Ovarian electrocautery versus human menopausal gonadotrophins and pure follicle stimulating hormone therapy in the treatment of patients with polycystic ovarian disease.
Eighty-eight clomiphene citrate-resistant infertile patients with oligomenorrhoea or amenorrhoea attributable to polycystic ovarian disease were divided at random into three groups. Twenty-nine patients were treated with ovarian electrocautery, 30 with human menopausal gonadotrophins (hMG) and 29 with pure follicle stimulating hormone (FSH). Successful ovulation was induced in 71.4, 70.6 and 66.7% of the cycles in the groups respectively. Ten patients conceived after electrocautery and pure FSH therapy while 15 conceived after hMG medication (chi-squared = 1.6464, P = 0.439). The six-cycle cumulative pregnancy rate in the three consecutive groups was 52.1, 55.4, and 38.3%. Four further pregnancies were achieved after treating 10 patients in the electrocautery group with clomiphene citrate (100 mg/day for 5 days) for 25 cycles. The rate of pregnancy wastage in the corresponding groups was 21.4, 53.3 and 40% (chi-squared = 3.127, P = 0.2039). Ovarian electrocautery is equally effective as hMG and pure FSH in the treatment of PCO patients resistant to clomiphene citrate therapy.


Classic and late-onset neurological disease in two siblings with glutaryl-CoA dehydrogenase deficiency.
Late-onset neurological disease has rarely been reported in patients with glutaryl-CoA dehydrogenase (GCDH) deficiency. We present two siblings with GCDH deficiency. One of them presented with the classic neurological disease (patient 1). Routine investigation of family members revealed that her apparently unharmed 13-year-old sister was also affected (patient 2). Patient 2 started to have academic difficulties in the months prior to our assessment. Her clinical examination was normal, with the exception of a cranial circumference of 57 cm (slightly over the 98 th centile). A severe leukoencephalopathy was demonstrated on MRI. Neuropsychological assessment showed an IQ within the normal-low range and a mild impairment of memory and executive function. Previous reports on late-onset neurological disease in GCDH deficiency have revealed that progressive leukoencephalopathy develops over time. Following the recently published guideline for the diagnosis and management of GCDH deficiency, both patients are receiving dietary treatment in combination with L-carnitine supplementation. We emphasize the need to search for chronic neurological changes of late-onset type in apparently unaffected GCDH deficiency cases diagnosed in routine family investigations.


Study design of endoscopic polypectomy on clopidogrel (EPOC): A randomised controlled trial.
Concurrent cardiovascular disease and antiplatelet use (clopidogrel, prasugrel and ticagrelor) use poses a significant peri-endoscopic management challenge with a paucity of high-quality evidence available. Antiplatelet temporary interruption places patients at risk of serious cardiovascular thrombotic events. Continuing these agents potentially increases the risk of procedure related bleeding however this risk could be sufficiently mitigated by cold snare polypectomy and endoscopic clipping to manage intraprocedural bleeding, making routine colonoscopy on continued antiplatelet agents safe. The EPOC trial will examine whether continuation of antiplatelet therapy (clopidogrel, prasugrel or ticagrelor) as single or dual therapy with aspirin, is inferior or superior to temporary interruption of antiplatelet therapy, current standard of care, with regard to the use of endoscopic rescue clips or clinically significant post-polypectomy bleeding after cold snare polypectomy of polyps ≤10 mm. EPOC is a parallel group, proceduralist-blinded randomized controlled trial comparing recruiting patients on antiplatelet therapy undergoing elective colonoscopy. This trial is underway throughout Australia and New Zealand with a view to expanding to additional sites. 496 subjects in each arm are required for this study. EPOC is the first randomised controlled trial comparing temporary interruption with continuation of antiplatelet therapy in patients undergoing elective colonoscopy.


[Increase in tumor microvascular pressure by angiotensin-induced hypertension: implication for pharmacokinetic analysis of drug delivery into tumor tissue].
Tumor microvascular pressure was measured by using a newly developed transparent chamber of rat. The pressure of tumor vessels, 20-100 microns in diameter, increased from 9.2 +/- 2.6 cm H2O to 15.4 +/- 3.2 cm H2O when the mean arterial pressure was elevated from 103.3 +/- 8.6 mmHg to 159.2 +/- 7.9 mmHg with continuous infusion of angiotensin II. It was frequently observed that the blood began to flow into the vessels in tumor tissue, where the statis of flow had been seen, when the pressure was elevated from normotension to hypertension by angiotensin II. Based on the results obtained, the mechanism of drug delivery into tumor tissue was discussed in correlation with the enhancement of chemotherapeutic effects in both animal experiments and cancer patients by induced hypertension chemotherapy.


High-resolution manometry patterns of lower esophageal sphincter complex in symptomatic post-fundoplication patients.
There has been an increase in the number of patients seeking treatment after an anti-reflux surgical procedure. The objective of this study is to describe high-resolution manometry (HRM) topography as it relates to the post-fundoplication anatomy. Retrospective review of a prospectively maintained database was conducted to identify patients who underwent esophagogastroduodenoscopy and HRM at Creighton University Medical Center (CUMC) between November 2008 and October 2010, for symptoms after a previous fundoplication. Patients were categorized as having intact, intrathoracic, disruptured, twisted, or slipped fundoplication based on endoscopic findings. Sixty-one patients {intact, 17(28%), disrupted, 2(3%), twisted, 3(5%), intra-thoracic, 18(30%), slipped, 21(34%)} are included in this study. A double high-pressure zone (HPZ) configuration was identified in both intra-thoracic and slipped fundoplication. This was not noted in appropriately positioned fundoplications. In intra-thoracic fundoplications, the HPZ below the fundoplication was lower pressure and showed respiratory variations. In slipped fundoplication, the higher HPZ had lower pressure and no respiratory variations. In appropriately positioned fundoplication, the lower esophageal sphincter (LES) pressure and extent of relaxation in the single HPZ correlated with intact (normal pressure and good relaxation), disrupted (low pressure and good relaxation), and twisted (high pressure with incomplete relaxation) fundoplication. Patients with only a recurrent para-esophageal hernia had characteristics of an appropriately positioned fundoplication. LES complex HRM findings correlate well with anatomical status of the fundoplication.


Recurrence quantification analysis of gait in normal and hypovestibular subjects.
The study of postural control processes during locomotion may provide useful outcome measures of stability for people with unilateral vestibular hypofunction (UVH). Since nonlinear analysis techniques can characterize complex behaviour of a system, this may highlight mechanisms underlying dynamic stability in locomotion, although only few efforts have been made. In particular, there have been no studies that use recurrence quantification analysis (RQA), which can be applied even to short and non-stationary data. The purpose of this study was to develop a new method for walking balance assessment measuring the complexity of head, trunk and pelvis three-dimensional accelerations and angular velocities during normal overground locomotion by means of RQA in normal subjects and UVH patients. The results showed differential effect of upper body parts on pattern regularity, with better head than pelvis stabilization in both groups of subjects. The RQA outputs such as percent determinism and recurrence were nevertheless significantly lower in the UVH group for all measures, suggesting that body accelerations and angular velocities, although not significantly different in amplitude, were more chaotic in patients. The observed lower regularity of upper body movements in UVH is consistent with an important role of the vestibular system in controlling dynamic stability during walking. The findings suggest that RQA can be used as a quantitative tool to assess walking performance and rehabilitation outcome in patients with different balance disorders.


Ex vivo histological analysis of the thermal effects created by a 445-nm diode laser in oral soft tissue biopsy.
The aim of this study was to evaluate, ex vivo, the histological effects of 445-nm diode laser (Eltech K-Laser srl, Treviso, Italy), during an oral soft tissue biopsy. Thirty samples from pig cadaver tongues were obtained, through five laser settings, in continuous and pulsed wave (CW and PW). Samples were divided into six groups of five pieces each. A control specimen was taken by a scalpel. All samples were examined with an optical microscope by a blinded pathologist. Thermal effects on epithelium and connective tissues were measured with LAS 4.8 software. Finally, a statistical evaluation was made using GraphPadPrism 7.0 software. All specimens, except one, showed a damage lower than 1 mm. Readability was always optimal; there was a different thermal effect between epithelial and connective tissue and in CW and PW samples, confirmed by statistical analysis too. A 445-nm diode laser creates a minimum thermal effect, that has no implications in the histological evaluation of benign lesions. In suspicious lesions, a safety margin of 1 mm, compared with a scalpel, is preferable. A 445-nm diode laser has excellent surgical properties and can manage many arduous clinical cases, such as vascularized lesions. In the excision of suspected lesions, it is necessary to compare, case by case, clinical advantages to possible histological implications.


Intravenous omeprazole: effect of a loading dose on 24-h intragastric pH.
To determine the effect of three times daily dosing with intravenous omeprazole on intragastric acidity, 24 h intragastric pH was measured continuously with a monocrystalline antimony electrode system in II patients with inactive duodenal ulceration during fasting conditions. After a baseline investigation, two different dosage regimens of intravenous omeprazole were compared in a double-blind crossover study, with regard to their ability to keep the pH greater than or equal to 4 for as long as possible. Success in the individual patient was defined as pH greater than or equal to 4 for at least 90% over the 24-h period. Two doses of omeprazole [40 mg t.d.s. (120 mg) and 80 mg + 40 mg + 40 mg (160 mg)] were compared. Omeprazole (120 mg) increased the median of individual median intragastric 24-h pH from 1.49 to 6.67. The pH was greater than or equal to 4 for greater than or equal to 90% of the 24 h in three of the 11 patients. With omeprazole, 160 mg (a loading dose of 80 mg), the median of individual median intragastric 24-h pH increased to 7.33. The pH was greater than or equal to 4 for greater than or equal to 90% of the 24 h in seven of the 11 patients. Median time to reach pH 4 was 39 min after 40 mg and 20 min after 80 mg omeprazole. An initial loading dose of 80 mg omeprazole seems preferable to 40 mg to achieve a fast and sustained increase in intragastric pH to above 4 in the fasting patient.


Solitary fibrous tumours of the pleura: report of two cases and literature review.
Solitary fibrous tumours of the pleura (SFTPs) are rare pleural mesenchymal neoplasms with distinct clinicopathological and immunohistochemical features, accounting for less than 5 % of all neoplasms involving the pleura. We present two cases of SFTP with a review of the current literature. Clinical presentation varies according to size and intrathoracic localisation. The molecular pathology of SFTPs is largely unknown. Complete surgical resection is recommended with long-term clinic and radiographic follow-up due to its malignant potential. This is a summary of available literature outlining current clinical practice in the diagnosis, management, and treatment of SFTPs in Ireland.


