Climate change, air quality, and human health.
Weather and climate play important roles in determining patterns of air quality over multiple scales in time and space, owing to the fact that emissions, transport, dilution, chemical transformation, and eventual deposition of air pollutants all can be influenced by meteorologic variables such as temperature, humidity, wind speed and direction, and mixing height. There is growing recognition that development of optimal control strategies for key pollutants like ozone and fine particles now requires assessment of potential future climate conditions and their influence on the attainment of air quality objectives. In addition, other air contaminants of relevance to human health, including smoke from wildfires and airborne pollens and molds, may be influenced by climate change. In this study, the focus is on the ways in which health-relevant measures of air quality, including ozone, particulate matter, and aeroallergens, may be affected by climate variability and change. The small but growing literature focusing on climate impacts on air quality, how these influences may play out in future decades, and the implications for human health is reviewed. Based on the observed and anticipated impacts, adaptation strategies and research needs are discussed.


Global hotspots for the occurrence of compound events.
Compound events (CEs) are weather and climate events that result from multiple hazards or drivers with the potential to cause severe socio-economic impacts. Compared with isolated hazards, the multiple hazards/drivers associated with CEs can lead to higher economic losses and death tolls. Here, we provide the first analysis of multiple multivariate CEs potentially causing high-impact floods, droughts, and fires. Using observations and reanalysis data during 1980-2014, we analyse 27 hazard pairs and provide the first spatial estimates of their occurrences on the global scale. We identify hotspots of multivariate CEs including many socio-economically important regions such as North America, Russia and western Europe. We analyse the relative importance of different multivariate CEs in six continental regions to highlight CEs posing the highest risk. Our results provide initial guidance to assess the regional risk of CE events and an observationally-based dataset to aid evaluation of climate models for simulating multivariate CEs.


Quantitative clinical assessment of chronic anterior myocardial infarction with delayed enhancement magnetic resonance imaging and QRS scoring.
Both the regional and global myocardial extent of chronic myocardial infarction (MI) are important prognostic factors for length and quality of life and also crucial for the choice of therapy in patients with ischemic heart disease. Our aim was to develop and validate techniques for comparison between regional and global size of remote anterior MI in the left ventricle quantified with both magnetic resonance imaging (MRI) and electrocardiogram (ECG). Delayed-enhancement (DE) MRI was used as a clinical "gold standard" for MI size to evaluate the extent of MI estimated with the commonly available standard 12-lead ECG. A method for comparing global and regional quantifications of MI with DE-MRI and ECG was developed. The Selvester QRS-scoring system was used for estimating MI size electrocardiographically. Twenty-five patients with chronic single anterior MI, documented with DE-MRI, were studied. The best agreement for mean % MI per regional segment of the left ventricle was found in the middle third (26% vs 27%), whereas the most significant discrepancy was found in the apex (56% vs 30%). The global MI size of the left ventricle averaged 21 +/- 9% with DE-MRI and 22% +/- 12% with ECG, with a correlation of r = 0.40 (P <.05). The current Selvester QRS scoring system performs well for quantifying anterior MI in the mid-regions of the left ventricle. The diagnostic performance of the Selvester QRS-scoring system for quantifying MI in the other regions, particularly the left ventricular apex, can potentially be improved, with DE-MRI as the gold standard.


The MMP activity in developing rat molar roots and incisors demonstrated by in situ zymography.
Matrix metalloproteinases (MMPs) have been expressed during root development and periodontal tissue formation, whereas it is not known if these MMP molecules are enzymatically active to degrade the extracellular matrices (ECMs). The present study was designed to investigate the gelatinolytic and collagenolytic activity in rat molar root and incisor development. Three-week old rat mandibles were frozen and cut without fixation or decalcification and processed for in situ zymography using substrates gelatin and collagen. The enzymatic activity was assessed according to the intensity of fluorescence due to the lysis of the substrates. Odontoblasts, predentin, cementum, bone and the enamel matrix showed the high activity. The present study demonstrated MMP activity in calcified tissues using in situ zymography for the first time and the possible involvement of the MMP activity in molar root and incisor development and periodontal tissue formation.


Evaluation of Lassa virus vaccine immunogenicity in a CBA/J-ML29 mouse model.
Lassa fever (LF) is one of the most prevalent viral hemorrhagic fevers in West Africa responsible for thousands of deaths annually. The BSL-4 containment requirement and lack of small animal model to evaluate Lassa virus (LASV)-specific cell-mediated immunity (CMI) complicate development of effective LF vaccines. Here we have described a CBA/J-ML29 model allowing evaluation of LASV-specific CMI responses in mice. This model is based on Mopeia virus reassortant clone ML29, an attractive immunogenic surrogate for LASV. A single intraperitoneal (i.p.) immunization of CBA/J mice with ML29 protected animals against a lethal homologous intracerebral (i.c.) challenge with 588 LD(50). The ML29-immunized mice displayed negligible levels of LASV-specific antibody titers, but LASV-specific CMI responses were detectable early and peaked on day 8-10 after immunization. A T cell cytotoxicity assay in vivo showed a correlation between LASV-specific cytotoxicity and the timing of protection induced by the ML29 immunization. Notably, CBA/J mice that received CD8+ T cell-depleted splenocytes from ML29-immunized donors all succumbed to a lethal i.c. challenge, demonstrating that CD8+ T cells are critical in protection. The CBA/J-ML29 model can be useful immunological tool for the preliminary evaluation of immunogenicity and efficacy of vaccine candidates against LASV outside of BSL-4 containment facilities.


Relapse prevention by citalopram in SAD patients responding to 1 week of light therapy. A placebo-controlled study.
We have tested the relapse-preventive effect of citalopram when compared with placebo in 282 patients with Seasonal Affective Disorder (SAD) responding to 1 week of light therapy. The response rate to 1-week light therapy and relapse during the continuation phase of 15 weeks were assessed by use of the Hamilton Depression Rating Scale (HAM-D17), the six-item subscale (HAM-D6), the Melancholia Scale (MES), and the combined HAM-D/SIGH-SAD. The response rate to light therapy was 62.5% on the HAM-D17 and the HAM-D6, 56.1% on the HAM-D/SIGH-SAD, 52.8% on the MES. In the continuation phase, citalopram was found superior to placebo on all scales, but the difference was only of statistical significance on the HAM-D6 and the MES. Mean citalopram dose was 26.3 mg. Light therapy was found to have and early onset of action. On the HAM-D6 and the MES citalopram significantly reduced the relapse rate in the continuation phase.


The use of biological amniotic membranes in the treatment of recurrent macular holes.
To evaluate the clinical therapeutic effects of a technique in which biological amniotic membranes (bAMs) are used in the treatment of patients with recurrent macular holes. In this prospective nonrandomized case series study, 23 eyes of 23 patients with recurrent macular holes who had already undergone surgery with pars plana vitrectomy with internal limiting membrane peeling were evaluated. In the surgery, a bAM was used to cover the macular area, and C3F8 tamponade was performed on these patients. Phacoemulsification combined with intraocular lens implantation was performed simultaneously in patients who had cataracts. Patients were followed up for at least half a year. The main outcomes were whether the macular hole closed, the morphological changes in the macular graft, the best-corrected visual acuity, intraocular pressure (IOP) and other indicators. In all eyes, the recurrent macular holes were closed. Two cases (8.69%, 2/23) had bAM shifting half a month after surgery, and these patients underwent a second surgery to adjust the position of the bAM and perform C3F8 tamponade. In the 6-month follow-up, 21 patients (91.30%, 21/23) had improved visual acuity (VA), and 2 patients (8.69%, 2/23) had no change in VA. The mean VA increased from 1.73 ± 0.32 before surgery to 1.12 ± 0.42 after surgery (t = 10.63, P = 0.00 < 0.01), and the mean IOP decreased from 22.13 ± 5.56 before surgery to 17.23 ± 1.71 after surgery (t = 5.14, P = 0.00 < 0.01). No serious complications occurred in any of the cases. The technique of using a biological amniotic membrane can be an effective treatment for patients with recurrent macular holes.


The effects of hypertonic glucose solutions on hepatic bile formation.
Bile secretion in the isolated guinea-pig liver was studied during perfusion with equi-osmolar hypertonic solutions containing either glucose, galactose, mannose, mannitol or sodium chloride. Perfusates made hypertonic with glucose, galactose or mannose decreased bile flow to the same extent and had similar effects on the ionic composition of bile: sodium, potassium and bicarbonate concentrations all increased. Mannitol had a smaller inhibitory effect and caused different changes in ionic composition: the increase in bile potassium concentration was proportionately greater; bicarbonate concentration did not change, but chloride was increased. Thus, glucose, galactose and mannose, can inhibit bile flow independently of extrinsic neural and hormonal mechanisms and exert a greater cholestatic effect than a non-metabolisable carbohydrate of similar molecular weight. The results also provide evidence for glucose reabsorption in the guinea-pig biliary tree, as shown in other species, and that galactose competes for this transport.


Renal infarction following endovascular aortic aneurysm repair: incidence and clinical consequences.
To investigate the incidence of renal infarction following endovascular abdominal aortic aneurysm (AAA) repair, with particular emphasis on a comparison of suprarenal versus infrarenal endograft placement. Ninety-nine patients (92 men; average age 68 years) who had undergone endovascular AAA repair between July 1995 and July 1999 and who had at least 12 months' follow-up were studied with spiral computed tomographic scans to identify suprarenal endograft deployment and renal infarction. Among the 193 renal arteries available for study, partial or complete transrenal endograft placement was found in 69 (36%). Sixteen (8.3%) renal infarctions were identified by the postoperative imaging studies. Perfusion of these kidneys was supplied by 6 (8.7%) of the 69 overstented renal arteries and 7 (5.6%) of the 124 uncovered arteries (p > 0.05). In the 3 other cases, intentional accessory renal artery occlusion by the stent-graft fabric led to frank segmental renal infarctions, which were visualized as territorial-perfusion defects affecting up to 27% of the renal volume. In the other 13 infarcted kidneys, the punctate deficits involved <10% of the parenchymal volume. Renal retention values were unaffected in 15 (94%) of 16 patients. Documented renal infarctions following endovascular aortic stent-graft placement are not common and do not appear to be associated with suprarenal endograft fixation.


Injection site leakage of depot neuroleptics: intramuscular versus subcutaneous injection.
In a cross-sectional study of injection site leakage of fluphenazine decanoate in 40 psychiatric outpatients, significantly more leakage occurred after intramuscular than after subcutaneous injection. Results of the study suggest that age, sex, body mass, and injection volume may also affect leakage.


