Vitamin D binding protein and post-surgical outcomes and tissue injury markers after hip fracture: a prospective study.
Hip fracture is a serious injury that can lead to increased morbidity and mortality. Vitamin D binding protein (DBP) could be a prognostic indicator of outcomes since it is important for actin scavenging and inflammation after tissue injury. To determine whether circulating DBP is associated with mobility or mortality after hip fracture and its association with acute tissue injury markers. A post-hoc analysis of a prospective study of 260 patients with hip fracture and mobility at 30-d and 60-d and mortality at 60-d after repair surgery. Biochemical markers were measured before and 2-4 days after surgery. Tissue injury markers were measured in 100 randomly selected patients and controls. Multi-site study in North America. The primary outcome was mobility and mortality by DBP tertiles. Secondary outcomes were assessment of pre- and post-operative biomarkers. Among all patients (81 ± 9y, BMI 25 ± 4 kg/m2; 72% female), those within the highest DBP tertile had greater mobility at 30-d (OR: 2.66; 95%CI: 1.43,4.92; P = 0.002) and 60-d (OR: 2.31; 95%CI: 1.17,4.54, P = 0.014) and reduced mortality (OR: 0.18; 95%CI: 0.04,0.86, P = 0.032) when compared to the lowest DBP tertile (<28.0 mg/dL). Total 25-hydroxyvitamin-D did not differ between tertiles (22.0 ± 9.5 ng/mL). Circulating DBP and gelsolin were lower and interleukin-6, C-reactive protein and F-actin were higher (P < 0.01) in patients compared to controls, and most worsened (p < 0.01) after surgery. High circulating DBP concentrations are associated with better mobility and reduced mortality after hip fracture surgery. The role of DBP as an acute phase reactant to tissue injury and clinical outcomes should be addressed in a future study.


The occurrence of Oesophagostomum multifoliatum Daubney and Hudson, 1932, in Nigerian cattle.
Oesophagostomum multifoliatum, previously known to occur only in Kenya, Rhodesia and Tanzania, was found on the Jos Plateau of Nigeria in cattle. Of the 120 cattle examined post-mortem, 78 (65%), were found to be infected. The faecal egg, of which only the size was hitherto known, is described and figured; it shows striking similarities to that of Nematodirus. The possibility is expressed that O. multifoliatum might have been mistaken for the more familiar but closely related species O. radiatum and O. columbianum or its egg with that of Nematodirus; it is probable that it is much more widespread than hitherto thought.


Developing a contemporary patient-reported outcomes measure for spinal cord injury.
To develop a spinal cord injury (SCI)-specific patient-reported outcome (PRO) measure of health-related quality of life (QOL) covering multiple domains of functioning, including physical, emotional, and social health. Focus groups. Four SCI Model Systems rehabilitation hospitals. Individuals with SCI (n=65) and clinicians (n=42). Not applicable. Spinal Cord Injury Quality of Life Measurement System (SCI-QOL). Qualitative analysis yielded 3 domains of primary importance: physical-medical health, emotional health, and social participation. Results were used to guide domain and item decisions in the development of the SCI-QOL PRO measurement system. Qualitative data were used to develop item pools with item content specific to individuals with SCI across a wide spectrum of functioning. When possible, items from other major measurement initiatives were included verbatim in the item pools to link the measurement systems and facilitate cross-study and cross-population comparisons. Issues that affect individuals' QOL after SCI are varied and several issues are unique to individuals who have had a traumatic injury. From these qualitative data, 3 major domains and 18 subdomains of functioning were identified. Item pools were developed in each of these 18 areas to measure functioning related to physical-medical issues, emotional status, and social participation.


In vitro method to assess the antimicrobial activity and potential efficacy of novel types of wound dressings.
To develop a simple, reproducible in vitro static diffusion method using cellulose disks and defined species to test antimicrobial efficacy of wound dressings. Cellulose disks were inoculated by immersion in cell suspensions of target species Staphylococcus epidermidis, Candida albicans and Fusobacterium nucleatum. Test and control wound dressings were cut into equal sized squares (25 x 25 mm) and applied to the surface of 10-mm thick tryptone yeast extract agar on test beds. Following a 2-h equilibration period, inoculated cellulose disks were inserted (one per dressing) at the interface between dressing and agar surface and a small weight applied over each square. At various sampling times, disks were removed and surviving cells enumerated by viable counts. Disk to disk variation for microbial loading was assessed using S. epidermidis for both initial (n = 16) and standard treatment (n = 16) conditions. The coefficient of variation was low (<5%) indicating good reproducibility for cell loading and treatment position on the test bed. Replicate assays (n = 6) using S. epidermidis and oxyzyme gels produced similar kill rates with low scatter (R2 > 0.9) indicating good reproducibility between assays. Significant differences (P < 0.05) in kill rates were observed for different target species, types of dressing and test bed conditions (+/-blood and nutrients). The method is reproducible and useful in tracking the death kinetics of test species, enabling the comparison of different types of dressing. The reported method has significant advantages over established test procedures; it can be applied equally across a wide range of target species (including anaerobes and yeasts), a wide range of conditions, and different types of surface dressings, including those relying upon oxygen diffusion.


Postnatal development of retinal projections in the brushtailed possum, Trichosurus vulpecula.
The postnatal development of retinal projections was studied in the brushtailed possum, Trichosurus vulpecula. [3H]proline was injected into one eye of 13 young possums aged 24-84 days in order to trace retinal pathways. The dorsal lateral geniculate nucleus (LGNd) can be identified in Nissl material at 19 days but not at 9-10 days. By 40 days some cytoarchitectural lamination of the LGNd is apparent and by 71 days the adult pattern of cell layers is present. At 24 days retinal fibers occupy by lateral part of the LGNd on both sides of the brain. By 38-40 days the retinal fibers fill be contralateral LGNd and the binocular part of the ipsilateral LGNd and there is a beginning of the segregation of retinal fibers into left and right eye territories. By 49-50 days a partial segregation is achieved, and complete segregation by 71 days. At 9-10 days the superior colliculus is not differentiated into layers and there is a thick zone of cell proliferation around the ventricle. By 23 days the superior colliculus has well-defined cell layers and there is still some indication of cell proliferation around the ventricle. By 40 days, the superior colliculus shows little evidence of cell proliferation. At 24 days retinal fibers fill the superficial layers of the contralateral optic tectum and are lightly distributed through the superficial layers of the rostral half of the ipsilateral tectum. By 38 days the ipsilateral retinal input is restricted to the deeper layers of the tectum. These results show that the adult pattern of retinal projections to the LGNd and optic tectum develops a number of weeks before eye opening occurs (at 90-120 days).


