Aerobic bioremediation of chlorobenzene source-zone soil in flow-through columns: performance assessment using quantitative PCR.
Flow-through aquifer columns were operated for 12 weeks to evaluate the benefits of aerobic biostimulation for the bioremediation of source-zone soil contaminated with chlorobenzenes (CBs). Quantitative Polymerase Chain Reaction (qPCR) was used to measure the concentration of total bacteria (16S rRNA gene) and oxygenase genes involved in the biodegradation of aromatic compounds (i.e., toluene dioxygenase, ring hydroxylating monooxygenase, naphthalene dioxygenase, phenol hydroxylase, and biphenyl dioxygenase). Monochlorobenzene, which is much more soluble than dichlorobenzenes, was primarily removed by flushing, and biostimulation showed little benefit. In contrast, dichlorobenzene removal was primarily due to biodegradation, and the removal efficiency was much higher in oxygen-amended columns compared to a control column. To our knowledge, this is the first report that oxygen addition can enhance CB source-zone soil bioremediation. Analysis by qPCR showed that whereas the biphenyl and toluene dioxygenase biomarkers were most abundant, increases in the concentration of the phenol hydroxylase gene reflected best the higher dichlorobenzene removal due to aerobic biostimulation. This suggests that quantitative molecular microbial ecology techniques could be useful to assess CB source-zone bioremediation performance.


ROR1-targeted delivery of OSU-2S, a nonimmunosuppressive FTY720 derivative, exerts potent cytotoxicity in mantle-cell lymphoma in vitro and in vivo.
Mantle-cell lymphoma (MCL) remains incurable despite numerous therapeutic advances. OSU-2S, a novel nonimmunosuppressive FTY720 (Fingolimod) derivative, exhibits potent cytotoxicity in MCL cell lines and primary cells. OSU-2S increased the surface expression of CD74, a therapeutic antibody target in MCL cells. OSU-2S, in combination with anti-CD74 antibody milatuzumab, enhanced cytotoxicity in MCL. Moreover, MCL tumor antigen receptor tyrosine kinase-like orphan receptor 1 (ROR1) targeted immunonanoparticle-carrying OSU-2S (2A2-OSU-2S-ILP)-mediated selective cytotoxicity of MCL in vitro, as well as activity in a xenografted mouse model of MCL in vivo. The newly developed OSU-2S delivery using ROR1-directed immunonanoparticles provide selective targeting of OSU-2S to MCL and other ROR1(+) malignancies, sparing normal B cells.


The brown and brite adipocyte marker Cox7a1 is not required for non-shivering thermogenesis in mice.
The cytochrome c oxidase subunit isoform Cox7a1 is highly abundant in skeletal muscle and heart and influences enzyme activity in these tissues characterised by high oxidative capacity. We identified Cox7a1, well-known as brown adipocyte marker gene, as a cold-responsive protein of brown adipose tissue. We hypothesised a mechanistic relationship between cytochrome c oxidase activity and Cox7a1 protein levels affecting the oxidative capacity of brown adipose tissue and thus non-shivering thermogenesis. We subjected wildtype and Cox7a1 knockout mice to different temperature regimens and tested characteristics of brown adipose tissue activation. Cytochrome c oxidase activity, uncoupling protein 1 expression and maximal norepinephrine-induced heat production were gradually increased during cold-acclimation, but unaffected by Cox7a1 knockout. Moreover, the abundance of uncoupling protein 1 competent brite cells in white adipose tissue was not influenced by presence or absence of Cox7a1. Skin temperature in the interscapular region of neonates was lower in uncoupling protein 1 knockout pups employed as a positive control, but not in Cox7a1 knockout pups. Body mass gain and glucose tolerance did not differ between wildtype and Cox7a1 knockout mice fed with high fat or control diet. We conclude that brown adipose tissue function in mice does not require the presence of Cox7a1.


Factors that affect regulation of cGMP synthesis in vertebrate photoreceptors and their genetic link to human retinal degeneration.
Cyclic GMP is essential for the ability of rods and cones to respond to the light stimuli. Light triggers hydrolysis of cGMP and stops the influx of sodium and calcium through the cGMP-gated ion channels. The consequence of this event is 2-fold: first, the decrease in the inward sodium current plays the major role in an abrupt hyperpolarization of the cellular membrane; secondly, the decrease in the Ca2+ influx diminishes the free intracellular Ca2+ concentration. While the former constitutes the essence of the phototransduction pathway in rods and cones, the latter gives rise to a potent feedback mechanism that accelerates photoreceptor recovery and adaptation to background light. One of the most important events by which Ca2+ feedback controls recovery and light adaptation is synthesis of cGMP by guanylyl cyclase. Two isozymes of membrane photoreceptor guanylyl cyclase (retGC) have been identified in rods and cones that are regulated by Ca2+-binding proteins, GCAPs. At low intracellular concentrations of Ca2+ typical for light-adapted rods and cones GCAPs activate RetGC, but concentrations above 500 nM typical for dark-adapted photoreceptors turn them into inhibitors of retGC. A variety of mutations found in GCAP and retGC genes have been linked to several forms of human congenital retinal diseases, such as dominant cone degeneration, cone-rod dystrophy and Leber congenital amaurosis.


New therapeutic targets in melanoma.
Research into molecular targets for drug development in melanoma is starting to bear fruit. Of the drugs tested to date in patients with metastatic melanoma, those that have yielded the best results are V600E BRAF inhibitors in melanomas carrying the V600E mutation; c-kit tyrosine kinase activity inhibitors in melanomas carrying c-kit mutations; and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies, which block the mechanisms involved in immune tolerance. Many problems have yet to be resolved in these areas, however, such as the rapid development of resistance to BRAF and c-kit inhibitors and the lack of biomarkers to predict treatment response in the case of CTLA-4 blockers. We review the results of targeted therapy with these and other drugs in metastatic melanoma and discuss what the future holds for this field.


Broadband fivefold reduction of vacuum fluctuations probed by dyes in photonic crystals.
We observed for the first time a strong angle-independent modification of spontaneous emission spectra from laser dyes in photonic crystals, made of inverse opals in titania. Comparison with spectra from such crystals with much smaller lattice spacing, for which emission is in the long wavelength limit, reveals inhibition of emission up to a factor approximately 5 over a large bandwidth of 13% of the first order Bragg resonance frequency. The center frequency and bandwidth of the inhibition agree with calculated total density of states, while the measured inhibition of vacuum fluctuations is much larger. Because of the specific location of the dye molecules, we likely probe the strongly modulated local photonic density of states.


Drug-in-mucoadhesive type film for ocular anti-inflammatory potential of amlodipine: Effect of sulphobutyl-ether-beta-cyclodextrin on permeation and molecular docking characterization.
Mucoadhesive type ocular film has been prepared for studying the anti-inflammatory potential of amlodipine (AML) on carrageenan-induced rabbit model and the effect of sulphobutyl-ether-beta-cyclodextrin on corneal permeation was tested. Hydroxypropyl methylcellulose (HPMC) ocular film was prepared after complexation of amlodipine with β-cyclodextrin, (BCD), hydroxypropyl β-cyclodextrin (HPCD), and sulfobutylether β-cyclodextrin (SBCD). The film without cyclodextrin showed a maximum swelling, and erosion to the highest extent. Both drug release and permeation were highly diffusion controlled and highest improvement was observed with SBCD due to increased dissolution, compared to other formulations with or without cyclodextrin. Highest binding energy and highest extent of amorphization were noticed in the SBCD film formulation. Improved amlodipine release in-vitro and ocular permeation were found by the HPMC film formulation after complexation of the drug with cyclodextrins wherein SBCD exhibited both to the highest extent. Binary and ternary systems molecular docking studies confirmed the lowest energy of binding between amlodipine and BCD compared to HBCD and SBCD. Signs of acute inflammation were mitigated within 2 h of film application in the cul-de-sac. Presence of sulphobutyl-ether β-cyclodextrin in the amlodipine-HPMC film can improve ocular permeation significantly and could be utilized as mucoadhesive type formulation for anti-inflammatory activity.


A survey of the praying mantises of Rwanda, including new records (Insecta, Mantodea).
We report the results of two surveys targeting praying mantises in four localities in Rwanda, specifically Akagera National Park, Nyungwe National Park, Volcanoes National Park, and the Arboretum de Ruhande at the National University of Rwanda. Using an assortment of collecting techniques, including metal halide light traps, sweep netting vegetation and general searching, we obtained 387 adult and 352 juvenile specimens, representing 41 species. A total of 28 novel species records for Rwanda are added to the 18 previously recorded species for the country, in addition to 20 novel species records for the broader region, including neighbouring Uganda and Burundi. This study provides high resolution images of the dorsal habitus of both sexes of representative species, both pinned and living. Species distribution records are presented and discussed. With a 155% increase in species recorded from Rwanda, this survey illustrates the need for further taxonomic work in the region.


Augmented lipid accumulation in ethyl methyl sulphonate mutants of oleaginous microalga for biodiesel production.
The aim of this work was to generate high lipid accumulating mutants of Chlorella minutissima (CM) using ethyl methyl sulphonate (EMS) as a random chemical mutagen. Amid the 5% surviving cells after exposure to EMS (2M), three fast growing mutants (CM2, CM5, CM7) were selected and compared with wild type for lipid productivity and biochemical composition. Among these mutants, CM7 showed the maximum biomass (2.4g/L) and lipid content (42%) as compared to wild type (1.5g/L; 27%). Further, the mutant showed high photosynthetic pigments with low starch content signifying the re-allocation of carbon flux to lipid. The obtained mutant showed no visible morphological changes in comparison to its WT. The fatty acid profile showed increase in monounsaturated fatty acids while decreased saturated and polyunsaturated fatty acids signifying good quality biodiesel. The mutant strain thus obtained can be optimized further and applied for enhanced biodiesel production.


Delayed hypersensitivity reaction following lip fillers, not one but four times in the same patient.
This case report describes a healthy 25-year-old woman who underwent lip filler augmentation and developed a delayed hypersensitivity reaction not once but four times. A Caucasian female with no medical history presented to the authors in March 2022 with diffuse painful swelling on the left upper lip. Upon examination, the affected area was soft and tender on palpation, with no palpable nodules or lumps. Five days later,the patient reported waking up with tenderness and swelling on her right upper lip this time. Two months after this incident the patient reported that she had experienced two similar incidents at the beginning of May. She again reported waking up with the same symptoms on her right upper lip, which spontaneously resolved within 48 h; and then four days later, she exhibited the same symptoms on her left upper lip. When questioned, she did not recall any flu-like symptoms or signs of COVID-19. She had been vaccinated against COVID-19, but this was long before she had lip fillers injected, namely, in 2020 (two years before the events described here). In this case, no obvious triggering factor was identified, apart from the fact that the patient had been stressed due to upcoming examination. Stress is known to cause flares of autoimmune or infectious diseases, such as herpes simplex virus, through complicated processes that influence immune function. Therefore, stress could have been the triggering factor in the current case.


