Ontogenetic expression of the murine erythrocyte glycophorins.
The major sialoglycoproteins or glycophorins of the murine erythrocyte membrane, gp2 (Mr 44,000) and gp3 (Mr 29,000), are expressed as identical or closely related antigens by the three erythroid cell lines that succeed each other in normal mouse development. The embryonic forms of gp2 and gp3 differ from the adult forms by their mobility on SDS-PAGE. The apparent Mr values are increased by 1000-2000 for gp2 and 500 for gp3. An increase in the microheterogeneity of both embryonic and fetal forms of gp2 is also detected. Variations in glycosylation account in part for the apparent differences in Mr. Sizing of O-glycosidically linked oligosaccharide chains reveals that fetal glycophorins contain predominantly trisaccharide units while their adult counterparts are mostly tetrasaccharides. The kinetics of gp2 and gp3 biosynthesis in fetal liver are comparable to those established for the splenic erythroblasts of adult anemic mice. Like their adult counterparts, fetal glycophorins incorporate [3H]palmitate and [3H]galactose. The results indicate that, in murine ontogeny, distinct but antigenically related sialoglycoproteins are produced at each erythropoietic stage.


Miniaturized Sample Preparation for Transmission Electron Microscopy.
Due to recent technological progress, cryo-electron microscopy (cryo-EM) is rapidly becoming a standard method for the structural analysis of protein complexes to atomic resolution. However, protein isolation techniques and sample preparation methods for EM remain a bottleneck. A relatively small number (100,000 to a few million) of individual protein particles need to be imaged for the high-resolution analysis of proteins by the single particle EM approach, making miniaturized sample handling techniques and microfluidic principles feasible. A miniaturized, paper-blotting-free EM grid preparation method for sample pre-conditioning, EM grid priming and post processing that only consumes nanoliter-volumes of sample is presented. The method uses a dispensing system with sub-nanoliter precision to control liquid uptake and EM grid priming, a platform to control the grid temperature thereby determining the relative humidity above the EM grid, and a pick-and-plunge-mechanism for sample vitrification. For cryo-EM, an EM grid is placed on the temperature-controlled stage and the sample is aspirated into a capillary. The capillary tip is positioned in proximity to the grid surface, the grid is loaded with the sample and excess is re-aspirated into the microcapillary. Subsequently, the sample film is stabilized and slightly thinned by controlled water evaporation regulated by the offset of the platform temperature relative to the dew-point. At a given point the pick-and-plunge mechanism is triggered, rapidly transferring the primed EM grid into liquid ethane for sample vitrification. Alternatively, sample-conditioning methods are available to prepare nanoliter-sized sample volumes for negative stain (NS) EM. The methodologies greatly reduce sample consumption and avoid approaches potentially harmful to proteins, such as the filter paper blotting used in conventional methods. Furthermore, the minuscule amount of sample required allows novel experimental strategies, such as fast sample conditioning, combination with single-cell lysis for "visual proteomics," or "lossless" total sample preparation for quantitative analysis of complex samples.


Anti-amoebic activity of acyclic and cyclic-samarium complexes on Acanthamoeba.
This work investigated the anti-amoebic activity of two samarium (Sm) complexes, the acyclic complex [bis(picrato)(pentaethylene glycol)samarium(III)] picrate-referred to as [Sm(Pic)2(EO5)](Pic)-and the cyclic complex [bis(picrato)(18-crown-6)samarium(III)] picrate-referred to as [Sm(Pic)2(18C6)](Pic). Both Sm complexes caused morphological transformation of the protozoa Acanthamoeba from its native trophozoite form carrying a spine-like structure called acanthopodia, to round-shaped cells with loss of the acanthopodia structure, a trademark response to environmental stress. Further investigation, however, revealed that the two forms of the Sm complexes exerted unique cytotoxicity characteristics. Firstly, the IC50 of the acyclic complex (0.7 μg/mL) was ~ 10-fold lower than IC50 of the cyclic Sm complex (6.5 μg/mL). Secondly, treatment of the Acanthamoeba with the acyclic complex caused apoptosis of the treated cells, while the treatment with the cyclic complex caused necrosis evident by the leakage of the cell membrane. Both treatments induced DNA damage in Acanthamoeba. Finally, a molecular docking simulation revealed the potential capability of the acyclic complex to form hydrogen bonds with profilin-a membrane protein present in eukaryotes, including Acanthamoeba, that plays important roles in the formation and degradation of actin cytoskeleton. Not found for the cyclic complex, such potential interactions could be the underlying reason, at least in part, for the much higher cytotoxicity of the acyclic complex and also possibly, for the observed differences in the cytotoxicity traits. Nonetheless, with IC50 values of < 10 μg/mL, both the acyclic and cyclic Sm complexes feature a promising potential as cytotoxic agents to fight amoebic infections.


The Role of the Physical and Social Environment in Observed and Self-Reported Park Use in Low-Income Neighborhoods in New York City.
Physical and social environments of parks and neighborhoods influence park use, but the extent of their relative influence remains unclear. This cross-sectional study examined the relationship between the physical and social environment of parks and both observed and self-reported park use in low-income neighborhoods in New York City. We conducted community- (n = 54 parks) and individual-level (n = 904 residents) analyses. At the community level, observed park use was measured using a validated park audit tool and regressed on the number of facilities and programmed activities in parks, violent crime, stop-and-frisk incidents, and traffic accidents. At the individual level, self-reported park use was regressed on perceived park quality, crime, traffic-related walkability, park use by others, and social cohesion and trust. Data were collected in 2016-2018 and analyzed in 2019-2020. At the community level, observed park use was negatively associated with stop-and-frisk (β = -0.04; SE = 0.02; p < 0.05) and positively associated with the number of park facilities (β = 1.46; SE = 0.57; p < 0.05) and events (β = 0.16; SE = 0.16; p < 0.01). At the individual level, self-reported park use was positively associated with the social cohesion and trust scale (β = 0.02; SE = 0.01; p < 0.05). These results indicate that physical and social attributes of parks, but not perceptions of parks, were significantly associated with park use. The social environment of neighborhoods at both community and individual levels was significantly related to park use. Policies for increasing park use should focus on improving the social environment of parks and surrounding communities, not only parks' physical attributes. These findings can inform urban planning and public health interventions aimed at improving the well-being of residents in low-income communities.


Urinary prostaglandins in the Lyon strains of hypertensive, normotensive, and low blood pressure rats.
A longitudinal study of the urinary excretion of prostaglandins (PGs) E and F alpha was performed in simultaneously selected hypertensive (LH), normotensive (LN), and low blood pressure (LL) female rats of the Lyon strains aged from 5 to 45 weeks. The urinary excretion of PGE did not significantly differ between LL and LN rats whereas in LH rats it was found to be significantly lower than that of LN or LL rats starting at the age of 32 weeks. The urinary excretion of PGF alpha was significantly reduced in both LL and LH rats; however, this decrease was more marked in LH than in LL animals and, from 9 weeks of age, the urinary PGF alpha were significantly lower in LH than in age-matched LL rats. In addition, both PGE and PGF alpha were found to be significantly and negatively related to the systolic blood pressure level in LH rate (r = -0.56, n = 58, p less than 0.001 for PGE; and r = -0.78, n = 58, p less than 0.001 for PGF alpha) but not in LN of LL animals. In conclusion, it seems unlikely that renal PGs could play a primary role in the spontaneous hypertension observed in the Lyon strain of rats.


Nocturic episodes in patients with benign prostatic enlargement may suggest the presence of obstructive sleep apnea.
Nocturia is a common symptom of benign prostatic enlargement (BPE) that is generally attributed to a urologic pathology. This study assessed whether nocturia severity in BPE patients may be related to an underlying sleep disorder. Cross-sectional study based in urban community primary care clinics. Study population included men aged 55 to 75 years old. The research group included patients with documented BPE and nocturia of at least once per night versus a comparison group without BPE and with either no or one nocturia episode per night. The presence of symptoms of obstructive sleep apnea (SOSA) was assessed using the Berlin questionnaire. Patients with BPE were significantly more likely to report weight gain (21% vs 10%), loudness of snoring (22.6% vs 4%), daytime sleepiness (35.3% vs 12.0%), and hypertension (61.8% vs 41.0%). Fifty-nine patients (57.8%) in the research group were considered high risk for OSA compared with 31 patients (31.0%) from the comparison group (P < .001). The odds ratio (OR) for SOSA gradually increased from 1.00 in patients reporting no nocturia to 2.44, 5.75, and 12.3 in patients reporting 1, 2 to 3, and >3 episodes of nocturia per night, respectively. The odds for SOSA increased log-linearly in correlation with the number of nocturia episodes. We imply that nocturic episodes in patients with BPE may suggest the presence of OSA. Physicians following patients with BPE who report frequent awakenings from sleep to urinate should suspect OSA as a possible comorbidity.


Transarterial chemoembolization combined donafenib with/without PD-1 for unresectable HCC in a multicenter retrospective study.
This multicenter retrospective study evaluated the efficacy and safety of transarterial chemoembolization (TACE) combined with donafenib and a programmed death-1 (PD-1) inhibitor (TACE+DP) and TACE combined with donafenib (TACE+D) for unresectable hepatocellular carcinoma (uHCC). The clinical data of 388 patients with uHCC who received TACE+DP or TACE+D as first-line treatment at six Chinese academic centers from July 2021 to July 2022 were collected and analyzed retrospectively. Patients in the TACE+DP group received an intravenous administration of a PD-1 inhibitor every three weeks and oral donafenib (0.2 g) twice daily until intolerable toxicity or disease progression. Patients in the TACE+D group received the same dose of donafenib for 3-5 days after TACE. Overall survival (OS) and progression-free survival (PFS)were analyzed by Kaplan-Meier method and log-rank test. The tumor response was compared between the two groups according to modified RECIST criteria. Adverse events were also analyzed between the two groups. The TACE+D group included 157 patients and the TACE+DP group included 166 patients. Patients in the TACE+DP group had a longer median OS (18.1 vs. 13.2 months, P<0.001) and longer median PFS (10.6 vs. 7.9 months, P<0.001) than those in the TACE+D group. Patients in the TACE+DP group achieved a greater objective response rate (ORR; 50.6% vs. 41.4%, P=0.019) and greater disease control rate (DCR) (89.2% vs. 82.8%, P=0.010) than those in the TACE+D group. No significant differences were found in the incidence or severity of adverse events between the TACE+DP and TACE+D groups (any grade: 92.9% vs. 94.6%, P=0.270; grade 3 or 4: 33.8% vs. 37.3%, P=0.253). With favorable safety and tolerability, TACE combined with donafenib and PD-1 inhibitors significantly improved PFS, OS, and ORR compared to TACE combined with donafenib.