Fungal pollution of indoor environments and its management.
Indoor environments play important roles in human health. The health hazards posed by polluted indoor environments include allergy, infections and toxicity. Life style changes have resulted in a shift from open air environments to air tight, energy efficient, environments, in which people spend a substantial portion of their time. Most indoor air pollution comes from the hazardous non biological agents and biological agents. Fungi are ubiquitous in distribution and are a serious threat to public health in indoor environments. In this communication, we have reviewed the current status on biotic indoor air pollution, role of fungi as biological contaminants and their impact on human health.


Role of prostaglandins and angiotensin II in experimental glomerulonephritis.
Moderate autologous nephrotoxic serum nephritis (NSN) in rats causes no reduction in GFR despite a reduction in ultrafiltration coefficient (Kf) to less than one-half of normal. An increase in intraglomerular hydraulic pressure maintains GFR, but the signal and efferent mechanisms for this adaptation remain unknown. Indomethacin and saralasin were used to study the possible roles of prostaglandins and angiotensin II (A-II) in the adaptation to NSN. Indomethacin decreased renal blood flow (RBF) in NSN (-8.6%, P less than 0.001), but not in controls. Renal vascular resistance (RVR) increased in NSN (+ 9.6%, P less than 0.01), but decreased in controls (-5.6%, P less than 0.01). GFR decreased in NSN (-22.3%, P less than 0.01), but increased in controls (+ 10.3%, P less than 0.001). Urinary PGE2 excretion decreased markedly both in NSN and controls. With combined treatment using indomethacin and saralasin, RBF increased in NSN (+ 22.4%, P less than 0.001), but did not change in controls. RVR decreased in NSN (-21.5%, P less than 0.001), but was unchanged in controls. GFR remained unchanged both in NSN and controls. With saralasin alone, RBF increased both in NSN (+ 21.4%, P less than 0.001) and in controls (+ 14.4%, P less than 0.001). RVR decreased both in NSN (-21.8%, P less than 0.001) and controls (-18.7% P less than 0.001). GFR increased (+ 12.3%, P less than 0.05) in NSN, but did not change in controls. Urinary PGE2 excretion was increased in NSN compared to controls, decreased markedly in NSN after either indomethacin or saralasin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)


High-level expression of a sika deer (Cervus nippon) Cu/Zn superoxide dismutase in Pichia pastoris and its characterization.
Production of a sika deer Cu/Zn-SOD was achieved in Pichia pastoris after the reconstituted expression vector pPIC9K was transformed into the strain GS115. By employing Saccharomyces cerevisiae secretion signal peptide (α-factor) under the regulation of the methanol-inducible promoter of the gene of alcohol oxidase 1 (AOX1), sika deer Cu/Zn-SOD with a molecular mass of 16kDa was expressed while recombinant sika deer Cu/Zn-SOD with an activity of 3500U/mL was obtained from a 5L bioreactor. After two successive steps of chromatography on DEAE-650C and Superdex75, recombinant sika deer Cu/Zn-SOD was obtained with 13.8% yield, 14.5-fold purification, and a specific activity of 3447U/mg. Its optimum temperature and optimum pH were 40°C and 7.0, respectively.


IGF-I stimulates Rab7-RILP interaction during neuronal autophagy.
Restoration of autophagy represents a potential therapeutic target for neurodegenerative disorders, but factors that regulate autophagic flux are largely unknown. When deprived of trophic factors, cultured Purkinje neurons die by an autophagy associated cell death mechanism. The accumulation of autophagic vesicles and cell death of Purkinje neurons is inhibited by insulin-like growth factor, by a mechanism that enhances autophagic vesicle turnover. In this report, we identify Rab7 as an IGF-I regulated target during neuronal autophagy. Purkinje neurons transfected with EGFP-Rab7-WT and constitutively active EGFP-Rab7-Q67L contained few RFP-LC3 positive autophagosomes and little co-localization with GFP-Rab7 under control conditions. Upon induction of autophagy, RFP-LC3 positive autophagosomes increased and co-localized with GFP-Rab7. Conversely, expression of the dominant negative mutant EGFP-Rab7-T22N increased the accumulation of autophagosomes under control conditions, which accumulated even further during trophic factor withdrawal. There was no vesicular co-localization between Rab7-T22N and RFP-LC3 under control or trophic factor withdrawal conditions. During prolonged trophic factor withdrawal, a condition that leads to the accumulation of autophagic vesicles and cell death, Rab7 activity decreased significantly. IGF-I, added at the time of trophic factor withdrawal, prevented the deactivation of Rab7 and increased the interaction of Rab7 with its interacting protein (RILP), restoring autophagic flux. These results provide a novel mechanism by which IGF-I regulates autophagic flux during neuronal stress.


