID assay assigned lower values for IgG1 and IgG4 determinations than the ELISA did. Furthermore, the "normal lower range values" provided by the RID assay were higher for each IgG subclass. When the sera from the healthy control subjects were analyzed with the RID assay, 12 (25%) of 48 subjects had values below the normal range for at least one subclass measurement. In contrast, with the CDC ELISA, all values were within the 95% confidence limits determined for the CDC ELISA. We suggest that age-specific normal limits be established with the use of sera from many healthy subjects for any assay measuring IgG subclass concentrations. As new groups of immunodeficiencies are defined and potential therapies are advocated, careful attention to assay standardization will result in a clearer delineation of these disease groups and of their response to treatment.


[Influence of medical outliers in patients with femoral neck fracture].
The objective is to describe and analyze how outlier admission influences hospital stay and the appearance of complications in patients with a femoral neck fracture treated with arthroplasty. A historical cohort study was carried out in which the group of patients with a displaced fracture of the femoral neck who had an outlier admission was defined as an exposed cohort, that is, they were admitted to a hospitalization area not belonging to the Orthopedic Surgery and Traumatology department, unlike the unexposed cohort, that included patients admitted to a hospitalization area assigned to the Orthopedic Surgery and Traumatology department. Outlier admission was a risk factor for requiring a postoperative transfusion (RR 1.52, 95% CI 1.05-2.21; P=.035), to have a postoperative stay longer than 5 days (RR 1.35, 95% CI 1.04-1.74; P=.038) and to suffer general postoperative complications (RR 1.35, 95% CI 1.02-1.78; P=.048). Outlier admission is a threat to the quality and safety of health care. In patients over 80 years of age, medical outliers is a risk factor for postoperative transfusion and systemic postoperative complications.


Color stability of dental enamel bleached with violet LED associated with or without Low concentration peroxide gels.
This study aimed to evaluate the in vitro color of dental enamel bleached with the violet LED, associated with or without low-concentration of peroxide; analyzed in two time intervals: 24 h later and 6 months after the treatment. Ninety fragments of bovine teeth (6 × 6 mm and 3 mm thick) were randomly divided into 6 groups according to bleaching treatment: NB - no bleaching, VL - Violet LED, HP- 7.5 % hydrogen peroxide, HP + VL - 7.5 % hydrogen peroxide + violet LED, CP - 22 % carbamide peroxide, CP + VL - 22 % carbamide peroxide + violet LED. The color change was analyzed by using a spectrophotometer, at time intervals of 24 h and 6 months after performing the bleaching techniques (n = 12). Scanning electron microscopy (SEM) was performed to verify the enamel surface morphology after treatment (n = 3). The color change data were analyzed using ANOVA and a post-hoc Tukey tests (α = 0.05). The VL group showed chromatic changes after 24 h of treatment, however the groups submitted to bleaching gel treatments associated with or without violet LED (CP + VL, CP, HP, HP + VL) showed the highest color change values at all time intervals analyzed, with color stability after 6 months of treatment for the CP + VL group. Scanning electron microscopy analysis showed the greatest change in enamel surface for Groups CP and HP. It could be concluded that violet LED had immediate bleaching effect without promoting significant changes in enamel morphology, however the association with carbamide peroxide 22 % showed color stability and greater bleaching efficacy than the use of violet LED alone, after 6 months.


The effect of local anaesthetics on epinephrine absorption following rectal mucosal infiltration.
This study was undertaken to investigate the effects of lidocaine and bupivacaine on epinephrine absorption following rectal mucosal infiltration, to assess the cardiovascular and metabolic effects of the absorbed epinephrine and to compare the systemic absorption of the local anaesthetics employed. Three groups of five greyhounds received 1.5 micrograms.kg-1 of epinephrine 1:200,000 in lidocaine 0.5 per cent, bupivacaine 0.5 per cent or 0.9 per cent saline. Plasma epinephrine, lidocaine, bupivacaine, lactate, glucose and potassium concentrations were measured at 1, 2, 5, 10, 15 and 30 minutes following infiltration. Plasma epinephrine concentrations were significantly higher in the lidocaine group at one and two minutes following infiltration. Plasma bupivacaine concentrations were significantly higher than plasma lidocaine concentrations throughout the study period. There were no significant differences in metabolic or biochemical indices within or between the three groups. A local vasodilatory action of lidocaine may enhance epinephrine absorption. Differences in hepatic uptake and rate of metabolism may explain the increased plasma bupivacaine measured. Lidocaine may be the local anaesthetic of choice for ano-rectal procedures, especially when large volumes of local anaesthetic are being infiltrated.