Age-dependent changes in the functions and compositions of photosynthetic complexes in the thylakoid membranes of Arabidopsis thaliana.
Photosynthetic complexes in the thylakoid membrane of plant leaves primarily function as energy-harvesting machinery during the growth period. However, leaves undergo developmental and functional transitions along aging and, at the senescence stage, these complexes become major sources for nutrients to be remobilized to other organs such as developing seeds. Here, we investigated age-dependent changes in the functions and compositions of photosynthetic complexes during natural leaf senescence in Arabidopsis thaliana. We found that Chl a/b ratios decreased during the natural leaf senescence along with decrease of the total chlorophyll content. The photosynthetic parameters measured by the chlorophyll fluorescence, photochemical efficiency (F v/F m) of photosystem II, non-photochemical quenching, and the electron transfer rate, showed a differential decline in the senescing part of the leaves. The CO2 assimilation rate and the activity of PSI activity measured from whole senescing leaves remained relatively intact until 28 days of leaf age but declined sharply thereafter. Examination of the behaviors of the individual components in the photosynthetic complex showed that the components on the whole are decreased, but again showed differential decline during leaf senescence. Notably, D1, a PSII reaction center protein, was almost not present but PsaA/B, a PSI reaction center protein is still remained at the senescence stage. Taken together, our results indicate that the compositions and structures of the photosynthetic complexes are differentially utilized at different stages of leaf, but the most dramatic change was observed at the senescence stage, possibly to comply with the physiological states of the senescence process.


Position Statement on the Diagnosis, Treatment, and Response Evaluation to Systemic Therapies of Advanced Neuroendocrine Tumors, With a Special Focus on Radioligand Therapy.
The aim of this study was to provide a guidance for the management of neuroendocrine tumors (NETs) in clinical practice. Nominal group and Delphi techniques were used. A steering committee of 8 experts reviewed the current management of NETs, identified controversies and gaps, critically analyzed the available evidence, and formulated several guiding statements for clinicians. Subsequently, a panel of 26 experts, was selected to test agreement with the statements through 2 Delphi rounds. Items were scored on a 4-point Likert scale from 1 = totally agree to 4 = totally disagree. The agreement was considered if ≥75% of answers pertained to Categories 1 and 2 (consensus with the agreement) or Categories 3 and 4 (consensus with the disagreement). Overall, 132 statements were proposed, which incorporated the following areas: (1) overarching principles; (2) progression and treatment response criteria; (3) advanced gastro-enteric NETs; (4) advanced pancreatic NETs; (5) advanced NETs in other locations; (6) re-treatment with radioligand therapy (RLT); (7) neoadjuvant therapy. After 2 Delphi rounds, only 4 statements lacked a clear consensus. RLT was not only recommended in the sequencing of different NETs but also as neoadjuvant treatment, while several indications for retreatment with RLT were also established. This document sought to pull together the experts' attitudes when dealing with different clinical scenarios of patients suffering from NETs, with RLT having a specific role where evidence-based data are limited.


Development of cell-active non-peptidyl inhibitors of cysteine cathepsins.
Cysteine cathepsins are an important class of enzymes that coordinate a variety of important cellular processes, and are implicated in various types of human diseases. However, small molecule inhibitors that are cell-permeable and non-peptidyl in nature are scarcely available. Herein the synthesis and development of sulfonyloxiranes as covalent inhibitors of cysteine cathepsins are reported. From a library of compounds, compound 5 is identified as a selective inhibitor of cysteine cathepsins. Live cell imaging and immunocytochemistry of metastatic human breast carcinoma MDA-MB-231 cells document the efficacy of compound 5 in inhibiting cysteine cathepsin activity in living cells. A cell-motility assay demonstrates that compound 5 is effective in mitigating the cell-migratory potential of highly metastatic breast carcinoma MDA-MB-231 cells.


Feasibility and initial efficacy of a high-intensity interval training program using adaptive equipment in persons with multiple sclerosis who have walking disability: study protocol for a single-group, feasibility trial.
There is considerable evidence for the efficacy of moderate-intensity continuous exercise benefitting clinically relevant outcomes in persons with multiple sclerosis (MS). However, persons with MS who have walking disability (pwMS-wd) are severely deconditioned and may achieve superior benefits by engaging in high-intensity interval training (HIIT), especially while utilizing adaptive equipment, such as recumbent arm/leg stepping (RSTEP). The proposed study will assess the feasibility of a 12-week, RSTEP HIIT program in pwMS-wd. The secondary aim will examine changes in aerobic fitness, physical activity, ambulation, upper arm function, cognition, fatigue, and depression as clinically relevant efficacy outcomes following the 12-week, RSTEP HIIT intervention. The study will recruit 15 pwMS-wd. Feasibility will be measured via process, resource, management, and scientific outcomes throughout the entirety of the research study. The secondary, clinically relevant outcomes will consist of a neurological exam, aerobic capacity, physical activity, ambulation, cognition, upper arm function, fatigue, and depression. Outcomes will be assessed at baseline (T1), midpoint (T2, following 6 weeks), and post-intervention (T3, following 12 weeks). The intervention will involve 12 weeks of supervised, individualized HIIT sessions two to three times per week. The individual HIIT sessions will each involve 10 cycles of 60-s intervals at the wattage associated with 90% VO2peak followed by 60 s of active recovery intervals at 15 W, totaling 20 min in length plus 5-min warm-up and cool-down periods. The feasibility design of the proposed study will provide experience and preliminary data for advancing towards a proof-of-concept study comparing HIIT to moderate-intensity continuous RSTEP for improving clinically relevant outcomes in a randomized control trial design. The results will be disseminated via manuscripts for publication and a report for distribution among the National Multiple Sclerosis Society. ClinicalTrials.gov NCT04416243 . Retrospectively registered on June 4, 2020.


Umbilical surgery in calves.
Calves benefiting from umbilical surgery can be affected by several different conditions. However, the practitioner should be able to correct any of these conditions surgically, especially in young calves, as a field procedure. Like other aspects of veterinary practice, the individual must decide what services he/she wishes to offer clients in the field or clinic setting and which ones will be referred. The objective of this article is to equip practitioners who wish to treat umbilical masses surgically with the information they need.


Prospect for vaginal delivery of growth restricted fetuses with abnormal umbilical artery blood flow.
The best mode of delivery in cases of intrauterine growth restriction (IUGR) with umbilical artery blood flow changes is not well elucidated. To evaluate outcome in IUGR with umbilical artery blood flow changes planned for vaginal delivery after a negative oxytocin challenge test (OCT). In 84 term singleton pregnancies with suspected IUGR and no unanimous indication for abdominal delivery, Doppler velocimetry and OCT were performed. Positive OCT cases were delivered by cesarean section, negative OCT cases planned for vaginal delivery. Umbilical artery Doppler velocimetry was normal in 51 cases (normal group) and abnormal in 33 cases (increased pulsatility index with maintained forward diastolic flow). Gestational age at delivery was shorter (p = 0.008), positive OCT more common (33% vs. 16%; p = 0.06), and vaginal delivery less common (40% vs. 63%; p = 0.04) in the abnormal blood flow group compared with the normal flow group. When in labor, 68% in the abnormal flow group and 76% in the normal flow group delivered vaginally (p = 0.6). One baby had a lethal malformation and another suffered meconium aspiration and pneumothorax, but was discharged home healthy. The vaginal delivery rate was significantly lower in the abnormal flow group compared with the normal flow group, but in cases finally destined for a trial of labor the vaginal delivery rates were similar. There was no indication that any fetus was exposed to detrimental hypoxia or distress.


SPECT/CT versus MRI in patients with nonspecific pain of the hand and wrist - a pilot study.
Hand and wrist pain is a diagnostic challenge for hand surgeons and radiologists due to the complex anatomy of the involved small structures. The American College of Radiology recommends MRI as the study of choice in patients with chronic wrist pain if radiographs are negative. Lately, state-of-the-art SPECT/CT systems have been introduced and may help in the diagnosis of this selected indication. This retrospective study included 21 patients with nonspecific pain of the hand/wrist. The diagnosis of nonspecific wrist pain was made by the referring hand surgeon based on patient history, clinical examination, plain radiography and clinical guidelines. All patients received planar early-phase imaging and late-phase SPECT/CT imaging as well as MRI. Lesions were divided into major (causative) and minor (not causative) pathologies according to clinical follow-up. Furthermore, oedema-like bone marrow changes seen on MRI were compared with focally increased tracer uptake seen on SPECT/CT images. MRI yielded a quite high sensitivity (0.86), but a low specificity (0.20). In contrast, SPECT/CT yielded a high specificity (1.00) and a low sensitivity (0.71). Oedema-like bone marrow changes were detected in 15 lesions in 11 patients. In ten lesions with bone marrow oedema on MRI, foci of elevated tracer uptake were detected on SPECT/CT. Overall, MRI was more sensitive, but SPECT/CT was more specific in the evaluation of causative pathologies. In this initial comparison, SPECT/CT showed higher specificity than MRI in the evaluation of causative pathologies in patients with nonspecific wrist pain. However, MRI was more sensitive. Thus, SPECT/CT was shown to be a useful problem-solving tool in the diagnostic work-up of these patients.


Encoding of luminance and contrast by linear and nonlinear synapses in the retina.
Understanding how neural circuits transmit information is technically challenging because the neural code is contained in the activity of large numbers of neurons and synapses. Here, we use genetically encoded reporters to image synaptic transmission across a population of sensory neurons-bipolar cells in the retina of live zebrafish. We demonstrate that the luminance sensitivities of these synapses varies over 10(4) with a log-normal distribution. About half the synapses made by ON and OFF cells alter their polarity of transmission as a function of luminance to generate a triphasic tuning curve with distinct maxima and minima. These nonlinear synapses signal temporal contrast with greater sensitivity than linear ones. Triphasic tuning curves increase the dynamic range over which bipolar cells signal light and improve the efficiency with which luminance information is transmitted. The most efficient synapses signaled luminance using just 1 synaptic vesicle per second per distinguishable gray level.