Patient-specific distractors for customized mandibular distraction osteogenesis to relieve upper airway obstruction in infants with Pierre Robin sequence.
The purpose of this article is to report the author's technique for using patient-specific distractors for customized distraction osteogenesis of the mandible in patients with Pierre Robin sequence and upper airway obstruction. The advantages of virtual planning and patient-specific plates in other aspects of craniomaxillofacial surgery, such as orthognathic and reconstructive surgery, have been reported previously. Similar to patient-specific plates, the theorized advantages of patient-specific distractors in infants with Robin sequence and upper airway obstruction include increased accuracy, decreased operating time, and less morbidity to vital anatomic structures such as the inferior alveolar nerve and developing tooth buds. This technique is novel in using patient-specific distractors in the craniomaxillofacial skeleton.


Preparative isolation of terpene trilactones from Ginkgo biloba leaves.
This study investigated and compared some techniques for the preparative isolation of terpene trilactones, including ginkgolides (GA and GB, etc.) and bilobalide (BB), from Ginkgo biloba leaves. The crude Ginkgo biloba L. extracts (GBE) were prepared using an extractor with solvent refluxing operated under an optimal extraction condition. The extraction yield was 20-23% and the purity of terpene trilactones was about 1.0-1.4 wt%. Before the isolation operations, the extracts were dissolved in de-ionized water. The isolation procedures included the method of liquid-liquid extraction and the method of column chromatography. For the method of liquid-liquid extraction using ethyl acetate as the organic solvent operated under the optimal extraction conditions, the purity, concentration ratio, and yield of terpene trilactones were 13.5-18.0%, 15-16, and >99%. For the method of column chromatography, XAD-7HP, XAD-4, and C-18 adsorbents with different polarities were used as the packing materials. Only for the XAD-7HP column, a part of more polar impurities was efficiently separated with the majority of terpene trilactones by a proper step-gradient elution, which resulted in an efficient isolation: the purity, concentration ratio, and yield of terpene trilactones were approximately 20, approximately 15, and approximately 80%. In comparison, the XAD-7HP column achieved the highest purity, but at the expense of the yield of terpene trilactones; on the contrary, the liquid-liquid extraction method, achieving the highest yield but with a slightly lower purity, was proved to be superior to the method of column chromatography in the current isolation stage.


Photodynamic therapy for endobronchial metastases from nonbronchogenic primaries.
Endobronchial metastases (EBM) occur in 2% of nonbronchogenic malignancies and frequently present with hemoptysis or dyspnea. This report summarizes our recent experience with photodynamic therapy (PDT) for EBM. All patients who have undergone PDT for the treatment of symptomatic EBM from nonbronchogenic primaries were identified in the Division of Thoracic Surgery database to determine number of treatments, frequency of symptom relief, and patient survival. Endobronchial PDT was administered to 27 patients from April 1997 through December 2000. The predominant primary tumor was renal cell (44%). Endobronchial metastases presented metachronously in 74% of patients. Patients underwent a median of two PDT treatments. Local anesthesia with sedation was used in 76% of treatments. Four patients (15%) developed immediate postoperative respiratory distress. Follow-up bronchoscopy 24 to 48 hours after initial treatment demonstrated tumor necrosis in all cases. Acute relief of hemoptysis and dyspnea was achieved in 85% of patients. Seven patients died within 6 weeks of treatment. Median survival time after PDT was 4 months (range 0.2 to 30 months). Patients with EBM treated with PDT had a median survival of 4 months and patients with limited metastatic disease survived up to 30 months. Photodynamic therapy was effective in palliating hemoptysis or dyspnea from EBM with an acceptable morbidity, although the 30-day mortality was 22%.


Trends, associations and predictions of insulin resistance in prepubertal children (EarlyBird 29).
Rising obesity has been observed in all age groups. Anthropometric cut-points have been used to predict metabolic risk in children, although they are not based on known outcomes. We examined the trends, associations and predictions of metabolic health from anthropometry in prepubertal children. Three hundred and seven healthy children were examined annually between 5 and 8 yr. height, weight, body mass index (BMI), sum of skinfold thickness at five sites (SSF) and waist circumference (WC). homeostasis model assessment of insulin resistance (HOMA-IR), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). Two hundred and thirty-one [131 boys (B) and 100 girls (G)] children had complete data sets at all four time points. (i) All measures of adiposity rose from 5 to 8 yr (BMI - B: +3.4%, G: +5.7%; WC - B: +10.4%, G: +11.8%; SSF - B: +23.3%, G: +30.7%, all p < 0.001). HOMA-IR unexpectedly fell (B: -16.6%, p = 0.01; G: -32.5%, p < 0.001). This fall was significant between 5 and 6 yr in both genders (5-6 yr - B: -17.8%, p < 0.001; G: -20.0%, p = 0.002) and between 6 and 7 yr in girls only (6-7 yr - B: -10.8%, p = 0.12; G: -19.2%, p = 0.001). HDL-C rose (B: +17.8%, G: +17.1%, both p < 0.001) and TG fell (B: -4.8%, p = 0.16; G: -11.6%, p = 0.006). (ii) Correlations between insulin resistance (IR) and anthropometry were poor at 5 yr but strengthened by 8 yr (BMI - B: r = 0.20/0.38, G: r = 0.28/0.49; WC - B: r = 0.25/0.40, G: r = 0.32/0.58; SSF - B: r = 0.11/0.36, G: r = 0.18/0.53). (iii) In girls, but not boys, adiposity at 5 yr predicted IR better at 8 yr (BMI - r(2 )= 0.17; WC - r(2 )= 0.28; SSF - r(2 )= 0.17, all p < 0.001) than it did at 5 yr (BMI - r(2 )= 0.08, p < 0.01; WC - r(2 )= 0.10, p < 0.01; SSF - r(2 )= 0.03, p = 0.07). Cross-sectional association cannot indicate direction of trend or predict the future. Predicting metabolic health from anthropometric measures in prepubertal children requires longitudinal data, tracking variables from childhood into adulthood. Until the data set reaches adulthood, it is probably not safe to make recommendations on which children to 'target' or whether early intervention would be of benefit.


Direct comparison of the diagnostic accuracy between blood and cerebrospinal fluid procalcitonin levels in patients with meningitis.
To compare the clinical utility of serum and cerebrospinal fluid (CSF) procalcitonin (PCT) for the diagnosis of bacterial meningitis (BM) among patients with suspected meningitis. Patients with meningitis-like symptoms (n=120), admitted to the Second People's Hospital of Wuxi or the Changhai Hospital of Shanghai between January 2011 and December 2013, were prospectively and consecutively enrolled in this study. BM was finally diagnosed by CSF culture, Gram staining, quantitative polymerase chain reaction (qPCR), and treatment response. The diagnostic accuracy of the serum and CSF PCT was assessed by receiver operator characteristic (ROC) curve analysis. The relationship between CSF and serum PCT levels as well as the CSF leukocyte count and protein level was analyzed by Spearman's correlation analysis. PCT level in both the serum and CSF was significantly increased in the BM patients. The area under ROC curve of serum PCT for the diagnosis of BM was 0.96 (95% confidence interval (CI): 0.93-1.00), significantly higher than that of CSF PCT (0.90, 95% CI: 0.83-0.96). Using 0.88ng/mL as the threshold, the diagnostic sensitivity, specificity, and accuracy of serum PCT for the diagnosis of BM were 0.87 (95% CI, 0.73-0.95), 1.00 (95% CI, 0.95-1.00), and 95%, respectively. The serum PCT level was positively correlated with the CSF PCT level, leukocyte count, and protein level. Both the serum and CSF PCT had a high diagnostic value for BM among suspected meningitis patients, and serum PCT demonstrated a superior diagnostic value compared to CSF PCT.


The astexin-1 lasso peptides: biosynthesis, stability, and structural studies.
Lasso peptides are a large family of natural products that owe their name to a unique structure formed by a side chain to backbone macrocyclization, resembling a knotted lasso. The unique structure has significant impact on their biological and physical properties, as lasso peptides are usually more stable than linear ones. Current work examines stability, structure, and biosynthesis of recently discovered lasso peptide astexin-1, a heat-sensitive lasso peptide. The obtained results revealed a new lasso structure with a tight loop and long tail as well as narrow specificity of the maturation machinery for some essential residues associated with the protease processing site, involved in macrolactam ring formation and entrapment of the tail. Using the astexin-1 structure, it was possible to rationally construct a thermostable variant of this lasso peptide.


Global prevalence of free-living amoebae in solid matrices - A systematic review with meta-analysis.
The ubiquitous free-living amoebae (FLA) are microorganisms of significant medical, sanitary, and ecological importance. However, their characterization within solid matrices such as soil, dust, sediment, mud, sludge, and compost remain to be systematized. In this study, we conducted a systematic review with meta-analysis to explore the global distribution of FLA in solid matrices. From the analysis of 104 out of 4,414 scientific articles retrieved from different databases, it was found that the general global prevalence of FLA in solid matrices was of 55.13% (95% confidence interval (CI) 49.32-60.94). Specifically, FLA prevalence was high in soil (72.40%, 95% CI 69.08-75.73), sediment (57.91%, 95% CI 50.01-65.81), mud (52.90%, 95% CI 24.01-81.78), dust (48.60%, 95% CI 43.00-54.19), and sewage sludge (40.19%, 95% CI 30.68-49.70). In aerosols it was comparatively lower (17.21%, 95% CI 12.76-21.66). Acanthamoeba spp. (52.23%) and Hartmanella/Vermamoeba spp. (36.06%) were found to be more prevalent, whereas Naegleria spp. (34.98%) and Balamuthia spp. (27.32%) were less prevalent. The distribution of the highest global prevalence values for species of Acanthamoeba spp., considering different publication periods of the studies, is as follows: A. hatchetti (51.46%), A. rhysodes (47.49%), A. polyphaga (36.37%), A. culbertsoni (34.31%), A. castellanii (34.21%), and A. lenticulata (32.82%). For other FLA species, the distribution is: Hartmannella/Vermamoeba vermiformis (91.57%), Naegleria fowleri (42.32%), Naegleria gruberi (32.39%), and Balamuthia mandrillaris (25%). The most prevalent Acanthamoeba genotypes were T4 (33.38%) and T3 (23.94%). Overall, the global prevalence of FLA in solid matrices is as high as or greater than that reported in water by previous systematic reviews. Thus, actions aimed at reducing exposure to FLA or exploring their ecological dynamics should consider not only water but also the various solid matrices. The finding outlined here can provide valuable insights for such actions, e.g., informing on the level of exposure to FLA, or on the microbial biodiversity of specific environmental compartments.