New strategy for the diagnosis of parotid gland lesions utilizing three-dimensional sialography.
Three-dimensional (3D) imaging for parotid gland lesions was performed using 3D sialography. This method provided a detailed surface structure of the parotid gland, and made it possible to overcome the disadvantages of X-ray sialography, planar CT, and MRI. Immediately after the conventional sialography via an oral route, CT scanning was performed with a slice-thickness of 3 mm using a helical CT scanner. CT data were analyzed on a workstation to reconstruct 3D images. 3D sialography was found to have the following advantages: (1) The structure of the acinar surface is visualized in detail; (2) The 3D structure of the entire parotid system from Stensen's duct to the gland is shown in one image; (3) The parotid gland can be assessed in the context of the bony architecture of facial bones; (4) The surface structure of the parotid gland can be understood very easily, like a scanning electron micrograph. We conclude that 3D sialography is a useful imaging technique for parotid gland lesions.


Outcome of a Combined Anterior Cruciate Ligament and Anterolateral Ligament Reconstruction Technique With a Minimum 2-Year Follow-up.
The anterolateral ligament has recently been identified as an important structure involved in rotational laxity after anterior cruciate ligament (ACL) rupture. Results of a combined ACL and anterolateral ligament (ALL) reconstruction technique have never been reported. To report subjective and objective outcomes after combined ACL and minimally invasive ALL reconstruction with a minimum 2-year follow-up. Case series; Level of evidence, 4. A total of 92 patients underwent a combined ACL and ALL reconstruction. Indications for a combined procedure were associated Segond fracture, chronic ACL lesion, grade 3 pivot shift, high level of sporting activity, pivoting sports, and radiographic lateral femoral notch sign. Patients were assessed pre- and postoperatively with objective and subjective International Knee Documentation Committee (IKDC) score, Lysholm score, and Tegner activity scale. Instrumented knee testing was performed with the Rolimeter arthrometer. The Knee injury and Osteoarthritis Outcome Score (KOOS) was obtained at the last follow-up. Complications including graft failure or contralateral ACL rupture were also recorded. The mean follow-up time was 32.4 ± 3.9 months. One patient (1.1%) was lost to follow-up, 1 patient (1.1%) suffered an ACL graft rupture, and 7 patients (7.6%) had a contralateral ACL rupture, leaving 83 patients for final evaluation. At the last follow-up, all patients had full range of motion. The Lysholm, subjective IKDC, and objective IKDC scores were significantly improved (all P < .0001). The Tegner activity scale at the last follow-up (7.1 ± 1.8) was slightly lower than before surgery (7.3 ± 1.7) (P < .01). The mean differential anterior laxity was 8 ± 1.9 mm before surgery and significantly decreased to 0.7 ± 0.8 mm at the last follow-up (P < .0001). Preoperatively, 41 patients had a grade 1 pivot shift, 23 had a grade 2, and 19 had a grade 3 according to the IKDC criteria. Postoperatively, 76 patients had a negative pivot shift (grade 0), and 7 patients were grade 1 (P < .0001). This study demonstrates that a combined reconstruction can be an effective procedure without specific complications at a minimum follow-up of 2 years. Longer term and comparative follow-up studies are necessary to determine whether these combined reconstructions improve the results of ACL treatment.


Quasi-near field terahertz generation and detection.
We describe a simple terahertz (THz) time domain spectrometer with a bandwidth extending up to 7.5 THz. We show that by keeping the generation and detection crystals close to each other a high signal-to-noise ratio (SNR) can be achieved without using lock-in detection and dry nitrogen flushing. The observed spectra show very good agreement with the spectra calculated based on a simple model which includes phase matching and absorption in the generation and detection crystals. Using this set-up we have measured the absorption lines in D-tartaric acid from 0.5 THz up to 7 THz. We show that the high frequency region > 3 THz is the better choice to measure small changes in the water content of a hygroscopic sample compared to the low frequency region.


Adaptation of the differential display RT-PCR technique to isolate sugarcane genes induced by plant association with endophytic nitrogen-fixing bacteria.
Differential Display RT-PCR is a powerful technique that has been used to isolate differentially expressed genes. This technique was first described by Liang & Pardee, in 1992. Afterwards, several modifications were introduced in the original version, including a simplification described by Sokolov & Prockop, in 1994. In this work, we describe an adaptation of the Sokolov & Prockop technique, in order to isolate sugarcane genes induced by plant association with endophytic nitrogen-fixing bacteria. Several modifications were introduced: the use of oligo-dT primer in the first strand cDNA synthesis, replicates of the PCR reactions, analysis of the amplified fragments on silver stained polyacrilamide gel and confirmation of cloning the differentially amplified selected band prior to its molecular characterisation. The methodology established was successfully used to identify a large number of differentially amplified sugarcane cDNAs. So far, one of these cDNAs was already isolated and characterized.


Analysis of the visual system in Friedreich ataxia.
To use optical coherence tomography (OCT) and contrast letter acuity to characterize vision loss in Friedreich ataxia (FRDA). High- and low-contrast letter acuity and neurological measures were assessed in 507 patients with FRDA. In addition, OCT was performed on 63 FRDA patients to evaluate retinal nerve fiber layer (RNFL) and macular thickness. Both OCT and acuity measures were analyzed in relation to genetic severity, neurologic function, and other disease features. High- and low-contrast letter acuity was significantly predicted by age and GAA repeat length, and highly correlated with neurological outcomes. When tested by OCT, 52.7% of eyes (n = 110) had RNFL thickness values below the fifth percentile for age-matched controls. RNFL thickness was significantly lowest for those with worse scores on the Friedreich ataxia rating scale (FARS), worse performance measure composite Z2 scores, and lower scores for high- and low-contrast acuity. In linear regression analysis, GAA repeat length and age independently predicted RNFL thickness. In a subcohort of participants, 21% of eyes from adult subjects (n = 29 eyes) had macular thickness values below the first percentile for age-matched controls, suggesting that macular abnormalities can also be present in FRDA. Low-contrast acuity and RNFL thickness capture visual and neurologic function in FRDA, and reflect genetic severity and disease progression independently. This suggests that such measures are useful markers of neurologic progression in FRDA.


Effects of photoperiod and feeding level on adipose tissue and muscle lipoprotein lipase activity and mRNA level in dry non-pregnant sheep.
The aim of the present study was to investigate the effects of photoperiod and feeding level on lipid metabolism in ovine perirenal and subcutaneous adipose tissues (AT) and in skeletal and cardiac muscles. Twenty dry non-pregnant ovariectomised ewes were divided into two groups and subjected to either 8 h or 16 h light/d, and underfed at 22 % energy requirements for 7 d. Half of the ewes in each group were slaughtered and the remaining ewes were refed at 190 % energy requirements for 14 d, until slaughtering. Refeeding increased (2.6-4.3-fold) malic enzyme (ME), fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G6PDH) and glycerol-3-phosphate dehydrogenase (G3PDH) activities in subcutaneous AT as well as lipoprotein lipase (LPL) activity in perirenal (3.5-fold) and subcutaneous (10-fold) AT and to a lesser extent (1.4-fold) in the skeletal longissimus thoracis and cardiac muscles. Moreover, variations of LPL mRNA level followed variations of LPL activity: refeeding increased perirenal AT- and cardiac muscle-mRNA levels (7.4- and 2-fold respectively). The main finding of this study is that, for a given level of food intake, long days (compared with short days) increased the LPL activity in the longissimus thoracis muscle and, in refed ewes, the activities of LPL and ME in subcutaneous AT. Furthermore, long days increased LPL mRNA level in cardiac muscle and perirenal AT. Thus, our results show that there are direct effects of photoperiod on sheep AT lipogenic potential, as well as on muscle LPL activity, which are not caused by changes in nutrient availability.


Activation of Smad2 but not Smad3 is required to mediate TGF-β signaling during axolotl limb regeneration.
Axolotls are unique among vertebrates in their ability to regenerate tissues, such as limbs, tail and skin. The axolotl limb is the most studied regenerating structure. The process is well characterized morphologically; however, it is not well understood at the molecular level. We demonstrate that TGF-β1 is highly upregulated during regeneration and that TGF-β signaling is necessary for the regenerative process. We show that the basement membrane is not prematurely formed in animals treated with the TGF-β antagonist SB-431542. More importantly, Smad2 and Smad3 are differentially regulated post-translationally during the preparation phase of limb regeneration. Using specific antagonists for Smad2 and Smad3 we demonstrate that Smad2 is responsible for the action of TGF-β during regeneration, whereas Smad3 is not required. Smad2 target genes (Mmp2 and Mmp9) are inhibited in SB-431542-treated limbs, whereas non-canonical TGF-β targets (e.g. Mmp13) are unaffected. This is the first study to show that Smad2 and Smad3 are differentially regulated during regeneration and places Smad2 at the heart of TGF-β signaling supporting the regenerative process.


The effects of cancer therapies on physical fitness before oesophagogastric cancer surgery: a prospective, blinded, multi-centre, observational, cohort study.
Neoadjuvant cancer treatment is associated with improved survival following major oesophagogastric cancer surgery. The impact of neoadjuvant chemo/chemoradiotherapy on physical fitness and operative outcomes is however unclear. This study aims to investigate the impact of neoadjuvant chemo/chemoradiotherapy on fitness and post-operative mortality. Patients with oesophagogastric cancer scheduled for chemo/chemoradiotherapy and surgery were recruited to a prospective, blinded, multi-centre, observational cohort study. Primary outcomes were changes in fitness with chemo/chemoradiotherapy, measured using cardiopulmonary exercise testing and its association with mortality one-year after surgery. Patients were followed up for re-admission at 30-days, in-hospital morbidity and quality of life (exploratory outcomes). In total, 384 patients were screened, 217 met the inclusion criteria, 160 consented and 159 were included (72% male, mean age 65 years). A total of 132 patients (83%) underwent chemo/chemoradiotherapy, 109 (71%) underwent chemo/chemoradiotherapy and two exercise tests, 100 (63%) completed surgery and follow-up. A significant decline in oxygen uptake at anaerobic threshold and oxygen uptake peak was observed following chemo/chemoradiotherapy: -1.25ml.kg -1.min -1 (-1.80 to -0.69) and -3.02ml.kg -1.min -1 (-3.85 to -2.20); p<0.0001). Baseline chemo/chemoradiotherapy anaerobic threshold and peak were associated with one-year mortality (HR=0.72, 95%CI 0.59 to 0.88; p=0.001 and HR=0.85, 0.76 to 0.95; p=0.005). The change in physical fitness was not associated with one-year mortality. Chemo/chemoradiotherapy prior to oesophagogastric cancer surgery reduced physical fitness. Lower baseline fitness was associated with reduced overall survival at one-year. Careful consideration of fitness prior to chemo/chemoradiotherapy and surgery is urgently needed.