Clay particle retention in small constructed wetlands.
Constructed wetlands (CWs) can be used to mitigate non-point source pollution from arable fields. Previous investigations have shown that the relative soil particle retention in small CWs increases when hydraulic load increases. This paper investigates why this phenomenon occurs, even though common retention models predict the opposite, by studying clay and silt particle retention in two Norwegian CWs. Retention was measured with water flow proportional sampling systems in the inlet and outlet of the wetlands, and the texture of the suspended solids was analyzed. The surface area of the CWs was small compared to the watershed area (approximately 0.07%), giving high average hydraulic loads (1.1 and 2.0 md(-1)). One of the watersheds included only old arable land, whereas the other included areas with disturbed topsoil after artificial land leveling. Clay particle retention was 57% for the CW in the first watershed, and 22% for the CW in the disturbed watershed. The different behavior of the wetlands could be due to differences in aggregate size and stability of the particles entering the wetlands. Results showed that increased hydraulic loads did affect CW retention negatively. However, as runoff increased, soil particles/aggregates with higher sedimentation velocities entered the CWs (e.g., the clay particles behaved as silt particles). Hence, clay particle settling velocity is not constant as assumed in many prediction models. The net result was increased retention.


Modeling COVID-19 effects on SDGs using system dynamics in Egypt.
The coronavirus disease 2019 (COVID-19) poses a significant threat to achieving the Sustainable Development Goals (SDGs). To address this challenge, a thorough examination of the pandemic's influence on four SDGs in Egypt is presented in a system dynamic model. The addressed goals are related to no poverty (SDG 1), zero hunger (SDG 2), decent work and economic growth (SDG 8), and climate action (SDG 13). The model is simulated over 35 years extending from 2015 to 2050. Furthermore, a web-based interactive learning environment is developed to analyze the interdependencies among public health activities and study the impacts of possible intervention countermeasures or prevention policies. Indicators including poverty line, food insecurity, gross domestic product (GDP) growth rate, and greenhouse gas (GHG) emissions are evaluated to track Egypt's performance in relation to SDGs 1, 2, 8, and 13. According to the simulation model, the poverty line will continue to decline until it reaches around 16% by 2050. According to the significant governmental efforts to follow its vision of 2030, Egypt can achieve a decreasing percentage of food insecurity, reaching 3% in 2030, and this percentage will continue to decrease until it reaches full sufficiency by 2050. The GDP growth rate will rise every year until it reaches 13.71% in 2050. With respect to climate, GHG emissions are predicted to fall to roughly 97 Mt CO2-equivalents by 2050. This approach revitalizes debates about the achievement of SDGs amid the crisis and acts as a powerful tool that aids decision-makers in identifying leverage points to avoid the long-term negative repercussions of the crisis on the economy, people, and environment.


Substance P and antinociception.
Substance P (SP)-induced antinociception is still a topic of controversy. Some investigators have failed to see an antinociceptive effect of SP, particularly following intraperitoneal administration. In the present experiments SP induced significant hot plate antinociception in male mice, following intraperitoneal administration. SP exhibited a bell-shaped dose response curve, and the antinociceptive effect was dependent on the pH of the vehicle. The antinociceptive effect of SP lasted for at least 1 hr and was naloxone-reversible. The antinociceptive effect of SP could be prevented by housing subjects collectively rather than individually during the experiment. In conclusion, the bell-shaped dose response curve, the solution pH and different testing procedures all influence the effects of SP on nociception. Given this complexity, it is not surprising that some experiments fail to demonstrate antinociception following SP administration.


[Clinical research in radiotherapy oncology in private sector: A reality with a possible future?]
Clinical research is one of the activities of medical practice, particularly in oncology including radiotherapy. It was developed in the public sector and then in the liberal sector, in compliance with regulatory institutions, resulting in a doubling of inclusions over the last decade. Setting up and developing clinical research in the liberal sector are major axes in terms of interests: improving the proposition of care, access to innovation, to keep patients, intellectual stimulation, encouraging recruitment, activity of scientific publications, financial valorisation, quality of visibility… An inventory on French national territory via the national union of iadiotherapists oncologists (SNRO) and the club of liberal oncologists (Colib) is reported in this article, as well as examples of structuring and organization.