Prediction of mean skin temperature in warm environments.
The data collected by the authors in four experimental series have been analysed together with data from the literature, to study the relationship between mean skin temperature and climatic parameters, subject metabolic rate and clothing insulation. The subjects involved in the various studies were young male subjects, unacclimatized to heat. The range of conditions examined involved mean skin temperatures between 33 degrees C and 38 degrees C, air temperatures (Ta) between 23 degrees C and 50 degrees C, ambient water vapour pressures (Pa) between 1 and 4.8 kPa, air velocities (Va) between 0.2 and 0.9 m.s-1, metabolic rates (M) between 50 and 270 W.m-2, and Clo values between 0.1 and 0.6. In 95% of the data, mean radiant temperature was within +/- 3 degrees C of air temperature. Based on 190 data averaged over individual values, the following equation was derived by a multiple linear regression technique: Tsk = 30.0 + 0.138 Ta + 0.254 Pa-0.57 Va + 1.28.10(-3) M-0.553 Clo. This equation was used to predict mean skin temperature from 629 individual data. The difference between observed and predicted values was within +/- 0.6 degrees C in 70% of the cases and within +/- 1 degrees C in 90% of the cases. It is concluded that the proposed formula may be used to predict mean skin temperature with satisfactory accuracy in nude to lightly clad subjects exposed to warm ambient conditions with no significant radiant heat load.


Advances in understanding the molecular structure of retinoschisin while questions remain of biological function.
Retinoschisin (RS1) is a secreted protein that is essential for maintaining integrity of the retina. Numerous mutations in RS1 cause X-linked retinoschisis (XLRS), a progressive degeneration of the retina that leads to vision loss in young males. A key manifestation of XLRS is the formation of cavities (cysts) in the retina and separation of the layers (schisis), disrupting synaptic transmission. There are currently no approved treatments for patients with XLRS. Strategies using adeno-associated viral (AAV) vectors to deliver functional copies of RS1 as a form of gene augmentation therapy, are under clinical evaluation. To improve therapeutic strategies for treating XLRS, it is critical to better understand the secretion of RS1 and its molecular function. Immunofluorescence and immunoelectron microscopy show that RS1 is located on the surfaces of the photoreceptor inner segments and bipolar cells. Sequence homology indicates a discoidin domain fold, similar to many other proteins with demonstrated adhesion functions. Recent structural studies revealed the tertiary structure of RS1 as two back-to-back octameric rings, each cross-linked by disulfides. The observation of higher order structures in vitro suggests the formation of an adhesive matrix spanning the distance between cells (∼100 nm). Several studies indicated that RS1 readily binds to other proteins such as the sodium-potassium ATPase (NaK-ATPase) and extracellular matrix proteins. Alternatively, RS1 may influence fluid regulation via interaction with membrane proteins such as the NaK-ATPase, largely inferred from the use of carbonic anhydrase inhibitors to shrink the typical intra-retinal cysts in XLRS. We discuss these models in light of RS1 structure and address the difficulty in understanding the function of RS1.


Differential Accumulation of Mercury and Selenium in Brown Trout Tissues of a High-Gradient Urbanized Stream in Colorado, USA.
Total mercury (THg) and selenium (Se) were analyzed by Inductively Coupled Plasma Mass Spectrometry in 11 internal and external tissues and stomach contents from 23 brown trout, Salmo trutta, of a 22.9-km reach of a high-gradient stream (upper Fountain Creek) in Colorado, USA, impacted by coal-fired power plants, shale deposits, and urbanization. Trout and water were sampled from four sites ranging from 2335 to 1818 m elevation. Lengths, weights, and ages of fish between pairs of the four sites were not significantly different. The dry weight (dw) to wet weight (ww) conversion factor for each tissue was calculated with egg-ovary highest at 0.379 and epaxial muscle fourth highest at 0.223. THg and Se in stomach contents indicated diet and not ambient water was the major source of Hg and Se bioaccumulated. Mean THg ww in kidney was 40.33 µg/kg, and epaxial muscle second highest at 36.76 µg/kg. None of the tissues exceeded the human critical threshold for Hg. However, all 23 trout had at least one tissue type that exceeded 0.02 mg/kg THg ww for birds, and four trout tissues exceeded 0.1 mg/kg THg ww for mammals, indicating that piscivorous mammals and birds should be monitored. Se concentrations in tissues varied depending on ww or dw listing. Mean Se dw in liver was higher than ovary at the uppermost site and the two lower sites. Liver tissue, in addition to egg-ovary, should be utilized as an indicator tissue for Se toxicity.


Nationwide study of mortality and sudden cardiac death in young persons diagnosed with chronic kidney disease.
The aim of this study was to compare short- and long-term risk of sudden cardiac death (SCD) among persons aged 18-49 years with and without chronic kidney disease (CKD). Using Danish nationwide health registries, all persons aged 18-49 years diagnosed with earlier stages of CKD or chronic kidney failure from 1 July 1995 through 2009 were identified. Non-exposed subjects matched on sex and birth-year were identified. All SCD in the Danish population aged 18-49 years in 2000-2009 have previously been identified using information from the Danish nationwide health registries, death certificates, and autopsy reports. In total, 9308 incident cases of earlier stage CKD and 1233 incident cases of chronic kidney failure were included. Among patients with earlier stage CKD, the absolute risk of SCD 1, 5, and 10 years after diagnosis was 0.14%, 0.37%, and 0.68%, respectively. Compared with age- and sex-matched subjects the corresponding relative risk (RR) was 20.3 [95% confidence interval (CI) 8.4-48.8], 7.1 (95% CI 4.2-12.0), and 6.1 (95% CI 3.8-9.7), respectively. Among patients with chronic kidney failure, the absolute 1-, 5-, and 10-year risk of SCD was 0.17%, 0.56%, and 2.07%, respectively. The corresponding RR was 12.5 (95% CI 1.4-111.6), 7.9 (95% CI 2.3-27.0), and 10.1 (95% CI 4.5-22.6). Persons with earlier stage CKD and chronic kidney failure had increased risk of SCD compared with the background population with a 6- to 20-fold increased risk of SCD. These findings underline the importance of early cardiovascular risk monitoring and assessment in persons with CKD.


Effect of Coformer Selection on In Vitro and In Vivo Performance of Adefovir Dipivoxil Cocrystals.
This study aimed to improve the in vitro dissolution, permeability and oral bioavailability of adefovir dipivoxil (ADD) by cocrystal technology and clarify the important role of coformer selection on the cocrystal's properties. ADD was cocrystallized with three small molecules (i.e., paracetamol (PA), saccharin (SAC) and nicotinamide (NIC)), respectively. The obtained ADD-PA cocrystal was characterized by DSC, TGA, PXRD and FTIR. Comparative study on dissolution rates among the three ADD cocrystals were conducted in water and pH 6.8 phosphate buffer. Besides, effects of coformers on intestinal permeability of ADD were evaluated via in vitro Caco-2 cell model and in situ single-pass intestinal perfusion model in rats. Furthermore, in vivo pharmacokinetic study of ADD cocrystals was also compared. Dissolution rates of ADD cocrystals were improved with the order of ADD-SAC cocrystal > ADD-PA cocrystal > ADD-NIC cocrystal. The permeability studies on Caco-2 cell model and single-pass intestinal perfusion model indicated that PA could enhance intestinal absorption of ADD by P-gp inhibition, while SAC and NIC did not. Further in vivo pharmacokinetic study showed that ADD-SAC cocrystal exhibited higher Cmax (1.4-fold) and AUC0-t (1.3-fold) of ADD than administration of ADD alone, and Cmax and AUC0-t of ADD-PA cocrystal were significantly enhanced by 2.1-fold and 2.2-fold, respectively, which was attributed to its higher dissolution and improved intestinal permeability. Coformer selection had an important role on cocrystal's properties, and cocrystallization of ADD with a suitable coformer was an effective approach to enhance both dissolution and bioavailability of ADD.


Extraction and Back-Extraction Behaviors of La(III), Ce(III), Pr(III), and Nd(III) Single Rare Earth and Mixed Rare Earth by TODGA.
N,N,N',N'-Tetraoctyl diglycolamide (TODGA), as a new extraction agent, is effective for its excellent performance and low environmental hazard, and it is very welcome for the rare earth separation process. In this paper, by controlling the extraction time, diluent type, acid type and its concentration, rare earth concentration, etc., the optimum extraction and back-extraction effects of TODGA on La(III), Ce(III), Pr(III), and Nd(III) and mixed rare earths were obtained. The experiment showed that 0.10 mol·L-1 TODGA had the best extraction effect on single rare earth under the conditions of using petroleum ether as diluent, 5 mol·L-1 nitric acid, 20 min extraction time, and 0.01 mol·L-1 rare earth. In the mixed rare earth extraction, the percentage concentrations of La(III), Ce(III), Pr(III), and Nd(III) could be achieved from 21.7%, 19.9%, 30.8%, and 22.2% at the initial stage to 90.5%, 37%, 51%, and 62% after extraction, respectively, by controlling the number of back-extraction cycles and the concentrations of hydrochloric acid and nitric acid in the back-extraction system. The TODGA-rare earth carrier system showed the best back-extraction effect when the hydrochloric acid concentration was 1 mol·L-1 and the back-extraction time was 20 min. At the same time, the mixed rare earth liquid system with low initial concentration was selected for extraction and separation of mixed rare earth. The separation effect was better, and the recovery rate was higher than that of mixed rare earth liquid system with a high initial concentration.


Pubertal timing predicts adult psychosexuality: Evidence from typically developing adults and adults with isolated GnRH deficiency.
Evidence suggests that psychosexuality in humans is modulated by both organizational effects of prenatal and peripubertal sex steroid hormones, and by activational effects of circulating hormones in adulthood. Experimental work in male rodents indicates that sensitivity to androgen-driven organization of sexual motivation decreases across the pubertal window, such that earlier puberty leads to greater sex-typicality. We test this hypothesis in typically developing men (n = 231) and women (n = 648), and in men (n = 72) and women (n = 32) with isolated GnRH deficiency (IGD), in whom the precise timing of peripubertal hormone exposure can be ascertained via the age at which hormone replacement therapy (HRT) was initiated. Psychosexuality was measured with the Sexual Desire Inventory-2 (SDI-2) and Sociosexual Orientation Inventory-Revised (SOI-R). In both sexes, earlier recalled absolute pubertal timing predicted higher psychosexuality in adulthood, although the magnitude of these associations varied with psychosexuality type and group (i.e., typically developing and IGD). Results were robust when controlling for circulating steroid hormones in typically developing participants. Age of initiation of HRT in men with IGD negatively predicted SOI-R. We discuss the clinical implications of our findings for conditions in which pubertal timing is medically altered.