Communication differences when patients and caregivers are seen separately or together.
Southern Adelaide Palliative Care Services introduced a nurse-led early introduction to a palliative care clinic in 2011. The clinic offers a thorough psychosocial assessment and the provision of information and an introduction to future care planning. The patients and their caregivers are seen together by the nurse practitioner initially for a physical assessment. They are then seen by a social worker to focus on advanced care planning and assessment of social and emotional factors. After the social work visit, the patient and caregiver are separated, and the patient sees the psychosocial nurse for coping and adjustment to illness and the carer sees the caregiver network facilitator to assess their informal supports to assist in the role of community-based caregiving. The pilot study looks at the nature of communication in the clinic where patient and carer are together and compares that to when they are separated. A total of 33 patients and their caregivers agreed for their coversations to be tape recorded between May and November of 2013. All tape recordings were transcribed verbatim. Ten patient transcripts (n=40) have been coded for quantitative analysis. The codes identify content and function of speech, cues for information and emotion and whether they are responded to by clinicians. Pilot results reveal that caregivers contribute little in the combined clinics and dominate the conversation in the private clinic. Patients, when seen alone, predominantly express emotion related cues, opposed to cues for information. The clinicians focus on their area of specialty, which results in little duplication in this clinic setting. An earlier evaluation of this clinic found that patients and their caregivers appreciate being separated in the clinic setting to have time and privacy to reveal fears and feelings related to end-of-life care. This current study quantifies the patient and caregiver experience and confirms those earlier findings.


Loss of protein phosphatase 2A regulatory subunit B56δ promotes spontaneous tumorigenesis in vivo.
Protein Phosphatase 2A (PP2A) enzymes counteract diverse kinase-driven oncogenic pathways and their function is frequently impaired in cancer. PP2A inhibition is indispensable for full transformation of human cells, but whether loss of PP2A is sufficient for tumorigenesis in vivo has remained elusive. Here, we describe spontaneous tumor development in knockout mice for Ppp2r5d, encoding the PP2A regulatory B56δ subunit. Several primary tumors were observed, most commonly, hematologic malignancies and hepatocellular carcinomas (HCCs). Targeted immunoblot and immunohistochemistry analysis of the HCCs revealed heterogeneous activation of diverse oncogenic pathways known to be suppressed by PP2A-B56. RNA sequencing analysis unveiled, however, a common role for oncogenic c-Myc activation in the HCCs, independently underscored by c-Myc Ser62 hyperphosphorylation. Upstream of c-Myc, GSK-3β Ser9 hyperphosphorylation occurred both in the HCCs and non-cancerous B56δ-null livers. Thus, uncontrolled c-Myc activity due to B56δ-driven GSK-3β inactivation is the likely tumor predisposing factor. Our data provide the first compelling mouse genetics evidence sustaining the tumor suppressive activity of a single PP2A holoenzyme, constituting the final missing incentive for full clinical development of PP2A as cancer biomarker and therapy target.


Primary polydipsia: Update.
In primary polydipsia pathologically high levels of water intake physiologically lower arginine vasopressin (AVP) secretion, and in this way mirror the secondary polydipsia in diabetes insipidus in which pathologically low levels of AVP (or renal responsiveness to AVP) physiologically increase water intake. Primary polydipsia covers several disorders whose clinical features and significance, risk factors, pathophysiology and treatment are reviewed here. While groupings may appear somewhat arbitrary, they are associated with distinct alterations in physiologic parameters of water balance. The polydipsia is typically unrelated to homeostatic regulation of water intake, but instead reflects non-homeostatic influences. Recent technological advances, summarized here, have disentangled functional neurocircuits underlying both homeostatic and non-homeostatic physiologic influences, which provides an opportunity to better define the mechanisms of the disorders. We summarize this recent literature, highlighting hypothalamic circuitry that appears most clearly positioned to contribute to primary polydipsia. The life-threatening water imbalance in psychotic disorders is caused by an anterior hippocampal induced stress-diathesis that can be reproduced in animal models, and involves phylogenetically preserved pathways that appear likely to include one or more of these circuits. Ongoing translational neuroscience studies in these animal models may potentially localize reversible pathological changes which contribute to both the water imbalance and psychotic disorder.


Does insufficient sleep affect how you learn from reward or punishment? Reinforcement learning after 2 nights of sleep restriction.
To learn from feedback (trial and error) is essential for all species. Insufficient sleep has been found to reduce the sensitivity to feedback as well as increase reward sensitivity. To determine whether insufficient sleep alters learning from positive and negative feedback, healthy participants (n = 32, mean age 29.0 years, 18 women) were tested once after normal sleep (8 hr time in bed for 2 nights) and once after 2 nights of sleep restriction (4 hr/night) on a probabilistic selection task where learning behaviour was evaluated in three ways: as generalised learning, short-term win-stay/lose-shift learning strategies, and trial-by-trial learning rate. Sleep restriction did not alter the sensitivity to either positive or negative feedback on generalised learning. Also, short-term win-stay/lose-shift strategies were not affected by sleep restriction. Similarly, results from computational models that assess the trial-by-trial update of stimuli value demonstrated no difference between sleep conditions after the first block. However, a slower learning rate from negative feedback when evaluating all learning blocks was found after sleep restriction. Despite a marked increase in sleepiness and slowed learning rate for negative feedback, sleep restriction did not appear to alter strategies and generalisation of learning from positive or negative feedback.


Short-term effects of neoadjuvant chemoradiation therapy on anorectal function in rectal cancer patients: a pilot study.
Neoadjuvant chemoradiation therapy followed by curative surgery has gained acceptance as the therapy of choice in locally advanced rectal cancer. However, deterioration of anorectal function after long-course neoadjuvant chemoradiation therapy combined with surgery for rectal cancer is poorly defined. The aim of this study was to evaluate the physiological and clinical change of anorectal function after neoadjuvant chemoradiation therapy for rectal cancer. We analyzed 30 patients on whom preoperative anorectal manometry data were available both before and after chemoradiation from October 2010 to September 2011. All patients underwent long-course neoadjuvant chemoradiation therapy. We compared manometric parameters between before and after neoadjuvant chemoradiation therapy. Of 30 patients, 20 were males and 10 females. The mean age was 64.9 ± 9.9 years (range, 48-82). Before nCRT, the rectal compliance was higher in patients with ulceroinfiltrative type (P = 0.035) and greater involvement of luminal circumference (P = 0.017). However, there was the tendency of increased rectal sensory threshold for desire to defecate when the patient had decreased circumferential ratio of the tumor (P = 0.099), down-graded T stage (P = 0.016), or reduced tumor volume (P = 0.063) after neoadjuvant chemoradiation. Neoadjuvant chemoradiation therapy did not significantly impair overall sphincter function before radical operation. The relationship between tumor response of chemoradiation and sensory threshold for desire to defecate may suggest that neoadjuvant chemoradiation may be helpful for defecatory function as well as local disease control, at least in the short-term period after the radiation in locally advanced rectal cancer patients.


Validation of the determinant-based classification and revision of the Atlanta classification systems for acute pancreatitis.
Two new classification systems for the severity of acute pancreatitis (AP) have been proposed, the determinant-based classification (DBC) and a revision of the Atlanta classification (RAC). Our aim was to validate and compare these classification systems. We analyzed data from adult patients with AP (543 episodes of AP in 459 patients) who were admitted to Hospital General Universitario de Alicante from December 2007 to February 2013. Imaging results were reviewed, and the classification systems were validated and compared in terms of outcomes. Pancreatic necrosis was present in 66 of the patients (12%), peripancreatic necrosis in 109 (20%), walled-off necrosis in 61 (11%), acute peripancreatic fluid collections in 98 (18%), and pseudocysts in 19 (4%). Transient and persistent organ failures were present in 31 patients (6%) and 21 patients (4%), respectively. Sixteen patients (3%) died. On the basis of the DBC, 386 (71%), 131 (24%), 23 (4%), and 3 (0.6%) patients were determined to have mild, moderate, severe, or critical AP, respectively. On the basis of the RAC, 363 patients (67%), 160 patients (30%), and 20 patients (4%) were determined to have mild, moderately severe, or severe AP, respectively. The different categories of severity for each classification system were associated with statistically significant and clinically relevant differences in length of hospital stay, need for admission to the intensive care unit, nutritional support, invasive treatment, and in-hospital mortality. In comparing similar categories between the classification systems, no significant differences were found. The DBC and the RAC accurately classify the severity of AP in subgroups of patients.


Delignification of sugarcane bagasse using glycerol-water mixtures to produce pulps for saccharification.
This paper describes the organosolv delignification of depithed bagasse using glycerol-water mixtures without a catalyst. The experiments were performed using two separate experimental designs. In the first experiment, two temperatures (150 and 190°C), two time periods (60 and 240 min) and two glycerol contents (20% and 80%, v/v) were used. In the second experiment, which was a central composite design, the glycerol content was maintained at 80%, and a range of temperatures (141.7-198.3°C) and time (23-277 min) was used. The best result, obtained with a glycerol content of 80%, a reaction time of 150 min and a temperature of 198.3°C, produced pulps with 54.4% pulp yield, 7.75% residual lignin, 81.4% delignification and 13.7% polyose content. The results showed that high contents of glycerol tend to produce pulps with higher delignification and higher polyoses content in relation to the pulps obtained from low glycerol content reactions. In addition, the proposed method shows potential as a pretreatment for cellulose saccharification.


[Effect of cyanocobalamin, cobamide coenzyme and the cytostatic hispen on changes in cobalamin levels in healthy rats and rats with transplanted sarcoma M-1].
The influence of cyanocobalamine (CN-B12), cobamide coenzyme (5'-deoxyadenosyl-B12, DBC) and the cytostatic hisphen on the level of cobalamines in the blood serum, liver, kidney, heart and in the tumor of healthy and sarcoma M-1 implanted rats was studied. In the above organs and tissues cobalamines were found to occur in the free and protein-bound state (cobalamine-protein complexes). The complexes were of different stability. The ratio of free to protein-bound cobalamines varied. The content of cobalamine-protein complexes in healthy and tumorous tissues was different. CN-B12, DBC and hisphen influenced specifically the redistribution of cobalamine and protein-bound complexes.