DNA topoisomerase II inhibition and gene amplification in V79/B7 cells.
Topoisomerase II inhibitors such as etoposide (VP16) are able to stabilize the enzyme-DNA complex by trapping the topoisomerase on DNA without affecting its strand-break activity. To test if this inhibition resulting in chromosomal breakage via double-strand breaks could underlie gene amplification, we performed VP16 treatments followed by selection for PALA resistance in V79/B7 Chinese hamster cells. We found that VP16 induced PALA-resistant cells very efficiently, and in a dose-dependent manner. On the other hand VP16 in combination with 3-aminobenzamide (3AB), an inhibitor of poly(ADP-ribose) polymerase involved in DNA repair, reduced the frequency of PALA-resistant cells. Cytogenetic analysis revealed a higher number of chromosomal aberrations in VP16-treated cells than in cells treated with VP16 plus 3AB. These results suggest a correlation between frequency of chromosomal aberrations and frequency of PALA-resistant cells, and are consistent with models which consider chromosomal breakage as an important step in initiating gene amplification.


Mechanical Unfolding of Proteins-A Comparative Nonequilibrium Molecular Dynamics Study.
Mechanical signals regulate functions of mechanosensitive proteins by inducing structural changes that are determinant for force-dependent interactions. Talin is a focal adhesion protein that is known to extend under mechanical load, and it has been shown to unfold via intermediate states. Here, we compared different nonequilibrium molecular dynamics (MD) simulations to study unfolding of the talin rod. We combined boxed MD (BXD), steered MD, and umbrella sampling (US) techniques and provide free energy profiles for unfolding of talin rod subdomains. We conducted BXD, steered MD, and US simulations at different detail levels and demonstrate how these different techniques can be used to study protein unfolding under tension. Unfolding free energy profiles determined by BXD suggest that the intermediate states in talin rod subdomains are stabilized by force during unfolding, and US confirmed these results.


Hospital Revenue, Cost, and Contribution Margin in Inpatient Versus Outpatient Primary Total Joint Arthroplasty.
Removal of primary total knee arthroplasty (TKA) and primary total hip arthroplasty (THA) from the inpatient-only list has financial implications for both patients and institutions. The aim of this study was to evaluate and compare financial parameters between patients designated for inpatient versus outpatient total joint arthroplasty. We reviewed all patients who underwent TKA or THA after these procedures were removed from the inpatient-only list. Patients were statistical significance into cohorts based on inpatient or outpatient status, procedure type, and insurance type. This included 5,284 patients, of which 4,279 were designated inpatient while 1,005 were designated outpatient. Patient demographic, perioperative, and financial data including per patient revenues, total and direct costs, and contribution margins (CMs) were collected. Data were compared using t-tests and Chi-squared tests. Among Medicare patients receiving THA, CM was 89.1% lower for the inpatient cohort when compared to outpatient (P < .001), although there was no statistical significance difference between cohorts for TKA (P = .501). Among patients covered by Medicaid or Government-managed plans, CM was 120.8% higher for inpatients receiving THA (P < .001) when compared to outpatients and 136.3% higher for inpatients receiving TKA (P < .001). Our analyses showed that recent costs associated with inpatient stay inconsistently match or outpace additional revenue, causing CM to vary drastically depending on insurance and procedure type. For Medicare patients receiving THA, inpatient surgery is financially disincentivized leaving this vulnerable patient population at a risk of losing access to care. Retrospective Cohort Study.


A cell membrane "gp70" associated with Fv-4 gene: immunological characterization, and tissue and strain distribution.
Fv-4r is a dominant resistance gene which controls susceptibility of mice to exogenous infection with ecotropic murine leukemia virus (MuLV). A MuLV env-gene product related to gp70 on cells from uninfected Fv-4r mice has been found. Expression of this molecule is closely linked to the resistance allele. Antigenic determinants on the Fv-4r gp70 are similar to many ecotropic and some dualtropic MuLV gp70s but different from xenotropic and amphotropic MuLV gp70s. The Fv-4r gp70 molecule also has unique antigenic determinants since it is recognized by Fv-4 specific antisera which do not recognize other cell membrane gp70s or viral gp70s. The Fv-4-specific cell membrane gp70 is detectable on cells from thymus, spleen, lymph node, bone marrow, and embryo fibroblasts from Fv-4r mice, but not from Fv-4s mice. Slight differences in electrophoretic mobility of Fv-4r gp70 are found on different tissues. This unique cell membrane gp70 may be causally related to Fv-4 resistance.