Collagen binding activity of recombinant and N-terminally modified annexin V (anchorin CII).
We have cloned the full coding cDNA sequence of chicken annexin V and of a mutant lacking 8 amino acid residues of the N-terminal tail for prokaryotic expression. Both proteins were synthesized in Escherichia coli upon induction with isopropyl thio-beta-D-galactoside, and were purified following two different protocols: one based on the ability of these proteins to interact reversibly with liposomes in the presence of calcium, and the other based on two sequential ion-exchange chromatographic steps. Spectroscopical analysis of recombinant annexin V revealed that binding of calcium did not change the circular dichroism spectra indicating no significant changes on the secondary structure; however, a conformational change affecting the exposition to the solvent of the tryptophan residue 187 was detected by analysis of fluorescence emission spectra. Recombinant annexin V binds with high affinity to collagen types II and X, and with lower affinity to collagen type I in a calcium-independent manner. Heat denaturing of collagen decreases this interaction while pepsin-treatment of collagen almost completely abolishes annexin V binding. Mutated annexin V interacts with collagen in a similar way as the nonmutated recombinant protein, indicating that the N-terminal tail of annexin V is not essential for collagen binding.


Mitotic phosphorylation of histone H3 at threonine 3.
Nuclear envelope-peripheral heterochromatin fractions contain multiple histone kinase activities. In vitro assays and amino-terminal sequencing show that one of these activities co-isolates with heterochromatin protein 1 (HP1) and phosphorylates histone H3 at threonine 3. Antibodies recognizing this post-translational modification reveal that in vivo phosphorylation at threonine 3 commences at early prophase in the vicinity of the nuclear envelope, spreads to pericentromeric chromatin during prometaphase and is fully reversed by late anaphase. This spatio-temporal pattern is distinct from H3 phosphorylation at serine 10, which also occurs during cell division, suggesting segregation of differentially phosphorylated chromatin to different regions of mitotic chromosomes.


PAM variants were associated with type 2 diabetes mellitus risk in the Chinese population.
This study aimed to assess the association between PAM single-nucleotide polymorphisms (SNPs) and T2DM risk in the Chinese population. We performed the genotype of PAM SNPs using Agena MassARRAY in 1002 subjects. The effect of PAM polymorphisms on T2DM occurrence was evaluated by logistic regression analysis. False-positive report probability (FPRP) was utilized to assess the noteworthiness of the significant results. This study showed that PAM rs406761, rs17154889, and rs6889592 were related to an increased risk of T2DM. The similar results were also in subjects with ≤ 60 years. Rs2431320 and rs406761 were related to an increased risk of T2DM in males, and rs6889592 was only found to be associated with T2DM risk in females. Rs2431320 and rs406761 increased T2DM risk in people with BMI > 24, and rs6889592 and rs26431 significantly correlated with T2DM risk in people with BMI ≤ 24. By comparing patients with no retinopathy with controls, the correlation between PAM rs406761 and rs17154889 and T2DM risk was observed. The significant association between T2DM risk and PAM SNPs was remarkable by FPRP values. PAM SNPs were correlated with T2DM risk in the Chinese population, illustrating the importance of PAM SNPs in the pathogenesis of T2DM.


Effects of long-term removal of sheep-grazing in a series of British upland plant communities: Insights from plant species composition and traits.
Environmental and management pressures are considered a threat for preserving plant communities worldwide. Identification of long-term impacts of changing management practices on plant community composition must, therefore, be a major priority to ensure improvement in conservation value. Land abandonment/wilding is one topical area where there is little available information on long-term impacts. To address this, here, we describe plant species compositional change over relatively long-time scales in a range of four British upland communities (high-level grasslands, intermediate grasslands, blanket bogs and high-level bogs) and its relationships with a series of life-history and plant trait variables. Our aims were to determine whether the business-as-usual sheep grazing practice was maintaining these communities, and if grazing was to be removed as part of abandonment/wilding strategies, would there be a conservation benefit. We used a series of long-term experimental grazing-exclosure studies at twelve sites (>40 years) on the Moor House National Nature Reserve in northern England. Each site consisted of paired plots; i.e. sheep-grazed versus ungrazed. Our results showed that there was relatively little change in dominant plant species with most change occurring within sub-dominant species. Similarly, different temporal responses in plant species richness were detected between the experiments (richness was reduced in three experiments, only one increased). In any case, the vegetation temporal trajectories were moving in similar direction in grazed and ungrazed plots at most sites. Interestingly, blanket bog experiments showed a clear compositional convergence for both grazed and ungrazed plots, although, the between-site differences related to a combination of elevation and past burning testament. Finally, the bryophytes (especially liverworts) and lichens were the groups that contributed most to the reductions in species richness. Moreover, implementation of a no-stock grazing strategy under a land abandonment/wilding approach will not bring about much plant change in the short-term in the plant communities studied here.


Comparison of strength of sacrocolpopexy mesh attachment using barbed and nonbarbed sutures.
We aimed to assess the pull-out strength of barbed and nonbarbed sutures used in sacrocolpopexy mesh fixation. We hypothesized there are no differences in the force needed to dislodge mesh from tissue using barbed and nonbarbed sutures of similar size. Using the rectus fascia of three unembalmed cadavers, a 6 × 3 cm strip of polypropylene mesh was anchored to the fascia with sutures. The barbed sutures investigated were 2-0 V-Loc 180 (nine trials) and 3-0 bidirectional Quill™ SRS PDO (five trials). The nonbarbed sutures included 2-0 PDS (nine trials), CV-2 GORE-TEX (nine trials) and 2-0 Prolene (nine trials). The free-end of the mesh was anchored to a pulley system fixed to a tensiometer to measure the peak force applied at the moment of mesh dislodgement (termed the pull-out force). The pull-out force was recorded. Continuous variables are presented as medians and interquartile ranges (IQR). Analysis of variance was used to compare the forces across the suture types. The highest pull-out force observed was with GORE-TEX (median 65.14 N, IQR 53.37-68.77 N) followed by Prolene (median 58.98 N, IQR 54.64-62.59 N), V-Loc (median 55.23 N, IQR 51.60-58.57 N), PDS (53.96 N, IQR 51.60-57.88 N), and Quill (44.44 N, IQR 17.27-47.38 N). All 2-0 and CV-2 caliber sutures had greater pull-out forces than 3-0 Quill sutures (p < 0.01). No significant differences in pull-out forces were observed between 2-0 and CV-2 caliber sutures (p > 0.05). In 35 of the 41 trials (85%), the mesh sheared from the tissue. CV-2 ad 2-0 barbed and nonbarbed sutures had similar pull-out forces in an assessment of mesh fixation strength.


The prevalence of body dysmorphic disorder and its clinical correlates in a VA primary care behavioral health clinic.
We examined the prevalence of body dysmorphic disorder (BDD) in a Veterans Affairs (VA) primary care behavioral health clinic. Of 100 Veterans, 11% (95% CI = 6.3-18.6%) had current BDD and 12% (95% CI = 7.0-19.8%) had lifetime BDD. However, only 8.3% of these Veterans had been diagnosed with BDD. BDD was significantly associated with a substantially elevated rate of suicide attempts, major depression, and obsessive-compulsive disorder. This severe disorder appears to be underdiagnosed in VA settings.


The anticipatory dopamine response in addiction: A common neurobiological underpinning of gambling disorder and substance use disorder?
The dopamine system is associated with reward processes in both gambling disorder and substance use disorder, and may constitute a common neurobiological underpinning in addiction. The present review examines differences and similarities of dopaminergic reward processes in gambling disorder and substance use disorder. First, it is suggested that baseline binding potentials of the dopamine system may not be a common pathway, since substance use disorder is associated with reduced binding potentials, whereas gambling disorder is not. Second, it is suggested that dopaminergic reward response may be not a common pathway, since substance use disorder is associated with a blunted dopamine response toward drugs, while conflicting findings of reward response has been reported in gambling disorder. Instead, it is suggested that the anticpatory dopamine response may constitute a common underpinning of gambling disorder and substance use disorder, which may be associated with increased dopamine activity in both types of disorder, and does not involve the intake of substances. The notion of the anticipatory dopamine response as a common underpinning of gambling disorder and substance use disorder is consistent with dopaminergic models of addictions such as the incentive-sensitization model, the ingrative neurodevelopmental model of vulnerability toward addiction and the reward prediction error model.


Effects of dietary supplementation of myco-fabricated zinc oxide nanoparticles on performance, histological changes, and tissues Zn concentration in broiler chicks.
A five weeks biological experiment was planned to investigate the impacts of dietary supplementation with zinc oxide nanoparticles (ZnONPs) synthesized by the endophytic fungus Alternaria tenuissima on productive performance, carcass traits, organ relative weights, serum biochemical parameters, histological alteration in some internal organs and concentration of this element in the serum, liver, thigh and breast muscle in broiler chicks. A total of 108 3-day-old commercial broiler chicks (Cobb 500) were individually weighed and equally distributed in a completely randomized design arrangement according to the dose of ZnONPs supplementation into 3 dietary experimental groups. There were 6 replications having 6 birds per replicate (n = 36/ treatment) for each treatment. The three experiential dietary treatments received corn-soybean meal-based diets enhanced with 0 (control), 40 and 60 mg/kg diet of ZnONPs respectively with feed and water were provided ad libitum consumption through 5 weeks life span. Present results indicated that after 5 weeks of feeding trial and as compared to control, the ZnONPs supplementation groups recorded higher body weight, improved feed consumption, feed conversion ratio and performance index. Serum biochemical analyses revealed that serum cholesterol, triglyceride, low density lipoprotein and uric acid decreased significantly, while high density lipoprotein and liver enzyme concentrations were increased significantly. Meanwhile, zinc accumulation in serum, liver and breast and thigh muscle were linearly increased with increasing zinc supplementation. It could be concluded that supplementation of ZnONPs to broiler diet at 40 or 60 mg/kg improved productive performance, birds' physiological status and the lower levels Zn (40 mg/kg diet) revealed promising results and can be used as an effective feed additive in broilers.