Creatinine kinetics in the rabbit.
To evaluate the kinetics of creatinine in the rabbit, two radiotagged creatinine forms were used, with 14C in the amidino group or with it in the carboxyl group. Five animals were injected intravenously with tracer amounts, and plasma samples were taken for 250-300 min; urine and feces samples were taken over longer periods. A chromatographic method was used to separate unchanged creatinine from other components of the samples prior to measurement for chemical and radioactivity content. Equations for the proposed flow model were derived and fitted to specific activity data, and values for transfer constants, production rates, and pool sizes were calculated. Evidence supported the concept that a two-compartment model is required and that production occurs in the peripheral compartment. Evidence also indicated that muscle represented a major part of the peripheral compartment. Small amounts of metabolites, chiefly guanido compounds, were detected when amidino-labeled creatinine was used. Also, small amounts of unchanged creatinine and metabilites were found in the feces.


Metachronous sarcomas in a patient with bilateral retinoblastomas. A case report.
This is the first reported case of two metachronous sarcomas developing in a patient after treatment of bilateral retinoblastomas. The histogenesis of the tumours is not clear.


Phorbol diacetate potentiates na(+)-k(+) ATPase inhibition by a putative endogenous ligand, marinobufagenin.
Several vasoconstrictor agents can regulate the phosphorylation status of the Na(+)-K(+) ATPase (NKA). We have recently demonstrated that mammalian tissues contain an endogenous bufadienolide, digitalis-like alpha(1)-NKA-selective ligand, marinobufagenin (MBG). Protein kinase C induces phosphorylation of the alpha(1)-NKA isoform, the major isoform in vascular smooth muscle, kidney, and heart cells. We hypothesized that protein kinase C-induced phosphorylation of NKA can potentiate the effect of endogenous digitalis-like ligands, and that such potentiation can occur in an NKA isoform-specific fashion. A protein kinase C activator, phorbol 12,13-diacetate (PDA, 50 nmol/L), induced phosphorylation of the alpha1-NKA from human mesenteric artery (HMA) sarcolemma and rat kidney but not that of the alpha(3)-NKA from rat fetal brain. In HMA sarcolemma, which predominantly contains alpha(1)-NKA, PDA (50 nmol/L) potentiated the NKA-inhibitory effect of MBG at the level of high-affinity binding sites (0.05 +/- 0.03 nmol/L versus 4.0 +/- 1.7 nmol/L, P<0.05). In contrast, PDA did not affect the NKA inhibition by ouabain, an alpha(3)-NKA ligand. In isolated endothelium-denuded HMA artery rings, 50 nmol/L PDA potentiated the MBG-induced vasoconstriction (EC(50), 17 +/- 6 nmol/L versus 150 +/- 40 nmol/L; P<0.01). Our results suggest that alpha(1)-isoform-specific NKA inhibition by the endogenous digitalis-like ligand, MBG, is substantially enhanced via NKA phosphorylation by protein kinase C. Thus, an interaction of protein kinase C-dependent phosphorylation and MBG on NKA activity may underlie the synergistic vasoactive effects of MBG and other endogenous vasoconstrictors in hypertension.


Maggot debridement therapy for serious horse wounds - a survey of practitioners.
Hoof disease and injuries are common and serious problems for equines. Maggot debridement therapy (MDT) has been used to treat problematic wounds in humans, but has been used only rarely in other animals. US veterinarians who had employed MDT were surveyed to investigate their reasons for the choice of this treatment and their clinical experiences with it. Between 1997 and 2003, 13 horses were treated by eight veterinarians who used MDT to control infection or debride wounds, which could not easily be reached surgically or were not responding to conventional therapy. Seven animals were lame, and six were expected to require euthanasia. Following maggot therapy, all infections were eradicated or controlled, and only one horse had to be euthanased. No adverse events were attributed to maggot therapy for any of these cases, other than presumed discomfort during therapy. The data collected suggest that maggot therapy could be useful for treating some serious equine hoof and leg wounds.


Women's decision-making autonomy in the household and the use of maternal health services: An Indonesian case study.
The study aimed to examine the influence of Indonesian women's decision-making within the household regarding the use of maternal health services. It explored whether women who had high involvement in household decision-making experienced a higher likelihood of using antenatal care services, delivery services assisted by skilled birth attendance, and facility-based delivery compared to those with limited autonomy. The study used the individual subset data on women from the 2017 Indonesia Demographic and Health Survey, which included 3435 women of reproductive age (15-49 years) who had given birth within one year preceding the survey. The study also used the Women's Participation Index to measure women's decision-making autonomy in the household. Descriptive statistics and multiple logistic regression analyses were conducted to identify the association of women's autonomy with the use of three key maternal health services. The Women's Participation Index had a significant positive relationship to adequate antenatal care service use, but no effect on the use of skilled birth attendance and facility-based delivery, after adjusting for maternal and sociodemographic variables. Women with more autonomy experienced 1.7 (95% confidence interval: 1.17-2.45) times higher odds of using adequate antenatal care services. In addition, the likelihood of the utilization of adequate antenatal care services, skilled birth attendance, and facility-based delivery was higher among women who were age ≥35 years at birth, attained a higher education level, and were in the richest quintile compared to their respective counterparts. Women's decision-making autonomy had a significant effect on the use of adequate antenatal care services only. Initiatives that are more gender-sensitive to promote husband involvement should be conducted to increase men's awareness of the importance of maternal health services.


Direct synthesis of [DOTA-DPhe1]-octreotide and [DOTA-DPhe1,Tyr3]-octreotide (SMT487): two conjugates for systemic delivery of radiotherapeutical nuclides to somatostatin receptor positive tumors in man.
Direct attachment of unprotected DOTA (1,4,7,10-tetraazacyclododecane-N',N",N"',N""-tetraacetic acid) to partially suitably protected octreotide or [Tyr3]-octreotide leads after deprotection to [DOTA-DPhe1]-octreotide (III) and [DOTA-DPhe1,Tyr3]-octreotide (IV). These DOTA-containing somatostatin analogs, when labeled with a radiotherapeutic nuclide, are useful as antitumor agents. The partially protected peptides are accessible via solid phase peptide synthesis (SPPS) followed by selective cleavage under mild acidic conditions from the resin.


Management of a massive pediatric cerebral infarct with mass effect.
A preschool child presented with a large middle cerebral artery (MCA) infarct with midline shift, overt signs of raised intracranial pressure and hemodynamic instability. Aggressive management including ventilatory support was instrumental in the successful outcome. Raising awareness of pediatric stroke is crucial to improving overall care of these children.


The recurrent laryngeal nerve and the inferior thyroid artery--anatomical variations during surgery.
Recognition of variations of the inferior laryngeal nerve is essential. We aimed to investigate the relationship of the inferior laryngeal nerve with the inferior thyroid artery. A study was undertaken between August 2005 and August 2006. A total of 253 adult patients undergoing thyroid surgery were included in this prospective, non-randomized study. Both sides of the thyroid gland were considered separately. Sixteen variations of the nerve were clarified. In the most observed variation, the nerve was deep to the artery. Two and three nervous branches were seen in 22.5% and 1.6% of the patients, respectively. Bifurcation of the nerve was mostly observed on the left side. No non-recurrent laryngeal nerve was found. To avoid the risk of nerve damage during thyroid surgery, a good knowledge of the variations of the inferior laryngeal nerve is essential. This is important to achieve an undisturbed quality of life for the thyroid patient.


Polybrominated Diphenyl Ether Exposure and Thyroid Function Tests in North American Adults.
Polybrominated diphenyl ethers (PBDEs) are flame-retardant chemicals that are added to many consumer products. Multiple animal studies have shown PBDEs to be thyroid hormone (TH) disruptors. Epidemiologic evidence of PBDE exposure associated with TH disruption has been inconclusive. We used repeated measures to estimate associations between serum PBDE concentrations and THs in a North American adult cohort. From 2010 to 2011, we collected ≤ 3 serum samples at approximately 6-month intervals from 52 healthy adult office workers from Boston, Massachusetts, for analysis of PBDE congeners and THs. The geometric mean sum concentrations of the most prevalent PBDE congeners (BDE-28, BDE-47, BDE-99, BDE-100, and BDE-153) were 22 ng/g lipid in winter 2010, 23 ng/g lipid in summer 2010, and 19 ng/g lipid in winter 2011. BDE-47 was the predominant congener. Based on a multivariable mixed regression model, we estimated that on average, a 1-ng/g serum increase in BDE-47 was associated with a 2.6-μg/dL decrease in total thyroxine (T4) (95% CI: -4.7, -0.35). Total T4 was inversely associated with each PBDE congener. Serum concentrations of PBDEs were not strongly associated with total triiodothyronine (T3), free T4, or thyroid-stimulating hormone (TSH). These results are consistent with those from animal studies showing that exposure to PBDEs is associated with a decrease in serum T4. Because the other TH concentrations did not appear to be associated with BDE exposures, our findings do not indicate effects on the pituitary-thyroid axis. Taken together, our findings suggest that PBDE exposure might decrease the binding of T4 to serum T4 binding proteins. Makey CM, McClean MD, Braverman LE, Pearce EN, He XM, Sjödin A, Weinberg JM, Webster TF. 2016. Polybrominated diphenyl ether exposure and thyroid function tests in North American adults. Environ Health Perspect 124:420-425; http://dx.doi.org/10.1289/ehp.1509755.


Rolofylline, an adenosine A1 receptor antagonist, inhibits osteoclast differentiation as an inverse agonist.
Adenosine may be generated by hydrolysis of extracellular nucleotides by ectonucleotidases, including ectonucleoside triphosphate diphosphohydrolase 1 (CD39), ecto-5'-nucleotidase (CD73), nucleotide pyrophosphatase phosphodiesterase 1 (NPP-1) and tissue non-specific alkaline phosphatase (TNAP). Previous work from our laboratory has uncovered a critical role for adenosine A1 receptors (A1 R) in osteoclastogenesis; blockade or deletion of these receptors diminishes osteoclast differentiation. Interestingly, selective A1 R agonists neither affect basal osteoclastogenesis nor do they reverse A1 R antagonist-mediated inhibition of osteoclastogenesis. In this study, we determined whether ectonucleotidase-mediated adenosine production was required for A1 R antagonist-mediated inhibition, and, when we saw no effect, determined whether A1 R was constitutively activated and the antagonist was acting as an inverse agonist to diminish osteoclast differentiation. Osteoclast formation derived from wild-type, CD39 knockout (KO), CD73 KO, NPP-1 KO and TNAP KO mice was examined by tartrate-resistant acid phosphatase staining of receptor activator of NF-κB ligand-macrophage colony-stimulating factor-stimulated osteoclasts and osteoclast gene expression (Ctsk, Acp5, MMP-9 and NFATc1). Intracellular cAMP concentration was determined by elisa. Rolofylline inhibited osteoclast formation in a dose-dependent manner (IC50 = 20-70 nM) in mice lacking all four of these phosphatases, although baseline osteoclast formation was significantly less in precursors from CD73 KO mice. Rolofylline (1 μM) stimulates cAMP production in bone marrow macrophages by 10.23 ± 0.89-fold. Based on these findings, we hypothesize that the A1 R is constitutively activated in osteoclast precursors, thereby diminishing basal AC activity, and that A1 R antagonists act as inverse agonists to release A1 R-mediated inhibition of basal AC activity and permit osteoclast differentiation. The constitutive activity of A1 R promotes osteoclast formation and down-regulation of this activity blocks osteoclast formation.