Syphilitic hepatitis: a case report and review of the literature.
Syphilis is a common disease that has been researched and focused on for many years, however, syphilitic hepatitis has not been well-recognized. We report this case of syphilitic hepatitis with intrahepatic cholestasis and liver granulomas to make a deeper impression. A 47-year-old male was admitted with jaundice and rashes. The laboratory examination showed abnormal liver enzymes with significant increases in ALP and GGT but mild increases in ALT and AST. His HBV surface antigen was weakly positive, with negative HIV antibody, HCV antibody, and undetectable HBV DNA. The rapid plasma reagin test and the Treponema pallidum particle assay tests for Syphilis were both positive. Abdominal ultrasonography and magnetic resonance cholangiopancreatography revealed the normal biliary tract, liver, and spleen. The liver pathological examination showed cholangiocyte inflammation and micro-granulomas with coagulation necrosis. After 2 months of benzathine penicillin treatment, his liver enzyme decreased rapidly and remained normal after 1-year of follow-up. Increased liver enzymes, intrahepatic cholestasis and liver granulomas with well-response to antibiotics may provide clues for the diagnosis of syphilitic hepatitis.


Fighting Cancer Resistance: An Overview.
The inherent or developed resistance of many cancer cells to chemotherapy and irradiation is actually the main challenge to overcome in cancer treatment. It is well known that cancer cells are characterized by several hallmarks, and it seems that the ability to evolve ways to evade stressful conditions and killing therapies must be consider another typical characteristic displayed by all malignant cells. This overview aims to provide a concise description of the main mechanisms involved in the promotion of resistance to anticancer therapy and to describe the most frequent challenges faced in the war against cancer therapy resistance.


Survival of pediatric patients requiring admission in the intensive care unit post hematopoietic stem cell transplantation: Prognostic factors associated with mortality.
Although hematopoietic stem cell transplantation (HSCT) is the only curative option for some children with malignant and nonmalignant disorders, the procedure itself carries a high risk of complications. A proportion of children undergoing HSCT develop severe transplant-related complications requiring hospitalization in the pediatric intensive care unit (PICU). A retrospective cohort study included 793 children with malignant and nonmalignant diseases that underwent 963 HSCTs in two large pediatric hospitals over 15 years. Ninety-one patients needed 105 (11%) PICU admissions. The objective of the study was to analyze the risk factors associated with morbidity and mortality in children post HSCT who were admitted to the PICU. Survival rate of a single PICU hospitalization was 43%. Long-term survival rate (classified as 1 year and 3 years) was 29.1% and 14.9% among PICU hospitalized patients compared with 74.6% and 53.3% among patients who had undergone HSCT and did not require PICU hospitalization. Factors found to have a significant negative association with PICU survival were respiratory failure as indication for PICU admission, neutropenia, graft-versus-host disease, mechanical ventilation, inotropic support, need for dialysis, and multiple-organ failure (MOF) with more than one systemic intensive intervention. The strongest prognostic factors associated with mortality were MOF (p < .001) and the need for inotropic support (p = .004). Neutropenia was found to be negatively associated with survival, suggesting non-engraftment and late engraftment are important risk factors for HSCT patients hospitalized in PICU. MOF and inotropic support were found to be the main negatively associated predictive factors with survival.


Photoaffinity labelling of the TSH receptor on FRTL5 cells.
An investigation of the properties of TSH receptors on FRTL5 cells using affinity labelling with a 125I-labelled photoactive derivative of TSH is described. Our studies suggest that FRTL5 cells contain 2 principal types of cell surface TSH receptors. One form, probably a precursor, consists of a single polypeptide chain (Mr 120,000) with an intrachain loop of amino acids formed by a disulphide bridge. The other type of receptor consists of a water-soluble A chain (Mr 55,000) linked to an amphiphilic B chain (Mr 35,000) by a disulphide bridge. The 2 chain structure is probably derived from the single chain 120,000 protein by enzymatic cleavage of peptide sequences within the loop of amino acids formed by the intrachain disulphide bridge.