Adult metachromatic leucodystrophy: clinicopathological report of two familial cases with slow course.
Two cases of adult metachromatic leucodystrophy in one family are reported. The main clinical features in both were predominantly psychiatric with alcoholism and an extremely long duration of the illness. Neuropathological examination revealed a similar distribution of the lesions in both, and scanty metachromatic accumulation in the CNS and not at all elsewhere. The great variability of the lengths of the courses is stressed. The duration in no way seems to be linked to the age of onset, except in the typical infantile form. The authors argue that different lengths of history correlate with distinct neuropathological findings, and may possibly be related to qualitative differences in the involved enzyme disturbance. Therefore, the authors suggest that the classification based on the age of onset be enlarged with a further one distinguishing between 'rapid' and 'slow' course types.


Pharmacokinetic determinants of cisplatin-induced subclinical kidney injury in oncology patients.
The ability to predict and detect clinical and subclinical nephrotoxicity early in the course of therapy has the potential to improve long-term outcomes in cancer patients receiving cisplatin chemotherapy. Pharmacokinetic parameters could serve as predictors of cisplatin-induced nephrotoxicity. Participants [n = 13] were treated with a 1-h cisplatin infusion [30-75 mg/m2]. Blood was collected pre-dose and up to 6 h post-dose. Urinary biomarkers [KIM-1, calbindin, clusterin, GST-pi, β2M, albumin, NGAL, osteopontin, clusterin, MCP-1, cystatin C, and TFF3] were measured at baseline, days 3 and 10. Total and unbound platinum concentrations were measured using ICP/MS. Noncompartmental analysis was performed, and correlation and regression analyses evaluated the relationships between platinum pharmacokinetics and nephrotoxicity. Peak platinum urinary concentrations correlated with urinary levels of KIM-1, calbindin, clusterin, GST-pi, β2M, albumin, NGAL, osteopontin, clusterin, cystatin C, and TFF3 at day 10. Unbound platinum plasma concentrations at 2 h also correlated with urinary clusterin, β2M, cystatin C, NGAL, osteopontin, and TFF3 at day 3. Regression analyses suggested 2-h total plasma platinum concentrations greater than 2000 ng/ml, and peak urinary platinum concentrations above 24,000 ng/ml may serve as potential approximations for elevated risk of nephrotoxicity. Platinum area under the plasma concentration time curve was associated with serum creatinine and estimated glomerular filtration rate. Peak plasma and urinary platinum concentrations and pharmacokinetic parameters were associated with risk of subclinical cisplatin-induced kidney injury as assessed using novel urinary biomarkers. Future studies will examine these relationships in larger clinical populations of cisplatin-induced acute kidney injury.


Spatial dynamics of active microeukaryotes along a latitudinal gradient: Diversity, assembly process, and co-occurrence relationships.
Recent global warming is profoundly and increasingly influencing the Arctic ecosystem. Understanding how microeukaryote communities respond to changes in the Arctic Ocean is crucial for understanding their roles in the biogeochemical cycles of nutrients and elements. Between July 22 and August 19, 2016, during cruise ARA07, seawater samples were collected along a latitudinal transect extending from the East Sea of Korea to the central Arctic Ocean. Environmental RNA was extracted and the V4 hypervariable regions of the reverse transcribed SSU rRNA were amplified. The sequences generated by high throughput sequencing were clustered into zero-radius OTUs (ZOTUs), and the taxonomic identities of each ZOTU were assigned using SINTAX against the PR2 database. Thus, the diversity, community composition, and co-occurrence networks of size fractionated microeukaryotes were revealed. The present study found: 1) the alpha diversity of pico- and nano-sized microeukaryotes showed a latitudinal diversity gradient; 2) three distinct communities were identified, i.e., the Leg-A, Leg-B surface, and Leg-B subsurface chlorophyll a maximum (SCM) groups; 3) distinct network structure and composition were found in the three groups; and 4) water temperature was identified as the primary factor driving both the alpha and beta diversities of microeukaryotes. This study conducted a comprehensive and systematic survey of active microeukaryotes along a latitudinal gradient, elucidated the diversity, community composition, co-occurrence relationships, and community assembly processes among major microeukaryote assemblages, and will help shed more light on our understanding of the responses of microeukaryote communities to the changing Arctic Ocean.


An analysis of distance variables that affect aftercare attendance.
Recent reserach has examined variables related to attendance of aftercare services because of the correlation between aftercare and posthospitalization treatment success. The present study, which examined aftercare attendance for 40 randomyl selected subjects following discharge from an inpatient alcohol treatment program, extends the list of variables found to influence attendance. A multiple-regression analysis of subject demographic variables and variables of a more programmatic nature found that distance variables (e.g., number of miles to an aftercare agency) significantly influenced aftercare attendance. The results are discussed with respect to aftercare program decisions.


The impact of transcatheter aortic valve implantation on quality of life: A mixed methods study.
To provide an in-depth understanding of patients' views about the impact of transcatheter aortic valve implantation on self-reported quality of life. Transcatheter aortic valve implantation is considered to be the gold standard of care for inoperable patients diagnosed with severe symptomatic aortic stenosis. Mid- to long-term clinical outcomes are favourable and questionnaire data indicates improvements in quality of life but an in-depth understanding of how quality of life is altered by the intervention is missing. A mixed methods study design with a total of 89 in-depth qualitative interviews conducted with participants (39% male; mean age 81.7 years), 1 and 3 months post TAVI, recruited from a regional centre in England. Data were triangulated with questionnaire data (SF-36 and EQ5D-VAS) collected, pre, 1 and 3 months post implantation. Participants' accounts were characterised by four key themes; shortened life, extended life, limited life and changed life. Quality of life was changed through two mechanisms. Most participants reported a reduced symptom burden and all explained that their life expectancy was improved. Questionnaire data supported interview data with gradual improvements in mean EQ-5D scores and SF-36 physical and mental domain scores at 1 and 3 months compared to baseline. Findings suggest that TAVI was of variable benefit, producing considerable improvements in either mental or physical health in many participants, while a smaller proportion continued to deteriorate.


Effects of exergaming on hippocampal volume and brain-derived neurotrophic factor levels in Parkinson's disease.
Cognitive impairment is among the most burdensome non-motor symptoms in Parkinson's disease (PD) and has been associated with hippocampal atrophy. Exercise has been reported to enhance neuroplasticity in the hippocampus in correlation with an improvement of cognitive function. We present data from the Training-PD study, which was designed to evaluate effects of an "" training protocol on neuronal plasticity in PD. We initiated a 6-week exergaming training program, combining visually stimulating computer games with physical exercise in 17 PD patients and 18 matched healthy controls. Volumetric segmentation of hippocampal subfields on T1- and T2-weighted magnetic resonance imaging and brain-derived neurotrophic factor (BDNF) serum levels were analyzed before and after the training protocol. The PD group showed a group-dependent significant volume increase of the left hippocampal subfields CA1, CA4/dentate gyrus (DG) and subiculum after the 6-week training protocol. The effect was most pronounced in the left DG of PD patients, who showed a significantly smaller percentage volume compared to healthy controls at baseline, but not at follow-up. Both groups had a significant increase in serum BDNF levels after training. The results of the present study indicate that exergaming might be a suitable approach to induce hippocampal volume changes in PD patients. Further and larger studies are needed to verify our findings.


Retracted: Dynamic Analysis of College Physical Education Teaching Quality Evaluation Based on Network under the Big Data.
[This retracts the article DOI: 10.1155/2021/5949167.].


A flow cytometry-based reporter assay identifies macrolide antibiotics as nonsense mutation read-through agents.
A large number of human diseases are caused by nonsense mutations. These mutations result in premature protein termination and the expression of truncated, usually nonfunctional products. A promising therapeutic strategy for patients suffering from premature termination codon (PTC)-mediated disorders is to suppress the nonsense mutation and restore the expression of the affected protein. Such a suppression approach using specific antibiotics and other read-through promoting agents has been shown to suppress PTCs and restore the production of several important proteins. Here, we report the establishment of a novel, rapid, and very efficient method for screening stop-codon read-through agents. We also show that, in both mammalian cells and in a transgenic mouse model, distinct members of the macrolide antibiotic family can induce read-through of disease-causing stop codons leading to re-expression of several key proteins and to reduced disease phenotypes. Taken together, our results may help in the identification and characterization of well-needed customized pharmaceutical PTC suppression agents. Establishment of a flow cytometry-based reporter assay to identify nonsense mutation read-through agents. Macrolide antibiotics can induce read-through of disease-causing stop codons. Macrolide-induced protein restoration can alleviate disease-like phenotypes.


Effect of oral milrinone on end-systolic relations in patients with severe congestive heart failure.
The new inotropic agent milrinone has both vasodilator and inotropic cardiovascular effects, but the importance of these effects in patients with severe congestive heart failure (CHF) is controversial. The left ventricular (LV) end-systolic pressure-diameter relation was used to determine the independent inotropic effect of milrinone. Seven patients with New York Heart Association class III CHF were invasively monitored with right-sided heart catheters and radial arterial lines. M-mode echocardiography was used to measure LV dimensions. The effect of a 10-mg oral dose of milrinone on hemodynamic, echocardiographic and end-systolic variables was determined. End-systolic pressure was measured at the dicrotic notch of the arterial pressure tracing and end-systolic LV dimensions at the time of aortic valve closure. Methoxamine (n = 6) or nitroprusside (n = 1) was used to alter afterload so that the end-systolic pressure-diameter relation could be determined. Arterial vasodilation from milrinone was evidenced by a decrease in mean arterial blood pressure (88 +/- 5 to 77 +/- 2 mm Hg, p less than 0.025) and an increase in cardiac index (from 2.7 +/- 0.2 to 3.2 +/- 0.2 liters/min/m2, p less than 0.025), with no change in heart rate (80 +/- 5 beats/min). Milrinone decreased preload as assessed by the pulmonary artery wedge pressure (from 17 +/- 2 to 10 +/- 2 mm Hg, p less than 0.01) and end-diastolic LV diameter (from 7.4 +/- 0.4 to 7.0 +/- 0.4 cm, p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)


Serum and plasma concentrations of clindamycin following a single intramuscular injection of clindamycin phosphate in maintenance haemodialysis patients and normal subjects.
Serum levels of clindamycin bioactivity and total clindamycin were studied after single intramuscular injections of 300 mg of clindamycin phosphate in a group of 6 normal subjects and a group of 6 maintenance haemodialysis patients. The patients were studied during a non-dialysis period and then again during haemodialysis. Peak levels tended to be higher and elimination half-lives shorter in the patients than in the normal subjects. Possible reasons for these differences are discussed. There was no evidence that haemodialysis per se influenced the pharmacokinetics of clindamycin phosphate. The proportion of unhydrolysed clindamycin phosphate tended to be higher in the renal failure patients and the reason for this is not apparent. Little, if any, dosage modification is necessary in severe renal fialure although there is probably little point in exceeding a dose of 300 mg intramuscularly every 5 h even in severe infections in patients with severe renal failure. The higher peak levels in patients with advanced renal failure indicate the need for further studies with repeated doses.


