Association of waist and hip circumferences with the presence of hypertension and pre-hypertension in young South African adults.
Obesity is one of the most important risk factors for cardiovascular diseases (CVDs) including hypertension (HT) which is itself a risk factor for CVDs. Recent studies suggest that waist circumference (WC) may be more sensitive than Body Mass Index (BMI) in determining individual risk scores for CVDs. The current study aimed at investigating the influence of various anthropometric variables on blood pressure status in a group of students from Walter Sisulu University. Informed consent was obtained from 216 male and female students from Walter Sisulu University with a mean age of 22.1±0.2 years. Anthropometric measurements were performed for each participant. Blood pressure was measured in triplicates after 10 minutes of rest and the average computed. Just over 46% of the subjects were diagnosed with hypertension (HT) and pre-HT. The gender specific prevalence of HT/pre-HT was higher in the male (76.7%) compared to the female (30.5%) group. Waist circumference (WC) and total body fat (TBF) correlated significantly with blood pressure and HT/pre-HT in females but not males. ROC analysis showed that with the exception of waist-to-hip (WHR), all other anthropometric measurements and ratios studied can be used to discriminate blood pressure in young adult females not males. Increased WC and HC were associated with HT and pre-HT in young adult females in the Walter Sisulu University.


Stroke volume increase to exercise in chronic obstructive pulmonary disease is limited by increased pulmonary artery pressure.
This study was designed to investigate the mechanisms by which the right ventricle is able to increase stroke volume (SV) during exercise in chronic obstructive pulmonary disease (COPD). A second aim was to determine whether resting pulmonary artery pressure (Ppa) is predictive of exercise SV. 16 COPD patients (GOLD stages II-IV) underwent right heart catheterisation at rest and during exercise. In this group and eight age-matched controls resting and exercise right ventricular SV, end-diastolic volume (RVEDV) and end-systolic volume (RVESV) were assessed by magnetic resonance imaging (MRI). The exercise protocol during both measurements consisted of 3 minutes of cycling in supine position at 40% of maximal workload. In all patients mean Ppa increased significantly in response to exercise (21 (8) vs 33 (11) mm Hg, p<0.01), whereas pulmonary vascular resistance did not change. In the patient group, RVEDV (129 (42) vs 135 (42) ml, p<0.05) and SV (63 (13) vs 69 (14) ml, p<0.05) increased significantly from rest to exercise, but RVESV and RV ejection fraction remained unaltered. In contrast, in healthy controls SV is augmented (81 (22) vs 101 (28) ml, p<0.05) by both increased RVEDV (123 (33) vs 134 134) ml, p<0.05) and reduced RVESV (37 (9) vs 27 (10) ml, p<0.05). Resting mean Ppa was related to SV during exercise (r = -0.59, p<0.02). As a consequence of unaltered pulmonary vascular resistance to exercise in COPD patients, Ppa increases and SV response to exercise is limited and results from an increased preload only. Ppa at rest predicts exercise SV.


Plasma-insulator transition of spin-polarized hydrogen.
A mixed classical-quantum density functional theory is used to calculate pair correlations and the free energy of a spin-polarized hydrogen plasma. A transition to an atomic insulator phase is estimated to occur around r(s)=2.5 at T=10(4) K, and a pressure P is approximately equal to 0.5 Mbar. Spin polarization is imposed to prevent the formation of H2 molecules.


Mast cell degranulation is negatively regulated by the Munc13-4-binding small-guanosine triphosphatase Rab37.
Mast cell degranulation is regulated by the small guanosine triphosphatases (GTPases) Rab27a and Rab27b, which have distinct and opposing roles: Rab27b acts as a positive regulator through its effector protein Munc13-4, a non-neuronal isoform of the vesicle-priming Munc13 family of proteins, whereas Rab27a acts as a negative regulator through its effector protein melanophilin, by maintaining integrity of cortical filamentous actin (F-actin), a barrier to degranulation. Here we investigated the role of Rab37, one of the Rab GTPases assumed to be implicated in regulated secretion during mast cell degranulation. Using the RBL-2H3 mast cell line, we detected Rab37 on the secretory granules and found that antigen-induced degranulation was extensively increased by either knockdown of Rab37 or overexpression of a dominant-active Rab37 mutant. This hypersecretion phenotype in the Rab37-knockdown cells was suppressed by simultaneous knockdown of Rab27a and Rab27b or of Munc13-4, but not by disruption of cortical F-actin. We further found that Rab37 interacted with Munc13-4 in a GTP-independent manner and formed a Rab27-Munc13-4-Rab37 complex. These results suggest that Rab37 is a Munc13-4-binding protein that inhibits mast cell degranulation through its effector protein, by counteracting the vesicle-priming activity of the Rab27-Munc13-4 system.


An analysis of behavioural objectives in the teaching of anatomy from the results of marks in MCQs.
Since 1972 behavioural objectives have been presented to the students in the Department of Anatomy, University of Cape Town, for certain sections of their course but not for others. Questions set to students in certifying multiple choice examination from 1972 to 1976 were divided into two categories (a) those set on sections of the course with objectives and (b) those set on sections of the course without objectives, and analysed in terms of (i) student performance, (ii) discriminative ability of the questions. Significant differences are noted in student performance in these two categories which support the setting of student objectives. Student discrimination however is noted to be less effective in the category of questions on objectives, but not significantly so.


Early molecular events in the interaction of enveloped viruses with cells. I. A fluorescence and radioactivity study.
The fluorescence depolarization of 1,6-diphenyl-hexatriene was used to study the dynamic properties of the hydrophobic regions of the lipid envelopes of ortho- and paramyxoviruses as well as of the Rous sarcoma virus and of the membrane lipids of susceptible and nonsusceptible cells. The systems investigated where active and inactive influenza viruses, and NDV virus acting on chick embryo fibroblasts and Rous sarcoma virus acting on susceptible (C/E) and nonsusceptible (C/B) chicken-cell. Polarization degrees and mean rotational correlation times of DPH embedded in viral lipids were significantly higher than those of DPH in the cell membranes, due to a higher rigidity of the virus envelopes. When suspensions of labelled viruses and unlabelled cells or unlabelled viruses and labelled cells were mixed, a characteristic change of the fluorescence polarization degrees with time was observed. This behaviour was ascribed to label transfer from virus to cell membranes or vice versa. While the rate constants of label transfer from virus to cells and cells to virus were about the same for the penetrating viruses the rate constants of label release from inactive virus to cells were much larger than for the migration in the opposite direction.


Higher risk for influenza-associated pulmonary aspergillosis (IAPA) in asthmatic patients: A Swiss multicenter cohort study on IAPA in critically ill influenza patients.
Influenza-associated pulmonary aspergillosis (IAPA) is an important complication of severe influenza with high morbidity and mortality. We conducted a retrospective multicenter study in tertiary hospitals in Switzerland during 2017/2018 and 2019/2020 influenza seasons. All adults with PCR-confirmed influenza infection and treatment on intensive-care unit (ICU) for >24 h were included. IAPA was diagnosed according to previously published clinical, radiological, and microbiological criteria. We assessed risk factors for IAPA and predictors for poor outcome, which was a composite of in-hospital mortality, ICU length of stay ≥7 days, mechanical ventilation ≥7 days, or extracorporeal membrane oxygenation. One hundred fifty-eight patients (median age 64 years, 45% females) with influenza were included, of which 17 (10.8%) had IAPA. Asthma was more common in IAPA patients (17% vs. 4% in non-IAPA, P = 0.05). Asthma (OR 12.0 [95% CI 2.1-67.2]) and days of mechanical ventilation (OR 1.1 [1.1-1.2]) were associated with IAPA. IAPA patients frequently required organ supportive therapies including mechanical ventilation (88% in IAPA vs. 53% in non-IAPA, P = 0.001) and vasoactive support (75% vs. 45%, P = 0.03) and had more complications including ARDS (53% vs. 26%, P = 0.04), respiratory bacterial infections (65% vs. 37%, P = 0.04), and higher ICU-mortality (35% vs. 16.4%, P = 0.05). IAPA (OR 28.8 [3.3-253.4]), influenza A (OR 3.3 [1.4-7.8]), and higher SAPS II score (OR 1.07 [1.05-1.10]) were independent predictors of poor outcome. High clinical suspicion, early diagnostics, and therapy are indicated in IAPA because of high morbidity and mortality. Asthma is likely an underappreciated risk factor for IAPA.


Erythrocyte-bound immune complexes trigger the release of interleukin-1 from human monocytes.
We have demonstrated herein that immune complexes (IC) bound to O+ human erythrocytes trigger the release of interleukin-1 (IL-1) from human monocytes in vitro. The efficiency of monocytes stimulation by erythrocyte-bound IC is in sharp contrast to the lack of stimulation of monocytes by soluble IC. The IL-1 activity triggered by erythrocyte-bound IC was lower than that induced by insoluble IC or opsonized fluorescent latex beads, but was greater than that induced by anti-D-treated O+ human erythrocytes. The magnitude of IL-1 release induced by insoluble IC and erythrocyte-bound IC were similar up to 18 hr of incubation. The IL-1 activity decreased in the supernatant of monocytes exposed to erythrocyte-bound IC for 40 hr, while the activity of IL-1 induced by insoluble IC remained at a high level. The physiological and physiopathological significance of triggering IL-1 release by erythrocyte-bound IC are discussed.


Metal enrichment in sediments and bioaccumulation in edible bivalve Saccostrea cucullata from mudflats of a tropical estuary, India: a study to investigate toxicity and consumption suitability.
Mudflat sediment cores from lower (C-1), middle (C-2), and lower regions of upper (C-3) Chapora Estuary were investigated for grain size composition, total organic carbon, total and bioavailable Fe, Mn, Cu, Co, Ni, and Zn to assess metal contamination. Accumulation of metals by Saccostrea cucullata was studied to understand metal toxicity. In core C-1, Fe, Mn, Cu, Co, Ni, and Zn showed an average concentration of 1.73%, 648 ppm, 12 ppm, 12 ppm, 16 ppm, and 25 ppm, respectively, while core C-2 revealed their average concentration as 1.34%, 709 ppm, 10 ppm, 11 ppm, 13 ppm, and 28 ppm respectively. In core C-3, an average concentration of Fe, Mn, Cu, Co, Ni, and Zn was 1.72%, 907 ppm, 14 ppm, 13 ppm, 18 ppm, and 31 ppm respectively. Metals in sediments varied within the estuary due to hydrodynamics, discrepancies in metal sources and sand mining-induced remobilization of metals. Correlation and principal component analysis revealed Fe oxides as the key regulator of trace metal distribution in sediments along with clay and total organic carbon. Enrichment factor (EF) and geo-accumulation index (Igeo) showed more or less moderate contamination of Mn in core C-3. Also, the potential contamination index (PCI) indicated moderate contamination of Mn in core C-3 using the shale value as background concentration, whereas the application of upper crustal value revealed moderate contamination of Fe, Mn, Cu, Co, and Ni in core C-1, Mn, Co, and Ni in core C-2 and of Cu, Co, and Ni in core C-3. Mn was severely to very severely contaminated in core C-3. The mean probable effect level quotient and mean effect range median quotient showed medium to low-level contamination of Cu, Ni, and Zn. Metals were considerably allied to Fe-Mn oxide and organic/sulphide fractions which revealed their bioavailability. Mn was 36% in labile form (lower estuary) and indicated a high risk to biota. Mn, Ni, and Zn in Saccostrea cucullata exceeded the permissible limit and suggested toxicity and non-suitability for human consumption.