Latest OECD figures confirm Canada as a public health laggard.
Despite the Canadian public health community's commitments to promoting public policy that supports health, evidence indicates that Canada's public health picture continues to decline. This may be due in part to the failure of public health agencies and local public health units to engage in public policy advocacy and public education about the social determinants of health. Examples of such activities by local public health units are now available and provide a model for such activity.


Adenosine deaminase inhibitors. Synthesis and biological evaluation of aralkyladenines (ARADS).
Several 9-aralkyladenines have been prepared and their ADA inhibitory activity was determined. A minimum of two carbon atoms separating the aromatic ring from the adenine-bearing carbon (C3') was found essential for potent activity.


Clinical outcomes and 30-day readmissions for heart failure with reduced ejection fraction with cardiorenal syndrome: A National Cohort Study.
Literature regarding outcomes of cardiorenal syndrome (CRS) among heart failure with reduced ejection fraction (HFrEF) is limited. To study the clinical outcomes and 30-day readmission rates of CRS patients with HFrEF. Data from the Nationwide Readmissions Database (NRD) that constitutes 49.1% of the stratified sample of all hospitals in the United States (US), representing >95% of the national population, was analyzed for the CRS with HFrEF visits from 2018 to 2019. CRS was defined by the ICD-10 codes. Out of the 1,530,749 index CRS-related hospitalizations (mean age:64.37 ± 13.30 years; 38.6%females) 73,126 (6.0%) CKD I-II, 883,119 (72.6%) CKD III-IV, and 258,835 (21.3%) CKD V-and-more related encounters were recorded. Mortality was higher among CKD stage V-and-more in comparison to other subgroups(7.6%vs5.73%;p < 0.001). AKI with underlying CKD was more common among stage III-IV compared to other subgroups (55.9%vs43.7%;p < 0.001). Respiratory failure, the second major complication, was more common among stage V-and-more compared to other subgroups (32.5%vs30%;p < 0.001). The overall CRS-related 30-day readmission rate was 22.7%, with CKD V-and-more accounting for highest rates(29.89%), followed by CKD stage III-IV(20.05%) and CKD I-II(12.99%). The primary etiology for 30-day readmission was cardiovascular among all subgroups (54.2%, 54.6%, and 41.80%, which corresponds to CKD I-II, CKD III-IV and CKD V-and-more, respectively). CRS among HFrEF accounts for substantial healthcare burden with high 30-day readmission rates. Higher all-cause mortality and 30-day readmissions were associated with worse renal disease. This would suggest that more vigilance is needed by physicians for discharge planning among this patient population.


Comparing rivers to lakes: Implications for drowning prevention.
To contrast unintentional fatal drowning in rivers with lakes to determine appropriateness for application of existing river drowning prevention strategies. A total population retrospective cross-sectional analysis using coronial data. Australia, 1 July 2013 to 30 June 2018. Children and adults (n = 342) who died from unintentional drowning in a river or lake. Incidence, crude fatality rates, relative risk (95% confidence interval) and chi-square tests of independence for risk factors for unintentional fatal drowning. Subset analysis of land management for lake drowning locations. Four-fifths (82%) occurred in rivers. Lake drowning was more likely among 0- to 17-year-olds, Aboriginal and Torres Strait Islander people and when swimming or using watercraft. River drowning most commonly occurred following a fall into water and with alcohol involvement. Drowning risk in very remote areas was elevated for both lakes (relative risk = 18.34; 95% confidence interval: 1.61-209.44) and rivers (relative risk = 15.89; 95% confidence interval: 5.56-45.37) compared to major cities. Those responsible for land and water management at lakes were primarily local government (59%), water authorities (32%) and parks and wildlife authorities (7%). In contrast to a focus on adults and alcohol in existing river drowning prevention strategies, lake interventions must target children, Aboriginal and Torres Strait Islander peoples and recreational lake users. Fatal drowning rates are high for remote rivers and lakes, necessitating focused effort. There are opportunities to embed drowning prevention strategies within land and water management plans. Lake drowning prevention requires broader engagement with land and water managers and Aboriginal and Torres Strait Islander peoples.


Variation in human platelet 3H-imipramine binding.
Platelet 3H-imipramine binding values from 45 normal controls and 20 depressed subjects were collected over a 2-year period. During this time, wide inter-individual variations in the affinity constant (Kd) and maximal number of binding sites (Bmax) were observed in the control population; however, we failed to observe a seasonal change in platelet 3H-imipramine binding. The Kd and Bmax values of depressed subjects were not significantly different from those of controls.