Development and validation of a novel PCR-RFLP based method for the detection of 3 primary mitochondrial mutations in Leber's hereditary optic neuropathy patients.
Leber's Hereditary Optic Neuropathy (LHON; MIM 535000) is one of the most commonly inherited optic neuropathies and it results in significant visual morbidity among young adults with a peak age of onset between the ages of 15-30. The worldwide incidence of LHON is approximately 1 in 31,000. 95 % of LHON patients will have one of 3 primary mitochondrial mutations, G3460A (A52T of ND1), G11778A (R340H of ND4) and T14484C (M64V of ND6). There is incomplete penetrance and a marked gender bias in the development of visual morbidity with approximately 50 % of male carriers and 10 % of female carriers developing optic neuropathy. Visual recovery can occur but is dependent on the mutation present with the highest level of visual recovery seen in patients who have the T14484C mutation. The 3 primary mutations are typically identified by individual end-point PCR-restriction fragment length polymorphism (RFLP) or individual targeted bi-directional Sanger sequencing reactions. The purpose of this study was to design a simple multiplex PCR-RFLP that could detect these 3 primary LHON mutations in one assay. PCR primers were designed to incorporate a MaeIII restriction site in the presence of 3460A and 14484C mutations with the 11778A mutation naturally incorporating a MaeIII site. A multiplex PCR-RFLP assay was developed to detect the 3 common mutations in a single assay. Synthetic LHON controls based on the mitochondrial genome harbouring the 3 common mutations were synthesized and cloned into plasmids to act as reliable assay controls. DNA from previously tested patients and the synthetic LHON controls were subjected to the multiplex PCR-RFLP assay. The RFLP products were detected by agarose gel electrophoresis. The novel PCR-RFLP assay accurately detects the 3 primary mutations both in patient DNA and in synthesized DNA control samples with a simple visual mutation detection procedure. The synthesized DNA was demonstrated to be a robust control for the detection of LHON Mutations. In this paper, we describe a novel, robust and simple PCR-RFLP based method for the detection of mutations causing LHON, and report the generation of a series of LHON DNA controls suitable for all currently published assays.


Social Media for the Promotion of Holistic Self-Participatory Care: An Evidence Based Approach. Contribution of the IMIA Social Media Working Group.
As health information is becoming increasingly accessible, social media offers ample opportunities to track, be informed, share and promote health. These authors explore how social media and holistic care may work together; more specifically however, our objective is to document, from different perspectives, how social networks have impacted, supported and helped sustain holistic self-participatory care. A literature review was performed to investigate the use of social media for promoting health in general and complementary alternative care. We also explore a case study of an intervention for improving the health of Greek senior citizens through digital and other means. The Health Belief Model provides a framework for assessing the benefits of social media interventions in promoting comprehensive participatory self-care. Some interventions are particularly effective when integrating social media with real-world encounters. Yet not all social media tools are evidence-based and efficacious. Interestingly, social media is also used to elicit patient ratings of treatments (e.g., for depression), often demonstrating the effectiveness of complementary treatments, such as yoga and mindfulness meditation. To facilitate the use of social media for the promotion of complementary alternative medicine through self-quantification, social connectedness and sharing of experiences, exploration of concrete and abstract ideas are presented here within. The main mechanisms by which social support may help improve health - emotional support, an ability to share experiences, and non-hierarchal roles, emphasizing reciprocity in giving and receiving support - are integral to social media and provide great hope for its effective use.


Multiplicity does not significantly affect outcomes in brain metastasis patients treated with surgery.
Brain metastasis quantity may be a negative prognostic factor for patients requiring resection of at least one lesion. We retrospectively reviewed patients who underwent surgical resection of brain metastases from July 2018 to June 2019 at our institution, and examined outcomes including overall survival (OS), progression free survival (PFS), and rates of local failure (LF). Patients were grouped according to the number of metastases at the time of surgery (single vs multiple). We identified 130 patients who underwent surgical resection as the initial treatment modality. At the time of surgery, 87 patients had only one lesion (control) and 43 had multiple (>1). Two-year OS for the entire cohort was 46%, with equal rates in both the multiple metastases group and the control group (P = .335). 2-year PFS was 27%; 21% in the multiple metastases group and 31% in the control group (P = .766). The rate of LF at 2 years was 32%, with equal rates in both the multiple lesion group and control group (P = .889). On univariate analysis, multiplicity was not significantly correlated to OS (HR = 0.80, 95% CI: 0.51-1.26, P = .336), PFS (HR = 1.06, 95% CI: 0.71-1.59, P = .766) or LF (HR = 1.06, 95% CI: 0.57-1.97, P = .840). Multivariate analysis revealed preoperative tumor volume of the resected lesion to be the single correlate for OS (P = .0032) and PFS (P = .0081). Having more than one metastasis does not negatively impact outcomes in patients treated with surgery. In carefully selected patients, especially those with large tumors, surgery should be considered regardless of the total number of lesions.


Giant aneurysms in CT and angiography.
Giant intracranial aneurysms are frequently observed as incidental findings on CT and angiograms obtained for purposes other than subarachnoid hemorrhage, such as slowly evolving nerve palsy or hemiparesis. Since giant aneurysms often thrombose, the CT scan may demonstrate a larger aneurysmal volume than the angiogram. This paper presents CT and angiogram findings in cerebral aneurysms with a diameter of 25 mm-60 mm. The discussion covers: sort of aneurysm (congenital, arteriosclerotic); type and degree of thrombosis; long-term results after spontaneous thrombosis; and CT examination after using epsilon-aminocaproic acid.


The in vivo effects of a polyamine analogue on tissue stem cell proliferation.
We have studied by autoradiography the effects of 1,3-diaminopropane (DAP) upon cellular proliferation in a number of tissues in vivo in the rat. DAP is a structural analogue of the naturally occurring polyamine putrescine, and is believed to block cellular polyamine synthesis by supressing the induction of ornithine decarboxylase (the rate-limiting enzyme for polyamine biosynthesis). The continuous infusion of DAP into rats that had been partially hepatectomised prevented the subsequent waves of spermidine and DNA synthesis from taking place in the regenerating liver. The inhibition of DNA synthesis is accounted for primarily by a block in the entry of hepatocytes into S phase and not by a reduction in the rate of DNA synthesis itself. In contrast to the regenerating liver, DAP exerted minimal effects upon the proliferation of the gut epithelium and bone marrow elements. The proliferation of stem cells of these latter tissues, which are normally in a state of rapid and continuous proliferation unlike the liver, is thus much more resistant to perturbations in polyamine biosynthesis and function. DAP is consequently unable to arrest and so protect normal rapidly proliferating tissues from damage caused by anti-cancer drugs (e.g. hydroxyurea) that kill only proliferating cells. DAP cannot therefore be employed to selectively protect normal cells but not tumour cells from cytotoxic damage according to a principle we have previously established in tissue culture.


Serum uric acid level as a risk factor for acute kidney injury in hospitalized patients: a retrospective database analysis using the integrated medical information system at Kochi Medical School hospital.
Recent studies have shown that both low and high levels of serum uric acid (SUA) before cardiovascular surgery are independent risk factors for postoperative acute kidney injury (AKI). However, these studies were limited by their small sample sizes. Here, we investigated the association between SUA levels and AKI by performing a retrospective database analysis of almost 30 years of data from 81,770 hospitalized patients. Hospitalized patients aged ≥18 years were retrospectively enrolled. AKI was diagnosed according to the Kidney Disease: Improving Global Outcomes 2012 Clinical Practice Guideline (KDIGO) criteria. Multivariate logistic regression analyses were performed to investigate the independent association between SUA levels and the incidence of AKI. SUA levels were treated as categorical variables because the relationship between SUA and the incidence of AKI has been suggested to be J-shaped or U-shaped. In addition to stratified SUA levels, we considered kidney function and related comorbidities, medications, and procedures performed prior to AKI onset as possible confounding risk factors. The final study cohort included 59,219 adult patients. Adjusted odds ratios of AKI incidence were higher in both the high- and low-SUA strata. Odds ratios tended to become larger in the higher range of SUA levels in women than in men. Additionally, this study showed that AKI risk was elevated in patients with SUA levels ≤7 mg/dL. An SUA level >7 mg/dL is considered the point of initiation of uric acid crystallization. SUA level could be an independent risk factor for AKI development in hospitalized patients. Additionally, our results might suggest that intervention to lower SUA levels is necessary, even in cases of moderate elevation that does not warrant hyperuricemia treatment. Results also showed that SUA levels that require attention are lower for women than for men.


Milk yield estimation of Ogaden cattle breed based on methods of weigh-suckle-weigh and calves' growth.
Daily milk yield of Ogaden cattle was estimated from milk suckled by 269 calves born and maintained between 1994 and 2004 at Haramaya University Beef Farm, Ethiopia. The weigh-suckle-weigh method and the growth of calves were used to estimate the yield. Mean predicted daily milk yield of the breed based on the weigh-suckle-weigh method was 4.39 ± 0.03 kg day(-1). Daily milk yield estimated from the growth of calves up to 3 months of age was 4.59 ± 1.43 kg day(-1). The milk yield was significantly affected by seasons of calving (p < 0.001), parities of the dams (p < 0.05), weeks of lactation (p < 0.001) and birth weights of calves (p < 0.05). A relatively higher milk yield was observed from cows calved during the long rain season. A higher milk yield was produced by cows in fifth parity. Heavier calves at birth suckled more milk than lighter calves. Daily milk yield was significantly higher in 3-6 weeks of lactation. The result of this study indicated that the milk yield produced by Ogaden breed was relatively higher than the yield of some Zebu breed measured by partial suckling system in Ethiopia and was comparable to the yield from Zebu cattle in the tropics estimated by the same method.


Shape-selective stereo processing in human object-related visual areas.
Object related areas in the human ventral stream were previously shown to be activated, in a shape-selective manner, by luminance, motion, and texture cues. We report on the preferential activation of these areas by stereo cues defining shape. To assess the relationship of this activation to object recognition, we employed a perceptual stereo effect, which profoundly affects object recognition. The stimuli consisted of stereo-defined line drawings of objects that either protruded in front of a flat background ("front"), or were sunk into the background ("back"). Despite the similarity in the local feature structure of the two conditions, object recognition was superior in the "front" compared to the "back" configuration. We measured both recognition rates and fMRI signal from the human visual cortex while subjects viewed these stimuli. The results reveal shape selective activation from images of objects defined purely by stereoscopic cues in the human ventral stream. Furthermore, they show a significant correlation between recognition and fMRI signal in the object-related occipito-temporal cortex (lateral occipital complex).