A comparison of post-operative complications following wisdom tooth surgery performed with sterile or clean gloves.
This randomised prospective study aimed at evaluating possible differences in the post-operative complication rate following lower wisdom tooth surgery performed with either sterile or clean surgical gloves. The microbiological profiles of the tooth sockets and glove surfaces were also evaluated and compared. A total of 275 ASA I, non-smoking and non-drinking patients consented to be randomly assigned into two groups for lower wisdom tooth surgery, performed by operators wearing either sterile or clean gloves. All the patients returned for a post-operative assessment visit one week later. An additional 40 patients were recruited and randomised into the sterile glove group (n = 20) or the clean glove group (n = 20) for the microbiology study. Specimens were taken from the glove surfaces and the post-operative socket wounds during wisdom tooth surgery. This clinical trial showed no significant difference between the sterile and clean glove groups in the incidence of acute inflammation, acute infection and dry sockets in the wounds. No single peri-operative factor had a statistically significant effect on post-operative pain intensity. Most of the bacterial isolates from the clean gloves were Gram-positive cocci or spore-forming bacilli. The total number of colony forming units and the variety of bacterial isolates from the socket wounds in the sterile and clean glove groups were similar. The study concluded that there was no advantage in using sterile surgical gloves rather than clean gloves to minimize post-operative complications in wisdom tooth surgery. There was also no apparent relationship between the bacteria contaminating the clean glove surfaces and those isolated from the socket wounds.


Replacement of brain-resident myeloid cells does not alter cerebral amyloid-β deposition in mouse models of Alzheimer's disease.
Immune cells of myeloid lineage are encountered in the Alzheimer's disease (AD) brain, where they cluster around amyloid-β plaques. However, assigning functional roles to myeloid cell subtypes has been problematic, and the potential for peripheral myeloid cells to alleviate AD pathology remains unclear. Therefore, we asked whether replacement of brain-resident myeloid cells with peripheral monocytes alters amyloid deposition in two mouse models of cerebral β-amyloidosis (APP23 and APPPS1). Interestingly, early after repopulation, infiltrating monocytes neither clustered around plaques nor showed Trem2 expression. However, with increasing time in the brain, infiltrating monocytes became plaque associated and also Trem2 positive. Strikingly, however, monocyte repopulation for up to 6 mo did not modify amyloid load in either model, independent of the stage of pathology at the time of repopulation. Our results argue against a long-term role of peripheral monocytes that is sufficiently distinct from microglial function to modify cerebral β-amyloidosis. Therefore, myeloid replacement by itself is not likely to be effective as a therapeutic approach for AD.


Deviation from Murray's law is associated with a higher degree of calcification in coronary bifurcations.
Murray's law describes the optimal branching anatomy of vascular bifurcations. If Murray's law is obeyed, shear stress is constant over the bifurcation. Associations between Murray's law and intravascular ultrasound (IVUS) assessed plaque composition near coronary bifurcations have not been investigated previously. In 253 patients plaque components (fibrous, fibro-fatty, necrotic core, and dense calcium) were identified by IVUS in segments proximal and distal to the bifurcation of a coronary side branch. The ratio of mother to daughter vessels was calculated according to Murray's law (Murray ratio) with a high Murray ratio indicating low shear stress. Analysis of variance was used to detect independent associations of Murray ratio and plaque composition. Patients with a high Murray ratio exhibited a higher relative amount of dense calcium and a lower amount of fibrous and fibro-fatty tissue than those with a low Murray ratio. After adjustment for age, sex, cardiovascular risk factors or concomitant medications, the Murray ratio remained significantly associated with fibrous volume distal (F-ratio 4.90, P=0.028) to the bifurcation, fibro-fatty volume distal (F-ratio 4.76, P=0.030) to the bifurcation, and dense calcium volume proximal (F-ratio 5.93, P=0.016) and distal (F-ratio 5.16, P=0.024) to the bifurcation. This study shows that deviation from Murray's law is associated with a high degree of calcification near coronary bifurcations. Individual deviations from Murray's law may explain why some patients are prone to plaque formation near vessel bifurcations.


Being human: Religion: bound to believe?
Atheism will always be a harder sell than religion, Pascal Boyer explains, because a slew of cognitive traits predispose us to faith.


Contrast and correlations between coarse and fine particulate matter in the United States.
The characteristics of concentrations of PM₁₀₋₂.₅, PM₂.₅, and PM₁₀ at 77 sites in the United States are evaluated. PM₁₀ concentrations show strong spatial variability, with highest levels occurring in the southwestern United States, driven primarily by PM₁₀₋₂.₅. PM₁₀₋₂.₅ and PM₂.₅ concentrations show different spatial patterns. The highest concentrations of PM₁₀₋₂.₅ were observed at sites in the southwestern US, leading to the highest PM₁₀ concentrations there. The PM₂.₅ concentrations are the major contributors to the average PM₁₀ concentrations at many sites in the eastern United States. Poor correlations were generally found between PM₁₀₋₂.₅ and PM₂.₅, suggesting that PM₁₀₋₂.₅ and PM₂.₅ are generally influenced by different sources. PM₁₀₋₂.₅ is generally more variable than PM₂.₅ because PM₁₀₋₂.₅ has a higher deposition velocity and is primarily emitted from mechanical processes (e.g. agricultural harvest and construction) that are more influenced by factors including human operation and wind speed leading to a strong episodic nature. As a result of its high variability, PM₁₀₋₂.₅ acts as the major driver for PM₁₀ extremes. PM₁₀₋₂.₅ is significantly correlated with PM₁₀ at all investigated sites, with the average correlation value R(2)=0.79. Correlations of PM₂.₅ with PM₁₀ (average of 0.37) are overall considerably lower than those between PM₁₀₋₂.₅ and PM₁₀. Different seasonal, weekly, and diurnal patterns were observed between PM₁₀₋₂.₅ and PM₂.₅ at agricultural, on-road traffic, quarrying, airport, and marine sites. At investigated agricultural sites, while the concentrations of PM₂.₅ are higher in winter when there are few agricultural activities, PM₁₀₋₂.₅ concentrations are lower in winter months than in summer and autumn months, with highest levels corresponding to harvest and planting. The harvest and planting signatures were not observed in PM₂.₅ concentrations at any of these sites, suggesting that agricultural activities do not have a strong influence on PM₂.₅ concentrations.