Towards analysis of mykotoxins in beverages with molecularly imprinted polymers for deoxynivalenol and zearalenone.
Due to ease of use and generally cost effective production molecularly imprinted polymers offer the possibility generating highly selective separation and enrichment materials. Therefore, they are considered a serious competitor to conventional biological agents such as antibodies, proteins and cells for affinity separations. Molecular imprinting applied in the present study is based on non-covalent self-assembly of the template with functional monomers prior to polymerization. Free radical polymerization with a cross-linking monomer is stabilizing (freezing) these template-functional monomer complexes, resulting in a mechanically and thermally stable polymer. After template extraction, rebinding may take place via non-covalent interactions.Selective polymeric phases intended for use in solid-phase extraction of deoxynivalenol (DON) and zearalenone (ZON) from beverages have been prepared [1]. Using crystalline deoxynivalenol, zearalenone and quercetin, molecularly imprinted polymers (MIPs) have been developed by a non-covalent imprinting approach via photo initiated addition polymerization. Prepared polymers are based on 4-vinylpyridine (4-VP) as functional monomer and ethylenglycoldimethacrylat (EDMA) as crosslinking monomer. Selectivity of generated molecularly imprinted polymers has been investigated by application of prepared MIPs as stationary phase in high pressure liquid chromatography (HPLC) experiments. Retention and elution behavior of template compounds were determined and compared. Achieved results promise future application of molecularly imprinted polymers as highly selective matrix for clean-up and enrichment of deoxynivalenol and zearalenone from natural sources such as grains and beer.


Chronic kidney disease (CKD) patients are exposed to more proton pump inhibitor (PPI)s compared to non-CKD patients.
Proton pump inhibitor use is associated with incident chronic kidney disease, chronic kidney disease progression and end-stage renal disease. However, the extent of proton pump inhibitor prescriptions to chronic kidney disease patients is still unclear. In a retrospective study, we enrolled patients (>18 years old) who received proton pump inhibitor in the out-patient setting from 2014 through 2015. All data was obtained from electronical medical records of Soonchunhyang Medical Center. The prescription patterns and characteristics of proton pump inhibitors were analyzed according to individual estimated glomerular filtration rate of the patients. During the study period 178,228 patients visited the out-patient clinic. Proton pump inhibitors were prescribed to 9,109 (5.11%) patients. In our sample, 50% were females and 9.8% were chronic kidney disease (eGFR<60mL/min/1.73 m2) patients. Among the patients with chronic kidney disease, 730 (8.0%) were categorized as stage 3 or 4 and 166 (1.8%) were categorized as stage 5 or end-stage renal disease. The prevalence of proton pump inhibitors prescription among chronic kidney disease patients was higher than in the non-chronic kidney disease group (p<0.001). Median duration of usage was 120 [interquartile range 63-273] days in the stage 3-4 group, 106 [56-266] days in the stage 5-end-stage renal disease group and 90 [56-176] days in the non-chronic kidney disease group. Patients in stage 3-4 group were prescribed longer duration of proton pump inhibitors than the non-chronic kidney disease group even after adjusting for age and sex (p<0.001). The main departments of medicine which prescribed proton pump inhibitors for the stage 3-4 group were gastroenterology (40.0%), cardiology (29.6%), nephrology (9.5%) and neurology (4.8%). Compared to the non-chronic kidney disease group, the stage 3-4 and stage 5-end-stage renal disease group were taking larger number of drugs simultaneously (6.90±4.17 vs4.54±2.43; p<0.001, 5.64±2.87 vs 4.54±2.34; p<0.001, respectively). Chronic kidney disease patients are taking proton pump inhibitors for a much longer duration compared to non-chronic kidney disease patients. Physicians should pay careful attention when prescribing proton pump inhibitors to high risk groups.


Do We Need to Delineate the Humeral Head in Breast Cancer Patients?
Humeral heads can be unintentionally exposed during breast radiotherapy, particularly when regional lymph nodes are targeted. Moreover, rotational intensity-modulated radiation therapy techniques, such as helical tomotherapy (HT), increase the low-dose bath, the consequences of which are subject to debate. The aim of this study was to analyze late adverse events involving humeral heads occurring after adjuvant locoregional breast radiotherapy with HT. This single-center retrospective study included 159 breast cancer patients locoregionally irradiated, including the regional lymph nodes, in an adjuvant setting with HT at Institut Curie (Paris, France), between January 2010 and 2016. After a median delay of 48 months, six patients (3.8%) developed localized bone pain, three (1.9%) developed a shoulder functional limitation and one (0.6%) developed a traumatic humeral head fracture. The average mean and maximum doses to humeral heads were 9.18 Gy and 24.41 Gy, respectively, and were not statistically associated with humeral head adverse events. Adverse events were statistically more frequent after mastectomy than after breast-conserving surgery. Berg's level 1 and 2/3 irradiation, and right-sided radiotherapy were associated with an increased maximum dose. In summary, clinical adverse events were rare, and radiation exposure to humeral heads was low. No correlation was found between dosimetric parameters and late toxicity.


Loss of phenotypic expression is related to tumour progression in early gastric differentiated adenocarcinoma.
To evaluate the relationship between phenotypic expression and tumour progression as represented by macroscopic features, submucosal invasion and lymph node metastasis in early differentiated gastric adenocarcinoma. One hundred and fifty-five cases of early gastric differentiated adenocarcinoma without any poorly differentiated components were studied. The mucosal and submucosal components of carcinomas and lymph node metastatic lesions were classified into four categories, gastric type (G-type), incomplete intestinal type (I-type), complete intestinal type (C-type) and unclassified type (U-type), based on the combination of the phenotypic expression of HGM (gastric foveolar epithelium), MUC 6 (gastric pyloric glands), MUC 2 (intestinal goblet cells) and CD 10 (small intestinal brush border). In addition, a new classification representing a phenotypic shift from mucosa to submucosa or from primary lesion to lymph node metastasis was established with the categories of preserved group (P-group), loss group (L-group) and acquired group (A-group). (1) In submucosal carcinoma, U-type was more common in the submucosa (39%) than in the mucosa (9%). (2) U-type was more common in the metastatic lesions (42%) than in the primary lesions (5%). (3) The submucosal component and lymph node metastatic lesions were classified as P-group in 48% and 43% of cases, respectively, and as L-group in 50% and 52% of cases, respectively. (4) Lymph node metastatic lesions comprising undifferentiated carcinoma were classified as L-group in 100% of cases. During the course of tumour progression, early differentiated adenocarcinoma at first tends to lose its phenotypic expression despite preserving its morphology, but subsequently morphological dedifferentiation occurs.


Right colon cancer: long-term results after curative surgery and prognostic significance of duration of symptoms.
Between 1976 and 1986, a consecutive series of 195 patients with right colon cancer were admitted at the First Department of Surgery of the University of Rome. Patients were divided into five groups according to the absence of intestinal symptoms (group 1) and the duration of the symptomatic phase (groups 2-5). Analysis of the preoperative investigation showed that colonoscopy was able to identify 33 (26.2%) of tumors misdiagnosed by double contrast X-ray barium enema. We did not notice any correlation among symptom duration and tumor stage, tumor differentiation, operability rate, and survival. Patients admitted in the asymptomatic phase presented tumors of less advanced stage and, thus, had the best survival rate (71.4%). In this group, patients promptly treated had a better survival rate (87.5%) than those treated after 2 months (50%). Our study suggests that only neoplasms diagnosed in asymptomatic patients and treated promptly are related to a good survival rate. We, therefore, emphasize the importance of education of patients and family physicians about right colon cancer and the necessity to investigate all patients with a suspected right colon cancer by means of colonoscopy.


Evaluation of independent self-collected blood specimens for COVID-19 antibody detection among the US veteran population.
Feasibility of home blood sample collection methods for the presence of SARS-CoV-2 antibodies from VA Million Veteran Program (MVP) participants was tested to determine COVID-19 infection or vaccination status. Participants (n = 312) were randomly assigned to self-collect blood specimens using the Neoteryx Mitra Clamshell (n = 136) or Tasso-SST (n = 176) and asked to rate their experience. Mitra tip blood was eluted and Tasso tubes were centrifuged. All samples were stored at -80 °C until tested with InBios SCoV-2 Detect™ IgG ELISA, BioRad Platelia SARS-CoV-2 Total Ab Assay, Abbott SARS-CoV-2 IgG and AdviseDx SARS-CoV-2 IgG II assays. Participants rated both devices equally. The Abbott assay had the highest sensitivity (87% Mitra, 98% Tasso-SST) for detecting known COVID infection and/or vaccination. The InBios assay with Tasso-SST had the best sensitivity (97%) and specificity (80%) for detecting known COVID-19 infection and/or vaccination. Veterans successfully collected their own specimens with no strong preference for either device.


Animal-assisted activity among patients with cancer: effects on mood, fatigue, self-perceived health, and sense of coherence.
To identify to what extent an animal-assisted activity (i.e., visits with a dog) affects the mood, self-perceived health, and sense of coherence among patients undergoing radiation therapy. Pretest/post-test between and within groups. Radiation oncology units of two hospitals in a mid-sized, midwestern city. 30 adult patients undergoing nonpalliative radiation therapy. After giving informed consent, participants were randomly assigned to receive 12 dog visits, 12 human visits, or 12 quiet reading sessions over a four-week period. No statistically significant differences were found; however, compared with others their age, patients receiving dog visits viewed their health as improved over the four-week period. Participants described each of the three activities as beneficial. The study is primarily useful as a basis for planning additional research. The study warrants replication with a larger sample to determine applicability of animal-assisted activity in patients with cancer who are undergoing radiation therapy. Patients may want and express benefit from animal-assisted activity dog visits, but the outcomes of the visits may not be measureable. Nurses should assess to what extent patients believe that such visits are beneficial by asking them. The visits may be valued by patients as helping to relieve their anxiety and as distractions from their disease and therapy.