Computational complexity of inferring phylogenies from chromosome inversion data.
In systematics, parsimony methods construct phylogenies, or evolutionary trees, in which characters evolve with the least evolutionary change. The chromosome inversion, or polymorphism, parsimony criterion is used when each character of a population may exhibit homozygous or heterozygous states, but when the heterozygous state must evolve uniquely. Variations of the criterion concern whether or not the ancestral states of characters are specified. We establish that problems of inferring phylogenies by these criteria are NP-complete and thus are so difficult computationally that efficient optimal algorithms for them are unlikely to exist.


Collective circumcision performed in Sudan: evaluation in terms of early complications and alternative practice.
To present the results and complications of a collective circumcision application performed using a thermocautery device with the patient under local anesthesia in Sudan. A total of 5871 children aged 7 days to 17 years (mean 5.7 years) living in different regions of Sudan were circumcised from May 3 to 25, 2012. The circumcision procedures were performed by an experienced urologist and specialized healthcare officers with the patients under local anesthesia using a Thermo-Med TM 806 cautery device. The outcomes were evaluated in terms of early complications. None of the patients experienced bleeding that required surgical intervention. Mild hemorrhage developed in 3 cases but resolved with cauterization. One child developed tachycardia and syncope after the injection; however, no treatment was needed, and observation was sufficient. One patient developed a scrotal abscess, which was surgically treated. None of the patients developed complications from the local anesthetic agent. Although we are not in favor of collective circumcisions, our results have demonstrated that this type of circumcision can be performed safely with appropriate equipment and personnel in those regions in which circumcisions cannot be performed in a hospital setting for socioeconomic reasons.


Antigen identification using SEREX.
Serological analysis of recombinant cDNA expression libraries (SEREX) allows systematic identification of antigens recognized by the spontaneous autoantibody repertoire of patients with cancer and autoimmune disease. SEREX is based on screening of lambda phage expression libraries constructed from diseased tissue with the autologous patient's serum. This chapter provides the key protocols for SEREX immunoscreening and for downstream validation of autoantigens.


Performance of the Rowland Universal Dementia Assessment Scale in Screening Mild Cognitive Impairment at an Outpatient Setting.
Mild cognitive impairment (MCI) is defined as the symptomatic pre-dementia phase on the continuum of cognitive decline. Early recognition and application of potential interventions could prevent or delay the progression to dementia. The Rowland Universal Dementia Assessment Scale (RUDAS) shows good performance in the screening of dementia but has limited data regarding its diagnostic properties in the screening of MCI. The objectives of this study were to assess the psychometric properties of the Thai version of the RUDAS (RUDAS-Thai) in the screening of MCI, identify associated factors for the RUDAS performance, and determine the optimal cutoff point in detecting MCI. This was a cross-sectional study conducted from January 2020 to March 2021. Older patients at the outpatient clinic of an internal medicine department at a tertiary care hospital in Thailand were examined. Baseline data were collected, and the RUDAS-Thai was administered to each patient. Afterward, a geriatrician assessed each patient for MCI. A total of 150 patients were included, of whom 42 cases (28%) had MCI. The overall performance of the test using an area under the receiver operating characteristic curve (AUC) was 0.82 (95% confidence interval 0.75-0.89). At the optimal cutoff point of 25/30, the AUC was 0.76 with sensitivity and specificity of 76.2 and 75%, respectively. The educational level affected the test performance according to regression analysis. For patients with years of education ≤6 and >6, the optimal cutoff points were 25/30 and 26/30, respectively. The RUDAS-Thai performed well in differentiating patients with MCI from normal cognition; however, it was affected by educational level. A score of 25/30 or lower for persons with ≤6 years of education or 26/30 or lower for persons with higher than 6 years of education is the optimal cutoff point for indication of developing MCI.


Which Procedures Contribute Most to the System-Wide Burden of Postoperative Venous Thromboembolism?
While clinical risk assessment models examine patient-level characteristics that portend morbidity, there is a paucity of literature exploring which procedures contribute most to the system-wide burden of venous thromboembolism (VTE). We aimed to identify highly contributory procedures as potential targets for quality improvement. All patients in the 2020 National Surgical Quality Improvement Program (NSQIP) Public User File were included. Current Procedural Terminology (CPT) codes were analyzed individually and grouped by National Healthcare Safety Network groupings. We counted prevalence of VTE and calculated VTE rate for each CPT and for each grouping. Of 902,968 included patients, 7501 (.83%) sustained postoperative VTE. Of 2748 unique CPT codes, VTE occurred for 762 (28%). Twenty procedure codes (.7%) contributed 39% of the total VTE. VTE rates of these procedures ranged from high-volume procedures with low VTE rates such as laparoscopic cholecystectomy (.25%) and laparoscopic hysterectomy (.32%) to lower volume procedures with high VTE rate such as Hartmann's procedure (4.32%), Whipple procedure (3.85%), and distal pancreatectomy (3.82%). The CPT grouping with the most VTE was colon surgeries (1275/7501). A small number of procedures contributes to the system-wide burden of VTE. High-risk procedures are important targets for standardized prophylaxis protocols. For low-risk procedures, careful attention should be paid to patient-specific factors that may increase VTE risk such as obesity, cancer, or limited mobility, as many common procedures contribute greatly to the systemic burden of VTE. Overall, surveillance can perhaps be targeted on a smaller number of procedures, allowing for more efficient use of quality improvement resources.


Genotoxicity studies on selected organosilicon compounds: in vitro assays.
A series of 12 organosilicon compounds representing potential intermediates in the synthesis and degradation of polydimethylsiloxanes were evaluated for genotoxic potential with a battery of in vitro assays. Microbial assays included the Ames bacterial reverse mutation in Salmonella, mitotic gene conversion in Saccharomyces cerevisiae D4 and DNA repair in E. Coli pol A +/-. These assays were conducted with and without a metabolic activation system containing Aroclor 1254-induced rat-liver homogenate. Forward gene mutation, sister-chromatid exchange, DNA alkaline elution and chromosome aberration potential were evaluated in mouse lymphoma L5178Y tissue culture cells. The tissue culture assays were performed with and without metabolic activation mixture utilizing uninduced mouse-liver S-9. The use of this enzyme preparation was felt to more closely mimic the actual in vivo situation and to be more compatible with mouse cells employed in the assay. No evidence of gene mutation was observed. However, six of the 12 compounds evaluated demonstrated potential in vitro clastogenic (chromosome damaging) activity.


Contrast detection in infants with fragile X syndrome.
Studies have reported that a selective deficit in visual motion processing is present in certain developmental disorders, including Williams syndrome and autism. More recent evidence suggests a visual motion impairment is also present in adults with fragile X syndrome (FXS), the most common form of inherited mental retardation. The goal of the current study was to examine low-level cortical visual processing in infants diagnosed with FXS in order to explore the developmental origin of this putative deficit. We measured contrast detection of first-order (luminance-defined) and second-order (contrast-defined) gratings at two levels of temporal frequency, 0 Hz (static) and 4 Hz (moving). Results indicate that infants with FXS display significantly higher detection thresholds only for the second-order, moving stimuli compared to mental age-matched typically developing controls.


The roles of tumor-derived exosomes in non-small cell lung cancer and their clinical implications.
Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases, and it is one of the leading causes of cancer death in both men and women worldwide due to diagnosis in the advanced stage, rapid metastasis, and recurrence. At present, precision molecular targeted therapeutics directed toward NSCLC driven genes has made great progress and significantly improved the overall survival of patients with NSCLC, but can easily lead to acquired drug resistance. New methods are needed to develop real-time monitoring of drug efficacy and drug resistance, such as new molecular markers for more effective early detection and prediction of prognosis. Exosomes are nano-sized extracellular vesicles, containing proteins, nucleic acids and lipids, which are secreted by various cells, and they play an important role in the development of lung cancer by controlling a wide range of pathways. Tumor-derived exosomes are of great significance for guiding the targeted therapy of NSCLC and exosomes themselves can be a target for treatment. In this review, we describe the potential roles of tumor-derived exosomes and their clinical significance in NSCLC.


The Notch Intracellular Domain Has an RBPj-Independent Role during Mouse Hair Follicular Development.
Ligand-dependent activation, γ-secretase-processed cleavage, and recombining binding protein Jk (RBPj)-mediated downstream transcriptional activities of Notch receptors constitute the "canonical" Notch signaling pathway, which is essential for skin organogenesis. However, in Msx2-Cre mice, keratinocyte-specific deletion of the Rbpj gene in utero produced a significantly milder phenotype than either global Notch or γ-secretase loss. Herein, we investigated the underlying mechanisms for this apparent noncanonical signal using mouse genetics. We found no evidence that ligand back-signaling contributed to skin organogenesis. The perdurance of RBPj protein did not establish an epigenetic memory of a canonical signal in the youngest epidermal stem cells, and Notch targets were not derepressed. We provide evidence that γ-secretase-dependent but RBPj-independent Notch intracellular domain activity operating in the first hair follicles is responsible for a delay in follicular destruction, which results in lower serum thymic stromal lymphopoietin levels, milder B-cell lymphoproliferative disease, and improved survival in Msx2-Cre(+/tg);Rbpj(f/f) mice. Minimal amounts of the Notch intracellular domain were sufficient for rescue, which was not mediated by transcription, suggesting that the Notch intracellular domain is acting through a novel mechanism.