Cellular and non-cellular compositions of crescents in human glomerulonephritis.
The composition of glomerular crescents was examined on the frozen kidney sections obtained from 10 patients (5 patients with IgA nephropathy, two with Henoch-Schönlein purpura nephritis and three with glomerulonephritis due to undetermined etiology) using well-defined monoclonal and polyclonal antibodies to coagulation proteins, extracellular matrices, intermediate filament proteins and immune cells. Fibrinogen/fibrin related antigens (FRA), which were stained with anti-fibrinogen serum, were positive in the crescents of all the patients, but monoclonal antibody to crosslinked fibrin or von Willebrand factor (factor VIII related) antigen did not bind to the crescents. This suggests that the FRA deposited in the crescents is fibrinogen or its degradation products rather than fibrin. Staining for intrinsic components of renal basement membrane, including type IV and V collagens, laminin and fibronectin, were consistently positive in all stages of the crescents. Cytokeratin, showing cytoplasmic staining of the glomerular parietal epithelium and tubular epithelium in the normal kidney, was demonstrated in three patients with cellular crescents. Vimentin, which is normally distributed in parietal and visceral epithelial cells in the glomeruli and interstitial cells, was found at all stages of the crescents. These findings suggest that in the early stage of crescent formation, glomerular epithelial cells play an important role, and that the accumulation of intrinsic basement membrane constituents is associated with the formation and progression of the crescents. None of the crescent cells reacted with either of two monoclonal antibodies (Mo2 and FMC 32) to monocytes/macrophages or with nonspecific esterase staining. It seems that, at least in our patients, monocytes are a minor factor contributing to the formation of glomerular crescents.


Higher mortality in patients hospitalized for acute aortic rupture or dissection during weekends.
The management of acute aortic aneurysm rupture or dissection (AARD) requires specific medical expertise, diagnostic techniques, and therapeutic options, not always available in all hospitals through the entire week. The aim of our study was to evaluate whether an association exists between weekday (WD) or weekend (WE) admission and mortality for patients with ARRD. Based on the database of routinely collected hospital admissions of the region of Emilia Romagna (RER) of Italy, we examined the discharge sheets of all patients with AARD (January 1999 to December 2009). The risk of in-hospital death was calculated for admissions on the WE compared with the admissions during a WD. The analysis considered 4559 events in 4461 patients. AARD admissions were most frequent on Monday (14.7%) and Friday (14.8%) and less frequent on Saturday (12.6%). The percentage of events admitted on Sunday/holiday was 15.0%, whereas the distribution of death rate with respect to day of admission was significantly different (χ(2) = 23.472; P < .001) with the highest frequency peak on Sunday/holiday (17.4%) and the lowest on Tuesday (12.9%). WE admissions were associated with significantly higher in-hospital mortality (43.4%) than WD admissions (36.9%, P < .001). Multivariate regression analysis showed that WE admission was an independent risk factor for increased in-hospital mortality odds ratio 1.318; 95% confidence interval, 1.144-1.517; P < .001). Our findings show that hospitalization for AARD on WE is associated with a significantly higher mortality rate than hospitalization on WD. Further studies are needed to investigate whether ensuring optimal diagnostic and therapeutic approaches during the entire week might improve the overall survival of patients with ARRD.


Rhox6 regulates the expression of distinct target genes to mediate mouse PGCLC formation and ESC self-renewal.
Mouse embryonic stem cells (mESCs) not only retain the property of self-renewal but also have the ability to develop into primordial germ cell-like cells (PGCLCs). However, knowledge about the mechanisms of transcriptional regulation is still limited. Rhox6, a member of the homeobox family that is located on the X chromosome, is highly expressed within PGCLCs in vivo and in vitro. However, the detailed effects of Rhox6 on PGCLC specification and mESC maintenance remain unclear. In this study, we found that overexpression of Rhox6 favors the formation of PGCLCs, while depletion of Rhox6 inhibits the generation of PGCLCs. Mechanistically, Rhox6 directly induces the expression of Nanos3 during the specification of PGCLCs. Subsequently, downregulation of Nanos3 expression is sufficient to decrease the ability of Rhox6 to induce PGCLC formation. Moreover, we found that depletion of Rhox6 expression facilitates the self-renewal of mESCs. High-throughput sequencing revealed that suppression of Rhox6 transcription significantly increases the expression of pluripotency genes. Functional studies further demonstrated that Rhox6 directly represses the transcription of Tbx3. Therefore, knockdown of the expression of the latter impairs the self-renewal of mESCs promoted by Rhox6 downregulation. Our study reveals that overexpression of Rhox6 is beneficial for PGCLC generation through induction of Nanos3, while downregulation of Rhox6 contributes to mESC self-renewal by increasing Tbx3. These findings help elucidate the early development of mouse embryos.


Opening wedge high tibial osteotomy: navigation system compared to the conventional technique in a controlled clinical study.
This study aimed to verify if the navigation system used in high tibial osteotomy (HTO) adds precision to the procedure regarding mechanical axis correction and prevention of tibial slope increases. In this historically controlled study, patients with medial osteoarthrosis and genuvarum underwent HTO between 2004 and 2012; the first 20 were operated with the conventional technique, using pre-planning correction by the Dugdale method and 18 further patients were operated with the navigation system introduced in our hospital. The two groups were similar for pre-operative mechanical axis (mean 8.10 ± 3.14 for the control and 6.60 ± 2.50 for the navigated group), pre-operative tibial slope (mean 8.95 ± 3.47 versus 8.17 ± 3.11, respectively) and Lyshom score (40.85 ± 15.46 and 44.83 ± 16.86). After surgery, the control group presented mean mechanical axis of 3.35 ± 3.27, tibial slope of 13.75 ± 3.75 and Lyshom score of 87.60 ± 11.12. The navigated group showed a postoperative mechanical axis mean of 3.06 ± 1.70, tibial slope of 10.11 ± 0.18 and Lyshom score of 91.94 ± 11.61. The navigation system allowed a significantly better control of tibial slope. Patients operated with the navigation system had significantly better Lysholm scores.