Tuberculosis in children.
The World Health Organization estimates that 90 million cases of tuberculosis will occur throughout the world in the 1990s, and 30 million people will die from the disease. Although traditional epidemiology suggested that 90% of tuberculosis cases arise from reactivation of remote infection, urban studies in the United States using DNA fingerprinting techniques imply that up to 40% of current cases are due to recent acquisition, a finding that will alter some basic approaches to tuberculosis control. Drug resistance is emerging as a major obstacle to tuberculosis control in the United States and the world. New studies focusing on the genetic basis of drug resistance may lead to better diagnostic techniques and new drugs. New trends in treatment center on shorter but more intense and directly observed therapy to maintain adherence. The new emphasis in developed countries is to concentrate control efforts selectively on those individuals, with the greatest risk factors for development of tuberculosis infection and disease.


Histopathological and clinical characteristics of duodenal gastrointestinal stromal tumors as predictors of malignancy.
Although gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, they are very rare. This study evaluated clinical and histopathological characteristics of duodenal GISTs to identify factors useful in predicting prognosis for patients with these tumors. A retrospective study was performed on 20 patients who had undergone surgery between 1987 and 2009 for duodenal GISTs. Clinical, histopathological, and immunohistochemical data were evaluated. Survival analyses were conducted using Kaplan-Meier estimates. In 12 patients (60%), duodenal GISTs were diagnosed incidentally. Eight cases (40%) were classified as high risk grade GISTs. Skeinoid fibers (SkF), which are eosinophilic globular hyaline deposits in the extracellular interstitium of the tumor, were found in 12 patients. Skeinoid fibers were not recognized in 8 cases, and these included 3 cases (37.5%) where tumors recurred after surgery and the patient died. Tumors without SkF were larger (81 ± 92 vs. 23 ± 8 mm, P < 0.001) and had a higher mitotic count (224.0 ± 336.6 vs. 0.0 ± 0.0 /50 high-power field, P < 0.001) than those with SkF. Survival time was shorter in patients with tumors lacking SkF (52.9 ± 50.7 vs. 108.9 ± 86.5 months, P = 0.019). We have identified clinical and histopathological characteristics that were useful in predicting the prognosis of patients with duodenal GISTs. In this study, 60% of the tumors were found incidentally, SkF were not recognized in tumors from 40% of patients, and all cases of post-operative tumor recurrence and death occurred in this subgroup of patients.


Inventory management practices: implications on the pharmaceuticals expenditure of rabies vaccine in public health facilities, Namibia.
To achieve well-regulated distribution, storage, and utilization of the rabies vaccine, health facilities should adhere to standard operating procedures. In Namibia, information on inventory management, utilization, monitoring, and reporting of rabies vaccine adherence to standard operating procedures in public healthcare facilities is insufficient. The aim of this study was to assess adherence to rabies vaccine standard operating procedures and inventory management and to compare rabies vaccine expenditure to the number of patients who received rabies vaccination at the Ministry of Health and Social Services' public healthcare facilities from 2018 to 2020. A cross-sectional, web-based questionnaire consisting of closed-ended questions was sent to 147 pharmacy staff and warehouse managers working in the 14 regions of Namibia during the period of May 1, 2021, to June 2, 2021. The overall expenditure and the total number of patients vaccinated from 2018 to 2020 were obtained from national-level logistic and vaccination program coordinators. Data were coded and transcribed into Microsoft® Excel® 2013 and analyzed using SPSS® version 27. One hundred and thirty-three completed questionnaires were received from sixty-nine public health centers and hospitals. The group of respondents consisted of pharmacist assistants (50%), pharmacy technicians (12%), pharmacists (36.8%), senior pharmacists (0.8%), and chief pharmacists (1.5%). Overall, adherence to standard operating procedures was poor (27.1%). Rabies vaccine distributed to public health facilities from 2018 to 2020 was worth N$75,381,419.91 (~ US$4,074,671.46) and was expected to vaccinate 87,269 patients; however, only 95 cases of both rabies and rabid dog-bite patients were reported. The major inventory management challenges for public healthcare facilities include an inadequate number of pharmacy staff, poor adherence to standardized pharmaceutical warehousing, lack of regular supervision, and inadequate staff training. Inventory management practices in public healthcare facilities were not in compliance with standard operating procedures. There is a significant discrepancy between rabies vaccine expenditure and the number of patients that were vaccinated. Therefore, there is a need for adequate staff training on inventory management and regular facility supervision to enforce optimal rabies vaccine inventory management practices.


Assessment of selected heavy metals in honey samples using flame atomic absorption spectroscopy (FAAS), Ethiopia.
Honey is a natural, sugary and sticky liquid that is produced from the nectars of flowers by the bees. This study aimed to analyze the concentration of some selected heavy Metals in honey samples. 1 g of honey sample was digested by a hot plate using 9ml of HNO3 and 3ml of H2O2. The concentrations of the heavy metals in the digested were detected using a flame atomic absorption spectrometer. The results of this study found that the concentrations of the heavy metals in the honey samples were ranged from 1.97 to 2.04 µg/g for Zn, 1.93 µg/g to 2 µg/g for Cu, 0.83 to 1.01 µg/g for Mn, 0.25 to 0.45 µg/g for Cr, 0.025-0.031 µg/g for Cd. However, Pb was not detected in all honey samples. Hence, the levels of heavy metals found were below the permitted levels set by the World Health Organization. From the results, the levels of heavy metals found were below the permitted levels set by the World Health Organization. Thus, the heavy metals in the sampled honey are safe for human consumption in these selected areas.


Interpreting the results of freeze-etching.
Morphological data obtained by freeze-fracturing and other low temperature techniques must be interpreted in terms of molecular organization and function. Interpretation is aided by physical and biochemical approaches. Physical approaches such as rotary replication and ultralow temperature fracturing can improve resolution and preserve molecular arrangements which are difficult or impossible to observe with standard freeze-etching techniques. Biochemical approaches such as dissociation-reconstitution experiments can establish the molecular parameters underlying electron-microscopically visible forms. Both approaches are illustrated by investigations of the human erythrocyte membrane.


Development of the Penn Healthy Diet screener with reference to adult dietary intake data from the National Health and Nutrition Examination Survey.
There is a need for a feasible, user-friendly tool that can be employed to assess the overall quality of the diet in U.S. Our objectives were to develop the Penn Healthy Diet (PHD) screener, evaluate screener item correlations with Healthy Eating Index (HEI)-2015 components, and develop a simple scoring algorithm. National Health and Nutrition Examination Survey (NHANES) 2017-18 dietary recall data in adults were used to define food examples in screener food groups based on components of the HEI-2015, Diet Approach to Stop Hypertension, and Alternative Mediterranean diet approaches. Instrument Content Validity Index (I-CVI) was used to evaluate the clarity and relevance of the screener. Patient acceptability was evaluated by completion time and response rates. NHANES 2017-18 food recall data were used to simulate responses to the screener items, which were evaluated for association with HEI-2015 components. A scoring algorithm was developed based on screener items moderately or strongly associated with HEI-2015 components. Reproducibility was tested using NHANES 2015-16 data. The screener had strong clarity (I-CVI = 0.971) and relevance for nutrition counseling (I-CVI = 0.971). Median (IQR) completion time was 4 (3-5) minutes on paper and 4 (4-8) minutes online, and 73% of patients invited online completed the survey. Based on simulated NHANES participant screener responses, 15 of the 29 screener items were moderately or strongly associated with HEI-2015 components, forming the basis of the scoring algorithm with a range of 0-63 points, where higher score indicates a healthier diet. The median (IQR) screener and HEI-2015 scores were 14.96 (11.99-18.36) and 48.96 (39.51-59.48), respectively. The simulated PHD score was highly correlated with the HEI-2015 score (Spearman rho 0.75) in NHANES 2017-18 and confirmed in NHANES 2015-16 data (Spearman rho 0.75). The Penn Healthy Diet screener may be a useful tool for assessing diet quality due to its acceptable content validity, ease of administration, and ability to distinguish between servings of key food groups associated with a healthy versus unhealthy diet according to the HEI-2015. Additional research is needed to further establish the instrument's validity, and to refine a scoring algorithm.


Skin morphology and function.
Proper understanding of the cause, nature, and treatment of diseases affecting the skin requires an intimate knowledge of the anatomy and physiology of normal as well as pathologic skin. This article thus lays the groundwork for the discussions of specific pathologic conditions that follow in this issue.


Maternally-induced modification of progeny phenotypes in the C4 weed Echinochloa crus-galli: An analysis of seed constituents and performance.
To clarify the physiological basis of maternal inheritance we examined the effect of the thermal environment of mother plants of Echinochloa crus-galli on subsequent seed mass, content and quality. The same plants were grown in a warm and a cold environment until seeds were produced and, since E. crus-galli is a highly inbred species, the observed variation in seed production was a purely plastic response to the environment. When mother plants were grown at high temperature, average seed mass, variance and germinability were low. Cold maturation led to the production of more large seeds than warm maturing temperature. The latter seeds were deprived of reserve constituents. Seeds matured at high temperature had high concentrations of K+ and Mn2+ but lower concentrations of starch and protein.