Development of evidence-informed physical activity guidelines for adults with multiple sclerosis.
Most adults with multiple sclerosis (MS) are physically inactive. Physical activity guidelines are an important tool for exercise prescription, promotion, and monitoring. This article describes the application of international standards for guideline development in the creation of evidence-based physical activity guidelines for people with MS. The development process was informed by the Appraisal of Guidelines Research and Evaluation II instrument. The evidence base for the guidelines consisted of a systematic review of research examining the effects of exercise on fitness, fatigue, mobility, and health-related quality of life among people with MS. A multidisciplinary consensus panel deliberated the evidence and generated the guidelines and a preamble. Expert and stakeholder reviews of the materials led to refinement of the wording of both components of the guidelines. The resulting guidelines state that to achieve important fitness benefits, adults with MS who have mild to moderate disability need at least 30 minutes of moderate intensity aerobic activity 2 times per week and strength training exercises for major muscle groups 2 times per week. Meeting these guidelines may also reduce fatigue, improve mobility, and enhance elements of health-related quality of life. People with MS and health professionals are encouraged to adopt these rigorously developed guidelines.


Alteration of islet cell populations in spontaneously diabetic mice.
Endocrine-cell populations in the islets of Langerhans of mutant mice with a severe hypoinsulinemic diabetes (ob/ob or db/db on the C57BL/KsJ background) or with a mild hyperinsulinemic diabetes (ob/ob or db/db on the C57BL/6J background) were studied quantitatively by immunofluorescence and morphometry. In severely diabetic mice, islets presented a reduced proportion of insulin containing cells but increased glucagon-, somatostatin-, and pancreatic polypeptide (PP)-containing cells, as compared with islets of control (+/+) mice. An inverse change was observed in islets of mildly diabetic mice: islets were hypertrophic and composed mostly of insulin-containing cells, with decreased proportions of glucagon-, somatostatin-, and PP-containing cells. In both types of diabetic syndromes, the changes in cell populations induced a qualitative alteration of cellular interrelationships in the affected islets.


New Global Referencing Approach in a Camera-LCD Micro Positioning System.
In any precision manufacturing process, positioning systems play a very important role in achieving a quality product. As a new approach to current systems, camera-LCD positioning systems are a new technology that can provide substantial improvements enabling better accuracy and repeatability. However, in order to provide stability to the system a global positioning system is required. This paper presents an improvement of a positioning system based on the treatment of images on an LCD in which a new algorithm with absolute reference has been implemented. The method is based on basic geometry and linear algebra applied to computer vision. The algorithm determines the spiral center using an image taken at any point. Consequently, the system constantly knows its position and does not lose its reference. Several modifications of the algorithm are proposed and compared. The simulation and test of the algorithm provide an important improvement in the reliability and stability of the positioning system providing errors of microns for the calculation of the global position used by the algorithm.


Slow growth and delayed maturation in a Critically Endangered insular flying fox (Pteropus natalis).
Flying foxes (family Pteropodidae) have distinct life histories given their size, characterized by longevity, low reproductive output, and long gestation. However, they tend to decouple the age at which sexual maturity is reached from the age at which they reach adult dimensions. We examined growth, maturation, and reproduction in the Critically Endangered Christmas Island flying fox (Pteropus natalis) to determine the timing of sex-specific life cycle events and patterns of growth. We estimated that juvenile growth in forearm length and body mass increased at a mean rate of 0.029 ± 0.005 mm/day and 0.33 ± 0.07 g/day for both males and females alike. Using these growth rates, we determined that the birth of pups occurs between December and March, with young becoming volant between June and August. The age at maturation for P. natalis is one of the oldest among all bat species. Juvenile males began to mature 15 months after birth and reached maturity 27 months after birth. Females reached maturity 24 months after birth at a significantly smaller body mass (3.6%) and forearm length (1.4%) than males. Significant sexual dimorphism and bimaturation was observed, with juvenile males being 1.5% and adult males being 1.9% larger on average than females for skeletal dimensions only. Growth and maturation are even slower in P. natalis than in the few other Pteropus species studied to date. The slow growth and delayed maturation of P. natalis imply slower potential population growth rates, further complicating the recovery of this Critically Endangered single-island endemic.


Correlation between Location of Brain Lesion and Cognitive Function and Findings of Videofluoroscopic Swallowing Study.
To investigate whether patterns of swallowing difficulties were associated with the location of the brain lesion, cognitive function, and severity of stroke in stroke patients. Seventy-six patients with first-time acute stroke were included in the present investigation. Swallowing-related parameters, which were assessed videofluoroscopically, included impairment of lip closure, decreased tongue movement, amount of oral remnant, premature loss of food material, delay in oral transit time, laryngeal elevation, delay in pharyngeal triggering time, presence of penetration or aspiration, and the amount of vallecular and pyriform sinus remnants. The locations of brain lesions were classified into the frontal, parietotemporal, subcortical, medulla, pons, and cerebellum. The degree of cognitive impairment and the severity of stroke were assessed by the Mini Mental Status Examination (MMSE) and the National Institute of Health Stroke Scale (NIHSS), respectively. An insufficient laryngeal elevation, the amount of pyriform sinus, and vallecular space remnant in addition to the incidence of aspiration were correlated with medullary infarction. Other swallowing parameters were not related to lesion topology. Lip closure dysfunction, decreased tongue movement, increased oral remnant and premature loss were associated with low MMSE scores. A delayed oral transit time were associated with NIHSS scores. In-coordination of the lip, the tongue, and the oropharynx were associated with the degree of cognitive impairment and the stroke severity rather than with the location of the lesion, whereas incomplete laryngeal elevation and aspiration were predominant in medullary lesions.


Drill-specific head impact exposure in youth football practice.
OBJECTIVE Although 70% of football players in the United States are youth players (6-14 years old), most research on head impacts in football has focused on high school, collegiate, or professional populations. The objective of this study was to identify the specific activities associated with high-magnitude (acceleration > 40g) head impacts in youth football practices. METHODS A total of 34 players (mean age 9.9 ± 0.6 years) on 2 youth teams were equipped with helmet-mounted accelerometer arrays that recorded head accelerations associated with impacts in practices and games. Videos of practices and games were used to verify all head impacts and identify specific drills associated with each head impact. RESULTS A total of 6813 impacts were recorded, of which 408 had accelerations exceeding 40g (6.0%). For each type of practice drill, impact rates were computed that accounted for the length of time that teams spent on each drill. The tackling drill King of the Circle had the highest impact rate (95% CI 25.6-68.3 impacts/hr). Impact rates for tackling drills (those conducted without a blocker [95% CI 14.7-21.9 impacts/hr] and those with a blocker [95% CI 10.5-23.1 impacts/hr]) did not differ from game impact rates (95% CI 14.2-21.6 impacts/hr). Tackling drills were observed to have a greater proportion (between 40% and 50%) of impacts exceeding 60g than games (25%). The teams in this study participated in tackling or blocking drills for only 22% of their overall practice times, but these drills were responsible for 86% of all practice impacts exceeding 40g. CONCLUSIONS In youth football, high-magnitude impacts occur more often in practices than games, and some practice drills are associated with higher impact rates and accelerations than others. To mitigate high-magnitude head impact exposure in youth football, practices should be modified to decrease the time spent in drills with high impact rates, potentially eliminating a drill such as King of the Circle altogether.


[Craniocerebral civilian gunshot wounds: one hospital's experience].
In this study we have discussed the factors that affect our surgical results according to our experience on patients who were admitted to our hospital's Emergency Surgery Department for civilian craniocerebral gunshot wounds between 1997 and 2006. The clinical and radiological findings of 82 patients (74 males, 8 females) who were treated for civilian craniocerebral gunshot wounds were retrospectively recorded. Neurological and physical examination, cranial computerized tomography (CCT) findings, trauma types, treatment modalities, prognosis, complications, morbidity and mortality rates were analyzed. Seventy-four (90%) of the patients were male, the mean age was 29.2 year. The Glasgow Coma Scores (GCS) during admission were as following respectively: 3-5 in 35 patients, 6-8 in 9 patients, 9-12 in 19 patients and 13-15 in 19 patients. According to their radiological findings, most commonly subdural hematoma, intracerebral hematoma, multiple contusion, depressed fracture and subarachnoidal hematoma were encountered. Operation or debridement was performed in 51 patients totally. Forty-one patients died and the mortality rate of 82 patients was calculated as 50%. The mortality rate of craniocerebral gunshot wound is high. The patients with GCS higher than 8 and with unihemispheric lesions during admission have better prognosis. We concluded that all patients must undergo debridement and the patients that have mass effect must be operated as soon as possible.


Have the educated changed HIV risk behaviours more in Africa?
Theory predicts that when new health information becomes available, more educated individuals may adopt healthy behaviours sooner, resulting in lower morbidity and mortality among the highly educated. This may be the case for HIV in sub-Saharan Africa: Recent empirical work shows that incidence is falling and the reduction is concentrated in more educated populations. However, it is unclear whether the educated have indeed adopted HIV risk-reducing behaviours to a greater extent than the less educated. I used two rounds of demographic and health surveys (DHS) in eight African countries to examine whether HIV-related behavioural change over time is greater among the more highly educated. I examined changes in condom use, age of marriage, number of partners, extramarital partnerships, and HIV testing. Results showed that education has a robust positive association with condom use and HIV testing, but also with having more sexual partners. I found that the probability of HIV testing increased more between rounds among the more educated, relative to the less educated. More educated men also appeared to have larger reductions in the number of sexual partners and there was evidence that younger, more educated women may be marrying earlier than their predecessors did. The education gradient did not change significantly over time for condom use. These changes in behaviour may signal a shift in the future burden of the epidemic towards more marginalised and less educated populations.