Performance of Down syndrome subjects during a coincident timing task.
The time synchronization is a very important ability for the acquisition and performance of motor skills that generate the need to adapt the actions of body segments to external events of the environment that are changing their position in space. Down Syndrome (DS) individuals may present some deficits to perform tasks with synchronization demand. We aimed to investigate the performance of individuals with DS in a simple Coincident Timing task. 32 individuals were divided into 2 groups: the Down syndrome group (DSG) comprised of 16 individuals with average age of 20 (+/- 5 years old), and a control group (CG) comprised of 16 individuals of the same age. All individuals performed the Simple Timing (ST) task and their performance was measured in milliseconds. The study was conducted in a single phase with the execution of 20 consecutive trials for each participant. There was a significant difference in the intergroup analysis for the accuracy adjustment - Absolute Error (Z = 3.656, p = 0.001); and for the performance consistence - Variable Error (Z = 2.939, p = 0.003). DS individuals have more difficulty in integrating the motor action to an external stimulus and they also present more inconsistence in performance. Both groups presented the same tendency to delay their motor responses.


Morphological and functional changes of the lumbar spinous processes in the elderly.
Starting from about the 40th year of life the lumbar spinous processes of man undergo morphological changes, which mainly affect their posterior edges. These changes consist of asymptomatic osseous appositions or spurs radiologically visible in the lateral view, with a major incidence in the elderly. Spondyloarthritis is a constant accompanying finding. Histologically the condition corresponds' to a process of substitution by Haversian bone of a layer of calcified fibrocartilage, which constantly occupies the ligamentous and tendinous attachments for a variable distance. While in the young adult fibrocartilaginous metaplasia is limited to the bony attachments of the spinous ligaments, in the elderly it spreads to the greater part or to all of their thickness. The author believes that such a phenomenon is due to a reduced flexibility of the vertebral column as a whole and to exaggerated lumbar lordosis with ageing. The elongation of the lumbar spinous processes secondary to osseous appositions increases the posterior arm of the lever and favours the "extensores spinae" m.


Functionally distinct nucleosome-free regions in yeast require Rad7 and Rad16 for nucleotide excision repair.
In yeast, Rad7 and Rad16 are two proteins required for nucleotide excision repair (NER) of non-transcribed chromatin. They have roles in damage recognition, in the postincision steps of NER, and in ultraviolet-light-dependent histone H3 acetylation. Moreover, Rad16 is an ATP-ase of the SNF2 superfamily and therefore might facilitate chromatin repair by nucleosome remodelling. Here, we used yeast rad7 Delta rad16 Delta mutants and show that Rad7-Rad16 is also required for NER of UV-lesions in three functionally distinct nucleosome-free regions (NFRs), the promoter and 3'-end of the URA3 gene and the ARS1 origin of replication. Moreover, rapid repair of UV-lesions by photolyase confirmed that nucleosomes were absent and that neither UV-damage formation nor rad7 Delta rad16 Delta mutations altered chromatin accessibility in NFRs. The data are consistent with a role of Rad7-Rad16 in damage recognition and processing in absence of nucleosomes. An additional role in nucleosome remodelling is discussed.


Spectrophotometric determination of two N-(4-quinolyl) anthranilic acid derivative (glafenine and floctafenine).
Spectrophotometric methods were developed for the determination of glafenine and floctafenine. The first method depends upon the determination of glafenine in raw material and tablets as well as in the presence of its main degradation product glafenic acid (up to 40%). Differential first derivative spectral response at 245 nm in 0.1 N hydrochloric acid, where the corresponding degradation product exhibits no contribution in 0.1 N sodium hydroxide. The method allows the determination of 2.5-30 microg ml(-1). The second method depends upon the reaction of floctafenine with 2,3-dichloro 5,6-dicyano-p-benzoquinone (DDQ) in acetonitrile to give highly colored complex that could be measured quantitatively at (about) lambda(max) 538 nm. The method permits the determination of 40-180 microg ml(-1) or by measuring the first derivative spectral response of the color at 610 nm. The method permits the determination of floctafenine in presence of thiocolchicoside. The methods mentioned both simplicity and sensitivity, having excellent precision and accuracy (100.31 +/- 0.63, 100.78 +/- 0.77 and 99.90 +/- 0.56 for glafenine and floctafenine, respectively). The results were of comparable accuracy and reproducibility with the reported methods.


Genetic mutations, molecular markers and future directions in research.
Recent molecular studies have described a number of abnormalities associated with the pathogenesis of thyroid carcinoma. These distinct molecular events are often associated with specific stages of tumor development and may serve as prognostic factors and therapeutic targets. A better understanding of the mechanisms involved in thyroid cancer pathogenesis, will hopefully help translate these discoveries to improved patient care.


Formation of catalytic metal-molecule contacts.
We describe a new strategy for the in situ growth of molecular wires predicated on the synthesis of a trifunctional "primed" contact formed from metal-carbon multiple bonds. The ruthenium-carbon pi bond provides structural stability to the molecular linkages under ambient conditions, and density functional calculations indicate the formation of an efficient conduit for charge carriers to pass between the metal and the molecule. Moreover, the metal-carbon pi bond provides a chemically reactive site from which a conjugated molecular wire can be grown in situ through an olefin metathesis reaction.


Pyridine-2,3-dicarboxylate, quinolinic acid, induces 1N4R Tau amyloid aggregation in vitro: Another evidence for the detrimental effect of the inescapable endogenous neurotoxin.
Quinolinic acid (QA) known as a neuro-active metabolite associated with the kynurenine pathway. At high concentrations, QA is often involved in the initiation and development of several human neurologic diseases, like Alzheimer's disease. Because of the QA action as the NMDA receptor, it is considered as a potent excitotoxin in vivo. Since it is probable that different mechanisms are employed by QA, activation of NMDA receptors cannot fully explain the revealed toxicity and it is even believed that there are multiple unknown mechanisms/targets leading to QA cytotoxicity. Herein we report accelerated amyloid oligomerization of 1N4R Tau under the effect of QA, in vitro, then the molecular structure, morphology and toxicity of the protein aggregate were documented by using various theoretical/experimental approaches. The possible mechanism of action of QA-induced Tau oligomerization has also been explored.