Effects of age and speed on the ankle-foot system's power during walking.
Structural and functional changes in the foot have been associated with age-related changes in gait mechanics, but walking speed may be a confounding factor in this relationship. The aim of this study was to investigate the effect of aging and speed on the ankle-foot power output during level walking. The effects of speed and aging on features of the mechanical power and work of the ankle and foot were quantified with a gait analysis of 24 young and 16 older individuals walking at different speeds. We observed gait speed having a significant effect on all the investigated features: peak power and positive and negative work of the ankle, foot, and sum of the ankle and foot (average effect size: 0.64 ± 0.22, from 0.26 to 0.87). We observed age having no effect on these same features (average effect size: 0.23 ± 0.12, from 0.03 to 0.39), with the exception of age's effect when combined with speed on the negative work of the foot. We performed additional analysis to illustrate how the speed can become a confounding factor to the understanding of the age effect on the gait biomechanics. Based on the influence of gait speed on the mechanical power of the ankle-foot system, it is essential that studies control for the effect of gait speed if there is interest in understanding age-related effects, particularly when studying frail older individuals.


Impact of two or less missing treatment sessions on tDCS clinical efficacy: results from a factorial, randomized, controlled trial in major depression.
Transcranial direct current stimulation (tDCS) is a neuromodulatory intervention with recent clinical trials showing promising results in major depression treatment. Although tDCS has some appealing characteristics (e.g., low cost, ease of use, and relatively benign profile of adverse effects), one important drawback of the technique is the need to deliver consecutive, repeated sessions for several weekdays. However, no study investigated whether absences during this acute treatment phase impact on tDCS efficacy, and, if so, whether absences should be considered dropouts, therefore increasing attrition. To examine this issue, we used data from a randomized, factorial, sham-controlled tDCS study that recruited 120 depressed patients. In this trial, the acute treatment phase consisted of ten consecutive sessions delivered once daily from Monday to Friday; two nonconsecutive missed visits were allowed, with extra tDCS sessions being performed to complete the original number of sessions. Our main finding was that the procedure of granting one to two absences during the acute treatment phase did not impact on tDCS antidepressant efficacy. Moreover, out of 103 completers, only 41 (39.8%) patients presented no missing visits and 25 (24.3%) presented two absences. These patients did not differ in clinical and demographic characteristics; thus, absences were probably circumstantial (e.g., traffic congestion, personal obligations). Absences during the acute tDCS treatment phase are common, which support the use of flexible schedules in future tDCS trials as to minimize attrition. Also, further studies should access whether higher number of absences can compromise optimal tDCS efficacy.


Volumetric reduction in left subgenual prefrontal cortex in early onset depression.
Subgenual prefrontal cortex (SGPFC) volume reduction has been reported in middle age adults with major depression (MD) or bipolar affective disorder. In this study, the authors test the hypothesis that SGPFC reduction is present in adolescent onset MD, and examine differences in the magnitude of reduction in younger versus older women. Subgenual prefrontal cortex volume was measured from T1 weighted MR images in (1) 30 young women with early onset MD versus eight age-matched controls, and (2) 18 middle aged women with recurrent MD versus nine age-matched controls. Left SGPFC volume was reduced in adolescent and middle aged females with depression. The magnitude of the difference between depressed and control groups (average 19% difference) was similar in younger and older women. Left subgenual cingulate volume reductions are present in young women with adolescent onset MD.


Endolymphatic hydrops severity in magnetic resonance imaging evidences disparate vestibular test results.
It has been suggested that in Ménière's disease (MD) a dissociated result in the caloric test (abnormal result) and video head-impulse test (normal result) probably indicates that hydrops affects the membranous labyrinth in the horizontal semicircular canal (HSC). The hypothesis in this study is that based on endolymphatic hydrops' cochleocentric progression, hydrops should also be more severe in the vestibule of these patients than in those for whom both tests are normal. 22 consecutive patients with unilateral definite MD were included and classified as NN if both tests were normal or AN if the caloric test was abnormal. MRI evaluation of endolymphatic hydrops was carried out with a T2-FLAIR sequence performed 4h after intravenous gadolinium administration. The laterality and degree of vestibular endolymphatic hydrops and the presence or absence of cochlear endolymphatic hydrops were recorded. Demographic data, audiometric and vestibular evoked myogenic potentials were collected, and video head-impulse and caloric tests were performed. Patients in both groups (NN and AN) were similar in terms of demographic data and hearing loss. The interaural asymmetry ratio was significantly higher for ocular and cervical VEMP in patients in the AN group. There was a significantly higher degree of hydrops in the vestibule of the affected ear of AN patients (χ2; p=0.028). Significant canal paresis in the caloric test is associated with more severe endolymphatic hydrops in the vestibule as detected with gadolinium-enhanced MRI and with a more severe vestibular deficit. 2a.


A novel function for zinc(II) in a nucleic acid-binding protein. Contribution of zinc(II) toward the cooperativity of bacteriophage T4 gene 32 protein binding.
The contribution of Zn(II) toward the binding of bacteriophage T4 gene 32 single-stranded nucleic acid-binding protein (gp32) has been examined by the use of two independent approaches. Studies carried out with successively longer oligonucleotides which have the general structure p(dT)n, where n is equal to 8, 16, 24, or 32 nucleotides, suggest that removal of Zn(II) decreases the cooperativity of binding by as much as 30-fold. Hence, whereas apo-gp32 and native gp32 have similar apparent affinities for the single-site lattice p(dT)8, native gp32 has an approximately 10-fold higher affinity compared to apo-gp32 for a two-site lattice, such as p(dT)16. In contrast to native gp32, where full cooperativity (in terms of the strength of a single gp32-gp32 interaction) is reached with only a two-site lattice, the cooperativity of apo-gp32 binding appears to increase approximately 4-fold upon going from a two- to a four-site lattice such as p(dT)32. The conclusion reached from these oligonucleotide studies agrees well with a series of titrations with polyribo(ethenoadenylic) acid, in 0.275-0.40 M NaCl. These latter studies indicate that the 6-38-fold higher affinity of native gp32 as compared to apo-gp32 for polyribo(ethenoadenylic) acid results primarily from the higher cooperativity of binding of native gp32. By stabilizing a specific subdomain within gp32 that is essential along with the NH2-terminal domain (residues 1-9), Zn(II) contributes from 20 to 50% of the free energy of cooperative gp32-gp32 interactions that occur along a polynucleotide lattice.


Development of new cleanup method of polychlorinated dibenzo-p-dioxins/dibenzofurans in fish by freezing-lipid filtration.
Freezing-lipid filtration as a new method has been developed for the rapid determination of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDDs/Fs) in biological samples. This method can effectively reduce the time of sample pretreatment, labor and amount of solvents compared with conventional methods. By freezing-lipid filtration procedure, about 90% of lipids in extract could be removed without any significant loss of PCDD/Fs. For further cleanup of extracts after freezing-lipid filtration, automatic parallel LC columns including silica gel, alumina and carbon columns were applied. During automatic parallel LC columns cleanup, most of co-extracted interferences such as residue lipids and fatty acids could be eliminated and dioxins could be separated from many other dioxin-like congeners such as polychlorinated biphenyls by this procedure. The extracts after cleanup were analyzed by high-resolution gas chromatography (HRGC)/high-resolution mass spectrometry (HRMS) using an isotope dilution method. The average recoveries and relative standard deviation (R.S.D.) of 17 native congeners in the spiked fish samples at 8-80 pg/g (n=3) were ranged between 85.3 and 117.2% and 5.7-20.3%, respectively.


Economic burden of osteoporosis-related hip fracture in Asia: a systematic review.
This review analyzes the economic costs of HF in Asia. The availability and quality of studies on the burden of osteoporosis in Asia are very scarce. There is a need to encourage more quality cost of osteoporosis studies based on standardized methods to convince healthcare authorities in implementing appropriate strategies. Osteoporosis fractures, especially hip fractures, impose large economic costs to governments and societies. This review aimed to systematically analyze available evidence on healthcare costs associated with osteoporosis-related hip fractures (HF) in Asia. Articles were systematically sought from databases including PubMed, EMBASE, and EBSCOHost between 2000 and 2015. Total costs associated with HF care, the cost components, and length of stays were retrieved and analyzed. Study designs were also qualitatively analyzed. The availability of published studies on economic burden of HF in Asia is severely lacking with only 15 articles met the inclusion criteria. Even among the included studies, only two studies reported comprehensive costs evaluating all costs including indirect or intangible costs. Most studies satisfactorily reported criteria for conducting economic evaluation, but large variations existed in the methodological design. Due to study design and other influencing factors, large variation in the cost of HF treatment from US$774 to US$14,198.90 (median S$2943), representing an average of 18.95% (range: 3.58-57.05%) of the countries' 2014 GDP/capita, was observed. This highlighted the heavy burden of managing HF in Asia with about 40% of the included studies reported using more than one third of GDP/capita. There is a paucity of burden of illness studies of osteoporosis in the Asian region. For the few available studies, there was a lack of standardization in methodological approach in evaluating the economic burden of the disease. There is a need to encourage more quality burden of illness studies of osteoporosis to inform policymakers in healthcare planning.


Co-capping of ras proteins with surface immunoglobulins in B lymphocytes.
Cellular ras genes encode a family of membrane-associated proteins (p21ras) that bind guanine nucleotide and possess a low intrinsic GTPase activity. The p21ras proteins are ubiquitously expressed in mammalian cells and are thought to be involved in a growth-promoting signal transduction pathway; their mode of action, however, remains unknown. The ligand-induced movement of cell-surface receptors seems to be a primary event in the transduction of several extracellular signals that control cell growth and differentiation. In B lymphocytes, surface immunoglobulin receptors crosslinked by antibody or other multivalent ligands form aggregates called patches, which then collect into a single assembly, a cap, at one pole of the cell. This process constitutes the initial signal for the activation of a B cell. Here we show by immunofluorescence microscopy that p21ras co-caps with surface immunoglobulin molecules in mouse splenic B lymphocytes. In contrast, no apparent change in the distribution of p21ras occurs during the capping of concanavalin A receptors. The redistribution of p21ras is apparent at the early stages (patching) of immunoglobulin capping and is inhibited by metabolic inhibitors and the cytoskeleton-disrupting agents colchicine and cytochalasin D. The distribution of another membrane-associated guanine nucleotide-binding regulatory protein, the Gi alpha subunit, is not affected by surface immunoglobulin capping. These findings demonstrate that p21ras can migrate in a directed manner along the plasma membrane and suggest that p21ras may be a component of the signalling pathway initiated by the capping of surface immunoglobulin in B lymphocytes.


[A simple and reliable atrial pacemaker electrode: technique of transvenous implantation and clinical results with a metal hook electrode (author's transl)].
At present only about 1% of all implanted pacemakers are atrial triggered ones, although an indication for them exists in about 77% of cases. This disproportion is due to an overestimate of the difficulties encountered in fixing the electrode. The electrode developed by Irnich has now been modified to provide good fixation for atrial stimulation, as well as recording of atrial potentials. Preliminary results in 20 patients have been favourable. Over a seven-month observation period there have been no instances of dislocation or loss of effective stimulation.