Motivation to uphold physical activity in women with breast cancer during adjuvant chemotherapy treatment.
Physical activity (PA) is important for recovery after a breast cancer diagnosis; however, women's motivation to engage in PA can be impacted by disease and/or treatment, and can therefore be a challenge. This study explored factors associated with PA levels during chemotherapy among women with breast cancer. The study had a cross-sectional descriptive and comparative design using a study-specific questionnaire. One hundred women with breast cancer receiving adjuvant chemotherapy were included. Data were analysed by Pearson's correlation coefficient and linear regression. The open question was subjected to manifest content analysis. Identified factors associated with engaging in PA during chemotherapy treatment were: being physically active before diagnosis, and the information given by the oncology nurse before the treatment start. The physically active women experienced higher psychological wellbeing, less fatigue, and faster recovery after treatment. They also experienced an overall feeling of fitness. It seems that PA is associated with less fatigue, better recovery between chemotherapy treatments, and a better mental condition leading to wellbeing. Information given by the oncology nurse may be an important factor for being physically active. Women with breast cancer need to get specific advice about and support in engaging in PA to feel better during chemotherapy treatment. Further research is required to develop guidelines for advice about and support regarding PA during chemotherapy treatment.


Central alpha-adrenergic control of blood pressure. Effects of clonidine withdrawal.
Studies were undertaken to investigate the role of the CNS in withdrawal hypertension caused by abrupt cessation of long-term clonidine treatment. The studies were conducted on male wistar rats receiving clonidine, 100 micrograms/kg subcutaneously twice daily for seven days. Withdrawal hypertension occurred 16 to 18 hours following the last injection of clonidine. Pressor responses to posterior hypothalamic stimulation were significantly potentiated in the rats undergoing clonidine withdrawal, and the depressor response to a single injection of 10 micrograms of clonidine into the lateral cerebral ventricle was significantly attenuated in these animals. Studies on pithed rats demonstrated that destruction of the CNS eliminated the withdrawal hypertension. These data suggest that alpha-adrenoreceptors in the nucleus tractus solitarius play an important role in the normal maintenance of blood pressure, and a decrease in sensitivity of these receptors could result in the development of a hypertensive state.


Parameter identifiability and redundancy: theoretical considerations.
Models for complex biological systems may involve a large number of parameters. It may well be that some of these parameters cannot be derived from observed data via regression techniques. Such parameters are said to be unidentifiable, the remaining parameters being identifiable. Closely related to this idea is that of redundancy, that a set of parameters can be expressed in terms of some smaller set. Before data is analysed it is critical to determine which model parameters are identifiable or redundant to avoid ill-defined and poorly convergent regression. In this paper we outline general considerations on parameter identifiability, and introduce the notion of weak local identifiability and gradient weak local identifiability. These are based on local properties of the likelihood, in particular the rank of the Hessian matrix. We relate these to the notions of parameter identifiability and redundancy previously introduced by Rothenberg (Econometrica 39 (1971) 577-591) and Catchpole and Morgan (Biometrika 84 (1997) 187-196). Within the widely used exponential family, parameter irredundancy, local identifiability, gradient weak local identifiability and weak local identifiability are shown to be largely equivalent. We consider applications to a recently developed class of cancer models of Little and Wright (Math Biosciences 183 (2003) 111-134) and Little et al. (J Theoret Biol 254 (2008) 229-238) that generalize a large number of other recently used quasi-biological cancer models. We have shown that the previously developed concepts of parameter local identifiability and redundancy are closely related to the apparently weaker properties of weak local identifiability and gradient weak local identifiability--within the widely used exponential family these concepts largely coincide.


HapX Mediates Iron Homeostasis in the Pathogenic Dermatophyte Arthroderma benhamiae but Is Dispensable for Virulence.
For many pathogenic fungi, siderophore-mediated iron acquisition is essential for virulence. The process of siderophore production and further mechanisms to adapt to iron limitation are strictly controlled in fungi to maintain iron homeostasis. Here we demonstrate that the human pathogenic dermatophyte Arthroderma benhamiae produces the hydroxamate siderophores ferricrocin and ferrichrome C. Additionally, we show that the iron regulator HapX is crucial for the adaptation to iron starvation and iron excess, but is dispensable for virulence of A. benhamiae. Deletion of hapX caused downregulation of siderophore biosynthesis genes leading to a decreased production of siderophores during iron starvation. Furthermore, HapX was required for transcriptional repression of genes involved in iron-dependent pathways during iron-depleted conditions. Additionally, the ΔhapX mutant of A. benhamiae was sensitive to high-iron concentrations indicating that HapX also contributes to iron detoxification. In contrast to other pathogenic fungi, HapX of A. benhamiae was redundant for virulence and a ΔhapX mutant was still able to infect keratinized host tissues in vitro. Our findings underline the highly conserved role of the transcription factor HapX for maintaining iron homeostasis in ascomycetous fungi but, unlike in many other human and plant pathogenic fungi, HapX of A. benhamiae is not a virulence determinant.


Gleditsia sinensis fruit extract induced growth inhibition involves basic fibroblast growth factor and nitric oxide.
Recently we have shown the antiproliferative activity of Gleditsia sinensis fruit extract (GSE) on various solid tumour and leukaemia cell lines as well as primary cultured bone marrow cells isolated from patients with acute and chronic myelogenous leukaemia. We further studied whether the growth inhibitory effect of GSE involves basic fibroblast growth factor (bFGF) in cancer cell lines including breast cancer MDA-MB231, nasopharyngeal cancer CNE-2 and prostate cancer LNCaP. We also investigated whether GSE could alter the production of nitric oxide (NO) pattern from these cancer cell lines. Growth inhibition assay was quantitated by sulforhodamine B protein staining method. Enzyme linked immunosorbent assay (ELISA) was used to quantitate the total bFGF protein. The amount of NO secreted into culture medium in terms of nitrite ion concentration was measured by the Greiss method. ELISA showed that GSE could stimulate total bFGF protein level which was dose- dependent. NO production was also stimulated from these cancer cell lines after treating with GSE. Both of the increment in total bFGF and NO levels were correlated with the degree of growth inhibition. Changes involving cell shrinkage and detachment of cancer cells could readily be observed. Taken together, our results here suggest that growth inhibition induced by GSE in these solid tumour cell lines may involve both bFGF and NO regulations.


Engineering scalable biological systems.
Synthetic biology is focused on engineering biological organisms to study natural systems and to provide new solutions for pressing medical, industrial and environmental problems. At the core of engineered organisms are synthetic biological circuits that execute the tasks of sensing inputs, processing logic and performing output functions. In the last decade, significant progress has been made in developing basic designs for a wide range of biological circuits in bacteria, yeast and mammalian systems. However, significant challenges in the construction, probing, modulation and debugging of synthetic biological systems must be addressed in order to achieve scalable higher-complexity biological circuits. Furthermore, concomitant efforts to evaluate the safety and biocontainment of engineered organisms and address public and regulatory concerns will be necessary to ensure that technological advances are translated into real-world solutions.


Comparison of clinical characteristics between coronavirus disease 2019 pneumonia and community-acquired pneumonia.
Coronavirus disease 2019 (COVID-19) has high morbidity and mortality, and spreads rapidly in the community to result in a large number of infection cases. This study aimed to compare clinical features in adult patients with coronavirus disease 2019 (COVID-19) pneumonia to those in adult patients with community-acquired pneumonia (CAP). Clinical presentations, laboratory findings, imaging features, complications, treatment and outcomes were compared between patients with COVID-19 pneumonia and patients with CAP. The study group of patients with COVID-19 pneumonia consisted of 120 patients. One hundred and thirty-four patients with CAP were enrolled for comparison. Patients with COVID-19 pneumonia had lower levels of abnormal laboratory parameters (white blood cell count, lymphocyte count, procalcitonin level, erythrocyte sedimentation rate and C-reactive protein level) and more extensive radiographic involvement. More severe respiratory compromise resulted in a higher rate of intensive care unit admission, acute respiratory distress syndrome (ARDS) and mechanical ventilation (36% vs 15%, 34% vs 15% and 32% vs 12%, respectively; all p < .05). The 30 day mortality was more than twice as high in patients with COVID-19 pneumonia (12% versus 5%; p = .063), despite not reaching a statistically significant difference. Lower levels of abnormal laboratory parameters, more extensive radiographic involvement, more severe respiratory compromise, and higher rates of ICU admission, ARDS and mechanical ventilation are key characteristics that distinguish patients with COVID-19-associated pneumonia from patients with CAP.


Borderline personality disorder and childhood trauma: evidence for a causal relationship.
The debate over whether childhood trauma is a causative factor in the development of borderline personality disorder continues in the literature despite decades of research. This review examines this body of literature published from 1995 through 2007 to assess the strength of evidence for such a causal relationship. A unique conceptual approach was used, as we considered the literature in the context of Hill's classic criteria for demonstrating causation. Results of this review suggest that evidence supports the causal relationship, particularly if the relationship is considered as part of a multifactorial etiologic model. Directions for future research and clinical implications are discussed.


Fast and slow narrow complex tachycardia in one patient: two of a kind?
A 35-year-old female was referred to our hospital. For more than ten years, she had had complaints of two types of paroxysmal palpitations, both with a sudden onset. The first type was rapid and often accompanied by light-headedness; the second she described as much less rapid, better tolerated, and often terminated by the Valsalva manoeuvre. The incidence and duration of both types of paroxysms were increasing. In the emergency room of the referring hospital, the tachycardia was terminated with intravenous verapamil. The electrophysiological study revealed normal conduction parameters. Premature atrial beats (due to catheter manipulation) or delivered atrial extra stimuli over a wide range easily induced two types of tachycardia. AV node modification by radiofrequency ablation using the posterior approach was performed. With this approach, RF ablation of the caudal extension of the AV node is performed, which modifies the slow pathway, so that the reentrant circuit is interrupted. After this intervention, no tachycardia whatsoever could be induced and during followup (8 months), no recurrent arrhythmia of any kind occurred.


Evaluation of the structure function relationships of MHC class I antigens by molecular genetic techniques.
By combining the knowledge gained from several types of experiments we are beginning to understand the functional role of many structural features of the MHC class I antigens. Studies done by exon shuffling have defined the domains involved in recognition by T-cells and antibodies. As a result, we now know that the interaction between domains, as well as the structure of individual domains, is important for immune recognition. By in vitro mutagenesis we have shown that N-linked carbohydrate moieties appear to function primarily in facilitation of intracellular processing, having seen little effect on immunologic function by their removal. Two other highly conserved structures, the disulfide bridges of the C-1 and C-2 domains, appear by this methodology to function in both intracellular processing and immune recognition. Finally, we are hopeful that extension of the method of in vitro mutagenesis to the evaluation of individual polymorphic amino acids in the MHC class I antigens will yield significant information regarding the relationship of their structure to their function.