Surgical Approach and Reaming Depth Influence the Direction and Magnitude of Acetabular Center of Rotation Changes During Total Hip Arthroplasty.
Changes in acetabular or hip center of rotation (HCOR) commonly occur during acetabular component preparation during total hip arthroplasty (THA). HCOR displacement in mediolateral or superoinferior directions is known to influence offset and leg length, but the incidence and range of HCOR change in the anteroposterior direction is less understood as the sagittal plane cannot be measured on standard anteroposterior radiographs. This study assessed the 3-dimensional displacement of HCOR after cup implantation and evaluated for potential factors associated with increased acetabular component translations. A total of 894 THAs were performed using a posterior, lateral, or direct anterior approach. Only intraoperative data from the navigation device were included in the analysis. All THAs performed between September 2015 and October 2017 were included. Paired t -tests were used to compare native HCOR and new HCOR values. The mean HCOR displacement in 3 directions was 4.97mm medially (P < .001), 0.83mm superiorly (P < .001), and 0.64mm posteriorly (P < .001). Subgroup analysis revealed greater posterior HCOR displacement with the anterior approach than the lateral/posterior approach (2.32mm vs 0.44mm; P < .001). Increasing medial HCOR displacement also resulted in increased superior and posterior HCOR displacement across surgical cases (P < .001). HCOR displacement is commonly observed in medial, superior, and posterior directions. HCOR changes are influenced by surgical approach, potentially secondary to patient positioning, with greater posterior HCOR displacement observed in anterior cases. Surgeons should be aware of these factors, particularly in cases with deficient or reduced posterior column bone stock.


Formation of fumonisin artefacts in thermal treated food.
In order to study the formation of fumonisin artefacts and the binding of fumonisins to matrix components (e.g. starch and protein) in thermal treated food, model experiments were performed by heating fumonisin FB1 with amino acid derivatives (protein model) and methyl-a-D-glucopyranoside (starch model). The reaction products were analysed by highperformance liquid chromatography-electrospray ionisationtandem mass spectrometry (HPLC-MS/MS). Using MS/MS experiments the formed reaction products were characterized as conjugates between fumonisin B1 and the used substrates. The reaction product between fumonisin B1 and methyl-α-D-glucopyranoside was purified and identified by nuclear magnetic resonance (NMR) spectroscopy as the diester of fumonisin B1 and methyl-α-D-glucopyranoside. These studies indicate that fumonisins can bind to matrix components via their TCA side chains.


Gait analysis of cerebral palsy children before and after rhizotomy.
Over the past decade, selective posterior rhizotomy has been used successfully to reduce spasticity in patients with cerebral palsy. Although clinical evaluation of these patients revealed functional improvement following surgery, more objective analysis of the outcome of this surgery was sought. Kinematic gait analysis of 14 patients with spastic cerebral palsy was performed before and after selective posterior rhizotomy. Measurements of stride length, thigh range of motion, knee range of motion, average speed of walking, and cadence were made. Statistically significant increases in stride length, thigh range and knee range were found. Average speed was increased and cadence was virtually unchanged. These results corroborate clinical findings of improvement in gait of spastic patients with cerebral palsy following selective posterior rhizotomy.


Transforaminal Lumbar Interbody Fusion for Management of Recurrent Lumbar Disc Herniation.
Retrospective study. To study the surgical outcome of transforaminal lumbar interbody fusion (TLIF) combined with trans-pedicular screws fixation for management of selected cases of recurrent lumbar disc herniation. Recurrent lumbar disc herniation is a major cause of surgical failure, occurring in 5%-11% of cases. The optimal technique for treatment is controversial. Some authors believe that repeated simple discectomy is the treatment of choice, but approach-related complications can be considerable. Other surgeons prefer more removal of posterior elements (as lamina and facet joints) with posterior fusion. The study included 15 patients who presented with symptomatic recurrent lumbar disc herniation who underwent reoperation through posterior trans-pedicular screws and TLIF in our department from April 2008 to May 2010, with a 24-month follow-up. Japanese Orthopedic Association Scale (JOA) was used for low back pain. The results of surgery were also evaluated with the MacNab classification. The mean JOA score showed significant improvement, increasing from 9.5 before surgery to 24.0 at the end of follow-up (p<0.001). Clinical outcome was excellent in 7 patients (46% of cases), good in 6 patients (40%) and fair in only 2 patients (14%). There was a significant difference (p<0.05) between patients presenting with recurrent disc at the ipsilateral side and those at the contralateral side. In spite of the small number of patients and the short follow-up period, the good clinical and radiological outcome achieved in this study encourage the belief that TLIF is an effective option for the treatment of selected cases of recurrent lumbar disc herniation.


Revision of the NIST Standard for (223)Ra: New Measurements and Review of 2008 Data.
After discovering a discrepancy in the transfer standard currently being disseminated by the National Institute of Standards and Technology (NIST), we have performed a new primary standardization of the alpha-emitter (223)Ra using Live-timed Anticoincidence Counting (LTAC) and the Triple-to-Double Coincidence Ratio Method (TDCR). Additional confirmatory measurements were made with the CIEMAT-NIST efficiency tracing method (CNET) of liquid scintillation counting, integral γ-ray counting using a NaI(Tl) well counter, and several High Purity Germanium (HPGe) detectors in an attempt to understand the origin of the discrepancy and to provide a correction. The results indicate that a -9.5 % difference exists between activity values obtained using the former transfer standard relative to the new primary standardization. During one of the experiments, a 2 % difference in activity was observed between dilutions of the (223)Ra master solution prepared using the composition used in the original standardization and those prepared using 1 mol·L(-1) HCl. This effect appeared to be dependent on the number of dilutions or the total dilution factor to the master solution, but the magnitude was not reproducible. A new calibration factor ("K-value") has been determined for the NIST Secondary Standard Ionization Chamber (IC "A"), thereby correcting the discrepancy between the primary and secondary standards.