Explicit Spatializing Heat-Exposure Risk and Local Associated Factors by coupling social media data and automatic meteorological station data.
Extremely high temperatures, a major cause for weather-related public health issues, are projected to intensify and become more frequent. To mitigate the adverse effects, a low-cost and effective risk assessment method should be developed. Therefore, we applied automatic meteorological station data and population mobility data to develop a high spatiotemporal resolution temperature risk assessment method. The population mobility analysis results showed the working/residential complex pattern in Tianhe District, with hotspots of spatial clustering located in the north, southwest, and southeast of the study area. Taking the population mobility patterns into consideration, high-temperature risk assessment results with a resolution of 100 m were obtained. The total mortality cases in 2014 and 2015 were used to validate this result. The validation showed that the total mortality in the high-temperature risk areas accounted for over 36% of that in Tianhe District. Thus, the method introduced in this study is capable of reflecting weather-related risk. Furthermore, the high-temperature risk assessment results showed that most of the risky areas were located in the southwest of the study area. Two peak times of the risk areas were determined, being before dawn and in the evening. Compared with the risk areas during weekdays, those at weekends expanded. In addition, we used the geographically weighted regression model to investigate the potential influencing factors. Individual factor contributed more than 22.4% to the spatial distribution of heat exposure. Catering services, transportation services, and living services were higher than others, with mean R2 values of 0.28, 0.23, and 0.25, respectively. More than 47.9% of spatial distribution of heat exposure was attributed to joint function of influencing factors, with global R2 ranged from 0.23 to 0.34. Our research introduces a spatial-specific method to quantitatively assess high-temperature risk. Moreover, the mechanisms behind the spatial distribution of the high-temperature risk were discussed. The theoretical and management implications can help urban designers and energy governors to develop useful strategies to mitigate weather-related public health risks.


Detection of apoptosis of bone cells in vitro.
Studies during the last decade demonstrated that apoptosis is as important as mitosis for the growth and maintenance of the skeleton and provided information on the significance and molecular regulation of apoptosis of bone cells. It is now known that: (1) all osteoclasts die by apoptosis after completing a bone resorption cycle; (2) the majority of osteoblasts also die, whereas the remainder become lining cells or osteocytes; and (3) osteocytes, although long-living cells, also can die prematurely. Furthermore, mounting evidence indicates that systemic hormones, local growth factors, cytokines, and pharmacological agents, as well as mechanical forces regulate the rate of bone cell apoptosis. This chapter summarizes the methods developed in the last few years to examine apoptosis of cultured bone cells and identify the signaling pathways and molecules involved in apoptosis regulation by diverse skeletal stimuli.


The effects of nerve growth factor on the development of septal cholinergic neurons in reaggregate cell cultures.
Recent studies suggest that nerve growth factor is present within the central nervous system where it may exert selective trophic effects on cholinergic neurons. We have measured the effects of nerve growth factor on septal cholinergic neurons in three-dimensional reaggregating cell cultures, a system which closely simulates the cellular environment in situ. Septal cells obtained from 15-day-old mouse embryos were dissociated into a single cell suspension and then allowed to reaggregate in culture in a rotary incubator shaker. After 17 days in culture, half of the reaggregates from a flask were sonicated for measurement of choline acetyltransferase activity, and the remaining reaggregates were processed for acetylcholinesterase histochemistry. Addition of nerve growth factor to medium containing septal reaggregates resulted in greater than a three-fold increase in choline acetyltransferase activity and in the number of acetylcholinesterase-positive cells, as well as an enhancement in the staining of acetylcholinesterase-positive fibers. All of these effects of nerve growth factor could be neutralized by antibodies to nerve growth factor. In order to evaluate the possible role of endogenous hippocampal-derived nerve growth factor, antiserum to nerve growth factor was added to the culture media containing septal-hippocampal coaggregates. After 21 days in culture, the presence of nerve growth factor antibodies did not qualitatively affect the pattern or density of cholinergic fibers observed. Synapse formation between cholinergic axons and hippocampal target cells was still in evidence as revealed by electron microscopy. However, there was a modest decrease in choline acetyltransferase activity (20%) and cholinergic cell number (30%) when compared with coaggregates grown in culture medium either without nerve growth factor antiserum or with non-immune serum. The magnitude of these effects was markedly less than the effects observed when exogenous nerve growth factor was added to septal cells grown alone in reaggregate culture. These results suggest that nerve growth factor may play a role during central cholinergic development, but that additional trophic mechanisms are likely to be required.


Single-atomic-site platinum steers photogenerated charge carrier lifetime of hematite nanoflakes for photoelectrochemical water splitting.
Although much effort has been devoted to improving photoelectrochemical water splitting of hematite (α-Fe2O3) due to its high theoretical solar-to-hydrogen conversion efficiency of 15.5%, the low applied bias photon-to-current efficiency remains a huge challenge for practical applications. Herein, we introduce single platinum atom sites coordination with oxygen atom (Pt-O/Pt-O-Fe) sites into single crystalline α-Fe2O3 nanoflakes photoanodes (SAs Pt:Fe2O3-Ov). The single-atom Pt doping of α-Fe2O3 can induce few electron trapping sites, enhance carrier separation capability, and boost charge transfer lifetime in the bulk structure as well as improve charge carrier injection efficiency at the semiconductor/electrolyte interface. Further introduction of surface oxygen vacancies can suppress charge carrier recombination and promote surface reaction kinetics, especially at low potential. Accordingly, the optimum SAs Pt:Fe2O3-Ov photoanode exhibits the photoelectrochemical performance of 3.65 and 5.30 mA cm-2 at 1.23 and 1.5 VRHE, respectively, with an applied bias photon-to-current efficiency of 0.68% for the hematite-based photoanodes. This study opens an avenue for designing highly efficient atomic-level engineering on single crystalline semiconductors for feasible photoelectrochemical applications.


A focus on leucine in the nutritional regulation of human skeletal muscle metabolism in ageing, exercise and unloading states.
Muscle protein synthesis (MPS) and muscle protein breakdown (MPB) are influenced through dietary protein intake and physical (in)activity, which it follows, regulate skeletal muscle (SKM) mass across the lifespan. Following consumption of dietary protein, the bio-availability of essential amino acids (EAA), and primarily leucine (LEU), drive a transient increase in MPS with an ensuing refractory period before the next MPS stimulation is possible (due to the "muscle full" state). At the same time, MPB is periodically constrained via reflex insulin actions. Layering exercise on top of protein intake increases the sensitivity of SKM to EAA, therefore extending the muscle full set-point (∼48 h), to permit long-term remodelling (e.g., hypertrophy). In contrast, ageing and physical inactivity are associated with a premature muscle full set-point in response to dietary protein/EAA and contractile activity. Of all the EAA, LEU is the most potent stimulator of the mechanistic target of rapamycin complex 1 (mTORC1)-signalling pathway, with the phosphorylation of mTORC1 substrates increasing ∼3-fold more than with all other EAA. Furthermore, maximal MPS stimulation is also achieved following low doses of LEU-enriched protein/EAA, negating the need for larger protein doses. As a result, LEU supplementation has been of long term interest to maximise muscle anabolism and subsequent net protein accretion, especially when in tandem with resistance exercise. This review highlights current knowledge vis-à-vis the anabolic effects of LEU supplementation in isolation, and in enriched protein/EAA sources (i.e., EAA and/or protein sources with added LEU), in the context of ageing, exercise and unloading states.


Effects of rosuvastatin on serum asymmetric dimethylarginine levels and atrial structural remodeling in atrial fibrillation dogs.
Circulating asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, is increased in atrial fibrillation (AF). The purpose of this study was to investigate the effects of rosuvastatin on serum ADMA levels and atrial structural remodeling in AF dogs induced by chronic rapid atrial pacing. Twenty dogs were randomly divided into the sham-operated (n=6), control (n=7), or rosuvastatin (n=7) groups. Sustained AF was induced by rapid pacing of the right atrium at 400 beats per minute for 6 weeks. Rosuvastatin was administered orally (1 mg/kg d) for 3 days before rapid pacing and was continued for 6 weeks. Transthoracic and transesophageal echocardiography were performed to detect left atrial structure and function. Serum levels of nitric oxide and ADMA were measured. Interstitial fibrosis and cardiomyocyte apoptosis in the atria were also identified. After 6 weeks, compared with the control group, dramatic smaller left atrium and left atrial appendage volumes and higher atrial contractile function were observed in the rosuvastatin group. Serum nitric oxide concentration was increased, whereas ADMA was decreased in the rosuvastatin group compared with the control group. The percentages of interstitial fibrosis and atrial apoptosis in the control group were significantly higher than those in the sham-operated group, and rosuvastatin attenuated these changes induced by atrial rapid pacing. A short course of rosuvastatin treatment decreased apoptosis and prevented atrial structural remodeling in association with a decrease in ADMA levels in AF dogs.


Digestion-Promoting Effects and Mechanisms of Dashanzha Pill Based on Raw and Charred Crataegi Fructus.
Emerging evidence suggests that a high-fat diet (HFD) can influence endoplasmic reticulum (ER) stress and gut microbiota. Crataegi Fructus is a traditional Chinese herb widely used in formulas for dyspepsia, with Dashanzha Pill composed of raw Crataegi Fructus (DR) being a representative drug. Processing products of Crataegi Fructus, however, have a stronger pro-digestive effect, and we hypothesized that Dashanzha Pill composed of charred Crataegi Fructus (DC) is more effective. We found that the contents of glucose 1-phosphate and luteolin in DR and DC were substantially different via ultra-high performance liquid chromatography-hybrid quadrupole-Orbitrap high-resolution mass spectrometry. DC outperformed DR in improving histopathological changes, increasing gastrin and motilin, and decreasing vasoactive intestinal peptides in rats with HFD induced dyspepsia. Fecal microbiota analysis revealed that DC could restore the disturbed intestinal microbiota composition, including that of Bacteroides, Akkermansia, and Intestinimonas to normal levels. Furthermore, DC significantly reduced the mRNA and protein levels of glucose-regulated protein 78, protein kinase R-like ER kinase, and eukaryotic initiation factor 2α. Taken together, DC outperformed DR in relieving dyspepsia by regulating gut microbiota and alleviating ER stress.