Neoadjuvant Therapy Is Associated with Improved Chemotherapy Delivery and Overall Survival Compared to Upfront Resection in Pancreatic Cancer without Increasing Perioperative Complications.
The role of neoadjuvant chemoradiotherapy and/or chemotherapy (neoCHT) in patients with pancreatic ductal adenocarcinoma (PDAC) is poorly defined. We hypothesized that patients who underwent neoadjuvant therapy (NAT) would have improved systemic therapy delivery, as well as comparable perioperative complications, compared to patients undergoing upfront resection. This is an IRB-approved retrospective study of potentially resectable PDAC patients treated within an academic quaternary referral center between 2011 and 2018. Data were abstracted from the electronic medical record using an institutional cancer registry and the National Surgical Quality Improvement Program. Three hundred and fourteen patients were eligible for analysis and eighty-one patients received NAT. The median overall survival (OS) was significantly improved in patients who received NAT (28.6 vs. 20.1 months, p = 0.014). Patients receiving neoCHT had an overall increased mean duration of systemic therapy (p < 0.001), and the median OS improved with each month of chemotherapy delivered (HR = 0.81 per month CHT, 95% CI (0.76-0.86), p < 0.001). NAT was not associated with increases in early severe post-operative complications (p = 0.47), late leaks (p = 0.23), or 30-90 day readmissions (p = 0.084). Our results show improved OS in patients who received NAT, driven largely by improved chemotherapy delivery, without an apparent increase in early or late perioperative complications compared to patients undergoing upfront resection.


The role of chemokines in the pathogenesis of neurotropic flaviviruses.
Neurotropic flaviviruses are important emerging and reemerging arthropod-borne pathogens that cause significant morbidity and mortality in humans and other vertebrates worldwide. Upon entry and infection of the CNS, these viruses can induce a rapid inflammatory response characterized by the infiltration of leukocytes into the brain parenchyma. Chemokines and their receptors are involved in coordinating complex leukocyte trafficking patterns that regulate viral pathogenesis in vivo. In this review, we will summarize the current literature on the role of chemokines in regulating the pathogenesis of West Nile, Japanese encephalitis, and tick-borne encephalitis virus infections in mouse models and humans. Understanding how viral infections trigger chemokines, the key cellular events that occur during the infection process, as well as the immunopathogenic role of these cells, are critical areas of research that may ultimately guide a much needed effort toward developing specific immunomodulators and/or antiviral therapeutics.


The significance of microscopic involvement of the parametrium and/or pelvic lymph nodes in cervical cancer stages IB and IIA.
From 1961 through 1980, 388 patients with cervical carcinoma stage IB (272) and stage IIA (116) were treated by radical hysterectomy and pelvic lymphadenectomy. The operation specimens were divided into four groups: no involvement of the parametrium and pelvic lymph nodes (71.4%), involvement of the parametrium alone (7.2%), involvement of the pelvic lymph nodes alone (11.9%), and involvement of both the parametrium and pelvic lymph nodes (9.5%). Two hundred thirty-eight patients were followed for at least 5 years. The corrected 5-year survival figures for these four groups (stages IB and IIA together) were 90.3, 75.0, 62.1, and 50.0%, respectively. The differences are of statistical significance (P less than 0.005). Not only the stage of disease and involvement of the lymph nodes, but clearly also the involvement of the parametrium is of significance for the results of treatment in cervical cancer.


Analysis of the Impact of the Confinement Resulting from COVID-19 on the Lifestyle and Psychological Wellbeing of Spanish Pregnant Women: An Internet-Based Cross-Sectional Survey.
(1) Background: This study aimed to analyze the impact of the confinement due to the COVID-19 pandemics on the eating, exercise, and quality-of-life habits of pregnant women. (2) Methods: This was an internet-based cross-sectional survey which collected information about adherence to the Mediterranean diet, physical exercise, health-related quality of life (HRQoL), and perceived obstacles (in terms of exercise, preparation for delivery, and medical appointments) of pregnant women before and after the confinement. The survey was conducted in 18-31 May 2020. (3) Results: A total of 90 pregnant women participated in this study. There was a significant decrease in the levels of physical activity (p < 0.01) as well as in HRQoL (p < 0.005). The number of hours spent sitting increased by 50% (p < 0.001), 52.2% were unable to attend delivery preparation sessions because these had been cancelled. However, there were no significant differences in the eating pattern of these women (p = 0.672). Conclusions: These results suggest the need to implement specific online programs to promote exercise and reduce stress, thus improving the HRQoL in this population, should similar confinements need to occur again for any reason in the future.


Occurrence of delusions during repetitive transcranial magnetic stimulation (rTMS) in major depression.
Repetitive transcranial magnetic stimulation (rTMS) has been suggested as a potentially useful treatment for major depression. Nonpsychotic depressed patients appear to have a better outcome than those with psychotic symptoms. We report findings in a patient suffering from recurrent, nonpsychotic major depression (DSM-IV) who had 13 daily sessions of rTMS monotherapy within a 3 week period. During rTMS treatment, the patient developed recurrent severe delusions, which he had never experienced before. Psychotic symptoms remitted quickly with neuroleptic medication. In light of preclinical findings showing increased dopaminergic activity after rTMS treatment, occurrence of psychotic symptoms should be considered a potential side effect of rTMS treatment.


Modelling the role of redox-related mechanisms in musculoskeletal ageing.
The decline in the musculoskeletal system with age is driven at the cellular level by random molecular damage. Cells possess mechanisms to repair or remove damage and many of the pathways involved in this response are regulated by redox signals. However, with ageing there is an increase in oxidative stress which can lead to chronic inflammation and disruption of redox signalling pathways. The complexity of the processes involved has led to the use of computational modelling to help increase our understanding of the system, test hypotheses and make testable predictions. This paper will give a brief background of the biological systems that have been modelled, an introduction to computational modelling, a review of models that involve redox-related mechanisms that are applicable to musculoskeletal ageing, and finally a discussion of the future potential for modelling in this field.


Cryopreservation of human ovarian tissue by solid-surface vitrification.
To cryopreserve human ovarian tissue using solid-surface vitrification (SSV) technique for the first time. Human ovarian slices from each of 26 patients were randomly allocated to fresh, SSV, and slow-freezing groups, respectively. Histological observation and the TUNEL assay of the tissue were performed after cryopreservation. In vitro culture was done to study the initial recruitment of follicles and hormone production ability after SSV/slow-freezing. The majority of primordial follicles were maintained intact through either SSV or the slow-freezing method. No statistically significant destructive effect of SSV or slow-freezing for primordial follicles and stromal cells was found using the TUNEL assay. In the SSV and slow-freezing groups, estradiol and progesterone were secreted continuously during 10 days in culture, and the proportions of growing follicles increased significantly comparing to the uncultured fresh group. The follicular proportions and the concentrations of estradiol and progesterone exhibited no statistically significant differences between the SSV and slow-freezing groups. SSV is an effective, simple and inexpensive alternative for human ovarian tissue cryopreservation.


Age-related changes in GAD levels in the central auditory system of the rat.
Changes in the levels of gamma-aminobutyric acid (GABA) are known to occur in different parts of the brain during aging. In our study we attempted to define the effect that aging has on glutamate decarboxylase (GAD), the key enzyme in the synthesis of GABA, in the central parts of the auditory system. Age-related changes in GAD65 and GAD67 levels were investigated using immunohistochemistry and Western blotting in the inferior colliculus (IC), the auditory cortex (AC) and the visual cortex in Long-Evans rats. The results show that aging is associated with a decrease in the numbers of GAD65- and 67-immunoreactive neurons and the optical density of their somas in both the IC and AC. Western blot analysis revealed a pronounced age-related decline in the levels of GAD65 and 67 proteins in both the IC and AC. For comparison, in the visual cortex the decrease in both proteins was less pronounced than in the IC and AC. A similar pattern of age-related changes was found in Fischer 344 rats, a strain that manifests a rapid loss of hearing function with aging. The observed age-related decline in the levels of GAD65 and 67 may contribute significantly to the deterioration of hearing function that accompanies aging in mammals, including man.


Effects of biochar and straw application on the soil structure and water-holding and gas transport capacities in seasonally frozen soil areas.
To explore the effects of different regulation modes on the soil structure and gas transport characteristics in seasonal permafrost regions, freeze-thaw cycles (FTCs) were used as boundary conditions and three typical soils on the Songnen Plain were used: black soil, baijiang soil and meadow soil. Four treatments were established: biochar addition (B1), straw addition (S1), biochar combined with straw addition (B1S1) and an untreated control (CK). The changes in the proportion of soil water-stable aggregates, total soil porosity (TP), soil water characteristic curves (SWRCs), soil dissolved organic carbon (DOC) and soil air permeability (PL) were analyzed. The results showed that biochar and straw influenced the structure of the three soil types. The proportions of large (2-0.5 mm) and medium (0.5-0.25 mm) aggregates increased significantly. The soil aggregate stability indexes of the treated soils were better than those of the CK, and the three-phase ratios of the treated soils were closer to ideal. The different treatments had particularly obvious effects on the black soil; the generalized soil structure index (GSSI) values reached 95.59, 94.36 and 98.74 in the B1, S1 and B1S1 treatments, respectively. An interaction effect was observed between biochar and straw. B1S1 had a stronger effect than the other treatments, and the soil water holding capacity was significantly improved (FC = 0.317 cm3 cm-3). Under the B1S1 treatment, the DOC contents in black soil, baijiang soil and meadow soil were 160.78 mg/kg, 272.828 mg/kg and 271.912 mg/kg, respectively. Moreover, biochar and straw combined effectively reduced PL fluctuations under FTCs and improved the long-term stability of the soil structure. These results can aid in rational straw and biochar use to achieve comprehensive agricultural waste utilization.


The avian somatosensory system. I. Primary spinal afferent input to the spinal cord and brainstem in the pigeon (Columba livia).
The process of transganglionic transport was used to determine the pattern of primary afferent projections to the spinal cord and brainstem in the pigeon by (1) applying horseradish peroxidase (HRP) to various peripheral nerves in the leg or wing, (2) by injecting HRP-lectin into feather follicles of the wing or tail, and (3) by injecting HRP-lectin into various muscles of the leg or wing. In the spinal cord major peripheral nerves were represented heavily throughout the dorsal horn laminae but sparsely in more ventral laminae. The representations of these different nerves tended to be located in different mediolateral regions of the dorsal horn. Cutaneous nerves and feather follicles were represented predominantly in laminae I and II, and different sets of follicles were represented in different mediolateral regions of these laminae. Afferent labelling from muscles of the leg and wing was located in the lateral portion of the dorsal horn, predominantly in laminae I, II, and IV. In the caudal medulla the representation of the leg within the gracile nucleus was medial to and separate from that of the wing within the cuneate nucleus (Cu). The wing representation, however, extended laterally throughout the external cuneate nucleus (CuE) and lateral regions of the descending trigeminal tract. There was less evidence of separation of the limb representations at more rostral medullary levels where they both occupied predominantly CuE. Afferent labelling from cutaneous nerves and feather follicles was distributed lightly throughout Cu and CuE, and from muscles of both limbs primarily throughout CuE. There was also a small but specific projection from the limbs to the nucleus of the solitary tract, and from the wing to the principal sensory trigeminal nucleus. These results are discussed within a comparative context with a view to highlighting the similarities and differences in the pattern of primary afferent central projections in different vertebrates.