Identification and characterization of pro-interleukin-16 from mud crab Scylla paramamosain: The first evidence of proinflammatory cytokine in crab species.
IL-16 is a pro-inflammatory cytokine originally designated as a lymphocyte chemoattractant factor. In mammal and avian, it has been characterized as an essential regulator of various cellular processes including cell recruitment and activation against pathogen invasion. So far, neither of the full-length of IL-16 homologue nor the response mechanism against pathogen was reported in crab species. In the present study, the pro-IL-16 homologue was firstly cloned and characterized from mud crab Scylla paramamosain. The full-length Sp-pro-IL-16 consisted of 4107 bp with an opening reading frame encoding 1369 amino acids. Multiple alignment analysis showed the putative amino acid sequence of Sp-pro-IL-16 had about 73.86% identity with Litopenaeus vannamei pro-IL-16. Additionally, two conserved PDZ domains and protein binding sites were found in Sp-pro-IL-16 and showed high similarities about 94.19% and 51.14% with their Litopenaeus vannamei and Mus musculus counterparts. RT-PCR analysis indicated that Sp-pro-IL-16 transcripts were constitutively expressed in all tissues examined with an extreme high level in hepatopancreas. Moreover, Sp-pro-IL-16 transcripts in hepatopancreas were significantly up-regulated 15-fold at 72 h after Vibrio alginolyticus challenge and 3.5-fold at 12 h after virus-analog Poly (I:C) challenge. The Western blot analysis revealed that Sp-pro-IL-16 can be cleaved to its bioactive form, an approximately 35 kDa mature IL-16, and the protein levels of both pro-IL-16 and mature IL-16 increased after Vibrio alginolyticus challenge. It is the first experimental identification of pro-inflammatory cytokine IL-16 in arthropods. This study could shed new light on further understanding of the response mechanism of pro-inflammatory cytokine IL-16 in Scylla paramamosain against pathogens. Meanwhile, it brought new insight into the origin and evolution of IL-16 in crab species.


Exercise training improves peripheral chemoreflex function in heart failure rabbits.
An enhancement of peripheral chemoreflex sensitivity contributes to sympathetic hyperactivity in chronic heart failure (CHF) rabbits. The enhanced chemoreflex function in CHF involves augmented carotid body (CB) chemoreceptor activity via upregulation of the angiotensin II (ANG II) type 1 (AT(1))-receptor pathway and downregulation of the neuronal nitric oxide synthase (nNOS)-nitric oxide (NO) pathway in the CB. Here we investigated whether exercise training (EXT) normalizes the enhanced peripheral chemoreflex function in CHF rabbits and possible mechanisms mediating this effect. EXT partially, but not fully, normalized the exaggerated baseline renal sympathetic nerve activity (RSNA) and the response of RSNA to hypoxia in CHF rabbits. EXT also decreased the baseline CB nerve single-fiber discharge (4.9 +/- 0.4 vs. 7.7 +/- 0.4 imp/s at Po(2) = 103 +/- 2.3 Torr) and the response to hypoxia (20.6 +/- 1.1 vs. 36.3 +/- 1.3 imp/s at Po(2) = 41 +/- 2.2 Torr) from CB chemoreceptors in CHF rabbits, which could be reversed by treatment of the CB with ANG II or a nNOS inhibitor. Our results also showed that NO concentration and protein expression of nNOS were increased in the CBs from EXT + CHF rabbits, compared with that in CHF rabbits. On the other hand, elevated ANG II concentration and AT(1)-receptor overexpression of the CBs in CHF state were blunted by EXT. These results indicate that EXT normalizes the CB chemoreflex in CHF by preventing an increase in afferent CB chemoreceptor activity. EXT reverses the alterations in the nNOS-NO and ANG II-AT(1)-receptor pathways in the CB responsible for chemoreceptor sensitization in CHF.


Protein intake and incident frailty in the Women's Health Initiative observational study.
To evaluate the association between protein intake and incident frailty. Prospective cohort study. Subset of the Women's Health Initiative Observational Study conducted at 40 clinical centers. Twenty-four thousand four hundred seventeen women aged 65 to 79 who were free of frailty at baseline with plausible self-reported energy intakes (600-5,000 kcal/day) according to the Food Frequency Questionnaire (FFQ). Baseline protein intake was estimated from the FFQ. Calibrated estimates of energy and protein intake were corrected for measurement error using regression calibration equations estimated from objective measures of total energy expenditure (doubly labeled water) and dietary protein (24-hour urinary nitrogen). After 3 years of follow-up, frailty was defined as having at least three of the following components: low physical function (measured using the Rand-36 questionnaire), exhaustion, low physical activity, and unintended weight loss. Multinomial logistic regression models estimated associations for uncalibrated and calibrated protein intake. Of the 24,417 eligible women, 3,298 (13.5%) developed frailty over 3 years. After adjustment for confounders, a 20% increase in uncalibrated protein intake (%kcal) was associated with a 12% (95% confidence interval (CI)=8-16%) lower risk of frailty, and a 20% increase in calibrated protein intake was associated with a 32% (95% CI=23-50%) lower risk of frailty. Higher protein consumption, as a fraction of energy, is associated with a strong, independent, dose-responsive lower risk of incident frailty in older women. Using uncalibrated measures underestimated the strength of the association. Incorporating more protein into the diet may be an intervention target for frailty prevention.


Violet red bile 2 agar for stressed coliforms.
Counts on a new, autoclave-sterilizable violet red bile (VRB-2) agar were compared with counts on freshly boiled VRB agar. Yields on VRB-2 agar averaged 217, 180, 130, and 112% of counts obtained on the control medium for samples of water, cottage cheese, frozen vegetables, and raw milk, respectively. The general principle used for the development of VRB-2 agar could be applied to many other kinds of selective plating media.


[Surgical and orthopedic treatment methods in orbital defects and deformities].
On the basis of their own clinical material the authors distinguish five kinds of defects and deformations of the orbit and give well-grounded recommendations for choosing the methods of prosthetics and plastic operations for each of them. The authors emphasize that the necessary condition of successful elimination of defects of the orbit is the joint work of a maxillofacial surgeon and an orthopedist. Good cosmetic results were obtained when using complex surgical and orthopedic treatment of 12 patients.


Maternal self-medication and provision of nevirapine to newborns by women in Rakai, Uganda.
To assess the effectiveness of maternal self-administration of nevirapine for prevention of mother-to-child transmission (MTCT) of HIV, we conducted a program to provide maternal and newborn doses of nevirapine to pregnant women in rural Uganda. Women provided blood for HIV testing and were offered voluntary counseling and testing (VCT) during annual community HIV surveys. HIV-positive women who accepted VCT were offered nevirapine tablets and syrup. Blood samples were collected postpartum from women and their babies. Infants were tested for HIV by polymerase chain reaction (PCR), and a subsample of maternal and infant blood was assayed for nevirapine. Among the 981 women tested for HIV, 900 (91.7%) accepted VCT, of whom 105 (11.7%) were HIV-positive. Ninety-three women accepted nevirapine, of whom 81 (87.1%) were followed postpartum; 75 (92.6%) reported receipt of the drug, and 69 reported taking the tablets (85.2%). There were 81 liveborn babies (3 sets of twins), and 67 (84.8%) received the syrup. In a subsample of 25 mothers reporting receipt of the drug, nevirapine was detected in 22 (88.0%) and 24 (96.0%) babies tested. PCR of 67 infant blood samples identified 5 HIV-positive (MTCT rate = 7.5%, 95% confidence interval [CI]: 0.3%-16.6%). Mothers can administer nevirapine to themselves and their newborns and can achieve low rates of perinatal HIV infection.


Coupled water transport by rat proximal tubule.
Simultaneous microperfusion of proximal tubules and peritubular capillaries in kidneys of rats anesthetized with Inactin was used to examine water reabsorption by this epithelium. Osmolality of the luminal solution was varied with changes in NaCl concentration and by the addition of raffinose. Capillary perfusates contained either low (2 g/dl) or high (16 g/dl) concentrations of albumin. We used low-bicarbonate perfusates for both lumen and capillary so that we might apply the nonequilibrium thermodynamic model of transport for a single solute (NaCl) to interpret our observations. Linear regression with the volume flux equation Jv = -Lp delta II - Lp sigma delta C + Jav (where Jv is volume flux, Lp is hydraulic conductance, delta II is oncotic force, sigma is osmotic reflection coefficient, delta C is salt concentration difference, and Jav is the component of Jv not attributed to transepithelial hydrostatic or osmotic forces) revealed a tubule water permeability (Pf = 0.11 +/- 0.01 cm/s) and a sigma (0.74 +/- 0.08) in agreement with previous determinations. These transport parameters were unaffected by changes in peritubular protein. We also found that Jav was substantial, approximately three-fourths of the rate of isotonic transport under these perfusion conditions. Further, this component of water transport nearly doubled with the transition from low- to high-protein peritubular capillary perfusion. When expressed as a capacity for water reabsorption against an osmotic gradient, the salt concentration differences required to null volume flux were 13.2 +/- 2.4 and 29.4 +/- 4.0 mosmol/kgH2O under low and high peritubular protein. Our data suggest that this protein effect is, most likely, an increase in solute transport by the tubule epithelial cells.


Mapping of Human FOXP2 Enhancers Reveals Complex Regulation.
Mutations of the FOXP2 gene cause a severe speech and language disorder, providing a molecular window into the neurobiology of language. Individuals with FOXP2 mutations have structural and functional alterations affecting brain circuits that overlap with sites of FOXP2 expression, including regions of the cortex, striatum, and cerebellum. FOXP2 displays complex patterns of expression in the brain, as well as in non-neuronal tissues, suggesting that sophisticated regulatory mechanisms control its spatio-temporal expression. However, to date, little is known about the regulation of FOXP2 or the genomic elements that control its expression. Using chromatin conformation capture (3C), we mapped the human FOXP2 locus to identify putative enhancer regions that engage in long-range interactions with the promoter of this gene. We demonstrate the ability of the identified enhancer regions to drive gene expression. We also show regulation of the FOXP2 promoter and enhancer regions by candidate regulators - FOXP family and TBR1 transcription factors. These data point to regulatory elements that may contribute to the temporal- or tissue-specific expression patterns of human FOXP2. Understanding the upstream regulatory pathways controlling FOXP2 expression will bring new insight into the molecular networks contributing to human language and related disorders.