Polymorphisms of the GSTM1, GSTP1, MPO, XRCC1, and NQO1 genes in Chinese patients with non-small cell lung cancers: relationship with aberrant promoter methylation of the CDKN2A and RARB genes.
An association between functional polymorphisms of genes resulting in decreased detoxification of carcinogens or DNA repair and aberrant promoter methylation is an attractive hypothesis in lung carcinogenesis. The genotypes at polymorphic sites of the glutathione S-transferase (GST) M1 (null/wildtype) and P1 (nucleotide 2627 A/G), myeloperoxidase (MPO) (nucleotide -463 G/A), X-ray repair cross-complementing group 1 (XRCC1) (nucleotides 26304 C/T; 28152 G/A), and NADPH quinine oxidoreductase (NQO1) (nucleotide 609 C/T) genes in 75 Chinese patients with non-small cell lung cancer (NSCLC) were characterized with polymerase chain reaction-restriction fragment length polymorphism. Results were correlated with aberrant methylation of the CDKN2A (alias p16(INK4A)), retinoic acid receptor beta (RARB), methylguanine-DNA methyltransferase (MGMT), and death-associated-protein (DAP) kinase genes in the tumors. In comparison with an age-matched control, none of the polymorphisms were associated with increased lung cancer risks. In male patients, however, the MPO -463 GG homozygous state was associated with CDKN2A (alias p16(INK4A)) methylation (odds ratio OR=3.63, 95% confidence interval CI=1.26-10.51), and the XRCC1 26304 T allele in the heterozygous/homozygous state was associated with methylation of CDKN2A (OR=6.13, 95% CI=1.55-24.16) and RARB (OR=7.67, 95% CI=1.62-36.18). In female patients, the GSTP1 G allele in the heterozygous/homozygous state was associated with RARB methylation (OR=18.0, 95% CI=0.76-427.29). These results showed that functional deficiencies in metabolic pathways that protect cells from carcinogen induced DNA damage might be linked to aberrant promoter methylation of the CDKN2A and RARB genes during lung carcinogenesis.


A new radiometric assay for the quantitation of surface-bound IgG on sensitized erythrocytes.
We have developed a sensitive, straightforward method for the quantitation of surface-bound IgG on sensitized erythrocytes. The assay is based on the consumption by sensitized cells of anti-IgG antiserum. The remaining anti-IgG is quantitated in a second incubation by precipitation with 125I-IgG in the presence of polyethylene glycol. Calibration curves for this assay were constructed using known amounts of unlabeled IgG. The method can be performed in microtitre plates and eliminates the use of purified anti-erythrocyte antibodies, or highly purified specific anti-IgG antisera. The results were completely consistent with those of immunofluorescence assays, but our method was much more sensitive, less than 500 molecules of IgG per cell being detected reproducibly. The technique is not laborious and takes much less time than previously described methods with similar sensitivity. As an example of the applicability of this test, the implications of ligand density for the detection by EA rosetting of Fc receptors on human monocytes are shown. The results suggest that a large variation exists in the affinity of the different types of Fc receptors for their ligands.


Effects of iron manipulation on trace elements level in a model of colitis in rats.
Trace elements (TE) metabolism is altered in inflammatory bowel diseases. TE (zinc and copper) are constituents of antioxidant enzymes. Iron is involved in the pathogenesis of chronic inflammation. The aim was to evaluate zinc and copper status and the effects of iron manipulation in experimental colitis. Twenty-four male Sprague-Dawley rats were divided into four groups: standard diet, iron-deprived diet, iron-supplemented diet, and sham-treated controls. Macroscopic damage was scored. DNA adducts were measured in the colon. Liver and colonic concentration of TE were measured. Macroscopic damage was reduced in iron-deprived groups and increased in iron-supplemented rats. Damage to the DNA was reduced in iron-deprived groups and increased in iron-supplemented groups. Liver and colonic iron concentrations were reduced in iron-deprived and increased in iron-supplemented rats. Liver zinc concentration was reduced after supplementation whereas colonic levels were similar in controls and treated rats. Liver copper concentration was reduced in all the colitic groups except in the iron-supplemented group whereas colonic concentration was increased in iron-deprived rats. Iron deprivation diminishes the severity of DNBS colitis while supplementation worsens colitis. Zinc and copper status are modified by iron manipulation.


Efficient biocatalyst of L-DOPA with Escherichia coli expressing a tyrosine phenol-lyase mutant from Kluyvera intermedia.
L-DOPA (L-dihydroxyphenylalanine) is a promising drug for Parkinson's disease and thereby has a growing annual demand. Tyrosine phenol-lyase (TPL)-based catalysis is considered to be a low-cost yet efficient route for biosynthesis of L-DOPA. TPL is a tetrameric enzyme that catalyzes the synthesis of L-DOPA from pyrocatechol, sodium pyruvate, and ammonium acetate. The implementation of TPL for L-DOPA production has been hampered and the need for the most efficient TPL source with higher L-DOPA production and substrate conversion rate is prevailing. This study involves identifying a novel TPL from Kluyvera intermedia (Ki-TPL) and displayed a robust expression in Escherichia coli. The recombinant strain YW000 carrying Ki-TPL proved strong catalytic activity with a highest L-DOPA yield compared with 16 other TPLs from different organisms. With a further aim to improve this efficiency, random mutagenesis of Ki-TPL was performed and a mutant namely YW021 was obtained. The whole cells of YW021 as biocatalyst yielded 150.4 g L-1 of L-DOPA with a 99.99 % of pyrocatechol conversion at the optimum condition of pH 8.0 at 25 °C, which is the highest level reported to date. Further, the homology modeling and structural analysis revealed the mutant residues responsible for the extensive L-DOPA biosynthesis.


Predictors of Decision Regret among Caregivers of Older Canadians Receiving Home Care: A Cross-Sectional Online Survey.
Background. In Canada, caregivers of older adults receiving home care face difficult decisions that may lead to decision regret. We assessed difficult decisions and decision regret among caregivers of older adults receiving home care services and factors associated with decision regret. Methods. From March 13 to 30, 2020, at the outbreak of the COVID-19 pandemic, we conducted an online survey with caregivers of older adults receiving home care in the 10 Canadian provinces. We distributed a self-administered questionnaire through Canada's largest and most representative private online panel. We identified types of difficult health-related decisions faced in the past year and their frequency and evaluated decision regret using the Decision Regret Scale (DRS), scored from 0 to 100. We performed descriptive statistics as well as bivariable and multivariable linear regression to identify factors predicting decision regret. Results. Among 932 participants, the mean age was 42.2 y (SD = 15.6 y), and 58.4% were male. The most frequently reported difficult decisions were regarding housing and safety (75.1%). The mean DRS score was 28.8/100 (SD = 8.6). Factors associated with less decision regret included higher caregiver age, involvement of other family members in the decision-making process, wanting to receive information about the options, and considering organizations interested in the decision topic and health care professionals as trustworthy sources of information (all P < 0.001). Factors associated with more decision regret included mismatch between the caregiver's preferred option and the decision made, the involvement of spouses in the decision-making process, higher decisional conflict, and higher burden of care (all P < 0.001). Discussion. Decisions about housing and safety were the difficult decisions most frequently encountered by caregivers of older adults in this survey. Our results will inform future decision support interventions. This is one of the first studies to assess decision regret among caregivers of older adults receiving home and community care services and to identify their most frequent difficult decisions.Difficult decisions were most frequently about housing and safety. Most caregivers of older adults in all 10 provinces of Canada experienced decision regret.Factors associated with less decision regret included higher caregiver age, the involvement of other family members in the decision-making process, wanting to receive information about the options, considering organizations interested in the decision topic, and health care professionals as trustworthy sources of information. Factors associated with more decision regret included mismatch between the caregiver's preferred option and the decision made, the involvement of spouses in the decision-making process, higher decisional conflict, and higher burden of care.


Underweight and malnutrition in home care: A multicenter study.
This study aimed to provide representative figures about the prevalence of underweight and malnutrition among home care clients, and to determine the associated risk factors and the provided nutritional nursing interventions. In 2012, a multicenter point prevalence study was conducted among 878 randomly selected clients from 100 randomly selected home care services across Germany. Following a standardized study protocol, demographics, nutritional assessments (Body Mass Index, Malnutrition Universal Screening Tool (MUST), Mini nutritional Assessment - short form (MNA-sf), nurses' clinical judgment on nutritional status) and interventions were assessed. Common nutritional risk factors for underweight and malnutrition were analyzed in a logistic regression model. Malnutrition figures varied between 4.8% (MNA-sf) and 6.8% (MUST), underweight between 8.7% (BMI < 20 kg/m(2)) and 10.2% (clinical judgment). Missing values were high in both malnutrition assessments (MNA-sf 48.8%, MUST 39.1%) due to a lack of information on many clients' loss of weight within the past 3-6 months. Regular weighing was performed in 33.6-57.3% of all clients, depending on weight and nutritional status. Mental overload (OR 8.1/4.4), needs help with feeding (OR 5.0/2.8) and loss of appetite (OR 3.6/3.9) were highly associated with malnutrition/underweight. Malnutrition and underweight are important issues in home care clients. Regular weighing should be performed in all home care clients so that a potential weight loss can be detected in time.


A critical gerontological framing analysis of persistent ageism in NZ online news media: Don't call us "elderly"!
This study presents a critical gerontological framing analysis of how and why the term "elderly" is presently used in online news media articles in New Zealand, and the potential consequences of such constructions. The article contributes to conceptual debates on aging and later life research by challenging ageist (albeit perhaps subconscious) media practices. Analysis of online news media articles in New Zealand was conducted over an 18-month period before, during and since COVID. Findings revealed that "elderly" was framed as powerless, in predominantly negative (74% of data) stereotypical messages about older adults. The remaining positive stereotypes (26%) used human impact framing. Narratives of "elderly" as vulnerable, declining and a 'burden' may be dependent on several factors, including the media's role in both constructing and reflecting ageist societal attitudes and actions towards older adults. Recommendations are given to support re-framing societal attitudes towards age equality through non-discriminatory, respectful language.


Intraobserver and interobserver variability in first-trimester transvaginal ultrasound cervical length.
Objectives: To determine intraobserver and interobserver variability in the measurement of different cervical length (CL) components at the first trimester (endocervical canal and isthmus), describe the optimum measurement method (single line or two lines) and establish a normality curve of first trimester CL in our population.Methods: Women who attended the first-trimester US scan, between 11.0 and 13.6 weeks of gestation at Vall d'Hebron Universitary Hospital, Barcelona, Spain were included. Inclusion criteria were singleton pregnancies in women over 18 years of age, no gestational complications, uterine malformations or uterine surgery. Lengths of the endocervical canal and uterine isthmus were measured using two methods.Results: Both methods for endocervical canal measurement, single line and two lines, showed low intraobserver variability between examiners, with no statistical differences in the majority of measurements. A correct correlation existed between examiners using the single-line two-line measurements, with a concordance correlation coefficient of 0.76.Conclusions: Cervical length in the first trimester was reproducible for the same physician and between different physicians; however, it is essential to ensure examiners receive adequate training in the technique.