[Psychotherapy research--how it should (not) be done. An expert reanalysis of comparative studies by Grawe et al. (1994)].
22 psychotherapy outcome studies used in the Bernese meta-analysis by Grawe, Donati and Bernauer (1994) for a treatment comparison between behavioural and psychoanalytic-psychodynamic treatment concepts were reanalysed by 12 expert psychotherapy researchers independent of each other. Three clinical criteria served as basic criteria for the assessment of the methodological quality of the 22 comparative studies: treatment dosage, therapists' competence or expertise, and an adequate realisation of the intended treatment concept. The expert ratings were then compared with an evaluation of an assessment of a research team from the University of Ulm and with the one from the Bernese research team. Contrary to the Bernese meta-analysis, both the experts and the Ulm research group conclude that only 5 or 8 of the 22 studies, respectively, could be accepted for a relatively fair comparison between the treatments under study. Out of the 5/8 studies, none could be considered fully suitable for a treatment comparison, at the most only moderately suitable. These remaining 5 or 8 studies, respectively, do not prove superiority of one treatment over the other. Hence, the "Dodo Bird Verdict" stands up under scrutiny.


Development and experimental evaluation of a contrast medium for computed tomographic examination of the liver and spleen.
A lipoid based contrast material containing 53% of ethiodized oil in emulsion form was developed for computed tomography (CT) of the liver and spleen and tested in rabbits and monkeys. An intravenous dose of 0.2 ml/kg selectively opacified the liver and spleen, resulting in an average increase of 23 EMI units (500 scales) in the attenuation of the liver and a higher increase in the attenuation of the spleen. When injected into rhesus monkeys with carcinogen induced hepatomas there was a significant improvement in the visualization of the tumor, and small lesions, undetectable on the preliminary CT scan, became visible. Toxicity studies are in progress.


Effects of temperature, soil moisture and photoperiod on diapause termination and post-diapause development of the wheat blossom midge, Sitodiplosis mosellana (Géhin) (Diptera: Cecidomyiidae).
Sitodiplosis mosellana, one of the most important wheat pests, goes through larval diapause in a cocooned form. It is univoltine, but some individuals exhibit prolonged diapause. In this study, we documented diapause termination rate of cocooned larvae at different diapausing periods and time required for adult emergence when they were brought to 25°C from the field in northern China. We found that field larvae all entered diapause by June, but none terminated diapause until late September when the daily average temperature dropped to below 20°C. Furthermore, termination rate increased significantly as diapausing larvae underwent increasing chilling duration, reaching >95% from early December to early March. Our results suggest that chilling was necessary for diapause to terminate and that field diapause termination ended in early December. To explore low temperature and duration required, we cold-treated field diapausing larvae of different periods at different low temperatures for various lengths of time prior to the 25°C incubation. Chilling at 4-8°C for 60-90days resulted in a higher termination rate (>90%) and shorter adult emergence time in general. Additionally, we investigated the combined effect of temperature (18-30°C) and soil moisture (20-60%, on dry weight basis) as well as the effect of photoperiod (24:0-0:24L:D) on post-diapause development. While photoperiod did not affect adult emergence, soil moisture ranging from 30 to 50% and temperature from 22 to 26°C resulted in the highest adult emergence rates (>46%) within relatively short time (<18days). Mortality and/or prolonged diapause rate drastically increased when incubation conditions were outside the optimal range, especially at 30°C. These findings provide new insight into the diapause process of S. mosellana, and information will be useful for development of field forecasting and laboratory rearing techniques of this pest insect.


Brainstem location of serotonin neurons projecting to the caudal neurosecretory complex.
Serotonergic fibers in the caudal neurosecretory complex (CNc) of poeciliids originate from neurons within, and extrinsic to this spinal cord nucleus. In the present study, retrograde tracing and immunofluorescence techniques were combined to localize extrinsic serotonergic projection neurons. The entire spinal cord and brain were sectioned after Fast Blue (FB) or horseradish peroxidase (HRP) was implanted in the CNc. No HRP or FB filled neurons were found in the spinal cord. Retrogradely filled neurons were found bilaterally in dorsolateral and ventromedial reticular nuclei, and the dorsal midbrain tegmentum. Fusiform cells in the medullary fasciculus longitudinalis medialis filled with FB but not HRP. Serotonin immunopositive neurons were found surrounding the third ventricle, in the raphe and in medullary reticular nuclei. Double labelled neurons in the medial reticular nucleus were determined to be the source of serotonergic projections to the CNc. Reticular projection nuclei are strategically situated to receive visceral sensory input from rhombencephalic cranial nerves. These putative pathways may provide an anatomical substrate by which visceral sensory information is transmitted to the CNc.


Effect of cholesterol feeding and estrogen treatment on synthesis of fatty acids in liver.
The effect of cholesterol feeding and estrogen administration on synthesis of fatty acids in liver mitochondria, microsomes and cytoplasm of male rabbits has been investigated. The synthesis was measured by the incorporation of [1(-14)C] acetyl CoA or [2(-14)C]malonyl CoA into long chain fatty acids under optimal conditions. It was found that atherogenesis markedly decreased the fatty acid synthesis in cytoplasm. The mitochondrial fatty acid synthesis was not affected by the disease. There was a small but measurable decrease in the synthesis of fatty acids in microsomes. Estrogen had no effect on the synthesis of fatty acids in mitochondria or microsomes. But if effectively counteracted, after a short lag period, the decreased synthesis of cytoplasmic fatty acids observed in atherosclerosis. It is possible that liver fatty acid synthetase is one of the enzyme systems through which estrogens exert their atherosclerosis-retarding effect. The decreased cytoplasmic fatty acid synthesis observed in atherosclerosis might account for the low levels of saturated fatty acids reported in liver and plasma lipids of atherosclerotic animals.


Fall classification, incidence and circumstances in patients undergoing total knee replacement.
To propose a fall-classification framework for patients undergoing total knee replacement (TKR). In addition, we reinforced the available evidence on fall incidence and circumstances and compared the characteristics of fallers versus. nonfallers. Retrospective and prospective data were collected from 253 subjects with severe knee osteoarthritis who were waiting for primary TKR. Falls were classified considering the location of the destabilizing force, source of destabilization and fall precipitating factor. Fall incidence and circumstances were described; the characteristics of fallers and nonfallers in terms of functional and balance performance were compared with F-tests (95% CI). The fall incidence before surgery was 40.3% (95% CI 34.2% to 46.6%). This figure decreased to 13.1% (95% CI 9.2% to 18.0%) and to 23.4% (95% CI 17.8% to 29.6%) at 6 and 12 months after surgery, respectively. Most falls were caused by destabilizations in the base of support (n = 102, 72%) and were due to extrinsic factors (n = 78, 76%) and trip patterns. Significant differences between fallers and nonfallers were found in knee extensor strength and monopodal stability in the surgical limb (p < 0.05). Falls are prevalent in patients with severe knee osteoarthritis. Symptoms and functional performance improve after surgery, and fall incidence is reduced. Most fall events originate from disruptions in the base of support and are precipitated by extrinsic factors, generally trips during walking activities.


Urothelial Dysfunction, Suburothelial Inflammation and Altered Sensory Protein Expression in Men with Bladder Outlet Obstruction and Various Bladder Dysfunctions: Correlation with Urodynamics.
We investigated urothelial integrity, suburothelial inflammation and the expression of sensory proteins in the bladder urothelium of male patients with bladder outlet obstruction and various bladder dysfunctions. We prospectively enrolled 33 men with urodynamically proven bladder outlet obstruction as the study group. Bladder biopsies were obtained from all study patients and 10 control patients. The expression of E-cadherin, zonula occludens-1, tryptase, apoptosis, TRPV (transient receptor potential vanilloid) 1 and 4, β3 adrenoreceptor, M2 and M3 muscarinic receptors, P2X3 receptor, and inducible/epithelial nitric oxide synthase were compared between study and control patients. Study patients had significantly lower expression of E-cadherin, and a higher number of suburothelial mast and apoptotic cells than controls. Additionally, higher expression of P2X3 and M2 muscarinic receptors, and lower expression of M3 muscarinic receptor were detected in study patients. The detrusor underactivity subgroup was characterized by significantly higher expression of β3 adrenoreceptors and lower expression of inducible nitric oxide synthase than in controls. In study patients a significantly positive correlation was noted between voided volume and E-cadherin expression (r = 0.372), volume at first sensation of filling and β3 adrenoreceptor expression (r = 0.386), and detrusor pressure and M2 muscarinic receptor expression (r = 0.496) in the bladder urothelium (each p <0.05). Urothelial dysfunction, suburothelial inflammation, cellular apoptosis and alterations in sensory proteins are prominent in bladder dysfunction secondary to bladder outlet obstruction. Impaired urothelial signaling and sensory transduction pathways appear to reflect the pathophysiology of bladder dysfunction and detrusor underactivity in patients with bladder outlet obstruction.


Early and established status epilepticus: The impact of timing of intervention, treatment escalation and dosing on outcome.
We investigated the management and outcome of early and established status epilepticus including timing, dosing and selection of benzodiazepines along with the timing and efficacy of second line treatments. Retrospective single tertiary centre observational cohort study to identify all cases of SE between January 2019 and February 2022. 252 cases were identified. Seizures terminated spontaneously in 136 (54%) cases. 116 (46%) were given benzodiazepines, of which 29 (25%) were given at least one benzodiazepine by family/carers, and 72 (62.1%) received benzodiazepines by ambulance services. Benzodiazepines terminated seizures in 83 (71.6%) cases. The commonest benzodiazepine used was buccal midazolam (35.5%). Median time to first benzodiazepine was 14.5 (6-27) minutes. There was a positive correlation between time to first benzodiazepine and time to seizure cessation, progression to second- and third-line treatment, and respiratory complications (p<0.05). 73 (62.9%) cases received a correct benzodiazepine dose. Benzodiazepine underdosing was associated with longer seizure duration (p<0.05). 33 (28.4%) cases progressed to second-line treatment where mean time to treatment was 59.4 min (±32.3 min). The commonest second-line treatment was Levetiracetam (53.8%), followed by Phenytoin (43.6%) with SE termination in 57.5% cases. 14 (12.1%) cases progressed to third-line treatment; mean time to treatment was 60.6 min (±22.24 min). Respiratory complications occurred in 17 (6.75%) cases; none due to benzodiazepines. There were two deaths in refractory SE. Early administration of benzodiazepines and optimal dosing is associated with a higher rate of SE termination. Levetiracetam was the most commonly used second line treatment.