Polypharmacy and medication regimen complexity as factors associated with hospital discharge destination among older people: a prospective cohort study.
Older people often take multiple medications. It is a policy priority to facilitate older people to stay at home longer. Three-quarters of nursing home placements in the US are preceded by a hospitalization. To investigate the association between polypharmacy and medication regimen complexity with hospital discharge destination among older people. This prospective cohort study comprised patients aged ≥70 years consecutively admitted to the Geriatric Evaluation and Management unit at a tertiary hospital in Adelaide, Australia, between October 2010 and December 2011. Medication regimen complexity at discharge was calculated using the 65-item validated Medication Regimen Complexity Index (MRCI). Unadjusted and adjusted relative risks (RRs) with 95 % confidence intervals (CIs) were calculated for medication-related factors associated with discharge directly to home versus non-community settings (rehabilitation, transition care, and residential aged care). From 163 eligible patients, 87 were discharged directly to home (mean age 84.6 years, standard deviation [SD] 6.9; mean MRCI 26.1, SD 9.7), while 76 were discharged to non-community settings (mean age 85.8 years, SD 5.8; mean MRCI 29.9, SD 13.2). After adjusting for age, sex, comorbidity, and activities of daily living, having a high medication regimen complexity (MRCI >35) was inversely associated with discharge directly to home (RR 0.39; 95 % CI 0.20-0.73), whereas polypharmacy (≥9 medications) was not significantly associated with discharge directly to home (RR 0.97; 95 % CI 0.53-1.58). Having high medication regimen complexity was inversely associated with discharge directly to home, while polypharmacy was not associated with discharge destination.


Predictors of Long-term Success After Concomitant Surgical Ablation for Atrial Fibrillation.
According to guidelines, atrial fibrillation (AF) ablation success should be measured by 24-hour Holter electrocardiogram (ECG). However, information on long-term success, especially obtained by 24-hour Holter ECG, is rare. We therefore analyzed rhythm course and long-term outcomes of our patients undergoing concomitant surgical AF ablation. Between January 2003 and April 2011, 486 patients underwent concomitant surgical AF ablation in our institution. Patients with 24-hour Holter ECG rhythm status available between 5 and 10 years postoperatively were included in this retrospective data analysis (n = 155). Ablation lesions were limited to either a pulmonary vein isolation (n = 31, 20%), a more complex left atrial lesion set (n = 89, 57%), or biatrial lesions (n = 35, 23%). Primary end point of the study was freedom from AF during long-term follow-up. Mean patient age was 68.1 ± 8.4 years; 57.4% were male. Mean follow-up time was 5.9 years. Surgical AF ablation provided freedom from AF rate of 56.6% during long-term follow-up, with significantly better results in patients with paroxysmal than in those with persistent AF (67.2% vs 51.8% P = 0.03). A stable rhythm course was observed during follow-up, without statistically significant differences between 12 months and latest follow-up (63.2% vs 56.6%; P = 0.25). In multivariate analysis, preoperative paroxysmal AF, duration of AF, and left atrial diameter were predictors of long-term ablation success. Surgical AF ablation provided freedom from AF rate of 56.6% during long-term follow-up. Statistically significant predictors of ablation success at latest follow-up were preoperative paroxysmal AF, duration of AF, and a preoperative smaller left atrial diameter.


The M2 polarization of macrophage induced by fractalkine in the endometriotic milieu enhances invasiveness of endometrial stromal cells.
Fractalkine (FKN) is involved in the immunopathogenesis of inflammatory diseases, including endometriosis. Our objective was to investigate the role of FKN in the cross-talking between endometrial stromal cells (ESCs) and U937 (macrophage line) in the endometriotic milieu. We have found that FKN levels in peritoneal fluid and ESCs positively correlate with the progress of endometriosis. The expression of CX3CR1 in the normal ESCs were significantly lower than that in eutopic and ectopic ESCs from women with endometriosis. CX3CR1 expression in U937 was higher than that in ectopic ESCs. FKN secreted by eutopic ESCs could change the balance between the release of IL10 and IL12 of macrophages with the upregulation of IL10 production and downregulation of IL12 production. Moreover, FKN could induce M2 polarization of macrophage with decreased expression of CD86. FKN could increase the expression of matrix metalloproteinase 9 and decrease the expression of tissue inhibitor of metalloproteinase1 and 2, and promote the invasiveness of ESCs by activating p38MAPK and integrinβ1 signal pathway. In conclusion, the higher levels of FKN secreted by eutopic ESCs facilitate the onset and progression of endometriosis by inducing M2 polarization of macrophage which in turn enhances invasiveness of ESCs.


[Effecive observation of percutaneous reduction and Kirschner pin fixation for treatment of supracondylar fracture of humerus in children].
To study on the clinic effect of percutaneous reduction and Kirschner's pins fixation for treatment of supracondylar fracture of humerus in children. From June 2001 to Nov. 2007, 26 patients of supracondylar fracture of humerus in children were reviewed. All patients were treated by the fixation of percutaneous reduction and Kirschner's pins under the C-arm X-ray machine. These patients were included 16 males and 10 females with the age from 3 to 10 years. There were 17 cases on the left and 9 cases on the right. There were 24 cases of extension type and 2 cases of flexing type and all the cases were considered as closed fracture without any injury on nerve and vascular. These patients were all under operation from half an hour to 7 days after being injured, and 15 of them were sent to the hospital and received operation immediately. These 26 cases were followed-up for 3 to 9 months, all fractures of them were healing. According to the comprehensive evaluation, the result of 16 cases were excellent, 8 cases were good, and 2 cases were fine. From the research, the method of percutaneous reduction and Kirschner's pins fixation for treatment of supracondylar fracture of humerus in children with the assistance from C-arm X-ray machine is safe, convenient, less injured, with reliable fixation, complication-minimizing, and easy for functional recover.


Accidental deaths in young people with epilepsy and psychiatric comorbidity-A Danish nationwide cohort study.
The objective of this study was to investigate the accident-related mortality among people younger than 55 years of age with epilepsy compared with the general population and to study how psychiatric comorbidity influences this risk. This is a population-based cohort study of individuals born in Denmark between 1960 and 2015 (n = 3, 665 616). Persons diagnosed with epilepsy and psychiatric disorders were identified in the Danish National Patient Register and the Danish Central Psychiatric Central Register. We estimated the hazard ratio (HR) with 95% confidence intervals (CIs) of accidental death in people with epilepsy compared with persons without epilepsy. We identified 61 330 persons (1.7%) diagnosed with epilepsy. Median age at end of follow-up was 27.8 years. In people with epilepsy, 5253 died during follow-up, 480 (9%) of whom died from accidents. Among people without epilepsy, 52 588 died during follow-up, of whom 1280 (2.4%) died from accidents. People with epilepsy had a 3.7-fold (95% CI 3.4-4.1) increased risk of accidental death compared with persons without epilepsy. When we adjusted for psychiatric disorders, the risk remained significantly elevated in people with epilepsy compared to people without epilepsy (adjusted HR [aHR] 2.44, 95% CI 2.22-2.69). When stratifying the analyses on epilepsy and psychiatric disorders, people with epilepsy and psychiatric disorders had an aHR of 4.95 (95% CI 3.82-6.41) when compared with persons without epilepsy and psychiatric disorders. The risk of accidental death was increased in people with epilepsy and was particularly high among people with epilepsy with psychiatric comorbidity. The findings highlight the need for awareness and prevention strategies in people with epilepsy, especially in people with comorbid psychiatric disorders.


Evaluation of an alphaprodine-hydroxyzine combination as a sedative agent in the treatment of the pediatric dental patient.
This investigation proposed and evaluated a submucosally administered standard dose drug combination containing .6 mgm/kgm alphaprodine hydrochloride and .3 mgm/kgm hydroxyzine hydrochloride, in conjunction with nitrous oxide, oxygen, and lidocaine with epinephrine, in the sedation and treatment of uncooperative pediatric dental patients. Observations from this study include: The technique was successful in attaining a desirable, conscious sedation level that was characterized by rapid onset, maintenance throughout treatment, and rapid reversibility with naloxone and 100% oxygen. The protective airway reflexes remained intact during the procedures. Vital signs remained fairly constant throughout the treatment. Respiratory rate was slightly depressed during the sedation, but hemoglobin oxygen saturation levels remained constant. There were no incidences of respiratory depression, hypoxia, or apnea either during or after treatment, and no emergency medical or resuscitative efforts were necessary. Twenty-four hours after the appointment, few patients complained of the experience and more than half stated that they looked forward to returning. In view of these findings, the techniques and drug combination described in this investigation appear to provide a safe and effective means for the sedation and treatment of uncooperative pediatric dental patients. It should be emphasized, however, that the dentist using these methods should have a thorough knowledge of the agents involved, the ability to monitor patients and recognize possible adverse reactions, and the capacity to respond to any emergency situations should they arise. Consequently, only practitioners who have had extensive training and experience in all forms of anesthesia, especially pediatric anesthesia, should consider the use of these agents in their practices. It should be emphasized further that the agents and techniques should be used only for conscious sedation, the light level of sedation during which the patient retains the ability present before sedation to independently maintain an airway and respond appropriately to verbal command, and not for any deeper forms of anesthesia.


The impact of COVID-19 on opioid toxicity deaths for people who experience incarceration compared to the general population in Ontario: A whole population data linkage study.
To inform preparedness and population health action, we need to understand the effects of COVID-19 on health inequities. In this study, we assess the impact of COVID-19 on opioid toxicity deaths among people who experience incarceration compared to others in the general population in Ontario, Canada. We conducted a retrospective cohort study for the period of January 1, 2015 to December 31, 2020. We accessed and linked coronial data on all opioid toxicity deaths in Ontario with correctional data for people aged 18 years and older who were incarcerated in a provincial correctional facility. We used data from the Statistics Canada Census to calculate whole population rates. We used an interrupted time series design and segmented regression to assess for change in the level or rate of increase in deaths due to opioid toxicity coinciding with the COVID-19 pandemic. We compared the impact of COVID-19 on the opioid toxicity death rates for people exposed and not exposed to incarceration. Rates of opioid toxicity death increased with a linear positive slope in both persons exposed to incarceration and those not exposed over the study period. The start of COVID-19 measures coincided with a marked upward shift in the trend lines with modification of the effect of COVID-19 by both sex and exposure to incarceration. For persons exposed to incarceration, the risk ratio (RR) was 1.50 (95%CI 1.35-1.69) for males and 1.21 (95%CI 1.06-1.42) for females, and for persons not exposed to incarceration, the RR was 1.25 (95%CI 1.13-1.38) for males and not significant for females. COVID-19 substantially exacerbated the risk of opioid toxicity death, impacting males and females who experienced incarceration more than those who had not, with an immediate stepwise increase in risk but no change in the rate of increase of risk over time. Public health work, including pandemic preparedness, should consider the specific needs and circumstances of people who experience incarceration.