The impact of nutritional counseling on thyroid disorders in head and neck cancer patients after (chemo)radiotherapy: results from a prospective interventional trial.
To analyze the impact of nutritional counseling on the development of hypothyroidism after (chemo)radiotherapy in head and neck cancer patients to propose a new normal tissue complication probability (NTCP) model. At baseline, at the end of (chemo)radiotherapy, and during follow-up, thyroid-stimulating hormone (TSH) with free thyroxin (fT3 and fT4), nutritional status, and nutrient intake were prospectively analyzed in 46 out of 220 screened patients. Patients received (chemo)radiotherapy within an intervention (individual nutritional counseling every 2 weeks during therapy) and a control group (no nutritional counseling). Overall median follow-up was 16.5 [IQR: 12; 22] months. Fourteen patients (30.4%) presented with hypothyroidism after 13.5 [8.8; 17] months. During (chemo)radiotherapy, nutritional status worsened in the entire cohort: body mass index (p < 0.001) and fat-free mass index (p < 0.001) decreased, calorie deficit (p = 0.02) increased, and the baseline protein intake dropped (p = 0.028). The baseline selenium intake (p = 0.002) increased until the end of therapy. Application of the NTCP models by Rønjom, Cella, and Boomsma et al. resulted in good performance of all three models, with an AUC ranging from 0.76 to 0.78. Our newly developed NTCP model was based on baseline TSH and baseline ferritin. Model performance was good, receiving an AUC of 0.76 (95% CI: 0.61-0.87), with a sensitivity of 57.1% and specificity of 96.9% calculated for a Youden index of 0.73 (p = 0.004; area = 0.5). Baseline TSH and ferritin act as independent predictors for radiotherapy-associated hypothyroidism. The exclusion of such laboratory chemistry parameters in future NTCP models may result in poor model performance.


Chronically isolated cerebral hemisphere in the cat: effects of parenteral administration of penicillin.
Brain electrical activity (EEG) of cats with chronic, complete, neural isolation of the cortex of an entire cerebral hemisphere was studied prior to and following intramuscular administration of penicillin (250,000--300,000 units/kg). The most prominent feature of the isolated hemisphere's EEG during base-line recordings was irregular, aperiodic, slow-wave activity with intermittent sharp waves and occasional spike discharges. Following penicillin administration there was an increase in the number of spikes and sharp waves in the isolated hemisphere and an increase in amplitude of the background activity. Simultaneously recorded EEG activity of the intact hemisphere demonstrated the paroxysmal burts of sharp waves or spike-wave complexes that have been described previously in normal animals. There was complete independence of the electrical activity recorded from intact and isolated hemispheres. These results indicate that intramuscularly administered penicillin can exert a convulsant effect on cortical structures in the absence of subcortical connections, but the generalized epileptiform activity seen in normal animals is dependent on thalamocortical connections.


Harmful lifestyles on orthopedic implantation surgery: a descriptive review on alcohol and tobacco use.
Alcohol abuse and smoking habits have adverse effects on bone health and are a risk factor for osteoporosis, fractures and impaired fracture repair. Osteointegration processes around implanted biomaterials involve a coordinated cascade of complex events that are very similar to those occurring during fracture repair and require a suitable microenvironment and the coordinated action of cells and signal molecules. Therefore, diseases and harmful lifestyles that impair the normal bone healing process can reduce the success of implant surgery and may negatively influence the osteointegration of prostheses and implant devices for fracture fixation such as screws, nails and plates. Understanding the effects of harmful lifestyles on bone implant osteointegration is important for successful implant therapy, orthopedic reconstructive surgery and tissue-engineered-based therapies. However, the mechanisms by which smoking and alcoholism affect bone metabolism, bone mass and the balance of bone resorption and formation, also in the presence of an orthopedic implant, are not completely understood and remain inadequately elucidated. This review aims to analyze in vitro and in vivo studies regarding orthopedic implant integration in the presence of tobacco smoking and alcohol consumption with a focus on pathophysiology and local or systemic mechanisms of action on bone.


Atrophic rhinitis in swine fattener herds. A field study of the spread of the disease with infected pigs bought at market.
In three different fattener herds pigs primarily AR infected as baby piglets were mixed in the fattening units with healthy pigs at an age of 11--13 weeks. Snout alterations were registered on cut snouts at a slaughter weight of about 70 kg. Severe AR was registered in the groups of primarily infected pigs (Tables I--III). The incidence of snout alterations was lower in the groups of pigs infected at an age of 11--13 weeks, but was much higher than in the groups of healthy control pigs or in the normal pig population in the region (Table IV). The results indicate that pigs infected at a rather late age in the fattening units can develop severe atrophic rhinitis.


Hepatitis B control in China: knowledge and practices among village doctors.
To guide development of a hepatitis B control program in China, we investigated village doctors' sterilization practices, injection use, vaccination levels, and knowledge and counseling skills. The head doctor from each village health station in a rural county (n = 260) completed a self-administered questionnaire. Of the respondents, 94.2% reported adequate sterilization of needles; however, inadequate sterilization of syringes and acupuncture needles was common. Injections were found to be frequent and profitable. Of head doctors, 16.2% reported that most infants in their villages are vaccinated against hepatitis B. There was very high knowledge of modes of hepatitis B transmission, but it was not used to formulate advice for a hypothetical carrier. Knowledge of the consequences, prevalence, and use of condoms to prevent sexual transmission was lower. The sterilization of acupuncture needles, reuse of syringes, and frequent injections are practices that may transmit the hepatitis B virus. Research into issues of vaccine acceptance is needed to expand immunization. A review of treatment practices and better training in counseling for village doctors is suggested.


Fenamates and diltiazem modulate lipid-sensitive mechano-gated 2P domain K(+) channels.
A swelling-activated, background K(+) current in the corneal epithelium is characteristically activated by fenamates and inhibited by diltiazem. Fatty acids also stimulate this current, indicating that its origin is a lipid-sensitive mechano-gated 2P domain K(+) channel. In the present study, modulation of TREK-1, TREK-2, and TRAAK channels by fenamates and diltiazem was examined. TREK-1, TREK-2, and TRAAK currents transiently expressed in COS-7 cells were recorded by the perforated-patch configuration. As previously reported, arachidonic acid (20 microM) stimulated all of these channels, and a volatile anesthetic, halothane (1 mM) augmented TREK-1 and TREK-2 but not TRAAK. Flufenamic acid (FA, 100 microM), niflumic acid (NA, 100 microM), and mefenamic acid (MA, 100 microM) markedly stimulated TREK-1, TREK-2, and TRAAK. The potency sequence for the activation of TREK-1 and TREK-2 was FA > NA = MA, and the potency sequence for the activation of TRAAK was FA = NA > MA. Diltiazem (1 mM) inhibited TREK-1 and TREK-2, but not TRAAK. In conclusion, fenamates are openers of the lipid-sensitive mechano-gated 2P domain K(+) channels, and diltiazem may be a specific blocker for TREK. These novel findings could help to further understand channel functions of the mechano-gated 2P domain K(+) channels.


Lead isotopic analysis of infant bone tissue dating from the Roman era via multicollector ICP-mass spectrometry.
Archaeological samples originating from a cemetery of a Roman settlement, Pretorium Agrippinae (1st-3rd century A.D.), excavated near Valkenburg (The Netherlands) have been subjected to Pb isotopic analysis. The set of samples analysed consisted of infant bone tissue and possible sources of bone lead, such as the surrounding soil, garum, and lead objects (e.g., water pipes). After sample digestion with quantitative Pb recovery and subsequent quantitative and pure isolation of lead, the Pb isotopic composition was determined via multicollector ICP-mass spectrometry. The Pb isotope ratio results allowed distinction of three groups: bone, soil, and lead objects + garum. The 208Pb/206Pb ratio ranges were between 2.059 and 2.081 for the soils, between 2.067 and 2.085 for the bones, and between 2.087 and 2.088 for the lead objects. The garum sample is characterised by a 208Pb/206Pb ratio of 2.085. The bone group is situated on the mixing line between the soil and lead object groups, allowing the statement that diagenesis is not the main cause of the Pb found in the bones.


Description of two new major histocompatibility complex (MHC) class II DRB1 [Pan troglodytes (Patr)-DRB1] alleles.
Sequence-based typing strategy is used to identify polymorphism of Patr-DRB1. Two new Patr-DRB1 are described.


Pellagra encephalopathy as a differential diagnosis for Creutzfeldt-Jakob disease.
In the present study we evaluated cases referred as suspected Creutzfeldt-Jakob disease (CJD). Five out of 59 without prion disease showed neuropathological features of pellagra encephalopathy with widespread chromatolytic neurons (age range 40-48 years at death; one woman). These patients presented with a progressive neuropsychiatric disorder lasting for 2 to 24 months. Common symptoms included gait disorder, para- or tetraspasticity, extrapyramidal symptoms, incontinence, and myoclonus. Protein 14-3-3 in the cerebrospinal fluid was examined in a single patient and was positive, allowing the clinical classification as probable sporadic CJD. Pellagra encephalopathy may be considered as a differential diagnosis of CJD including detection of protein 14-3-3.


Retrograde cannulation of the thoracic duct and embolization of the cisterna chyli in the treatment of chylous ascites.
The authors offer a previously undescribed technique for cisterna chyli embolization in the treatment of chylous ascites. After the failure of conventional percutaneous direct cisterna chyli cannulation, the authors accessed the thoracic duct directly from the subclavian vein. Retrograde microcatheter access through the thoracic duct enabled embolization of the cisterna chyli. Embolization materials included fibered endovascular coils, gelatin sponge, and doxycycline. The patient's symptoms returned 10 days after embolization. This technique provided short-term success in the treatment of the patient's chylous ascites.


Myopathy of the Proteus syndrome: hypothesis of muscular dysgenesis.
The Proteus syndrome is a congenital disorder of growth regulation affecting tissues of mesodermal and ectodermal origin. It is expressed as hemihypertrophy, hemimegalencephaly, muscular overgrowth, verrucous epidermal nevi, haemangiomas and bony dysplasias. Muscle biopsies were examined at 7 and 10 yr of age from a girl with this disease. Several cytoarchitectural alterations of myofibres, proliferation of sarcolemmal nuclei, and other myopathic changes were demonstrated in regions adjacent to other with normal myofibres; the boundaries did not correspond to fascicular margins. A perinuclear and subsarcolemmal distribution of excessive desmin was also found. It is suggested that this myopathy represents a new category of neuromuscular disease, "muscular dysgenesis", due to faulty paracrine growth factors.