Complex regional pain syndrome in burn pathological scarring: A case report and review of the literature.
Chronic pain in burn pathological scarring is not an uncommon occurrence. The mechanisms of pain are not clearly understood and hence the management approach is often a daunting task. However, meticulous physical examination of these patients may classify them as complex regional pain syndrome, type I. We present a patient with classic signs and symptoms of complex regional pain syndrome associated with burn pathological scarring of her left forearm that had a favourable response to a thoracoscopic sympathectomy. The possible pathological mechanisms of burn pathological scarring, mechanisms of pain, and complex regional pain syndrome are reviewed.


Tensegrity: construction of rigid DNA triangles with flexible four-arm DNA junctions.
A tensegrity strategy has been explored to construct a rigid geometrical structure (triangles) from flexible DNA four-arm junctions. The resulting DNA triangles could self-assemble into 1D and 2D arrays. This tensegrity strategy is expected to play an important role in the design of biomimetic nanomaterials.


Effects of needs-based education for prenatal anxiety in advanced multiparas: a randomized controlled trial.
Prenatal anxiety is a common concern which may have adverse effects on maternal and infant health outcomes. Studies addressing needs-based education interventions for prenatal anxiety are limited. To explore the effects of needs-based education on alleviating prenatal anxiety among advanced multiparas when compared with routine prenatal health education. A total of 86 advanced multiparas were randomized into the intervention group (n = 43) or the control group (n = 43) in this study. The control group received routine prenatal care. The intervention group received five needs-based education programs presented by trained researchers. The Pregnancy-related Anxiety Questionnaire was used to evaluate changes in anxiety level of participants. Concurrent physiological parameters, including blood pressure, heart rate and non-stress test were also measured. Scores on the Pregnancy-related Anxiety Questionnaire of the intervention group were significantly lower than those of the control group (t = 4.21, P < 0.05). Systolic blood pressure (t = 3.64, P < 0.05) and heart rate (t = 2.39, P < 0.05) of the intervention group were also significantly lower than the control group whereas no differences were noted in diastolic blood pressure and non-stress test. A needs-based education program is an effective intervention strategy to allay prenatal anxiety in advanced multiparas. The trial was retrospectively registered in the Chinese Clinical Trial Registry as number ChiCTR2100047552 .


Rapid kinetics of an N-terminal mutant of cyanobacterial ribulose-1,5-bisphosphate carboxylase/oxygenase.
The transient changes in absorption of visible light upon addition of ribulose 1,5-bisphosphate to Co2(+)-activated ribulose-1,5-bisphosphate carboxylase/oxygenase were used to show altered catalytic properties of a mutant form of the enzyme from Anacystis nidulans. The mutant form of the enzyme had a modified N-terminus and a 10-fold greater Km for ribulose 1,5-bisphosphate than the natural cyanobacterial enzyme.


Measurements of intestinal permeability using low molecular weight polyethylene glycols (PEG 400). II. Application to normal and abnormal permeability states in man and animals.
A new approach to the measurement of intestinal permeability using low molecular weight polyethylene glycols (PEG 400) has been applied to the study of normal and abnormal permeability states in man and animals. Successful assessments of gastric, jejunal, ileal, and colonic permeability suggest that the technique has application to any area of the gastrointestinal tract. The method has shown that bile acids alter mucosal permeability in the stomach and colon and that celiac sprue is associated with decreased intestinal permeability. These examples illustrate the potential of the technique for studying the function of diseases intestine in man.


Neobladder long term follow-up.
One of the commonest forms of orthotopic bladder substitution for bladder cancer survivors, used in our institute, is the use of ileocecal segment. Sometimes, the need for Indiana pouch heterotropic continent diversion arises. To compare the long-term effect of orthotopic ileocecal bladder and heterotropic Indiana pouch following radical cystectomy in bladder cancer patients. Between January 2008 and December 2011, 91 patients underwent radical cystectomy/anterior pelvic exentration and orthotopic ileocecal bladder reconstruction (61 patients) and Indiana pouch (30 patients), when orthotopic diversion could not be technically or oncologically feasible. Convalescence was uneventful in most patients. All minor and major urinary leakage cases, in both diversions groups, where successfully conservatively treated. Only one patient in the ileocecal group with major urinary leak required re-exploration with successful revision of uretro-colonic anastomosis. Only one patient in the Indiana pouch group had accidentally discovered sub-centimetric stone, which was simply expelled. The overall survival proportion of ileocecal group was 100% compared to 80% in the Indiana pouch group (p<0.001). The disease free survival proportion of ileocecal group was 90.8% compared to 80% in the Indiana pouch group (p=0.076). Effective comparative daytime and nighttime urinary continence as well as renal function deterioration were not statistically significant between both reconstruction types. Both ileocecal bladder and Indiana pouch are safe procedures in regard to long-term effects over kidney function following radical cystectomy.


Small Fiber Neuropathy.
This narrative review aims to summarize advances in the field of small fiber neuropathy made over the last decade, with emphasis on novel research highlighting the distinctive features of SFN. While the management of SFNs is ideally aimed at treating the underlying cause, most patients will require pain control via multiple, concurrent therapies. Herein, we highlight the most up-to-date information for diagnosis, medication management, interventional management, and novel therapies on the horizon. Despite the prevalence of small fiber neuropathies, there is no clear consensus on guidelines specific for the treatment of SFN. Despite the lack of specific guidelines for SFN treatment, the most recent general neuropathic pain guidelines are based on Cochrane studies and randomized controlled trials (RCTs) which have individually examined therapies used for the more commonly studied SFNs, such as painful diabetic neuropathy and HIV neuropathy. The recommendations from current guidelines are based on variables such as number needed to treat (NNT), safety, ease of use, and effect on quality of life.


Preoperative neutrophil-to-lymphocyte ratio as a prognostic predictor after curative resection for hepatocellular carcinoma.
This study was designed to evaluate the impact of an elevated preoperative neutrophil-to-lymphocyte ratio (NLR) on outcome after curative resection for hepatocellular carcinoma (HCC). Patients undergoing resection for HCC from January 1994 to May 2007 were identified from the hepatobiliary database. Demographics, laboratory analyses, and histopathology data were analyzed. A total of 96 patients were identified with a median age at diagnosis of 65 (range, 15-85) years. The 1-, 3-, and 5-year overall survival rates were 80%, 58%, and 52%, respectively. Although the presence of microvascular invasion, NLR >or=5, and R1 resection margin were adverse predictors of overall survival, there were no independent predictors identified on multivariate analysis. The 1-, 3-, and 5-year disease-free survival rates were 74%, 63%, and 57%, respectively. Preoperative tumor biopsy, NLR >or= 5, multiple liver tumors, microvascular invasion, and R1 resection margin were all predictors of poorer disease-free survival. Multivariate analysis showed that a NLR >or= 5 and R1 resection margin were independent predictors of poorer disease-free survival. The median disease-free survival of those with a NLR >or= 5 was 8 months compared with 18 months for those with a NLR < 5. Preoperative NLR >or= 5 was an adverse predictor of disease-free and overall survival.


Widespread cortical morphologic changes in juvenile myoclonic epilepsy: evidence from structural MRI.
Atypical morphology of the surface of the cerebral cortex may be related to abnormal cortical folding (gyrification) and therefore may indicate underlying malformations of cortical development (MCDs). Using magnetic resonance imaging (MRI)-based analysis, we examined cortical morphology in patients with juvenile myoclonic epilepsy (JME). MRI data was collected for 24 patients with JME and 40 demographically matched healthy controls. FreeSurfer, an automated cortical surface reconstruction method, was applied to compare cortical morphology between patients and controls. Areas of anomalous cortical morphology were defined as regions of interest (ROIs) to contrast regional cortical parameters, such as surface area, average thickness, and mean curvature between patients and controls. In patients with JME, changes to cortical morphology were detected in several regions. In the left hemisphere, these were in insular and cingulate cortices, occipital pole, and middle temporal and fusiform gyri. In the right hemisphere, changes were detected in insular cortex, inferior temporal gyrus, and precuneus. Further analysis of ROIs revealed that these changes are related to differences in surface area rather than average cortical thickness. In addition, mean curvature abnormalities were detected in the insula bilaterally, the left cingulate cortex, and right inferior temporal gyrus. The morphologic findings in this study suggest that structural abnormalities in JME extend beyond mesial frontal lobe regions of the brain. These may be indicative of areas of subtle cortical folding abnormality related to early disruption of cortical development.


Carcass and Meat Quality Traits in an Embden×Toulouse Goose Cross Raised in Organic Dehesa.
This study assessed the influence of genetic type (Embden-Anser anser, EE; Toulouse-Anser anser, TT and F1 cross, ET) for meat characteristics (carcass, meat quality and fatty acid (FA) profiles), of domestic geese "Anser anser domesticus" raised in dehesa as an alternative, organic feeding system. Carcass and breast muscle weight (p<0.01) were greater for the ET group at the same live weight. None of the groups showed differences in the production of fatty liver with this type of feeding. Higher values were found for maximum Warner-Bratzler shear force (between 7.62 and 8.87 kg/cm(2)), which implies the improvement of this parameter. High levels of oleic FAs were obtained, especially for the TT group. The polyunsaturated/saturated FA ratio was highest for the ET group (p<0.001), reflecting the optimum nutritional values as a component of a healthy consumer diet.


A general approach to visualize protein binding and DNA conformation without protein labelling.
Single-molecule manipulation methods, such as magnetic tweezers and flow stretching, generally use the measurement of changes in DNA extension as a proxy for examining interactions between a DNA-binding protein and its substrate. These approaches are unable to directly measure protein-DNA association without fluorescently labelling the protein, which can be challenging. Here we address this limitation by developing a new approach that visualizes unlabelled protein binding on DNA with changes in DNA conformation in a relatively high-throughput manner. Protein binding to DNA molecules sparsely labelled with Cy3 results in an increase in fluorescence intensity due to protein-induced fluorescence enhancement (PIFE), whereas DNA length is monitored under flow of buffer through a microfluidic flow cell. Given that our assay uses unlabelled protein, it is not limited to the low protein concentrations normally required for single-molecule fluorescence imaging and should be broadly applicable to studying protein-DNA interactions.