Ghost cells unveiled: A comprehensive review.
Ghost cells (GCs) are cells with distinct intracytoplasmic keratinization, which leads to the preservation of the cellular outline with a clear area corresponding to the previous nucleus location. GCs may show various patterns, such as degeneration, tissue granulation, and calcification. Their true nature and the mechanism regulating the conversion of odontogenic epithelial cells into GCs remain unclear. GC keratinization is different from normal keratinization as they are larger than keratotic squames, are frequently vacuolated, and have prominent nuclear membrane remnants. Few cystic lesions, odontogenic tumors, and non-odontogenic tumors, such as calcifying odontogenic cyst, craniopharyngioma, pilomatrixoma, odontoma, dentinogenic ghost cell tumor, and ghost cell odontogenic carcinoma, exhibit GCs as a typical feature. The Wnt and Notch signaling pathways play a role in the histogenesis of the neoplasms. The review clarifies the various proposed hypotheses of the histogenesis of GCs, including molecular pathogenesis. Diagnostic workup for the identification of GCs, including special staining and immunohistochemistry, has been extensively discussed. A stepwise algorithm for identifying odontogenic and non-odontogenic lesions containing GCs has been proposed. Additionally, the prognostic role of GCs in the lesions has been elucidated. Among the various hypotheses of the origin of GCs, we suggest that aberrant keratinization is the most accepted based on various immunohistochemical studies and special staining characteristics. GCs are a distinct characteristic entity of many odontogenic and non-odontogenic lesions; however, it remains controversial whether their presence has any pathognomonic role in the biological nature of these lesions.


What's that gene (or protein)? Online resources for exploring functions of genes, transcripts, and proteins.
The genomic era has enabled research projects that use approaches including genome-scale screens, microarray analysis, next-generation sequencing, and mass spectrometry-based proteomics to discover genes and proteins involved in biological processes. Such methods generate data sets of gene, transcript, or protein hits that researchers wish to explore to understand their properties and functions and thus their possible roles in biological systems of interest. Recent years have seen a profusion of Internet-based resources to aid this process. This review takes the viewpoint of the curious biologist wishing to explore the properties of protein-coding genes and their products, identified using genome-based technologies. Ten key questions are asked about each hit, addressing functions, phenotypes, expression, evolutionary conservation, disease association, protein structure, interactors, posttranslational modifications, and inhibitors. Answers are provided by presenting the latest publicly available resources, together with methods for hit-specific and data set-wide information retrieval, suited to any genome-based analytical technique and experimental species. The utility of these resources is demonstrated for 20 factors regulating cell proliferation. Results obtained using some of these are discussed in more depth using the p53 tumor suppressor as an example. This flexible and universally applicable approach for characterizing experimental hits helps researchers to maximize the potential of their projects for biological discovery.


Unfolding and folding kinetics of amyotrophic lateral sclerosis-associated mutant Cu,Zn superoxide dismutases.
More than 110 mutations in dimeric, Cu,Zn superoxide dismutase (SOD) have been linked to the fatal neurodegenerative disease, amyotrophic lateral sclerosis (ALS). In both human patients and mouse model studies, protein misfolding has been implicated in disease pathogenesis. A central step in understanding the misfolding/aggregation mechanism of this protein is the elucidation of the folding pathway of SOD. Here we report a systematic analyses of unfolding and folding kinetics using single- and double-jump experiments as well as measurements as a function of guanidium chloride, protein, and metal concentration for fully metallated (holo) pseudo wild-type and ALS-associated mutant (E100G, G93R, G93A, and metal binding mutants G85R and H46R) SODs. The kinetic mechanism for holo SODs involves native dimer, monomer intermediate, and unfolded monomer, with variable metal dissociation from the monomeric states depending on solution conditions. The effects of the ALS mutations on the kinetics of the holoproteins in guanidium chloride are markedly different from those observed previously for acid-induced unfolding and for the unmetallated (apo) forms of the proteins. The mutations decrease the stability of holo SOD mainly by increasing unfolding rates, which is particularly pronounced for the metal-binding mutants, and have relatively smaller effects on the observed folding kinetics. Mutations also seem to favour increased formation of a Zn-free monomer intermediate, which has been implicated in the formation of toxic aggregates. The results reveal the kinetic basis for the extremely high stability of wild-type holo SOD and the possible consequences of kinetic changes for disease.