Transmission of two Australian strains of murine cytomegalovirus (MCMV) in enclosure populations of house mice (Mus domesticus).
To control plagues of free-living mice (Mus domesticus) in Australia, a recombinant murine cytomegalovirus (MCMV) expressing fertility proteins is being developed as an immunocontraceptive agent. Real-time quantitative PCR was used to monitor the transmission of two genetically variable field strains of MCMV through mouse populations after 25% of founding mice were infected with the N1 strain, followed by the G4 strain 6 weeks later. Pathogen-free wild-derived mice were released into outdoor enclosures located in northwestern Victoria (Australia). Of those mice not originally inoculated with virus, N1 DNA was detected in more than 80% of founder mice and a third of their offspring and similarly, G4 DNA was detected in 13% of founder mice and in 3% of their offspring. Thus, prior immunity to N1 did not prevent transmission of G4. This result is promising for successful transmission of an immunocontraceptive vaccine through Australian mouse populations where MCMV infection is endemic.


Microbial contamination of radionuclide generators.
Technetium-99m generators were grossly contaminted using 5 different strains of microorganisms. Elution of the generators showed that the number of microorganisms was reduced by a factor of 10(4)-10(6). There were no indications that the generators would support bacterial growth. It is concluded that it would be acceptable from a microbiologic point of view to omit autoclaving and membrane filtration of the final product provided that proper aseptic techniques are applied.


Incorporation du desmosterol-3-(3)h dans les sterols du tabac nicotiana tabacum.
The propionate of 3-(3)H desmosterol has been applied to the leaves of the tobacco Nicotiana tabacum Wisconsin. Radioactivity is incorporated into cholesterol and campesterol with a yield of about 0.5%; the C(29) sterols are not labelled in this experiment.


Effect of the stiffness of bone substitutes on the biomechanical behaviour of femur for core decompression.
Core decompression is the most common procedure for treatment of the early stages of osteonecrosis of the femoral head. The purpose of this study was to compare the biomechanical performance of four different bone graft substitutes combined with core decompression. Subject-specific finite element models generated from computed tomography (CT) scan data were used for a comprehensive analysis. Two different contact conditions were simulated representing states of osseointegration at the interface. Our results showed that the use of a low-stiffness bone substitute did not increase the risk of femoral fracture in the early postoperative phase, but resulted in less micromotion and interfacial stresses than high-stiffness bone substitutes.


Formation of Nanotwin Networks during High-Temperature Crystallization of Amorphous Germanium.
Germanium is an extremely important material used for numerous functional applications in many fields of nanotechnology. In this paper, we study the crystallization of amorphous Ge using atomistic simulations of critical nano-metric nuclei at high temperatures. We find that crystallization occurs by the recurrent transfer of atoms via a diffusive process from the amorphous phase into suitably-oriented crystalline layers. We accompany our simulations with a comprehensive thermodynamic and kinetic analysis of the growth process, which explains the energy balance and the interfacial growth velocities governing grain growth. For the 〈111〉 crystallographic orientation, we find a degenerate atomic rearrangement process, with two zero-energy modes corresponding to a perfect crystalline structure and the formation of a Σ3 twin boundary. Continued growth in this direction results in the development a twin network, in contrast with all other growth orientations, where the crystal grows defect-free. This particular mechanism of crystallization from amorphous phases is also observed during solid-phase epitaxial growth of 〈111〉 semiconductor crystals, where growth is restrained to one dimension. We calculate the equivalent X-ray diffraction pattern of the obtained nanotwin networks, providing grounds for experimental validation.


Neuropeptide-like immunoreactivities and carboxypeptide H activity associated with bovine brain clathrin coated vesicles.
Chromatographically purified clathrin coated vesicles (CCV) from bovine brain gray matter were collected and analyzed for their adaptor protein profile via SDS-PAGE, for their carboxypeptidase H (CPH) activity via radioenzymatic assays and for their NP (NPY1-36, CCK-8 and SS-14) content by radioimmunoassays. The results reveal the expression of CPH and neuropeptide-like immunoreactivities (NP-Li: NPY-Li, CCK-Li and SS-Li) associated with CCV. CPH activity associated with CCV is stimulated by cobalt, inhibited by 5 microM GEMSA and has an acidic pH optimum (4.5-6.5). The Michaelis-Menten kinetics assay of CPH in CCV reveals a Km = 28.9 microM and Vmax = 1.88 nmol/min/mg at pH 4.5 using 3H.Bz-FAR as a substrate. The NP-Li and CPH were mainly associated with the ascending portion of the CCV peak suggesting that these molecules are found in the larger diameter CCV subpopulation associated with CCV of the trans Golgi network (TGN), endocytic or recycling CCV. Analysis of the adaptor protein profile of the material eluting from the Sephacryl S-1000 column demonstrates a wide distribution of the Golgi-associated AP-1 (HA-I) molecules (AP47 and AP19) in relation to the CCV peak, spanning both the ascending and descending portions of the CCV peak. This adaptor protein pattern is consistent with the inherent size microheterogeneity of TGN CCV, large diameter CCV of the regulated secretory pathway and smaller diameter CCV of the lysosomal pathway.


Outcome in patients hospitalised for psoriatic arthritis.
Forty patients hospitalised for treatment of psoriatic arthritis (PsA) were followed for a mean of 8.0 years. At the end of this time none had died and only 8% were in functional class IV. 90% received second-line therapy. There was a high incidence of skin rashes on gold but hydroxychloroquine was well tolerated. Patients with psoriatic arthritis had a better outcome than patients with rheumatoid arthritis treated with the same regime.


Lymphokines. VI. Factors in human and other heterologous sera inhibiting the migration of guinea pig macrophages.
Different heterologous sera including human, rabbit, bovine and fetal calf serum (FCS) showed a strong inhibiting effect on the migration of guinea pig peritoneal macrophages (GPPM), compared to the migration of GPPM in homologous guinea pig serum. The inhibiting effect of these sera on the migration of horse monocytes on the other hand was much less marked. Fractionation of human and rabbit serum showed the 4 S fraction to be most inhibitory on GPPM migration. The migration inhibiting effect of heterologous sera on GPPM was prevented by addition of homologous (GP) serum, by absorption of the sera by various guinea pig cells, by heating at 56 degrees and by addition of alpha-L-fucose. Human sera were found to be strongly cytotoxic for 51Cr-labelled guinea pig erythrocytes and lymphocytes, but not for horse lymphocytes. Upon absorption with guinea pig erythrocytes, lymphocytes and kidney cells, the cytotoxicity of the human sera was strongly reduced. Accordingly, the role of heterophilic antibodies and/or of heat-labile MIF-like factors in heterologous sera has to be considered in al macrophage migration experiments where heterologous sera are being used. These factors may differ from the heat-stable MIF activity generated upon antigen- or mitogen-induced stimulation of cultured lymphocytes.


Bacteriophage T4 Vaccine Platform for Next-Generation Influenza Vaccine Development.
Developing influenza vaccines that protect against a broad range of viruses is a global health priority. Several conserved viral proteins or domains have been identified as promising targets for such vaccine development. However, none of the targets is sufficiently immunogenic to elicit complete protection, and vaccine platforms that can enhance immunogenicity and deliver multiple antigens are desperately needed. Here, we report proof-of-concept studies for the development of next-generation influenza vaccines using the bacteriophage T4 virus-like particle (VLP) platform. Using the extracellular domain of influenza matrix protein 2 (M2e) as a readout, we demonstrate that up to ~1,281 M2e molecules can be assembled on a 120 x 86 nanometer phage capsid to generate M2e-T4 VLPs. These M2e-decorated nanoparticles, without any adjuvant, are highly immunogenic, stimulate robust humoral as well as cellular immune responses, and conferred complete protection against lethal influenza virus challenge. Potentially, additional conserved antigens could be incorporated into the M2e-T4 VLPs and mass-produced in E. coli in a short amount of time to deal with an emerging influenza pandemic.


The practicalities of terminally ill patients signing their own DNR orders--a study in Taiwan.
To investigate the current situation of completing the informed consent for do-not-resuscitate (DNR) orders among the competent patients with terminal illness and the ethical dilemmas related to it. This study enrolled 152 competent patients with terminal cancer, who were involved in the initial consultations for hospice care. Comparisons of means, analyses of variance, Student's t test, chi(2) test and multiple logistic regression models. After the consultations, 117 (77.0%) of the 152 patients provided informed consent for hospice care and DNR orders. These included 21 patients (17.9%) who signed the consent by themselves, and 96 (82.1%) whose consent sheet was signed only by family members. The reasons why patients were not involved in the discussions toward the consent (n = 82) included poor physical or psychological condition (44.9%), concerns of the consultant hospice team (37.2%), and the family's refusal (28.2%). On a multivariate analysis, patients' awareness of their poor prognosis (odds ratio = 4.07, 95% confidence interval = 2.05 to 8.07) and their understanding of hospice care (2.27, 1.33 to 3.89) were two independent factors (p < 0.01) that influenced their participation in the discussions or their personal signature in the informed consent. The family-oriented culture in Asian countries may violate the principles of the Patient Self-Determination Act and the requirements of the Hospice Care Law in Taiwan, which inevitably poses an ethical dilemma. Earlier truth-telling and continuing education of the public by hospice care workers will be helpful in solving such ethical dilemmas.


Injectable photocurable Janus hydrogel delivering hiPSC cardiomyocyte-derived exosome for post-heart surgery adhesion reduction.
Postsurgical pericardial adhesions pose increased risks of sequelae, prolonged reoperation time, and reduced visibility in the surgical field. Here, we introduce an injectable Janus hydrogel, which exhibits asymmetric adhesiveness properties after photocrosslinking, sustained delivering induced pluripotent stem cell-derived cardiomyocyte exosomes (iCM-EXOs) for post-heart surgery adhesion reduction. Our findings reveal that iCM-EXOs effectively attenuate oxidative stress in hydrogen peroxide-treated primary cardiomyocytes by inhibiting the activation of the transcription factor nuclear factor erythroid 2-related factor 2. Notably, in rat cardiac postsurgery models, the Janus hydrogels loaded with iCM-EXOs demonstrate dual functionality, acting as antioxidants and antipericardial adhesion agents. These hydrogels effectively protect iCM-EXOs from GATA6+ cavity macrophage clearance by inhibiting the recruitment of macrophages from the thoracic cavity. These results highlight the promising potential of iCM-EXO-laden Janus hydrogels for clinical safety and efficacy validation in trials involving heart surgery patients, with the ultimate goal of routine administration during open-heart surgeries.