Complex interactions between tutor performance, tutorial group productivity and the effectiveness of PBL units as perceived by students.
Tutor performance and tutorial group productivity interact with each other in a complex manner. The aim of this study was to investigate how tutor performance, tutorial group productivity and the effectiveness of a PBL unit interact with each other. Three hypotheses were tested: (1) Does the tutor performance score differ across different levels of group productivity? (2) Does the group productivity score differ across different levels of tutor performance? and (3) Is the learning effectiveness score of a PBL unit related to tutor performance and group productivity? Students rated the tutor performance, the tutorial group productivity and the effectiveness of the PBL unit. In total 287 unique tutors were involved and were categorized as having a relatively low, average or relatively high score on tutor performance. This was also done for the group productivity score. For each combination, average effectiveness score were computed. Furthermore, partial correlation coefficients were computed. The results demonstrated that the average tutor performance score was higher if the productivity score was higher (hypothesis 1). The results also demonstrated that the average productivity score was higher if the tutor performance score was higher (hypothesis 2). Furthermore it was found that the effectiveness score was higher if the productivity score was higher. The effectiveness score was also higher if the tutor score was higher. The results furthermore demonstrated that the correlation coefficient between tutor performance and effectiveness of the PBL unit is 0.01 (n.s.) if the correlation between the two variables was controlled for group productivity (was 0.36). In addition, the correlation coefficient between group productivity and effectiveness became 0.39 if the correlation between these two variables was controlled for tutor performance (was 0.51) (hypothesis 3). It is concluded that tutor performance differs across different levels of group productivity and that the group productivity score differs across different levels of tutor performance. In addition, it is concluded that both group productivity and the tutor's performance have an impact on the effectiveness of a PBL unit, although the correlation between group productivity and effectiveness is higher than the correlation between tutor performance and effectiveness. This finding illustrates the importance of the group's productivity in PBL and the tutor's importance and implies that schools should put more efforts in improving tutorial group functioning as well as in improving a tutor's performance.


Analysis of mannosidase I activity in interphase and mitotic cells by lectin staining and endoglycosidase H treatment.
N-Glycosylation is a common protein modification catalyzed by a series of glycosylation enzymes in the endoplasmic reticulum and Golgi apparatus. Here, based on a previously established Golgi α-mannosidase-I-deficient cell line, we present a protocol to investigate the enzymatic activity of exogenously expressed Golgi α-mannosidase IA in interphase and mitotic cells. We describe steps for cell surface lectin staining and subsequent live cell imaging. We also detail PNGase F and Endo H cleavage assays to analyze protein glycosylation. For complete details on the use and execution of this protocol, please refer to Huang et al.1.


Changes of fluoresceindiacetate-hydrolysis and transport in mammalian cells after ultra-violet- and gamma irradiation.
Changes in the permeability of cell membranes and in the enzymatic activity of intact cells and their homogenates after irradiation were studied. CHO-cells, erythrocytes and their homogenates were irradiated with cobalt-gamma radiation and UV-light. It was found that the esterases are more radio-sensitive in intact cells than in the corresponding homogenates. The decrease of the enzymatic activity after irradiation can be described by a one-hit curve, whereas the loss of transport activity can be resolved into two one-hit curves. The slope associated with the more sensitive target mainly determines the course of the composed transport curve. Mechanisms for the decreases in the rate constants are discussed.


Selective bundle versus complete anterior-cruciate ligament reconstruction: A systematic review and meta-analysis.
Selective bundle reconstruction (SLB) refers to preservation of the intact bundle and reconstruction of the ruptured bundle in a partial tear while complete ACL reconstruction involves the removal of all remnant tissue and reconstruction of one or both bundles. As the evidence for SLB versus complete ACL reconstruction remains unclear, this study aimed to compare the two techniques. This study's hypothesis was that SLB reconstruction allows better function and stability compared to complete ACL reconstruction. A systematic search of PubMed, EMBASE, Scopus and Cochrane Library was conducted, identifying studies that compared SLB ('selective' group) versus complete ('complete' group) ACL reconstruction. Meta-analysis was conducted for post-operative functional scores, stability outcomes and complications as well as pre-operative to post-operative change. Eleven studies were included in the meta-analysis, with 1107 patients and a pooled mean follow-up of 29.5 months. Post-operatively, the Selective group had significantly reduced anterior laxity, shown by a lower mean arthrometry side-to-side difference (p<0.01). Analysis of change results showed that the Selective group had a lower mean improvement in arthrometry side-to-side difference as well (p<0.01). No significant difference was shown for all other post-operative outcomes. This study provides valuable insight to the management of partial tears. It has demonstrated that the preservation of the intact bundle offers stability and function that is as good as complete reconstruction and that SLB is a potentially viable option in the management of partial tears. Meta-analysis; Level of evidence, 4.


Effect of indium (III) doping on Ag3PO4 catalyst stabilization and its visible light photocatalytic activity toward toxic dyes in water.
Indium(III)-doped Ag3PO4 (In-AgP) catalysts at different weight percentages were elaborated by co-precipitation and subjected to XRD, SEM, UV-vis DRS, and FTIR characterization. The prepared catalysts were of spherical morphology and their diameters depends on doping dosage. The whole materials crystallize in a centered cubic system with a slight dissimilation in the positions of the characteristic peaks as a function of indium dosage. The photocatalytic performance of the catalysts under visible light was investigated in the photocatalytic degradation of anionic dye (methyl orange (MO)) and cationic dye (auramine O (AO)) in moderate acid, neutral, and basic pH conditions. Results showed more selectivity to MO than AO. Furthermore, indium-doped samples are more active in the acidic medium than the pure Ag3PO4 (AgP), and 10%In-AgP catalyst presents the highest activity. The degradation efficiency reached 99 % in 60 min for MO and in 180 min for AO. In addition, a high recycling stability was achieved and the catalyst retains its degradation capacity above 99 % after five cycles.


Comparison of magnetic resonance imaging of inhaled SF6 with respiratory gas analysis.
Magnetic resonance imaging of inhaled fluorinated inert gases ((19)F-MRI) such as sulfur hexafluoride (SF(6)) allows for analysis of ventilated air spaces. In this study, the possibility of using this technique to image lung function was assessed. For this, (19)F-MRI of inhaled SF(6) was compared with respiratory gas analysis, which is a global but reliable measure of alveolar gas fraction. Five anesthetized pigs underwent multiple-breath wash-in procedures with a gas mixture of 70% SF(6) and 30% oxygen. Two-dimensional (19)F-MRI and end-expiratory gas fraction analysis were performed after 4 to 24 inhaled breaths. Signal intensity of (19)F-MRI and end-expiratory SF(6) fraction were evaluated with respect to linear correlation and reproducibility. Time constants were estimated by both MRI and respiratory gas analysis data and compared for agreement. A good linear correlation between signal intensity and end-expiratory gas fraction was found (correlation coefficient 0.99+/-0.01). The data were reproducible (standard error of signal intensity 8% vs. that of gas fraction 5%) and the comparison of time constants yielded a sufficient agreement. According to the good linear correlation and the acceptable reproducibility, we suggest the (19)F-MRI to be a valuable tool for quantification of intrapulmonary SF(6) and hence lung function.


Islet recovery in chronic pancreatitis.
Chronic pancreatitis ablates a large majority of the acinar tissue which otherwise is a troublesome contaminant in preparing islet cells from higher mammals. Chronic pancreatitis was induced by dividing all pancreatic attachments to the duodenum, including major and minor ducts, in six dogs. After 10 weeks, biopsy of the pancreas showed marked acinar cell atrophy and fibrosis with preservation and even proliferation of islet cells. Intravenous glucose tolerance testing revealed only a minor decrease in K value from 3.4 +/- 1.0 to 2.1 +/- 0.4 during 10 weeks. All dogs then underwent total pancreatectomy and islet autotransplantation. The pancreas was dispersed to a cell suspension by perfusing the pancreatic ducts with collagenase until tissue integrity failed. The digested tissue was then chopped, dissociated by shaking, and filtered. The average cell yield from the pancreas was 7.6 X 10(7) cells of which greater than 95% were islet cells. Acid alcohol-extracted insulin values suggested an average 7% recovery of insulin content and essentially complete elimination of amylase content was demonstrated.


Inactivation of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase by koningic acid.
Koningic acid, a sesquiterpene antibiotic, is a specific inhibitor of the enzyme glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 22.214.171.124). In the presence of 3 mM of NAD+, koningic acid irreversibly inactivated the enzyme in a time-dependent manner. The pseudo-first-order rate constant for inactivation (kapp) was dependent on koningic acid concentration in saturate manner, indicating koningic acid and enzyme formed a reversible complex prior to the formation of an inactive, irreversible complex; the inactivation rate (k 3) was 5.5.10(-2) s-1, with a dissociation constant for inactivation (Kinact) of 1.6 microM. The inhibition was competitive against glyceraldehyde 3-phosphate with a Ki of 1.1 microM, where the Km for glyceraldehyde 3-phosphate was 90 microM. Koningic acid inhibition was uncompetitive with respect to NAD+. The presence of NAD+ accelerated the inactivation. In its absence, the charcoal-treated NAD+-free enzyme showed a 220-fold decrease in apparent rate constant for inactivation, indicating that koningic acid sequentially binds to the enzyme next to NAD+. The enzyme, a tetramer, was inactivated when maximum two sulfhydryl groups, possibly cysteine residues at the active sites of the enzyme, were modified by the binding of koningic acid. These observations demonstrate that koningic acid is an active-site-directed inhibitor which reacts predominantly with the NAD+-enzyme complex.


Stimulation of endometrium embryo transfer can improve implantation and pregnancy rates for patients undergoing assisted reproductive technology for the first time with a high-grade blastocyst.
To evaluate whether stimulation of endometrium embryo transfer (SEET) can improve implantation rate and pregnancy rate (PR) for patients undergoing assisted reproductive technology (ART) for the first time by injecting embryo culture supernatant into the uterus before blastocyst transfer (BT). Randomized, controlled trial. Private in vitro fertilization clinic. Forty-eight women in the BT group, 48 women in the stimulation group who had culture medium injected into the uterus before BT, and 48 women in the SEET group. Injection of embryo culture supernatant and injection of culture medium. Implantation rates and PRs. Odds ratios of successful implantation rate for stimulation and SEET in patients with high-grade blastocysts, having BT as reference, were 2.58 and 6.46 without adjustment, and 5.91 and 9.20 after adjusting for basal FSH levels and period of infertility. Odds ratios of clinical pregnancies were 2.47 and 4.32 without adjustment, and 4.46 and 5.10 with adjustment, respectively. In groups with low-grade blastocysts, such tendencies were not observed. The SEET may be an effective method for increasing implantation rate and PR for first-time ART patients who have a high-grade blastocyst.