The promoter region of the Zinnia elegans basic peroxidase isoenzyme gene contains cis-elements responsive to nitric oxide and hydrogen peroxide.
NO and H2O2 are important biological messengers in plants. They are formed during xylem differentiation in Zinnia elegans and apparently play important roles during the xylogenesis. To ascertain the responsiveness of the Z. elegans peroxidase (ZePrx) to these endogenous signals, the effects of NO and H2O2 on ZePrx were studied. The results showed that ZePrx is up-regulated by NO and H2O2, as confirmed by RT-qPCR, and that its promoter contains multiple copies of all the putative cis-elements (ACGT box, OCS box, OPAQ box, L1BX, MYCL box and W box) known to confer regulation by NO and H2O2. Like other OCS elements, the OCS element of ZePrx contains the sequence TACG that is recognized by OBF5, a highly conserved bZIP transcription factor, and the 10 bp sequence, ACAaTTTTGG, which is recognized by OBP1, a Dof domain protein that binds down-stream the OCS element. Furthermore, the ZePrx OCS element is flanked by two CCAAT-like boxes, and encloses one auxin-responsive ARFAT element and two GA3-responsive Pyr boxes. Results also showed that ZePrx may be described as the first protein to be up-regulated by NO and H2O2, whose mRNA contains several short-longevity conferring elements, such as a downstream (DST) sequence analogous to the DSTs contained in the highly unstable SAUR transcripts. The presence of these regulatory elements strongly suggests that ZePrx is finely regulated, as one may expect from an enzyme that catalyzes the last irreversible step of the formation of lignins, the major irreversible sink for the photosynthetically fixed CO2.


Vanadate inhibits uncoupled Ca efflux but not Na--Ca exchange in squid axons.
Nerve cells can maintain a very low intracellular calcium concentration ([Ca2+]i) against large Ca2+ electrochemical gradients (see ref. 1 for review). The properties of the calcium efflux from these cells depend on [Ca2+]i (ref. 2), and within the physiological range, most Ca efflux depends on ATP (which stimulates with high affinity) and is insensitive to Na1, Na0 and Ca0 (uncoupled Ca efflux). When the [Ca2+]i is well above the physiological range, Ca efflux becomes only partially dependent on ATP (acting now with low affinity), is inhibited by Nai and is stimulated by Na0 and Ca0 (Na--Ca exchange). Orthovanadate, a powerful inhibitor of the (Na+ + K+)ATPase and the Na pump, also inhibits the Ca-stimulated ATPase activity, which is the enzymatic basis for the uncoupled Ca pump, in human red cells. The experiments reported here show that in squid axons the ATP-dependent uncoupled Ca efflux can be fully and reversibly inhibited by vanadate, whereas concentrations of vanadate 10 times higher have no effect on the Na--Ca exchange. This is another indication that the uncoupled Ca efflux represents an ATP-driven Ca pump, and supports the suggestion that the uncoupled Ca efflux and Na--Ca exchange are mediated by different mechanisms.


Where are all the anthelmintics? Challenges and opportunities on the path to new anthelmintics.
Control of helminth parasites is a key challenge for human and veterinary medicine. In the absence of effective vaccines and adequate sanitation, prophylaxis and treatment commonly rely upon anthelmintics. There are concerns about the development of drug resistance, side-effects, lack of efficacy and cost-effectiveness that drive the need for new classes of anthelmintics. Despite this need, only three new drug classes have reached the animal market since 2000 and no new classes of anthelmintic have been approved for human use. So where are all the anthelmintics? What are the barriers to anthelmintic discovery, and what emerging opportunities can be used to address this? This was a discussion group focus at the 2019 8th Consortium for Anthelmintic Resistance and Susceptibility (CARS) in Wisconsin, USA. Here we report the findings of the group in the broader context of the human and veterinary anthelmintic discovery pipeline, highlighting challenges unique to antiparasitic drug discovery. We comment on why the development of novel anthelmintics has been so rare. Further, we discuss potential opportunities for drug development moving into the 21st Century.


Retreatment of a patient: Orthognathic surgery-first approach with customized lingual appliances combined with miniplate anchorage.
Orthognathic surgery is necessary when a patient's major complaints include skeletal discrepancies that cannot be corrected with orthodontic treatment alone. Currently, orthognathic surgery can be performed through conventional and surgery-first approaches. Some advantages are attributed to the surgery-first approach, such as shortened treatment time and immediate esthetic improvement. The aim of this case report is to present the retreatment of a patient presenting with a skeletal Class III malocclusion, with maxillary retrusion and mandibular protrusion, who was successfully treated with the surgery-first approach and customized lingual appliances, combined with miniplate anchorage in the postoperative orthodontic treatment. The total orthodontic treatment time was 8 months.


1H NMR study of the interaction of N,N',N"-triacetyl chitotriose with Ac-AMP2, a sugar binding antimicrobial protein isolated from Amaranthus caudatus.
The interaction between Ac-AMP2, a lectin-like small protein with antimicrobial and antifungal activity isolated from Amaranthus caudatus, and N,N',N"-triacetyl chitotriose was studied using 1H NMR spectroscopy. Changes in chemical shift and line width upon increasing concentration of N,N',N"-triacetyl chitotriose to Ac-AMP2 solutions at pH 6.9 and 2.4 were used to determine the interaction site and the association constant Ka. The most pronounced shifts occur mainly in the C-terminal half of the sequence. They involve the aromatic residues Phe18, Tyr20 and Tyr27 together with their surrounding residues, as well as the N-terminal Val-Gly-Glu segment. Several NOEs between Ac-AMP2 and the N,N',N"-triacetyl chitotriose resonances are reported.


A new age for older people? Policy shifts in health and social care.
This paper considers health and social policies for older persons from a cross-national perspective and attempts to uncover some of the factors influencing policy formulation and implementation. The focus is on community care, its meanings and practical implementation. Examples are drawn from Western Europe and the U.S.A. to illustrate and explain differences and similarities. Two sets of explanatory factors are considered crucial. First, the structure of health and social care systems create incentives for clients, care providers and planners in certain directions. The degree of organisational fragmentation and of public control are seen to be the most important structural factors. Second, it is argued that the political and ideological context within which health and social systems operate must be understood if one is to assess the likely directions of future policies.


Medication Discrepancies Associated With a Medication Reconciliation Program and Clinical Outcomes After Hospital Discharge.
To identify the frequency of unintended medication discrepancies 30 days postdischarge from medicine wards with interprofessional medication reconciliation processes and clinical import. Prospective cohort study of adults discharged between October 2013 and November 2014 from two teaching hospitals in Edmonton, Canada. The Best Possible Medication Discharge Plan (BPMDP) was prepared for all patients. Patients were called 30 days postdischarge to determine the medication discrepancy rate from the BPMDP and whether this was intentional or unintentional; three clinicians used standardized criteria to determine if the discrepancy was inconsequential. Electronic health records and patient contact were used to ascertain death, hospital readmissions, and emergency department (ED) visits at 90 days. Of 433 patients (mean age 64 yrs, 52% female, median discharge prescriptions 6 [interquartile range 4-9]), 168 (38.8%) had at least one unintentional medication discrepancy at 30 days (325 total discrepancies; median one [interquartile range 1-2 discrepancies per patient]). Patients with unintentional medication discrepancies were older (65.9 vs 61.9 yrs, p=0.03) with more discharge medications (7 vs 6, p=0.03). Most unintentional discrepancies (91.1%) were judged inconsequential. The presence of an unintentional medication discrepancy was not associated with 90-day readmission or death (42/167 [25.1%] vs 64/263 [24.3%], adjusted odds ratio 0.96 [95% confidence interval 0.60-1.54]) or ED visits (69 [41.3%] vs 101 [38.4%], adjusted odds ratio 1.11 [95% confidence interval 0.74-1.67]. Despite the presence of an interprofessional medication reconciliation process, over one-third of patients had a medication discrepancy within 30 days of discharge, although most were inconsequential and there was no association between unintended medication discrepancies and risk of readmission, ED visit, or death 3 months after discharge.


Cigarette smoking cessation attempts by recovering alcoholics.
Survey data on the smoking cessation experiences of 77 recovering alcoholics are reported. A comparison of successful and unsuccessful quitters addressed questions about optimal timing of cessation efforts, relative severity of alcohol and tobacco abuse histories, and the impact of cessation efforts on the maintenance of sobriety. Findings suggest that recovering alcoholics can successfully quit smoking without jeopardizing sobriety but that individuals with more severe substance abuse histories may be less successful. Although successful quitters tended to wait longer before attempting cessation, a comparison of the two groups was not statistically significant.


Approach to Cognitive Impairment in Parkinson's Disease.
Cognitive dysfunction is common in Parkinson's disease (PD) and predicts poor clinical outcomes. It is associated primarily with pathologic involvement of basal forebrain cholinergic and prefrontal dopaminergic systems. Impairments in executive functions, attention, and visuospatial abilities are its hallmark features with eventual involvement of memory and other domains. Subtle symptoms in the premotor and early phases of PD progress to mild cognitive impairment (MCI) which may be present at the time of diagnosis. Eventually, a large majority of PD patients develop dementia with advancing age and longer disease duration, which is usually accompanied by immobility, hallucinations/psychosis, and dysautonomia. Dopaminergic medications and deep brain stimulation help motor dysfunction, but may have potential cognitive side effects. Central acetylcholinesterase inhibitors, and possibly memantine, provide modest and temporary symptomatic relief for dementia, although there is no evidence-based treatment for MCI. There is no proven disease-modifying treatment for cognitive impairment in PD. The symptomatic and disease-modifying role of physical exercise, cognitive training, and neuromodulation on cognitive impairment in PD is under investigation. Multidisciplinary approaches to cognitive impairment with effective treatment of comorbidities, proper rehabilitation, and maintenance of good support systems in addition to pharmaceutical treatment may improve the quality of life of the patients and caregivers.


Two Rapidly Growing Mycobacterial Species Isolated from a Brain Abscess: First Whole-Genome Sequences of Mycobacterium immunogenum and Mycobacterium llatzerense.
Rapidly growing mycobacteria are rarely found in central nervous system infections. We describe a case of polymicrobial infection in a brain abscess including two rapidly growing Mycobacterium species, M. immunogenum and M. llatzerense. The Mycobacterium isolates were distinguishable by molecular methods, and whole-genome sequencing showed <60% pairwise nucleotide identity.