Raman spectroscopy and partial least squares analysis in discrimination of peripheral cells affected by Huntington's disease.
Huntington's disease (HD) is a neurodegenerative disorder caused by trinucleotide CAG (Cytosine-Adenine-Guanine) expansion on the Huntingtin gene (HTT) encoding for the Huntingtin protein (Htt). The protein has been linked in peripheral fibroblasts with dysregulation of cellular components which are part of lipid rafts in plasma membrane sub-domains. Therefore the analysis of the plasma membrane might be a useful diagnostic biomarker for the detection of the presence and possible onset of HD in readily accessible peripheral cells. Here Raman spectroscopy has been used with a chemometric approach in the form of Partial Least Square (PLS) for an initial corroboration that the plasma membrane is indeed a sub-cellular biomarker discriminator for HD identification. Observations were made in the spectral regions from 400 to 1800 cm(-1) and 2700 to 3200 cm(-1) with the former region displaying the most significant differences and peak displacement between plasma membranes extracted from HD and control fibroblast cells. The major differences in plasma membrane composition reside in sub-cellular elements putatively associated to cholesterol, phospholipids (mainly phophatidylinositol) as well as proteins containing tyrosine. These findings are indicative of the plasma membrane as an amenable biomarker for HD for further in vitro research with possible applications in vivo models.


A modified ELISA technique for anti-hapten antibodies.
Polystyrene tubes pretreated with glutaraldehyde in phosphate buffer were used in a solid-phase enzyme-linked immunoassary (ELISA). The hapten o-dinitrocarboxyphenol (o-DNCP) was used as coat. The binding of homologous rabbit antibodies was measured with phosphatase-labelled staphylococcal protein A (SPA-PH). This method is both very sensitive (serum dilutions greater than 2 x 10(-6) were still positive) and highly reproducible. Anti-DNP rat IgE was detected with o-DNCP hapten as a coat using avidin/biotin as a marker.


Social class discrimination during adolescence as a mediator of socioeconomic disparities in actigraphy-assessed and self-reported sleep.
To examine social class discrimination as a mediator of socioeconomic disparities in sleep outcomes in an adolescent sample. Sleep was assessed from established actigraphy (efficiency, long wake episodes, duration) and self-report (sleep/wake problems, daytime sleepiness) measures among 272 high school students in the Southeastern region of the United States (35% low income; 59% White, 41% Black, 49% female, Mean age = 17.3, SD = 0.8). Social class discrimination was assessed using a new measure, the Social Class Discrimination Scale (SCDS; 22-items), and an established measure, the Experiences of Discrimination Scale (EODS; 7-items). Socioeconomic disadvantage (SED) was measured as an aggregate of six indicators. The SCDS was associated with sleep efficiency, long wake episodes, sleep/wake problems and daytime sleepiness (but not sleep duration), and significantly mediated the socioeconomic gradient in each sleep outcome. Black males experienced higher levels of social class discrimination than Black females, White males, or White females. A race by gender moderation effect was evident for two of the five sleep outcomes (sleep efficiency and long wake episodes) suggesting a stronger association between social class discrimination and sleep problems for Black females than White females but no clear race differences among males. The EODS was not associated with objective sleep outcomes or SED but was associated with self-reported sleep and showed a similar pattern of moderation effects. Findings suggest that social class discrimination may contribute to socioeconomic disparities in sleep problems, with some variability across measures and demographic groups. Results are discussed in light of evolving trends in socioeconomic health disparities.


Acute abdomen in ruptured interstitial pregnancy following unilateral salpingectomy.
Interstitial pregnancy is an infrequent type of ectopic pregnancy. Two cases of acute abdomen due to ruptured interstitial pregnancy following salpingectomy, a rare event, are presented. Both patients were young women who had had a previous salpingo-oophorectomy due to ovarian cyst. The presenting symptoms were in the first case abdominal pain followed by hemorrhagic shock, and in the second a right iliac fossa syndrome simulating acute appendicitis. Surgical intervention consisted of wedge resection of the uterine segment involved. A review of the literature and practical considerations are presented.


The Intensive Care Unit diary - A significant complement in the recovery after intensive care. A focus group study.
The aim of this study was to gain an increased understanding of the intensive care unit diary and how it affects patients' recovery after intensive care. The study had a qualitative design and was conducted by two focus group interviews in October 2021 and was analysed with thematic analysis. Ventilator treated intensive care patients with a length of stay ≥ 72 hours who had received a written diary were included. The study was conducted at two university hospitals in the south of Sweden. The intensive care unit diary can be an important complement to the medical record and notes taken by family members by enhancing understanding of critical illness. The patients experience several prominent feelings from reading the diary such as guilt, fear, and anxiety as well as feelings of being cared for. The design and content of the diary can be important used as a tool in patients' recovery after intensive care. Understanding their critical illness and the time in intensive care seems important to former intensive care patients. In this respect, the intensive care unit diary on its own does not provide significant information and thus need to be complemented by information from the medical record and notes taken by family members. Therefore, the diary can be used as a complement that might increase patients' sense of coherence and facilitate recovery after intensive care.


Radiological evaluation of the urinary tract in children with urinary infection.
This article in to study the association of structural abnormalities of the urinary tract in children with urinary tract infection (UTI) using ultrasound examination. 262 children with culture proven urinary tract infection were studied. Antibiotics were given as per sensitivity pattern. All children had an ultrasound of the abdomen done within 3 weeks. A micturating cystourethrogram (MCU) was done in those with abnormalities of the lower urinary tract detected on ultrasound, as well as in those who had recurrence of infection, after a normal ultrasound. IVU and renal isotope scans were done in selected cases. All children were followed up until one year after the study period. Fifty-four patients had an underlying urinary tract anomaly; 42 were picked up by ultrasound and 12 by MCU. 22.9% of males and 15.9% of females had anomaly of the urinary tract. Children less than 2 years had the highest incidence of anomalies. Pelviureteric junction obstruction with hydronephrosis, vesicoureteric reflux and non-refluxing megaureter are the major anomalies picked up. 20% of children with urinary tract infections have an underlying structural abnormality of the urinary tract, three-fourth of which are picked up on ultrasound. An ultrasound abdomen is recommended in all children after the first UTI. In addition, an MCU is also indicated in all boys below 2 years with UTI, since one-third of anomalies will be missed if only ultrasound is done.


14-3-2 protein in rat brain synapses.
The distribution of the 14-3-2 protein in rat brain synapses was studied by immuno electron microscopy. The protein was localized to the postsynaptic web and to the postsynaptic membrane, but was also prominent both in the presynaptic membrane and in the presynaptic densities. No significant activity was observed in the synaptic vesicles.


Severity and mortality associated with COVID-19 among children hospitalised in tertiary care centres in India: a cohort study.
It is critical to identify high-risk groups among children with COVID-19 from low-income and middle-income countries (LMICs) to facilitate the optimum use of health system resources. The study aims to describe the severity and mortality of different clinical phenotypes of COVID-19 in a large cohort of children admitted to tertiary care hospitals in India. Children aged 0-19 years with evidence of SARS-CoV-2 infection (real time polymerase chain reaction or rapid antigen test positive) or exposure (anti-SARS-CoV-2 antibody, or history of contact with SARS-CoV-2) were enrolled in the study, between January 2021 and March 2022 across five tertiary hospitals in India. All study participants enrolled prospectively and retrospectively were followed up for three months after discharge. COVID-19 was classified into severe (Multisystem Inflammatory Syndrome in Children (MIS-C), severe acute COVID-19, 'unclassified') or non-severe disease. The mortality rates were estimated in different phenotypes. Among 2468 eligible children enrolled, 2148 were hospitalised. Signs of illness were present in 1688 (79%) children with 1090 (65%) having severe disease. High mortality was reported in MIS-C (18.6%), severe acute COVID-19 (13.3%) and the unclassified severe COVID-19 disease (12.3%). Mortality remained high (17.5%) when modified MIS-C criteria was used. Non-severe COVID-19 disease had 14.1% mortality when associated with comorbidity. Our findings have important public health implications for low resource settings. The high mortality underscores the need for better preparedness for timely diagnosis and management of COVID-19. Children with associated comorbidity or coinfections are a vulnerable group and need special attention. MIS-C requires context specific diagnostic criteria for low resource settings. It is important to evaluate the clinical, epidemiological and health system-related risk factors associated with severe COVID-19 and mortality in children from LMICs. Department of Biotechnology, Govt of India and Department of Maternal, Child and Adolescent Health and Aging, WHO, Geneva, Switzerland.


Acetabular penetration of sliding screw.
Case report of disengagement of sliding screw from the plate and penetration through the acetabulum into the pelvic cavity. The mechanism was probably technical failure in combination with osteoporosis and a new trauma in the region. We find that it is possible to remove the screw through the old incision, but the patient should be prepared for laparotomy.


Unlocking the story of resistance to Zymoseptoria tritici in Tunisian old durum wheat germplasm based on population structure analysis.
Septoria tritici blotch (STB) remains a significant obstacle to durum wheat cultivation on a global scale. This disease remains a challenge for farmers, researchers, and breeders, who are collectively dedicated to reduce its damage and improve wheat resistance. Tunisian durum wheat landraces have been recognized as valuable genetic ressources that exhibit resistance to biotic and abiotic stresses and therefore play a crucial role in breeding program aimed at creating new wheat varieties resistant to fungal diseases as STB, as well as adapted to climate change constraints. A total of 366 local durum wheat accessions were assessed for resistance to two virulent Tunisian isolates of Zymoseptoria tritici Tun06 and TM220 under field conditions. Population structure analysis of the durum wheat accessions, performed with 286 polymorphic SNPs (PIC > 0.3) covering the entire genome, identified three genetic subpopulations (GS1, GS2 and GS3) with 22% of admixed genotypes. Interestingly, all of the resistant genotypes were among GS2 or admixed with GS2. This study revealed the population structure and the genetic distribution of the resistance to Z. tritici in the Tunisian durum wheat landraces. Accessions grouping pattern reflected the geographical origins of the landraces. We suggested that GS2 accessions were mostly derived from eastern Mediterranean populations, unlike GS1 and GS3 that originated from the west. Resistant GS2 accessions belonged to landraces Taganrog, Sbei glabre, Richi, Mekki, Badri, Jneh Khotifa and Azizi. Furthermore, we suggested that admixture contributed to transmit STB resistance from GS2 resistant landraces to initially susceptible landraces such as Mahmoudi (GS1), but also resulted in the loss of resistance in the case of GS2 susceptible Azizi and Jneh Khotifa accessions.