Intrinsic Brain Connectivity in Chronic Pain: A Resting-State fMRI Study in Patients with Rheumatoid Arthritis.
Rheumatoid arthritis (RA) is commonly accompanied by pain that is discordant with the degree of peripheral pathology. Very little is known about the cerebral processes involved in pain processing in RA. Here we investigated resting-state brain connectivity associated with prolonged pain in RA. 24 RA subjects and 19 matched controls were compared with regard to both behavioral measures of pain perception and resting-resting state fMRI data acquired subsequently to fMRI sessions involving pain stimuli. The resting-state fMRI brain connectivity was investigated using 159 seed regions located in cardinal pain processing brain regions. Additional principal component based multivariate pattern analysis of the whole brain connectivity pattern was carried out in a data driven analysis to localize group differences in functional connectivity. When RA patients were compared to controls, we observed significantly lower pain resilience for pressure on the affected finger joints (i.e., P50-joint) and an overall heightened level of perceived global pain in RA patients. Relative to controls, RA patients displayed increased brain connectivity predominately for the supplementary motor areas, mid-cingulate cortex, and the primary sensorimotor cortex. Additionally, we observed an increase in brain connectivity between the insula and prefrontal cortex as well as between anterior cingulate cortex and occipital areas for RA patients. None of the group differences in brain connectivity were significantly correlated with behavioral parameters. Our study provides experimental evidence of increased connectivity between frontal midline regions that are implicated in affective pain processing and bilateral sensorimotor regions in RA patients.


Application of finite element modeling to optimize flap design with tissue expansion.
Tissue expansion is a widely used technique to create skin flaps for the correction of sizable defects in reconstructive plastic surgery. Major complications following the inset of expanded flaps include breakdown and uncontrolled scarring secondary to excessive tissue tension. Although it is recognized that mechanical forces may significantly impact the success of defect repair with tissue expansion, a mechanical analysis of tissue stresses has not previously been attempted. Such analyses have the potential to optimize flap design preoperatively. The authors establish computer-aided design as a tool with which to explore stress profiles for two commonly used flap designs, the direct advancement flap and the double back-cut flap. The authors advanced both flaps parallel and perpendicular to the relaxed skin tension lines to quantify the impact of tissue anisotropy on stress distribution profiles. Stress profiles were highly sensitive to flap design and orientation of relaxed skin tension lines, with stress minimized when flaps were advanced perpendicular to relaxed skin tension lines. Maximum stresses in advancement flaps occurred at the distal end of the flap, followed by the base. The double back-cut design increased stress at the lateral edges of the flap. The authors conclude that finite element modeling may be used to effectively predict areas of increased flap tension. Performed preoperatively, such modeling can allow for the optimization of flap design and a potential reduction in complications such as flap dehiscence and hypertrophic scarring.


Multiple neuroendocrine tumours in transgenic mice induced by c-kit-SV40 T antigen fusion genes.
Transgenic mice carrying either a 1.008 or a 4.225 kb of the mouse c-kit 5'-flanking sequences linked to the oncogenic large T antigen (TAg) region of the simian virus 40 (SV40) genome were generated to test if the c-kit promoter could be used to develop useful mouse models. Both constructs promote tumourigenesis in the pituitary and the thyroid with high efficiency. The cell types from which each of these tumours derives were identified. Tumours of the pituitary derive from alpha-MSH-expressing cells located in the intermediate lobe. Transformed cells of the thyroid were calcitonin-positive, implying that the tumours derive from C cells or their precursors. Chromogranin A and neuron-specific enolase, general neuroendocrine cell markers, were expressed in both tumour types. Furthermore a variety of tumours appeared in the transgenic mice. Several of them stained positively for chromogranin A and/or neuron-specific enolase. This suggests a previously unsuspected tissue-specificity of the c-kit 5' flanking sequences for neuroendocrine cells. The Kit-TAg transgenic mouse lines may represent a valuable model for the study of the development and the biology of neuroendocrine tumours.


Epidemiologic investigation of hornet and paper wasp stings in forest workers and electrical facility field workers in Japan.
Forestry and field workers who work outdoors are at high risk for Hymenoptera stings and may develop occupation-related allergies from being stung. However, clinical and immunological surveys of Hymenoptera stings in the occupational setting have rarely been reported. We surveyed the natural history of Hymenoptera stings in Japanese forestry workers (FWs) and electrical facility field workers (EFFWs), and we assessed the utility of measuring specific (s)IgE Ab to Hymenptera venom. Questionnaires on hornet and paper wasp stings were completed by 999 FWs, 354 EFFWs, and 365 office workers as controls between July and November 2009. Sera from these participants were tested for sIgE Ab levels to Hymenptera venom with a CAP system using a fluoroenzyme immunoassay. Of the participants who had experienced Hymenoptera stings, 914 (91.5%) were FWs, 293 (82.8%) were EFFWs, and 295 (80.8%) were controls. Of the participants who had experienced systemic reactions, 210 (21.0%) were FWs, 51 (14.4%) were EFFWs, and 39 (10.7%) were controls. sIgE Ab in response to hornet and wasp venom was positive (≥ class 2) in 42.4% and 41.4% of FWs, 30.1% and 31.4% of EFFWs, and 15.1% and 18.1% of controls, respectively. The likelihood of being sIgE-positive to wasp and hornet venom was significantly higher in FWs and EFFWs than in controls (P < 0.05). 21% of FWs and 14% of EFFWs had experienced systemic reactions to Hymenoptera stings with a higher frequency compared with office workers in the same area. 40% of FWs and 30% of EFFWs had sera that were sIgE positive to Hymenoptera venom.


Physiological responses of resistant and susceptible buffalograsses to Blissus occiduus (Hemiptera: Blissidae) feeding.
The impact of Blissus occiduus Barber feeding on resistant ('Prestige') and susceptible ('378') buffalograsses, Buchloë dactyloides (Nuttall) Engelmann, was evaluated through measurement of carbon exchange rate, light and carbon assimilation (A-C(i)) curves, chlorophyll a fluorescence, and nonstructural carbohydrates. No significant differences in carbon exchange rates were observed between infested and control plants for 378 at 5 and 10 d after infestation; however, at 20 d after chinch bug introduction, significant differences in carbon exchange rates between infested and control 378 plants were detected. Carbon exchange rates were similar between infested and control Prestige plants at 5,10, and 20 d after infestation, suggesting that resistant plants can allocate energy for recovery from chinch bug injury. Significant differences in the photochemical efficiency of photosystem II (PSII) and the apparent photosynthetic electron transport ratio were observed between infested and control 378 plants, whereas, no significant differences in the photochemical efficiency of PSII and the electron transport ratio were detected between control and infested Prestige plants. Blissus occiduus-infested 378 and Prestige plants consistently had similar or higher levels of nonstructural carbohydrates compared with their respective control plants. These data suggest that both resistant and susceptible buffalograsses increase levels of nonstructural carbohydrates in response to B. occiduus feeding. This research also suggests compensatory photosynthesis takes place in Prestige but not in 378.


Reciprocal positive regulation of hypoxia-inducible factor 1alpha and insulin-like growth factor 2.
Hypoxia-inducible factor 1 (HIF-1) activates transcription of genes encoding glucose transporters, glycolytic enzymes, vascular endothelial growth factor, and other proteins involved in O2 homeostasis and tumor progression. The expression and transcriptional activity of the HIF-1alpha subunit is regulated by the cellular O2 concentration. We demonstrate that insulin, insulin-like growth factor (IGF)-1, and IGF-2 induce expression of HIF-1alpha, which is required for expression of genes encoding IGF-2, IGF-binding protein (IGFBP)-2 and IGFBP-3. These data provide a novel mechanism by which HIF-1alpha overexpression may occur in tumor cells and contribute to an autocrine growth factor loop.


The Louisiana Mental and Behavioral Health Capacity Project Trauma-Informed Integrated Care Model and Improved Posttraumatic Stress Outcomes.
The Mental and Behavioral Health Capacity Project in Louisiana has been addressing health disparities by increasing accessibility and availability through integrating services into primary care clinics. Integrated health is becoming the standard of care, providing an opportunity to address the trauma-specific needs of communities, and allowing for informed and less stigmatized services. The purpose of this study is to test the efficacy of the Mental and Behavioral Health Capacity Project in Louisiana model in the primary care settings to reduce posttraumatic stress symptoms and physical health complaints. A pre-experimental time series design was used on the basis of participants self-reporting at least 1 trauma at intake and follow-up collected at 1-, 3-, and 6-month intervals. The hypotheses were that posttraumatic stress and physical health complaints would significantly decrease over the course of treatment. This study was part of a larger study to evaluate the effectiveness of the Mental and Behavioral Health Capacity Project in Louisiana-integrated health efforts. Sample parameters included (1) intake date from January 2013 through December 2015; (2) at least 18 years of age; and (3) presented at 1 of 5 primary health care clinics in Southeast Louisiana. A total of 235 patients were selected; the mean age was 44.7 years (SD = 13.6) and the majority were white (68%) and female (76%). Brief behavioral-based trauma treatment was delivered using both on-site and telemedicine therapies provided by a psychologist, psychiatrist, or through a combined treatment model. The main outcome measures were the Posttraumatic Stress Civilian Checklist (PCL-C) and the Patient Health Questionnaire (PHQ-15). The hypothesis was supported. Statistically significant decreases in posttraumatic stress symptoms and physical health complaints were shown over the course of treatment, with 63% of the group demonstrating clinically significant change. This study supports brief trauma treatment in primary care clinics as an effective method of reducing trauma and physical health symptoms in postdisaster environments.