GARP on hepatic stellate cells is essential for the development of liver fibrosis.
Glycoprotein A repetitions predominant (GARP) is a membrane protein that functions as a latent TGF-β docking molecule. While the immune regulatory properties of GARP on blood cells have been studied, the function of GARP on tissue stromal cells remains unclear. Here, we investigate the role of GARP expressed on hepatic stellate cells (HSCs) in the development of liver fibrosis. The function of GARP on HSCs was explored in toxin-induced and metabolic liver fibrosis models, using conditional GARP-deficient mice or a newly generated inducible system for HSC-specific gene ablation. Primary mouse and human HSCs were isolated to evaluate the contribution of GARP to the activation of latent TGF-β. Moreover, cell contraction of HSCs in the context of TGF-β activation was tested in a GARP-dependent fashion. Mice lacking GARP in HSCs were protected from developing liver fibrosis. Therapeutically deleting GARP on HSCs alleviated the fibrotic process in established disease. Furthermore, natural killer T cells exacerbated hepatic fibrosis by inducing GARP expression on HSCs through IL-4 production. Mechanistically, GARP facilitated fibrogenesis by activating TGF-β and enhancing endothelin-1-mediated HSC contraction. Functional GARP was expressed on human HSCs and significantly upregulated in the livers of patients with fibrosis. Lastly, deletion of GARP on HSCs did not augment inflammation or liver damage. GARP expressed on HSCs drives the development of liver fibrosis via cell contraction-mediated activation of latent TGF-β. Considering that systemic blockade of TGF-β has major side effects, we highlight a therapeutic niche provided by GARP and surface-mediated TGF-β activation. Thus, our findings suggest an important role of GARP on HSCs as a promising target for the treatment of liver fibrosis. Liver fibrosis represents a substantial and increasing public health burden globally, for which specific treatments are not available. Glycoprotein A repetitions predominant (GARP) is a membrane protein that functions as a latent TGF-β docking molecule. Here, we show that GARP expressed on hepatic stellate cells drives the development of liver fibrosis. Our findings suggest GARP as a novel target for the treatment of fibrotic disease.


A global quality control system to check PT-INR portable monitor for Antivitamin K antagonists.
Although most guidelines for quality assessment of INR PMs recommend specific procedures, no clear regulation or methodology is required for outpatients in our country. We have developed a specific INR portable monitor (PM) quality control system within our telemedicine organization to check over time quality performances and plan corrective actions. Based on current guidelines for laboratory QC, the following aspects were assessed: suitability of PM, defined in terms of imprecision and accuracy; intra-assay imprecision, defined according to monthly revision of Levey-Jennings cards with data from each peripheral healthcare unit (PHU), using an internal QC provided by the manufacturer (CV ± 20% considered as acceptable); quarterly accuracy study, for assessing agreement between analytical instruments, based on duplicate analysis of three samples with INR values reflecting different therapeutic ranges (differences ± 0.5 considered as acceptable); external quality assessment (NEQAS). In the nine PHU, 18 portable monitors were used to perform 22 929 test during year 2010. Analytical imprecision was low, showing CVs always <5%. Accuracy check showed two of 216 results out of range (0.92%), thus providing timely indication for instrument replacement. The external QC NEQAS showed optimal performance. The current protocol for INR PMs quality assessment was effective to establish and maintain a reliable control of devices, ensuring the quality of analytical data over time. National authorities should be prompted to guarantee and apply correct protocols for INR-PM use.


PvMSP-3α and PvMSP-3β genotyping reveals higher genetic diversity in Plasmodium vivax parasites from migrant workers than residents at the China-Myanmar border.
The genetic diversity of malaria parasites traces the origin and spread of new variants and can be used to evaluate the effectiveness of malaria control measures. Therefore, this study aims to improve the understanding of the molecular epidemiology of Plasmodium vivax malaria at the China-Myanmar border by genotyping the PvMSP-3α and PvMSP-3β genes. Blood samples were collected from P. vivax malaria patients along the China-Myanmar border. The PvMSP-3α and PvMSP-3β genes were amplified by polymerase chain reaction (PCR) and the genetic polymorphism and haplotype of the two genes were analyzed. A total of 422 blood samples were used for this study, of which 224 were analyzed at PvMSP-3α and 126 at PvMSP-3β. Samples mainly were from young adults aged 18-45 years, although local patients were significantly younger than migrant laborers crossing the border at Tengchong (P < 0.0001). Molecular evolutionary analysis revealed that PvMSP-3α and PvMSP-3β underwent diversifying natural selection, and intragenic recombination contributed to the diversity of the isolates. Based on the length of the genes, we identified three types of PvMSP-3α [1.9-2.0 kb (Type-A), 1.4-1.5 kb (Type-B), and 1.1-1.3 kb (Type-C)] and two types of PvMSP-3β [1.7-2.2 kb (Type-A) and 1.4-1.5 kb (Type-B)]. Migrant laborers returning to China through Tengchong bore P. vivax infections displaying significantly higher genetic diversity than local residents. Both PvMSP-3 paralogs were subjected to diversifying selection in each sample population. Clustering of alleles supports ephemeral endemic differentiation of alleles, but the broader phylogeny suggests that alleles transit the globe, perhaps accelerated by movements of migrants such as those transiting Tengchong.


Screening Hesitancy of a Universal Voluntary-based Rapid Antigen Test for coronavirus disease 2019 (COVID-19) During Omicron Wave in Hong Kong.
The Hong Kong government distributed rapid antigen test (RAT) kits to households across the city and called for a universal voluntary testing exercise for three consecutive days during the Omicron wave to identify infected persons early for quarantine and disrupt transmission chains in the community. We conducted a survey to evaluate the participation rates and explore the determinants of voluntary RAT adoption and hesitancy. This cross-sectional survey was conducted through computer-assisted telephone interviews from 19 May to 16 June 2022 using an overlapping dual-frame telephone number sampling design. Information on willingness to adopt voluntary RAT, four themes of personal qualities, attitudes toward the government's health policies, incentives to motivate RAT adoption, and personal sociodemographic factors were collected. Logistic regression analysis was used to examine the factors associated with RAT adoption. Of the 1010 participants, 490 successfully responded to the fixed-line and 520 to the mobile phone survey, with response rates of 1.42% and 1.63% and screen hesitancy rates of 36.1% and 39.3%, respectively. Participants of adoption RAT were those aged 30-49 years, with high perceived COVID-19 infection severity, ≥ 3 doses of COVID-19 vaccination, and more agreement with the health policies on material resources and quarantine orders. Individuals who were less risk seeking and more altruistic reported a higher adoption of voluntary RAT. Understanding the willingness to participate in a voluntary universal testing programme might shed light on effective ways to minimise screening hesitancy in future public health strategies and campaigns.


Preserving replication fork integrity and competence via the homologous recombination pathway.
Flaws in the DNA replication process have emerged as a leading driver of genome instability in human diseases. Alteration to replication fork progression is a defining feature of replication stress and the consequent failure to maintain fork integrity and complete genome duplication within a single round of S-phase compromises genetic integrity. This includes increased mutation rates, small and large scale genomic rearrangement and deleterious consequences for the subsequent mitosis that result in the transmission of additional DNA damage to the daughter cells. Therefore, preserving fork integrity and replication competence is an important aspect of how cells respond to replication stress and avoid genetic change. Homologous recombination is a pivotal pathway in the maintenance of genome integrity in the face of replication stress. Here we review our recent understanding of the mechanisms by which homologous recombination acts to protect, restart and repair replication forks. We discuss the dynamics of these genetically distinct functions and their contribution to faithful mitoticsegregation.


Evidence of a brief surge in safer sex practices after HIV testing among a sample of high-risk men and women.
We investigated the association between recent HIV testing and safer sex among clients of a publicly funded sexually transmitted disease (STD) clinic. Of 401 men and women who were anonymously assessed on sexual risk, HIV testing, STD history, motivations for behavior change, and exposure to HIV prevention education, we studied 292 sexually active respondents who reported previous testing for HIV. Outcome measures included condom use at last intercourse and frequent (at least "most of the time") condom use during the past 3 months. Logistic regression was used to examine the association between each outcome and length of time since HIV testing, controlling for other putative predictors of condom use. The sample consisted mainly of African-American (79%) heterosexual (95%) men and women, almost half (44%) of whom were less than 26 years old. Regression analyses indicated that recent HIV testing was significantly associated with safer sex. Prevalence of condom use at last intercourse was highest among respondents who received an HIV test <3 months before the survey, whereas frequent condom use during the past 3 months peaked among clients who had been tested 3 to 5 months before assessment. The occurrence of a brief "surge" in safer sex among recent HIV counseling and testing clients, regardless of serostatus, suggests that these individuals may be particularly amenable to additional interventions designed to achieve longer term reductions in risky behaviors.


Aggregation and removal of copper oxide (CuO) nanoparticles in wastewater environment and their effects on the microbial activities of wastewater biofilms.
The transport behaviors of copper oxide (CuO) NPs in wastewater matrix and their possible impacts on microbial activities of stable wastewater biofilms cultivated in a lab scale rotating biological contactor (RBC) were investigated. Significant aggregation of CuO NPs was observed in the wastewater samples, depending on their mass concentrations. Extracellular polymeric substance (EPS)-adsorbed copper accounted for a large proportion of the total copper accumulated in biofilms. The microelectrode profiles showed that a single pulse exposure to 50mg/L CuO resulted in a deeper penetration depth of oxygen in biofilms compared to the CuO NP free biofilms. The maximum oxygen consumption rate shifted to the deeper parts of biofilms, indicating that the respiration activities of bacteria in the top region of the biofilms was significantly inhibited by CuO NPs. Biofilms secreted more EPS in response to the nano-CuO stress, with higher production of proteins compared to polysaccharides.


Nutrition assessment and geriatric associated conditions among free living elderly people in Birjand, East of Iran: a cross-sectional study.
Few data are available on the nutritional status of Iranian geriatric population. The present study aimed to determine the nutritional status of older adults' population in Birjand, East of Iran. The community-based cohort study was performed on older adults population (60 years and older) living in urban and rural areas of Birjand. The mini nutritional assessment (MNA) questionnaire was used to assess nutritional status. Anthropometric and biochemical evaluation were also performed for all of the participants. A total of 1417 geriatric person were enrolled in this study, which, most of them were female (51.9 %). According to MNA tool, most of the participants (73.3 %) had normal nutrition (MNA score ≥ 24). Malnourished (MNA score < 17) and at high risk of malnutrition (MNA score: 17- 23.5) were constituted 0.9 % and 25.8 % of the participants, respectively. Marital status, occupation, period of education and family member were associated with nutritional status. Multiple logistic regression showed that with increase of body mass index (BMI) (OR = 0.96), education years (OR = 0.95), hemoglobin (OR = 0.86) and lymphocyte (OR = 0.98), the odds of malnutrition decreased, but with increase of age the odds (1.03) of malnutrition is also elevated. MNA could successfully forecast the risk of malnutrition and malnourished people. Sociodemographic factors are associated with the nutritional status.