A role for adipocyte-derived lipopolysaccharide-binding protein in inflammation- and obesity-associated adipose tissue dysfunction.
Circulating lipopolysaccharide-binding protein (LBP) is an acute-phase reactant known to be increased in obesity. We hypothesised that LBP is produced by adipose tissue (AT) in association with obesity. LBP mRNA and LBP protein levels were analysed in AT from three cross-sectional (n = 210, n = 144 and n = 28) and three longitudinal (n = 8, n = 25, n = 20) human cohorts; in AT from genetically manipulated mice; in isolated adipocytes; and in human and murine cell lines. The effects of a high-fat diet and exposure to lipopolysaccharide (LPS) and peroxisome proliferator-activated receptor (PPAR)γ agonist were explored. Functional in vitro and ex vivo experiments were also performed. LBP synthesis and release was demonstrated to increase with adipocyte differentiation in human and mouse AT, isolated adipocytes and human and mouse cell lines (Simpson-Golabi-Behmel syndrome [SGBS], human multipotent adipose-derived stem [hMAD] and 3T3-L1 cells). AT LBP expression was robustly associated with inflammatory markers and increased with metabolic deterioration and insulin resistance in two independent cross-sectional human cohorts. AT LBP also increased longitudinally with weight gain and excessive fat accretion in both humans and mice, and decreased with weight loss (in two other independent cohorts), in humans with acquired lipodystrophy, and after ex vivo exposure to PPARγ agonist. Inflammatory agents such as LPS and TNF-α led to increased AT LBP expression in vivo in mice and in vitro, while this effect was prevented in Cd14-knockout mice. Functionally, LBP knockdown using short hairpin (sh)RNA or anti-LBP antibody led to increases in markers of adipogenesis and decreased adipocyte inflammation in human adipocytes. Collectively, these findings suggest that LBP might have an essential role in inflammation- and obesity-associated AT dysfunction.


"Please, Mr. Postman:" Exploring the Use of Letter Writing to Address Loneliness.
Informed by prior research and influenced by concerns that the COVID-19 pandemic heightened social isolation, this project examined the impact of a 12-month long letter writing project on levels of loneliness. Through partnerships with local anti-poverty agencies, pen pals were paired between MSW students and community members who utilize services at these organizations. Participants completed the UCLA Loneliness Scale before and after the intervention. We found a mean decrease in loneliness at the end of the intervention. Letter writing was a successful way to attend to loneliness due to its accessibility to the participants. Our letter writing intervention is different in many ways from e-mail and texting. Participants noted that the waiting process between letter gave them time to think more deeply about their response as well as event to look forward to (e.g. getting mail). We found that the low-tech aspects of the project might have been helpful to some participants. Letter writing is an easily replicable, low-cost, low-tech activity for use by practitioners, which may be useful in a variety of social work settings to reduce loneliness.


Femoral head vitality after femoral neck fracture. Comparison between pre- and peroperative tetracycline labeling.
Using fluorescence microscopy, a ratio between tetracycline labeling of the femoral head and of the greater trochanter was calculated for 370 femoral neck fractures. Sixty-three patients were given tetracycline on admission to hospital and 307 on the operating table after closed reduction. The following results were obtained: Visual grading of labeling correlated well to a distribution analysis based on a morphometric point-wave pattern. No significant difference concerning the degree of labeling between the pre- and peroperative groups was found. A redistribution into groups according to fracture displacement (Garden I-IV) did not alter this fact. In the total material, labeling was significantly better for undisplaced than for displaced fractures. No difference was found between different degrees of displacement. For patients less than 50 years of age, labeling values were significantly lower. Intact femoral head vascularization (ratio greater than or equal to 0.90) was found in less than three per cent of the total material.


The Male of the Ant Genus Rhopalothrix (Hymenoptera: Formicidae: Myrmicinae).
The male caste is firstly described for the ant genus Rhopalothrix. The male was collected as attached to the gyne during copula. Due to the rarity of the genus, the gyne and male are tentatively associated with R. apertor Longino and Boudinot 2013. The apomorphic features of Rhopalothrix male are discussed, and a preliminary identification key based on males to the genera in the Basiceros-genus group (formerly tribe Basicerotini) is provided.


Neurotoxicity and risk assessment of brominated and alternative flame retardants.
Brominated flame retardants (BFRs) are widely used chemicals that prevent or slow the onset and spreading of fire. Unfortunately, many of these compounds pose serious threats for human health and the environment, indicating an urgent need for safe(r) and less persistent alternative flame retardants (AFRs). As previous research identified the nervous system as a sensitive target organ, the neurotoxicity of past and present flame retardants is reviewed. First, an overview of the neurotoxicity of BFRs in humans and experimental animals is provided, and some common in vitro neurotoxic mechanisms of action are discussed. The combined epidemiological and toxicological studies clearly underline the need for replacing BFRs. Many potentially suitable AFRs are already in use, despite the absence of a full profile of their environmental behavior and toxicological properties. To prioritize the suitability of some selected halogenated and non-halogenated organophosphorous flame retardants and inorganic halogen-free flame retardants, the available neurotoxic data of these AFRs are discussed. The suitability of the AFRs is rank-ordered and combined with human exposure data (serum concentrations, breast milk concentrations and house dust concentrations) and physicochemical properties (useful to predict e.g. bioavailability and persistence in the environment) for a first semi-quantitative risk assessment of the AFRs. As can be concluded from the reviewed data, several BFRs and AFRs share some neurotoxic effects and modes of action. Moreover, the available neurotoxicity data indicate that some AFRs may be suitable substitutes for BFRs. However, proper risk assessment is hampered by an overall scarcity of data, particularly regarding environmental persistence, human exposure levels, and the formation of breakdown products and possible metabolites as well as their toxicity. Until these data gaps in environmental behavioral and toxicological profiles are filled, large scale use of these chemicals should be cautioned.