Antimicrobial antibodies by phage display: Identification of antibody-based inhibitor against mycobacterium tuberculosis isocitrate lyase.
The increasing incidence reports of antibiotic resistance highlights the need for alternative approaches to deal with bacterial infections. This brought about the idea of utilizing monoclonal antibodies as an alternative antibacterial treatment. Majority of the studies are focused on developing antibodies to bacterial surface antigens, with little emphasis on antibodies that inhibit the growth mechanisms of a bacteria host. Isocitrate lyase (ICL) is an important enzyme for the growth and survival of Mycobacterium tuberculosis (MTB) during latent infection as a result of its involvement in the mycobacterial glyoxylate and methylisocitrate cycles. It is postulated that the inhibition of ICL can disrupt the life cycle of MTB. To this extent, we utilized antibody phage display to identify a single chain fragment variable (scFv) antibody against the recombinant ICL protein from MTB. The soluble a-ICL-C6 scFv clone exhibited good binding characteristics with high specificity against ICL. More importantly, the clone exhibited in vitro inhibitory effect with an enzymatic assay resulting in a decrease of ICL enzymatic activity. In silico analysis showed that the scFv-ICL interactions are driven by 23 hydrogen bonds and 13 salt bridges that might disrupt the formation of ICL subunits for the tertiary structure or the formation of active site β domain. However, further validation is necessary to confirm if the isolated clone is indeed a good inhibitor against ICL for application against MTB.


afsB stimulates transcription of the actinorhodin biosynthetic pathway in Streptomyces coelicolor A3(2) and Streptomyces lividans.
The pleiotropic regulatory gene, afsB, from Streptomyces coelicolor A3(2), possibly encoding a DNA-binding protein, is required for actinorhodin production in this organism. Northern blot hybridization using a DNA fragment covering part of the set of cloned actinorhodin biosynthetic gene cluster (act) as the probe showed lack of the act transcripts in an afsB-negative mutant of S. coelicolor A3(2); the transcripts were restored on introduction of a cloned afsB gene. Introduction of the cloned afsB gene into Streptomyces lividans stimulated transcription of the act genes under conditions in which they are normally silent in this strain, leading to production of actinorhodin in large quantity. These data show that afsB exerts its positive regulatory effect by means of transcriptional stimulation of its target genes.


Using social media records to inform conservation planning.
Citizen science plays a crucial role in helping monitor biodiversity and inform conservation. With the widespread use of smartphones, many people share biodiversity information on social media, but this information is still not widely used in conservation. Focusing on Bangladesh, a tropical megadiverse and mega-populated country, we examined the importance of social media records in conservation decision-making. We collated species distribution records for birds and butterflies from Facebook and Global Biodiversity Information Facility (GBIF), grouped them into GBIF-only and combined GBIF and Facebook data, and investigated the differences in identifying critical conservation areas. Adding Facebook data to GBIF data improved the accuracy of systematic conservation planning assessments by identifying additional important conservation areas in the northwest, southeast, and central parts of Bangladesh, extending priority conservation areas by 4,000-10,000 km2 . Community efforts are needed to drive the implementation of the ambitious Kunming-Montreal Global Biodiversity Framework targets, especially in megadiverse tropical countries with a lack of reliable and up-to-date species distribution data. We highlight that conservation planning can be enhanced by including available data gathered from social media platforms.


Multiple sclerosis disease-related knowledge measurement instruments show mixed performance: a systematic review.
This review aimed to summarize the evidence on the measurement properties of available disease-related knowledge measurement instruments in people with multiple sclerosis. We performed a literature search in the MEDLINE (PubMed), CINAHL (EBSCOhost), and PsycINFO (EBSCOhost) databases from inception to February 10, 2021. Eligible studies were reports developing a disease-related knowledge measurement instrument or assessing one or more of its measurement properties. We assessed the methodological quality of the included studies independently using the "COSMIN Risk of Bias" checklist. We graded the quality of the evidence using a GRADE approach. Twenty-four studies provided information on 14 measurement instruments. All instruments showed sufficient evidence for content validity, three for structural validity, and seven for hypothesis testing for construct validity. Cross-cultural validity and criterion validity were not assessed in any instrument. Only two instruments showed sufficient evidence for the internal consistency of their scores, and two others for their test-retest reliability. Responsiveness was assessed in one instrument, but it was rated as indeterminate. Based on the available evidence, two instruments can be recommended for use, two are unrecommended, and five have the potential to be recommended for use but require further research.


Structural insights into the design of reversible fluorescent probes for metallo-β-lactamases NDM-1, VIM-2, and IMP-1.
Metallo-β-lactamases (MBLs) are enzymes that are capable of hydrolyzing most β-lactam antibiotics and all clinically relevant carbapenems. We developed a library of reversible fluorescent turn-on probes that are designed to directly bind to the dizinc active site of these enzymes and can be used to study their dynamic metalation state and enzyme-inhibitor interactions. Structure-function relationships with regards to inhibitory strength and fluorescence turn-on response were evaluated for three representative MBLs.


Overuse tendon conditions: time to change a confusing terminology.
In overuse clinical conditions in and around tendons, frank inflammation is infrequent, and is associated mostly with tendon ruptures. Tendinosis implies tendon degeneration without clinical or histological signs of intratendinous inflammation, and is not necessarily symptomatic. Patients undergoing an operation for Achilles tendinopathy show similar areas of degeneration. When the term tendinitis is used in a clinical context, it does not refer to a specific histopathological entity. However, tendinitis is commonly used for conditions that are truly tendinoses, and this leads athletes and coaches to underestimate the proven chronicity of the condition. Paratenonitis is characterized by acute edema and hypermia of the paratenon, with infiltration of inflammatory cells, possibly with production of a fibrinous exudate that fills the tendon sheath, causing the typical crepitus that can be felt on clinical examination. The term partial tear of a tendon should describe a macroscopically evident subcutaneous partial tear of a tendon, an uncommon acute lesion. Most articles describing the surgical treatment of 'partial tears' of a given tendon in reality deal with degenerative tendinopathies. The combination of pain, swelling, and impaired performance should be labeled tendinopathy. According to the tissues affected, the terms tendinopathy, paratendinopathy, or pantendinopathy should be used.


Signaling through Toll-like receptor 4 and mast cell-dependent innate immunity responses.
Signal transduction through Toll-like receptors (TLRs) has been one of the main topics in immunology research in recent years. Because of their signaling particularities based on the homotypic recognition of protein domains in multiple adaptors and selective activation of protein kinases, TLRs have become a paradigm to study ligand recognition coupled to dynamic and highly specific transcriptional and secretory responses in immune cells. Particularly, deleterious effects of Gram-negative bacteria-associated immune reactions has promoted intense research in the field, leading to the description of a number of canonical molecules connecting lipopolysaccharide-induced TLR4 activation with NFκB-dependent transcription. However, the diversity of immune cell phenotypes and the activity of distinct immune receptors in the same cell, strongly suggest that a number of elements in TLR4 signaling cascade, such as novel coreceptors, tyrosine kinases, and molecules regulating the secretion of preformed mediators remain to be described. Recent investigations have placed the mast cells, widely known by their role on allergic responses, as important effectors of innate immunity reactions against Gram-negative bacteria. Their remarkable capacity of cytokine storage, synthesis and release, and the large number of inflammatory reactions controlled by their activation, suggest the existence of new modulators of TLR4 signaling in this particular cell type.


The structure of human 4F2hc ectodomain provides a model for homodimerization and electrostatic interaction with plasma membrane.
4F2hc (CD98hc) is a multifunctional type II membrane glycoprotein involved in amino acid transport and cell fusion, adhesion, and transformation. The structure of the ectodomain of human 4F2hc has been solved using monoclinic (Protein Data Bank code 2DH2) and orthorhombic (Protein Data Bank code 2DH3) crystal forms at 2.1 and 2.8 A, respectively. It is composed of a (betaalpha)(8) barrel and an antiparallel beta(8) sandwich related to bacterial alpha-glycosidases, although lacking key catalytic residues and consequently catalytic activity. 2DH3 is a dimer with Zn(2+) coordination at the interface. Human 4F2hc expressed in several cell types resulted in cell surface and Cys(109) disulfide bridge-linked homodimers with major architectural features of the crystal dimer, as demonstrated by cross-linking experiments. 4F2hc has no significant hydrophobic patches at the surface. Monomer and homodimer have a polarized charged surface. The N terminus of the solved structure, including the position of Cys(109) residue located four residues apart from the transmembrane domain, is adjacent to the positive face of the ectodomain. This location of the N terminus and the Cys(109)-intervening disulfide bridge imposes space restrictions sufficient to support a model for electrostatic interaction of the 4F2hc ectodomain with membrane phospholipids. These results provide the first crystal structure of heteromeric amino acid transporters and suggest a dynamic interaction of the 4F2hc ectodomain with the plasma membrane.


Effect of climate change on reservoir water balance and irrigation water demand: a case of Gidabo irrigation project, Rift Valley Basin, Ethiopia.
The consequences of climate change on agriculture water demand are among the current and prospective challenges. The amount of water needed by crops is significantly affected by the regional climate. The influence of climate change on irrigation water demand and reservoir water balance components were examined. The results of seven regional climate models were compared, and the top-performing model was chosen for the study area. After model calibration and validation, the HEC-HMS model was used to forecast future water availability in the reservoir. The results show that under the RCP 4.5 and RCP 8.5 emission scenarios, the reservoir's water availability in the 2050s will decline by approximately 7% and 9%, respectively. The CROPWAT results showed that the required irrigation water might rise by 26 to 39% in the future. However, the water supply for irrigation may be drastically reduced due to the drop in reservoir water storage. As a result, the irrigation command area could drop up to 21% (2878.4 ha) to 33% (4502 ha) in future climatic conditions. Therefore, we recommend alternative watershed management techniques and climate change adaptation measures to endure upcoming water shortages in the area.