Imaging Cancer in Neuroradiology.
Neuroimaging plays a pivotal role in the diagnosis, management, and prognostication of brain tumors. Recently, the World Health Organization published the fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS5), which places greater emphasis on tumor genetics and molecular markers to complement the existing histological and immunohistochemical approaches. Recent advances in computational power allowed modern neuro-oncological imaging to move from a strictly morphology-based discipline to advanced neuroimaging techniques with quantifiable tissue characteristics such as tumor cellularity, microstructural organization, hemodynamic, functional, and metabolic features, providing more precise tumor diagnosis and management. The aim of this review is to highlight the key imaging features of the recently published CNS5, outlining the current imaging standards and summarizing the latest advances in neuro-oncological imaging techniques and their role in complementing traditional brain tumor imaging and management.


Ultracytochemical distribution of myelin basic protein after injection into the cerebrospinal fluid. Evidence for transport through the blood-brain barrier and binding to the luminal surface of cerebral veins.
Distribution of myelin basic protein (MBP) in the central nervous system (CNS) following injection into the cerebrospinal fluid (CSF) was studied by different qualitative and quantitative immunelectron -microscopic techniques. Endogenous MBP was present in myelin sheaths in injected as well as in control animals. After injection of exogenous MBP into CSF this protein was present in the subarachnoid space, on the surface of meningeal cells, on the surface of collagen fibers, in the basement membrane of the glia limitans, in vessel walls, and in the extracellular space of spinal roots. In meningeal veins, endothelial vesicles filled with peroxidase reaction product were found on the abluminal side of endothelial cells, in the endothelial cytoplasm and sometimes opening into the vascularllumen . In addition patchy staining of the luminal surface of endothelial cells was noted, indicating binding of antigen at this location. Quantitative immunelectron microscopy (an indirect technique with rabbit anti-MBP serum as primary layer and gold-labeled anti-rabbit IgG as secondary layer) revealed highly significant MBP binding on the luminal surface of endothelial cells after injection of this antigen into the CSF. The present results indicate that MBP, when liberated in CNS is transported through the blood-brain barrier and presented on the luminal surface of endothelial cells of the cerebral and meningeal veins. This observation may be important in interpretation of pathogenesis of initial inflammatory infiltrates in experimental allergic encephalitis (EAE).


Heat and disasters spur climate researchers.
Climate researchers are bouncing back in spite of fresh criticism of the IPCC management and are looking to understand catastrophic individual events.


Early Operative Treatment of Acetabular Fractures Does Not Increase Blood Loss: A Retrospective Review.
To compare cell salvage (CS) volume, intraoperative blood loss, intraoperative blood transfusions, and operative time for acetabular fractures undergoing early (≤48 hours from admission) versus delayed fixation (>48 hours from admission). Retrospective. Level one trauma center. One hundred thirty-one patients with unilateral acetabular fractures involving at least one column. Open reduction and internal fixation performed through the anterior intrapelvic approach or posterior approach. CS volume, estimated blood loss (EBL), intravenous fluids (IVFs), intraoperative packed red blood cells (PRBCs), and operative time. Early versus delayed fixation through the posterior approach was associated with shorter operative times and less intraoperative PRBCs (140 vs. 301 mL, MD -161 mL, 95% confidence interval -25 to -296 mL) with no differences in CS, EBL, or IVF. Early versus delayed fixation through an anterior intrapelvic approach was more common in less severe fracture patterns with no differences in PRBCs, CS, EBL, or IVF. CS, through either approach, was successful in returning blood to 77% of patients for an average of 267 ± 168 mL (range, 105-900 mL). Fixation of acetabular fractures within 48 hours of admission did not increase blood loss or intraoperative transfusions. CS was successful in returning an average of one unit of blood to a majority of patients. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Developmental genetic underpinnings of a symbiosis-associated organ in the fungus-farming ambrosia beetle Euwallacea validus.
Mutualistic interactions between organisms often mediate the innovation of traits essential to maintain the relationship. Yet our understanding of these interactions has been stymied due to various hurdles in studying the genetics of non-model animals. To understand the genetic mechanisms by which such traits develop, we examined the function of genes breathless (btl), trachealess (trh), and doublesex in the development of a novel fungus-carrying organ (mycangium) that facilitates an obligate relationship between fungus-farming ambrosia beetles and specific fungal partners. Gene knockdown by RNA interference and subsequent micro-computed tomography visualization suggest btl and trh are required for initiation of mycangia and that tubulogenesis may have been co-opted for early mycangial development.


Predictors of not maintaining regular medical follow-up after stroke.
Regular medical follow-up after stroke is important to reduce the risk of post-stroke complications and hospital readmission. Little is known about the factors associated with stroke survivors not maintaining regular medical follow-up. We sought to quantify the prevalence and predictors of stroke survivors not maintaining regular medical follow-up over time. We conducted a retrospective cohort study of stroke survivors in the National Health and Aging Trends Study (2011-2018), a national longitudinal sample of United States Medicare beneficiaries. Our primary outcome was not maintaining regular medical follow-up. We performed a cox regression to estimate predictors of not maintaining regular medical follow-up. There were 1330 stroke survivors included, 150 of whom (11.3%) did not maintain regular medical follow-up. Stroke survivor characteristics associated with not maintaining regular medical follow-up included not having restrictions in social activities (HR 0.64, 95% CI 0.41, 1.01 for having restrictions in social activities compared to not having restrictions in social activities), greater limitations in self-care activities (HR 1.13, 95% CI 1.03, 1.23), and probable dementia (HR 2.23, 95% CI 1.42, 3.49 compared to no dementia). The majority of stroke survivors maintain regular medical follow-up over time. Strategies to retain stroke survivors in regular medical follow-up should be directed towards stroke survivors who do not have restrictions in social activity participation, those with greater limitations in self-care activities, and those with probable dementia.


Hyaluronidase decreases neutrophils infiltration to the inflammatory site.
To evaluate the in vivo anti-inflammatory potential of bovine hyaluronidase (HYAL) using two different models of acute inflammation. Air pouches were produced in the dorsal subcutaneous of mice and injected with phosphate saline solution or HYAL. The antiinflammatory action of HYAL was evaluated in carrageenan (Cg)-inflamed air pouches. After 4 and 24 h the cellular influx, protein exudation, cytokines and lipid mediators were evaluated. The action of HYAL on the rolling and adhesion of leukocytes was investigated in the LPS-stimulated mesenteric microcirculation by intravital microscopic. Treatment with HYAL reduced the cellular influx and protein exudation in non-inflamed and inflamed air pouches. HYAL treatment of Cg-inflamed air pouch reduced the production of tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), leukotriene B4 (LTB4) and LTC4, whereas prostaglandins E2 (PGE2) and D2 (PGD2) concentrations were unchanged. Histological analyses showed that HYAL administration diminished cell infiltration in the air-pouch lining. In LPS-stimulated mesenteric microcirculation, HYAL usage decreased rolling and adhesion of leukocytes, but did not affect the blood vessels diameters. The results demonstrate that HYAL inhibited cellular recruitment, edema formation and pro-inflammatory mediators production, resulting in decreased adherence of leukocytes to blood vessels and tissue infiltration. Our data suggest that HYAL may be considered an effective candidate to ameliorate acute inflammation.


The sole rupture of flexor digitorum tendons to the index finger following volar locking plate fixation of distal radius fracture: A case report.
Distal radius fracture is a common injury, especially in elderly people, and internal fixation with volar locking plate (VLP) is becoming an increasingly popular technique for the management of displaced and/or unstable distal radius fractures. One of the most common complications of this treatment is the flexor tendon rupture, mostly of the flexor pollicis longus (FPL). While the rupture of flexor digitorum tendons to the index (FDI) mostly occurs concomitantly with the rupture of FPL after the treatment using volar plating for distal radial fracture, sole rupture of the FDI without FPL rupture is very rare. Here, we report a case of the sole rupture of FDI after volar locking plating and analyze its pathogenesis indicating that the lift-up of the distal ulnar edge of the plate related to the malcorrection of the fracture site is the culprit for this specific complication.


National Evaluation of HIV Service Resource Allocation in Tanzania.
Using time-driven activity-based costing (TDABC), we examined resource allocation and costs for HIV services throughout Tanzania at patient and facility levels. This national, cross-sectional analysis of 22 health facilities quantified costs and resources associated with 886 patients receiving care for five HIV services: antiretroviral therapy, prevention of mother-to-child transmission, HIV testing and counseling, voluntary medical male circumcision, and pre-exposure prophylaxis. We also documented total provider-patient interaction time, the cost of services with and without inclusion of consumables, and conducted fixed-effects multivariable regression analyses to examine patient- and facility-level correlates of costs and provider-patient time. Findings showed that resources and costs for HIV care varied significantly throughout Tanzania, including as a function of patient- and facility-level characteristics. While some variation may be preferable (e.g., needier patients received more resources), other areas suggested a lack of equity (e.g., wealthier patients received more provider time) and presented opportunities to optimize care delivery protocols.


Aromatic amines and the pathogenesis of lupus erythematosus.
The acetylation pathway of drug metabolism is the pathway by which aromatic amines and hydrazines are metabolized. Hydralazine and procainamide are aromatic amines or hydrazines that are metabolized by this pathway. Persons who are genetically slow acetylators are predisposed to development of lupus from these two drugs, suggesting that the free amine or hydrazine moiety is the inciting agent. When acetylprocainamide was given as an antiarrhythmic drug to patients with procainamide-induced lupus, the disease went into remission, indicating that the free amine group on procainamide had induced the disease. The genetic acetylator phenotypes of persons with idiopathic lupus were studied, and an excess of genetic slow acetylators was observed. This suggests amines or hydrazines induce some cases of this disease. One patient was identified with a lupus-like illness due to occupational exposure to hydrazine itself.


Postnatal vascular growth in the cerebellar cortex of normal and protein-deprived rats. Morphometric studies.
The postnatal vascular growth in the cortex of vermis cerebelli folium IX of normal and pre- and postnatally protein-deprived rats was examined. The rate of increase in specific length of vessels seem to parallel the functional maturation of neurons in all cortical layers. From the first postnatal week there is a higher specific length of vessels in the Purkinje cell layer than in the adjoining parts of the molecular and granular layers. The results indicate that such differences are present also after the period of rapid vascular growth. Protein deprivation appears to affect the postnatal increase in specific length of vessels less in the Purkinje cell layer than in the granular and molecular layer where a significant reduction compared to controls was seen for the interval 7--20 days of age. At 90 days of age no significant differences were seen between control and protein-deprived rats.