[Comparison of different MRT techniques in the diagnosis of degenerative cartilage diseases. In vitro study of 50 joint specimens of the knee at T1.5].
An experimental study was performed on joint specimens of the knee to assess the advantages and disadvantages of 14 generally available sequences in cartilage imaging. Each of the 50 surgically exposed cadaveric joints of the knee was examined by the following sequences: T1, proton- and T2 weighted spin echo(SE) sequences, proton- and T2 weighted Turbo-SE, T1 weighted SE with fat suppression, MTC combined with T1-weighted SE and T2 weighted FLASH-2 D, STIR, FISP-3 D, FLASH-3 D (with fat suppression), and MR arthrography. We assessed the image quality by a scale, signal to noise-ratio of cartilage and joint fluid, and the accuracy in detection of cartilage lesions. Pathology and arthroscopy were reference methods to MRI, and demonstrated grade 1-4 lesions on 186 of 300 joint facettes. Advanced stages of cartilage lesions (65 grade 3 and 4 lesions) were detected by standard SE sequences in 67-94%. Application of volume techniques (FISP-3 D, FLASH-3 D), high definition matrix (512 pixel), MTC with FLASH-2 D and MR-arthrography improved the sensitivity up to 82-100%. Superficial lesions (65 grade 2 lesions) were demonstrated in 3-38%, and on MR arthrography in 45%. Structural changes (56 Grade 1 lesions) were recorded on MR) in only 10%. With regard to standard SE sequences, the detectability of cartilage lesions can be improved by techniques that use 512 matrices, selective cartilage imaging, and volume acquisition.


Machine learning applications in tobacco research: a scoping review.
Identify and review the body of tobacco research literature that self-identified as using machine learning (ML) in the analysis. MEDLINE, EMABSE, PubMed, CINAHL Plus, APA PsycINFO and IEEE Xplore databases were searched up to September 2020. Studies were restricted to peer-reviewed, English-language journal articles, dissertations and conference papers comprising an empirical analysis where ML was identified to be the method used to examine human experience of tobacco. Studies of genomics and diagnostic imaging were excluded. Two reviewers independently screened the titles and abstracts. The reference list of articles was also searched. In an iterative process, eligible studies were classified into domains based on their objectives and types of data used in the analysis. Using data charting forms, two reviewers independently extracted data from all studies. A narrative synthesis method was used to describe findings from each domain such as study design, objective, ML classes/algorithms, knowledge users and the presence of a data sharing statement. Trends of publication were visually depicted. 74 studies were grouped into four domains: ML-powered technology to assist smoking cessation (n=22); content analysis of tobacco on social media (n=32); smoker status classification from narrative clinical texts (n=6) and tobacco-related outcome prediction using administrative, survey or clinical trial data (n=14). Implications of these studies and future directions for ML researchers in tobacco control were discussed. ML represents a powerful tool that could advance the research and policy decision-making of tobacco control. Further opportunities should be explored.


[Studying of cytokine dynamics in injured persons with severe burns for estimation of severity and prognosis].
Dynamics of a blood serum concentration of tumor necrosis factor-alpha (TNF- alpha), interleukines (IL-1beta, IL-10) in 35 patients, suffering severe burn, and possibility of application of these indices as biomarkers of the severity state and the complications prognosis, were studied. During the investigation there was established, that TNF-alpha concentration on the 8 - 10th and 19 - 21th day after trauma does the best for characterization of a burn total area, while the IL-1beta concentration on the 8 - 10th day after trauma - the deep affections severity and the IL-10 concentration on the 19 - 21th day after trauma - the deep affections severity. Hyperreactivity, caused by enhanced production of TNF-alpha, IL-1beta and IL-10, witnesses the raised risk of development of the organs complications. And adversely, hypo- and areactivity in extended and deep burns witnesses about enhanced risk of lethality. The blood serum concentration of TNF-alpha, IL-1beta and IL-10 is expedient to use as a biomarkers of the patients state severity and for the course prognosis of pathological process.


Elevated Levels of Urinary Extracellular Vesicle Fibroblast-Specific Protein 1 in Patients with Active Crescentic Glomerulonephritis.
Extracellular vesicles (EVs), including exosomes, are present in various bodily fluids, including urine. We and others previously reported that cells expressing fibroblast-specific protein 1 (FSP1) accumulate within damaged glomeruli, and that urinary FSP1, as well as urinary soluble CD163, could potentially serve as a biomarker of ongoing glomerular injury. To test that idea, we collected urine samples from 37 patients with glomerular disease; purified the urinary EVs; characterized them using Nanosight, western blotting, and immunoelectron microscopy; and determined FSP1 and soluble CD163 levels using enzyme-linked immunosorbent assays. Deemed to be mainly exosomes based on their size distribution, the EVs in urine contained FSP1, and a portion of the FSP1-positive vesicles was also positive for podocalyxin. FSP1 levels in urinary EVs were (1) positively correlated with rates of biopsy-proven cellular crescent formation (r = 0.562, p < 0.001) and total crescent formation (r = 0.448, p = 0.005) among total glomeruli; (2) significantly higher in patients with cellular crescents affecting 20% or more of their glomeruli than in those with fewer affected glomeruli (p = 0.003); and (3) significantly decreased after glucocorticoid and immunosuppressant therapy (p < 0.05). A positive correlation between FSP1 levels in urinary EVs and urinary soluble CD163 levels was confirmed (r = 0.367, p < 0.05). These data suggest that a portion of urinary FSP1 is secreted as EVs originating from podocytes, and that FSP1 levels reflect active and ongoing glomerular injury and disease activity, such as cellular crescent formation.


Major depression, C-reactive protein, and incident ischemic heart disease in healthy men and women.
To investigate how C-reactive protein (CRP) and major depressive disorder (MDD) relate to each other and to incident ischemic heart disease (IHD). Studies have shown that both depression and raised CRP concentration predict IHD and that elevated CRP is linked with increased risk of depression. A prospective case-control study of healthy men and women, aged 45 to 79 years, was undertaken within the United Kingdom European Prospective Investigation into Cancer (EPIC)-Norfolk study. CRP concentration was measured for 726 (fatal or nonfatal) IHD cases and 1688 matched controls who completed a baseline MDD self-assessment, defined by restricted Diagnostic and Statistical Manual of Mental Disorders, 4th Edition diagnostic criteria. Past-year MDD was associated with increased CRP concentration levels (4.31 mg/L for participants who reported episodes of MDD in the past year versus 3.65 mg/L for those who did not; p = .003), and the odds ratio for incident IHD associated with higher CRP concentration was 2.02 (comparing the top versus bottom quartile of CRP; 95% Confidence Interval (CI) = 1.52-2.68), adjusted for cigarette smoking, diabetes, systolic blood pressure, body mass index, and cholesterol. The association between past-year MDD and IHD was independent of CRP (odds ratio = 1.55; 95% CI = 1.01-2.37, with adjustments as above, and additionally for CRP). Evidence from this study is supportive of an association between MDD and CRP although it suggests that CRP does not account for the association between MDD and future IHD.


Induction of the sticky plant defense syndrome in wild tobacco.
Many plants engage in protective mutualisms, offering resources such as extrafloral nectar and shelters to predatory arthropods in exchange for protection against herbivores. Recent work indicates that sticky plants catch small insects and provide this carrion to predators who defend the plants against herbivores. In this study, we investigated whether wild tobacco, Nicotiana attenuata, fits this sticky plant defense syndrome that has been described for other sticky plants. We developed a bioassay for stickiness involving the number of flies that adhered to flowers, the stickiest tissues. In surveys conducted over three field seasons at four sites, we found that the number of carrion that adhered to a plant was positively correlated with the number of predators that we observed foraging over its surfaces. The number of predators was positively correlated with the number of seed capsules that the plant produced, a measure of lifetime female reproductive success. Structural equation modeling indicated strong support for the causal path linking carrion numbers to predator numbers to capsule production. We investigated whether stickiness was an inducible trait and examined two potential cues. We found that experimental clipping of rosette leaves induced greater stickiness, although clipping of neighboring sagebrush leaves did not. Damage to leaf tissue is likely to be a more reliable predictor of risk than is damage to a neighboring plant. The sticky plant defense syndrome is a widespread protective mutualism; its strength and ecological relevance can adjust as risk of herbivory changes.


[Typologic characteristics of central hemodynamics in the monkey in reclining and upright positions].
By tetrapolar rheography central hemodynamics was investigated in 74 rhesus monkeys in the reclining and orthostatic position. The basic hemodynamic parameters were examined in relation to the entire sample, to the groups with a higher or lower blood pressure (BPmean), and to four states of central circulation in orthostatic animals. The typological circulatory differences in the orthostatic state were shown to be determined by qualitatively different hemodynamic mechanisms responsible for BPmean. The hemodynamic characteristics in the reclining and orthostatic position were found to be reciprocally related. It is recommended to take into consideration the typological differences of hemodynamics that can modify cardiovascular responses to various effects.


Pax-6, Prox 1, and Chx10 homeobox gene expression correlates with phenotypic fate of retinal precursor cells.
To study the expression patterns of the homeobox genes Pax-6, Prox 1, and Chx10 during chick retinal development in vivo and in vitro. Sections of paraformaldehyde-fixed, paraffin-embedded eyes were obtained at a range of developmental stages. In situ hybridization was carried out on tissue sections using digoxigenin-labeled sense and antisense RNA probes that recognize chicken Pax-6 and Prox 1 (whose sequences were already available), and chicken Chx10 (which was cloned and sequenced as part of this study). Selected developmental stages were also studied by immunocytochemistry with antibodies against Pax-6 and Prox 1, and by Northern blot analysis using 32P-labeled probes. Until embryonic day (ED) 5, in situ hybridization shows widespread, diffuse distribution of all three genes. Between ED 6 and ED 8, however, they acquire distinct, topographically specific patterns of expression. The Prox 1 signal is predominantly expressed in the prospective horizontal cell layer of the neuroepithelium, decreases vitreally, and is absent from ganglion cells and the prospective photoreceptor layer. Pax-6 is strongly expressed only in the prospective ganglion-cell and amacrine-cell regions at the same stages, and is not detected in prospective photoreceptors. Chx10 expression becomes concentrated in the future bipolar-cell region of the inner nuclear layer. Similar patterns are maintained by ED 15 through ED 18, after cell differentiation has taken place. Pax-6 and Prox 1 immunoreactive materials showed nuclear localization and a pattern of laminar distribution equivalent to that seen by in situ hybridization. These results suggest that the differentiated fate of retinal precursor cells may be influenced by Pax-6, Prox 1, or Chx10, this hypothesis is now being tested using dissociated chick embryo retinal cell cultures.