Antibiotic prescribing in ambulatory care settings for adults with colds, upper respiratory tract infections, and bronchitis.
Imprudent prescribing of antibiotics for patients with colds, upper respiratory tract infections (URIs), and bronchitis may contribute to antibiotic resistance and waste economic resources. The purpose of this study was to determine the antibiotic prescribing rate for adults diagnosed with colds, URIs, and bronchitis in 1996 and to compare these rates with those reported for 1992. This was a retrospective, cross-sectional analysis of a US government data base of ambulatory physician practices. The number of adults ( > or = 18 years of age) with a diagnosis of cold, URI, or bronchitis and the percentage receiving antibiotics were determined from the 1996 National Ambulatory Medical Care Survey (NAMCS). The antibiotic prescribing rate was the main outcome measure. In 1996, approximately 13.9 million office visits resulted in a primary diagnosis of cold, URI, or acute bronchitis; of these visits, 46%, 47%, and 60%, respectively, resulted in the prescribing of an antibiotic. The respective rates in 1992 were 51%, 52%, and 66%. The rates of antibiotic prescribing were 12% to 16% higher when all drugs, not just the first drug listed in the NAMCS database, were analyzed. In 1996, antibiotic prescribing rates for persons 45 to 64 years of age and persons > 64 years of age were significantly lower than for those aged 18 to 44 years. The rates of potentially inappropriate antibiotic prescribing decreased modestly from 1992 to 1996; however, previous rates may have been underestimated. The antibiotic prescribing rates for colds, URIs, and acute bronchitis may be as high as 61%, 63%, and 72%, respectively, when all drug information is analyzed. Antibiotics are over-prescribed, which may increase antibiotic resistance and waste health care resources.


Mineralization generates megapascal contractile stresses in collagen fibrils.
During bone formation, collagen fibrils mineralize with carbonated hydroxyapatite, leading to a hybrid material with excellent properties. Other minerals are also known to nucleate within collagen in vitro. For a series of strontium- and calcium-based minerals, we observed that their precipitation leads to a contraction of collagen fibrils, reaching stresses as large as several megapascals. The magnitude of the stress depends on the type and amount of mineral. Using in-operando synchrotron x-ray scattering, we analyzed the kinetics of mineral deposition. Whereas no contraction occurs when the mineral deposits outside fibrils only, intrafibrillar mineralization generates fibril contraction. This chemomechanical effect occurs with collagen fully immersed in water and generates a mineral-collagen composite with tensile fibers, reminiscent of the principle of reinforced concrete.


A Case of Bifid Phallus and Bladder Neck Incompetence: Is This a Variant of Epispadias or Hypospadias?
Diphallia or duplication of the penis is an extremely rare congenital anomaly. Based on the presence of one or two corpora cavernosa in each of the penises, diphallia is classified into two major groups: bifid phallus and true diphallia. Because true diphallia associated with various anomalies is dominant in published studies, little is known about bifid phallus or isolated cases. Here we present a 9-month-old boy with an isolated bifid phallus. After successful reconstruction of the penis and urethra, urinary incontinence became apparent. To the best of our knowledge, this is the first case of complete bifid phallus associated with bladder neck incompetence.


Elevation of Liver Fibrosis Index FIB-4 Is Associated With Poor Clinical Outcomes in Patients With COVID-19.
COVID-19 is a potentially severe disease caused by the recently described SARS-CoV-2. Whether liver fibrosis might be a relevant player in the natural history of COVID-19 is currently unknown. We aimed to evaluate the association between FIB-4 and the risk of progression to critical illness in middle-aged patients with COVID-19. In this multicenter, retrospective study with prospective follow-up of 160 patients aged 35-65 years with COVID-19, FIB-4, clinical, and biochemical variables were collected at baseline. FIB-4 ≥2.67 defined patients with risk for advanced liver fibrosis. Risk for advanced fibrosis was estimated in 28.1% of patients. Patients with FIB-4 ≥2.67 more frequently required mechanical ventilation (37.8% vs 18.3%; P = .009). In multivariate analysis, FIB-4 ≥2.67 (odds ratio [OR], 3.41; 95% confidence interval [CI], 1.30-8.92), cardiovascular risk factors (OR, 5.05; 95% CI, 1.90-13.39), previous respiratory diseases (OR, 4.54; 95% CI, 1.36-15.10), and C-reactive protein (OR, 1.01; 95% CI, 1.01-1.02) increased significantly the risk of ICU admission. Bootstrap confirmed FIB-4 as an independent risk factor. In middle-aged patients with COVID-19, FIB-4 may have a prognostic role. The link between liver fibrosis and the natural history of COVID-19 should be evaluated in future studies.


Quantitative analysis of immunogold labellings of collagen types I, III, IV and VI in healthy and pathological human corneas.
We studied the distribution of collagen types I, III, IV and VI in one healthy human cornea and in seven pathological human corneas, in which the disorders were three cases of pseudophakic bullous keratopathy (two severe, one moderate) and one case each of stage IV keratoconus, chronic ulcer, vascularized cornea and disciform keratitis. Transmission electron microscopy examinations were performed on post-embedding immunogold-labelled sections. The staining was evaluated by gold particle count in the different tissues. The presence or absence of a given antigen was determined by statistical analysis, using a d-value test. Our results on healthy corneal tissues corroborate the data available from previous studies, except for collagen type VI, which we found to be absent in Bowman's layer. In pathological corneas with a collagenous layer posterior to Descemet's membrane, collagen types I, III and especially IV were detected in this collagenous layer. Collagen types I, III and VI were detected in the anterior healed stroma of other pathological corneas, except for the keratoconus cornea, in which intense collagen III staining was observed. The presence of collagen types I and III in the posterior collagenous layer of our pseudophakic bullous keratopathy corneas suggests that this layer corresponds to scar tissue secreted by stimulated endothelial cells.


Focal cone ERGs of rhodopsin Pro347Leu transgenic rabbits.
A rhodopsin P347L transgenic (Tg) rabbit, a model of retinitis pigmentosa, has been generated in our laboratory. The purpose of this study was to determine the properties of focal areas of the retina in this rabbit model during the course of retinal degeneration. To accomplish this, we recorded focal ERGs from wild-type (WT) and Tg rabbits at ages 3, 6, and 12 months. A 15° stimulus spot was used to elicit the focal ERGs from the center of the visual streak and from four surrounding areas. We found that the amplitudes of the focal cone ERG b-waves and oscillatory potentials (OPs) of the Tg rabbits in the five areas decreased progressively with increasing age and became almost non-recordable at 12 months. There were no significant regional differences in the b-waves of Tg rabbits recorded from the 5 areas. The amplitudes of the OPs were better preserved than the b-waves and the OPs/b-wave ratio was higher than that in WT rabbits at every recording area. The summed OPs amplitudes, which most likely originate from the amacrine and/or ganglion cells, recorded from the area superior to the optic disc was significantly larger than that from other areas at 3- and 6-months-old. This indicated that the inner retinal neurons were not altered equally after photoreceptor degeneration in this rabbit model.


Immunohistochemical demonstration of steroid C-21 hydroxylase in normal and neoplastic salivary glands.
The presence of steroid C-21 hydroxylase in normal and neoplastic salivary glands was investigated immunohistochemically with the use of antibody against cytochrome P-450 specific for steroid 21-hydroxylation (P-450C21). In normal salivary glands, P-450C21 was exclusively present in the excretory duct system (intercalating, striated and large excretory ducts), and not observed in acini. In salivary gland tumors, P-450C21 was observed in most epithelial cells of duct origin within pleomorphic adenomas including cells of amorphous groups scattered in myxoid areas, and in adenolymphoma. Some mucous cells in mucoepidermoid tumor also were positive for this enzyme. These findings in the normal and neoplastic salivary gland suggest that the expression of P-450C21 is closely related to ductal differentiation.


Personalized Dental Medicine: Impact of Intraoral and Extraoral Clinical Variables on the Precision and Efficiency of Intraoral Scanning.
(1) Objectives: The aim is to measure the influence of different intraoral (crowding and molar inclination) and extraoral (surface material and ambient light) conditions on the efficacy and efficiency of intraoral scanning. (2) Methods: In a controlled in vitro experimental study, the samples were divided into six groups showing two types of intraoral conditions-lower incisor crowding (groups 1-3) and lower molar mesial tipping (groups 4-6). Each modified model was replicated using three types of materials with different light-absorption properties (n = 18 models). Each sample was scanned 30 times at light intensities of 0.0, 1800, or 3600 l×, yielding 3240 scans. Scanning efficiency (digital acquisition; scanning chair-time; and scanning failures) and scanning efficacy (undetected volume) were assessed using virtual superimpositions and Mecano Equate software. The intra- and interobserver error and reliability of the method were calculated and data analyses were performed using the t-test, paired t-test, and one-way analysis of variance (p < 0.05). (3) Results: Digital acquisition was influenced by the degree of crowding and molar inclination (p < 0.05). The scanning surface material affected the efficacy and efficiency, which were lower with a calcium sulfate hemihydrate A modified compound scanning surface (p < 0.05). Higher intensities of ambient light in the scanning room were associated with reduced scanning efficacy (p < 0.05). Moreover, the scanner showed greater amounts of undetected volume as the degrees of crowding and mesial tipping of the lower second molar increased over 25°, with mean error values of 0.97 mm3 and 1.12 mm3, respectively. (4) Conclusions: For scanning procedures employing digital acquisition, differences in the degrees of crowding and mesial tipping of the lower second molar, scanning surface material, and external light source intensity influence the efficacy and efficiency of the scanning procedures, scanning chair-time, scanning failures, and undetected volume.


A third isoform of cytochrome c oxidase subunit VIII is present in mammals.
The terminal enzyme of the mitochondrial respiratory chain, cytochrome c oxidase (COX), contains three mitochondrial and ten nuclear encoded subunits in mammals. Three of the nuclear subunits (VIa, VIIa, and VIII) have muscle and non-muscle-specific isoforms, subunit IV contains a lung-specific isoform, and subunit VIb contains a testes-specific isoform. For subunit VIII, the smallest nuclear encoded COX polypeptide, we have now found a third gene (COX 8-3), which has been identified in human, lemur, rat, and mouse, suggesting that it is present in a broad range of Eutherian mammals. Sequence similarity and gene structure support the homology of COX8-3 to the other subunit VIII isoforms, indicating that all three are the product of gene duplications. COX VIII-3 protein is mitochondrially-targeted, as shown by a fluorescent COX VIII3/DsRed fusion protein. Both the mitochondrial targeting and its sequence conservation suggest that COXVIII-3 functions as part of the COX holoenzyme and could have a tissue-specific role, as is the case for the other two isoforms. Questions remain about where COX8-3 is predominantly expressed. However, detection of full-length cDNAs, lower levels of sequence divergence at the first and second codon positions compared to the third, and a conserved gene structure indicate that COX VIII-3 is an expressed gene whose origin dates to at least 91 million years ago.