Advances in the microbial synthesis of the neurotransmitter serotonin.
Serotonin, as a monoamine neurotransmitter, modulates the activity of the nervous system. Due to its importance in the coordination of movement and regulation of mood, impairments in the synthesis and homeostasis of serotonin are involved in numerous disorders, including depression, Parkinson's disease, and anxiety. Currently, serotonin is primarily obtained via natural extraction. But this method is time-consuming and low yield, as well as unstable supply of raw materials. With the development of synthetic biology, researchers have established the method of microbial synthesis of serotonin. Compared with natural extraction, microbial synthesis has the advantages of short production cycle, continuous production, not limited by season and source, and environment-friendly; hence, it has garnered considerable research attention. However, the yield of serotonin is still too low to industrialization. Therefore, this review provides the latest progress and examples that illustrate the synthesis pathways of serotonin as well as proposes strategies for increasing the production of serotonin. KEY POINTS: • Two biosynthesis pathways of serotonin are introduced. • L-tryptophan hydroxylation is the rate-limiting step in serotonin biosynthesis. • Effective strategies are proposed to improve serotonin production.


The Condition of Air Pollution in Kraków, Poland, in 2005-2020, with Health Risk Assessment.
Air quality changes with human health risk assessment were investigated. The measurement results obtained by the Regional Environmental Protection Inspectorate (REPI) in Kraków and our deposited particulate-matter (PM) analysis, as well as United States Environmental Protection Agency (USEPA) methodology of risk assessment were used in the study. Annual pollutant contents kept decreasing, with the exception of O3. However, the permissible annual levels were exceeded in the cases of PM10, PM2.5, and NO2. Increased contents of SO2, CO, C6H6, PM10, and PM2.5, as well as of As, Pb, Cd, Ni, and polycyclic aromatic hydrocarbons (PAHs) in PM particles during winter months indicated that house heating was the source of pollution. Due to no significant change in the monthly NO2 contents, this measurement was used as an indicator of traffic sources of pollution. In winter months, the allowable 24 h PM2.5 and PM10 contents were constantly exceeded. PM was identified as the most significant air pollutant. Enrichment factors revealed that deposited PM was enriched with heavy metals. The potential ecological risk (ERI) was determined to be very high for Cd, considerable for Zn, and low for As, Co, Cr, Cu, Ni, Pb, and Tl. The total non-carcinogenic risk indices (HQ) for both adults (HQ = 15.0) and children (HQ = 26.4) exceeded the acceptable value of 1. The total carcinogenic risk indices (CR) for both adults (CR = 1.51 × 10-4) and children (CR = 1.77 × 10-4) exceeded the acceptable level of 1 × 10-4. In the years 2005-2020, a general decreasing tendency of annual pollutant contents was observed. However, the permissible contaminant contents were still exceeded. PM2.5, BaP, PM10, and NO2 were determined as the most dangerous pollutants in inhalational pathway.


Control strategies for ostertagiasis.
There are currently four major options for control of ostertagiasis and other ruminant gastrointestinal parasites. These are the traditional, suppressive, integrated and strategic approaches. Strategic dosing is the most realistic and beneficial approach for most regions of the world, including the U.S.A. It is effective, practical, labor-saving and can yield big economic returns. Today this approach is even more appropriate because of important advances in the technology of controlled release and pulse-release devices. Top priority in worm control programs should be given to dairy replacement heifers in their first year at pasture and to beef calves in the immediate post-weaning period. This is preferable to recommendations for blanket treatment of all beef and dairy cattle, regardless of age, immune status or pasture infectivity. An anthelmintic overkill is both wasteful and potentially harmful in that it increases the selection pressure for drug resistance. It is suggested that better dissemination of information is needed to make producers aware of the benefits of strategic dosing programs. This would eliminate much of the confusion about parasite control and focus attention on simple and effective programs that could significantly reduce current losses to the livestock industries.


The hemopexin domain of MMP-9 inhibits angiogenesis and retards the growth of intracranial glioblastoma xenograft in nude mice.
Matrix Metalloproteinase-9 (MMP-9) consists of a prodomain, catalytic domain with 3 fibronectin-like type II modules and C-terminal hemopexin-like (PEX) domain. These domains play distinct roles in terms of proteolytic activity, substrate binding and interaction with inhibitors and receptors. To assess the potential of the MMP-9-PEX domain to interfere with tumor progression, we stably transfected human glioblastoma cells with an expression vector containing a cDNA sequence of the MMP-9-PEX. The selected clones exhibited decreased MMP-9 activity and reduced invasive capacity. We assessed how secretion of MMP-9-PEX by glioblastoma cells affects angiogenic capabilities of human microvascular endothelial cells (HMECs) in vitro. MMP-9-PEX conditioned medium treatment caused a reduction in migration of HMECs and inhibited capillary-like structure formation in association with suppression of vascular endothelial growth factor (VEGF) secretion and VEGF receptor-2 protein level. The suppression of HMECs survival by conditioned medium from MMP-9-PEX stable transfectants was associated with apoptosis induction characterized by an increase in cells with a sub-G0/G1 content, fragmentation of DNA, caspase-3, -8 and -9 activation and poly (ADP-ribose) polymerase (PARP) cleavage. A significant tumor growth inhibition was observed in intracranial implants of MMP-9-PEX stable transfectants in nude mice with attenuation of CD31 and MMP-9 protein expression. These results demonstrate that MMP-9-PEX inhibits angiogenic features of endothelial cells and retards intracranial glioblastoma growth.


Hardikar syndrome: long term outcome of a rare genetic disorder.
Hardikar syndrome is a rare disorder of unknown etiology. Features of the syndrome are manifold with a predominance of liver and renal involvement. The syndrome is clearly distinct from other previously described syndromes such as Alagille syndrome, congenital hepatic fibrosis, Caroli disease, and Kabuki make-up syndrome. To date, only four cases of Hardikar syndrome have been published worldwide. We report here on the long term outcome of these patients.