Predicting cyclooxygenase inhibition by three-dimensional pharmacophoric profiling. Part II: Identification of enzyme inhibitors from Prasaplai, a Thai traditional medicine.
Prasaplai is a medicinal plant mixture that is used in Thailand to treat primary dysmenorrhea, which is characterized by painful uterine contractility caused by a significant increase of prostaglandin release. Cyclooxygenase (COX) represents a key enzyme in the formation of prostaglandins. Former studies revealed that extracts of Prasaplai inhibit COX-1 and COX-2. In this study, a comprehensive literature survey for known constituents of Prasaplai was performed. A multiconformational 3D database was created comprising 683 molecules. Virtual parallel screening using six validated pharmacophore models for COX inhibitors was performed resulting in a hit list of 166 compounds. 46 Prasaplai components with already determined COX activity were used for the external validation of this set of COX pharmacophore models. 57% of these components were classified correctly by the pharmacophore models. These findings confirm that the virtual approach provides a helpful tool (i) to unravel which molecular compounds might be responsible for the COX-inhibitory activity of Prasaplai and (ii) for the fast identification of novel COX inhibitors.


Frailty, cognitive impairment and mortality among the oldest old.
Both frailty and cognitive impairment are increasingly prevalent with advancing age. Nonetheless among the oldest old their relationship is poorly described. This study examines the association between frailty status and cognitive impairment at age 85 and their impact on 5-year mortality. A representative sample of 840 community dwelling people from the Jerusalem Longitudinal Cohort Study was comprehensively assessed at age 85. Frailty was defined according to the "phenotype of frailty", as including at least three of the following: weight loss, slowness, weakness, exhaustion and low physical activity levels. Pre frailty was defined as 1-2/5 criteria. Cognitive impairment was assessed according to the Mini Mental State Examination (MMSE). Mortality data was collected from age 85-90. A total of 164 (19.5%) were frail, 470 (56%) were pre frail and 206 (24.5%) were not frail, with prevalence of MMSE≤24 being 53.3%, 15%, and 7.4% respectively. A uniform pattern of increased adverse health, affective, disease and functional measures were associated with frailty status. Frailty status was significantly associated with cognitive impairment, with an Odds Ratios of 3.77 (95%CI 1.42-9.99) for MMSE≤24 after adjustment for socio demographic, medical mood and functional covariates. Among frail, pre frail and non frail subjects, 5-year mortality was 44.5%, 20.4%, 13.6% respectively. Mortality among frail subjects with or without cognitive impairment was 54.2% vs. 54.9%, p=0.9). Adjusting together for frailty, MMSE, education and gender, the Hazards ratio for 5-year mortality for frailty was 3.861 (95%CI 2.4-6.2), and for MMSE≤24 was 1.25 (95%CI 0.87-1.78). Among the oldest old, frailty status was significantly associated with cognitive impairment; after adjustment, frailty alone was predictive of subsequent mortality.


The Eight Hydrates of Strychnine Sulfate.
Commercial samples of strychnine sulfate were used as the starting material in crystallization experiments accompanied by stability studies. Eight hydrate forms (HyA-HyG), including five novel hydrates, were verified. The crystal structures of HyA ("pentahydrate") and HyF ("hexahydrate") were determined from single-crystal X-ray diffraction data. HyF was identified as the most stable hydrate at high water activities at room temperature (RT), and HyA and HyC were also found to be stable at ambient conditions. Long-time storage experiments over nearly two decades confirm that these three hydrates are stable at ambient conditions (20-60% relative humidity). The other five hydrates, HyB ("dihydrate"), HyD, HyE, HyG, and HyH, are only observable at the low(est) relative humidity (RH) levels at RT. Some of these latter forms can only exist within a very narrow RH range and are therefore intermediate phases. By applying a range of complementary experimental techniques such as gravimetric moisture sorption analysis, thermal analysis, moisture controlled PXRD measurements, and variable temperature IR spectroscopy in combination with principal component analysis, it was possible to identify the distinct hydrate phases and elucidate their stability and dehydration pathways. The observed (de)hydration routes, HyA ↔ HyB, HyC ↔ HyD ↔ HyE, HyF ↔ HyG ↔ HyH and HyF → HyA ↔ HyB, depended on the initial hydrate form, particle size, and atmospheric conditions. In addition, a transformation from HyC/HyA to HyF occurs at high RH values at RT. The specific moisture and temperature conditions of none of the applied drying regimes yielded a crystalline water-free form, which highlights the essential role of water molecules for the formation and stability of the crystalline strychnine sulfate phases.


Cohort Trends in the Association Between Sibship Size and Educational Attainment in 26 Low-Fertility Countries.
Children with many siblings have lower average educational attainment compared with children raised in smaller families, and this disadvantage by sibship size has been observed across many countries. We still know remarkably little, however, about how sibship size disadvantage has changed within countries and how such trends vary across countries. Using comparative data from 111 surveys from 26 low-fertility countries, we find an overall trend of growing sibship size disadvantage across cohorts in the majority of countries: between the 1931-1940 birth cohort and the 1971-1980 birth cohort, 16 of 26 countries showed a statistically significant increase in sibship size disadvantage in education, while only two countries showed a significant reduction in sibship size disadvantage. The disadvantage in years of education associated with having an additional sibling increased remarkably in post-socialist (0.3) and East Asian countries (0.34) and, to a lesser extent, Western European countries (0.2). In contrast, this disadvantage showed little change in Nordic countries (0.05) and even decreased in Anglo-Saxon countries (-0.11). We discuss explanations and implications of our comparative evidence in the context of the intergenerational transmission of education.


Trabecular microstructure of the human lunate in Kienbock's disease.
The trabecular microstructure of normal lunates and lunates with Kienböck's disease was investigated using micro-computed tomography (micro-CT). Five lunates with advanced Kienböck's disease were obtained during lunate excision and scaphocapitate fusion, and five control lunates were from embalmed cadavers. Microstructural morphometric parameters were measured using micro-CT images. Trabeculations of lunates with Kienböck's disease were 2.67 times denser and 1.84 times thicker than those of normal lunates. Furthermore, bone surface areas were 1.43 times greater and bone volume 2.67 times greater, and structural model indices were significantly lower in lunates with Kienböck's disease. The study estimated that high mechanical stress would be applied to lunates with Kienböck's disease, and suggests that new bone formation and collapse may play important roles in the microstructural changes in the lunate with advanced Kienböck's disease.


Recombinant expression and reconstitution of multiprotein complexes by the USER cloning method in the insect cell-baculovirus expression system.
The capacity to reconstitute complex biological processes in vitro is a crucial step in providing a quantitative understanding of these systems. It provides material for structural, biochemical and biophysical analyses and allows the testing of biological hypotheses and the introduction of chemical probes and tags for single molecule analysis. Reconstitution of these systems requires access to homogenous components, usually through their over-production in heterologous over-expression systems. Here we describe the application of the USER (Uracil-Specific Excision Reagent) ligation-free cloning method to assemble recombinant MultiBac transfer vectors for the generation of recombinant baculovirus suitable for the expression of multi-protein complexes in insect cells.


Educating Perioperative Nurses About Local Anesthetic Systemic Toxicity Using High-Fidelity Simulation.
The rarity of perianesthetic catastrophic events creates a challenge in training support staff in the treatment of emergencies such as local anesthetic systemic toxicity (LAST). Simulation learning offers a unique venue in which to safely encounter rare events. This study aimed to evaluate knowledge retention regarding LAST in perianesthetic nursing staff using high-fidelity simulation and a short didactic session. Nurses were recruited from perioperative locations to participate in a simulated scenario of LAST and engage in a short didactic session. Simulation and education occurred in the high-fidelity simulation center at the University of Wisconsin Hospital. Thirteen nurses from the preoperative, post-anesthesia, and block nursing teams participated in the study. Participants completed a pre-test before participating in the simulation, followed by a formal debrief and short lecture. They then completed post-tests and a short survey focused on self-efficacy and review of the simulation experience. Test scores, compared to the pre-test, improved significantly on the immediately-post, 1-month, and 3-month assessments. Participants felt more equipped to handle crisis scenarios. Experiential learning often results in significant knowledge acquisition and retention. Participants in this study improved their test scores regarding LAST and increased their sense of self-efficacy and ability to handle crisis scenarios after taking part in a high-fidelity simulation.


Evaluation of a plasmid-based 16S-23S rDNA intergenic spacer region array for analysis of microbial diversity in industrial wastewater.
A plasmid-based 16S-23S rDNA intergenic spacer region (ISR) array was developed and optimized for analysis of microbial diversity within complex environmental samples. Plasmid probes with 16S-23S rDNA ISR inserts (800-1500 bp) from industrial wastewater treatment plant (WWTP) microorganisms were arrayed onto glass slides. Hybridization of fluorescently labeled target sequences from two clones from the ISR WWTP library to arrayed probes showed that there was a good linear relationship between hybridization intensity and ISR similarity (r(2)=0.82). Hybridization was highly specific (average background from arrayed probes with less than 80% similarity in ISR sequence was less than 7%). Strong fluorescence intensity corresponded to near-perfect match clones (99% or greater similarity in ISR sequence). A majority of probes (79%) showed no background hybridization. However, weak background (less than 50% for arrayed probes with 90% and 95% similarity in the 16S rRNA genes) was observed from closely related microorganisms. Background fluorescence from the negative control (plasmid vector with no insert) was similar to water and dimethyl sulfoxide (DMSO)-negative controls. Hybridization using fluorescently labeled ISR sequences from a mixed community sample produced strong fluorescent signals with no background from negative controls. A Cy5-labeled reference standard, part of the vector and present in every spotted probe, was used to normalize hybridization values. These results indicate that arrayed plasmid containing ISR probe insert sequences provides specificity and sensitivity for microbial community analysis in a high-throughput array format.