Is depression comparable between asylum seekers and native Germans? An investigation of measurement invariance of the PHQ-9.
Asylum seekers show high prevalence of depressive disorders compared to native populations. For the assessment of depression, the Patient Health Questionnaire-9 (PHQ-9) is a widely used instrument that has shown high validity and reliability. However, it is largely unknown whether PHQ-9 scores are comparable between asylum seekers living in Western countries and native populations, and whether results can be interpreted without reservation. Data from asylum seekers living in Germany (n = 243) and Germans without a migration background (n = 171) were used to analyze measurement invariance of the PHQ-9. Configural, scalar, and metric invariance was investigated, and test functioning was determined. The PHQ-9 was not measurement invariant across Germans without a migration background and asylum seekers living in Germany. Differences were found regarding metric invariance and scalar invariance. The items anhedonia, depressed mood, appetite changes, psychomotor changes, and suicidal ideation had lower loadings and lower thresholds in asylum seekers compared to Germans without a migration background. That led to an overestimation translated into approximately one point on the sum-score. The study limitations include a heterogeneous sample of asylum seekers regarding countries of origin, and the utilization of the different language versions of the PHQ-9. Our results may have implications for studies comparing levels of depression between asylum seekers and native Western samples. Even with the same latent level of depression, asylum seekers may have higher scores on several items and consequently a higher sum score. Therefore, the present results suggest a new determination or differentiation of the cut-off scores that were derived from Western samples.


Effectiveness of routine reporting to identify minor and serious adverse outcomes in surgical patients.
To assess the effectiveness of routine reporting to identify surgical adverse outcomes in comparison with retrospective medical record review. Independent assessment of two methods applied to one sample. Surgeons and surgical residents routinely reported all adverse outcomes for patients in their care during admission. A trained research assistant, blinded to the surgeons' reporting data, retrospectively reviewed the medical records of selected patients and registered all adverse outcomes identified from paper or electronic patient records. Dutch university hospital. A 5% sample of patients (N = 150) discharged in 2002 was taken; oversampling of patients undergoing reoperations, sick patients (ASA >or=3), and those undergoing technically complex surgery was done to increase the yield of adverse outcomes. The number of adverse outcomes identified by each method was compared with the total number identified by either method. This was done both for all adverse outcomes and for serious adverse outcomes. Routine reporting identified fewer adverse outcomes than medical record review (62.5% v 78.2%). Complete agreement was achieved in only 40.7% of adverse outcomes. Routine reporting identified slightly more serious adverse outcomes (84.8% v 79.5% of the total), but this difference was not statistically significant. Extrapolating these results to the total number of admissions in 2002, routine reporting underestimated the annual adverse outcome incidence by 1.8% (increasing from 14.5% to 16.3%) and the incidence of serious adverse outcomes by 0.3% (increasing from 6.9% to 7.2%). Neither method identified all adverse outcomes. Routine reporting underestimated the incidence of minor events but was as accurate as record review in identifying serious adverse outcomes.


Alterations in the morphology of ganglion cell dendrites in the adult rat retina after optic nerve transection and grafting of peripheral nerve segments.
Transected ganglion cell axons from the adult retina are capable of reinnervating their central targets by growing into transplanted peripheral nerve (PN) segments. Injury of the optic nerve causes various metabolic and morphological changes in the retinal ganglion cell (RGC) perikarya and in the dendrites. The present work examined the dendritic trees of those ganglion cells surviving axotomy and of those whose served axons re-elongated in PN grafts to reach either the superior colliculus (SC), transplanted SC, or transplanted autologous thigh muscle. The elaboration of the dendritic trees was visualized by means of the strongly fluorescent carbocyanine dye DiI, which is taken up by axons and transported to the cell bodies and from there to the dendritic branches. Alternatively, retinofugal axons regrowing through PN grafts were anterogradely filled from the eye cup with rhodamine B-isothiocyanate. The transection of the optic nerve resulted in characteristic changes in the ganglion cell dendrites, particularly in the degeneration of most of the terminal and preterminal dendritic branches. This occurred within the first 1 to 2 weeks following axotomy. The different types of ganglion cells appear to vary in their sensitivity to axotomy, as reflected by a rapid degeneration of certain cell dendrites after severance of the optic nerve. The most vulnerable cells were those with small perikarya and small dendritic fields (type II), whereas larger cells with larger dendritic fields (type I and III) were slower to respond and less dramatically affected. Regrowth of the lesioned axons in peripheral nerve grafts and reconnection of the retina with various tissues did not result in a significant immediate recovery of ganglion cell dendrites, although it did prevent some axotomized cells from further progression toward posttraumatic cell death.


Scattered radiation effects on the extrinsic sensitivity and counting efficiency of a gamma camera.
An evaluation of the effect of scattered radiation on the performance of a gamma camera is carried out using a specially designed home-made homogeneous circular planar flood source filled with 0.2±0.01 GBq of (99m)Tc solution as a scattering medium. The scatter effects are assessed by analyzing the energy spectrum of (99m)Tc for the scatter fraction and calculating the camera's extrinsic counting efficiency and sensitivity, for five flood source thicknesses (12, 50, 100, 150 and 200 mm ) and three source-to-detector distances (0.7, 0.9 and 1.1 m). Results showed an increase in the scatter fraction from 0.29 to 22.96 as the source thickness increased. This increase was associated with a decrease in the extrinsic sensitivity from 121.36 to 49.58 counts/s GBq, and a decrease in counting efficiency as from 3.78 to 1.55%. With the increase in source-to-detector distance, the extrinsic sensitivity decreases from 121.36 to 118.77 counts/s GBq, while the counting efficiency increases from 3.78 to 11.66%. It was found that a source-to-detector distance of 0.96±9×10(-3) m is a good compromise for an acceptable extrinsic sensitivity and a reasonable counting efficiency.


What influences the implementation of kangaroo mother care? An umbrella review.
Kangaroo mother care (KMC) is an evidence-based intervention that reduces morbidity and mortality in preterm infants. However, it has not yet been fully integrated into health systems around the world. The aim of this study is to provide a cogent summary of the evidence base of the key barriers and facilitators to implementing KMC. An umbrella review of existing reviews on KMC was adopted to identify systematic and scoping reviews that analysed data from primary studies. Electronic English databases, including PubMed, Embase, CINAHL and Cochrane Library, and three Chinese databases were searched from inception to 1 July 2022. Studies were included if they performed a review of barriers and facilitators to KMC. Quality assessment of the retrieved reviews was performed by at least two reviewers independently using the Joanna Briggs Institute (JBI) critical appraisal checklist and risk of bias was assessed with the Risk of Bias Assessment Tool for Systematic Reviews (ROBIS) tool. This umbrella review protocol was documented in the PROSPERO registry (CRD42022327994). We generated 531 studies, and after the removal of duplicates and ineligible studies, six eligible reviews were included in the analysis. The five themes identified were environmental factors, professional factors, parent/family factors, access factors, and cultural factors, and the factors under each theme were divided into barriers or facilitators depending on the specific features of a given scenario. Support from facility management and leadership and well-trained medical staff are of great significance to the successful integration of KMC into daily medical practice, while the parents of preterm infants and other family members should be educated and encouraged in KMC practice. Further research is needed to propose strategies and develop models for implementing KMC.


Comparison of the conformations of cyclolinopeptide A in the solid state and in solution.
Cyclolinopeptide A, a cyclic nonapeptide isolated from linseed, has lately attracted large interest for its cytoprotective activity. The recent elucidation of its solid state structure has prompted us to undertake a detailed conformational analysis in solution. Room-temperature 1H-nmr spectra in several solvents (DMSO-d6, DMSO-d6/D2O/H2O, CD3OH, (CD3)2CDOH, CDCl3) all show very broad lines, indicating the presence of chemical exchange among several conformers. It proved possible to freeze a single conformational state in CDCl3 at 214 K. Unusual chemical shifts and nuclear Overhauser enhancements are consistent with the main features of the solid state structure.


Arthroscopic Deltoid Ligament Reconstruction in Rotational Ankle Instability.
Chronic lateral ankle instability is a common orthopaedic problem. The continuous stress applied by the lateral instability may affect the superficial deltoid ligament. The combination of lateral ankle instability and injury to the most anterior fascicles of the deltoid ligament contributes to rotational ankle instability. The purpose of this Technical Note is to describe the details of arthroscopic deltoid ligament reconstruction in rotational ankle instability. This minimally invasive approach allows other associated lesions to be detected and managed arthroscopically.


Inconsistencies over time in 5% of NetAffx probe-to-gene annotations.
DNA microarray probes are designed to match particular mRNA transcripts, often based on expressed sequences like ESTs, or cDNAs, many times incomplete. As a result, the relations between probes and genes can change as the sequence data are updated. However, it is frequent that the reported results of microarray analyses are given just as lists of genes without any reference to the underlying probes. We show for a particular commercial microarray design that the number of probes associated to some genes change with time. These changes concern approximately 5% of the probe sets across the history of annotation releases over a two year span. We recommend to report probe set identifiers when publishing microarray results, and to submit those analyses to microarray public databases to ensure that the interpretation of the data is updated with the latest set of annotations.


The protective function of galectin-9 in liver ischemia and reperfusion injury in mice.
Galectin-9 (Gal-9) has gained attention as a multifaceted player in adaptive and innate immunity. To elucidate the role of Gal-9, we used a mouse model of partial liver ischemia/reperfusion injury (IRI) with wild type (WT) and Gal-9 knockout (KO) mice as well as a recombinant galectin-9 (reGal-9) protein. We found that the expression of Gal-9 was enhanced endogenously in the liver especially by hepatocytes and Kupffer cells during warm IRI for a mouse liver, which causes massive destruction of liver tissue. Gal-9 was released into the extracellular space in the liver and the highest levels in the plasma at 1 hour after reperfusion. The present study elucidates a novel role of Gal-9 signaling in mouse liver IRI, by using Gal-9-deficient mice and a stable form of reGal-9 protein. In the circumstance of Gal-9 absence, liver damage due to ischemia/reperfusion (IR) exacerbated the severity as compared with WT. On the other hand, exogenously administered reGal-9 significantly ameliorated hepatocellular damage. It decreased the local infiltration of the inflammatory cells such as T cells, neutrophils, and macrophages, and it reduced the expression of proinflammatory cytokines/chemokines; then, it strongly suppressed the apoptosis of the liver cells. Interestingly, severe liver damage due to IR in Gal-9 KO mice was improved by the administration of reGal-9. In conclusion, Gal-9 engagement ameliorated local inflammation and liver damage induced by IR, and the present study suggests a significant role of Gal-9 in the maintenance of hepatic homeostasis. In conclusion, targeting Gal-9 represents a novel approach to protect from inflammation such as liver IRI. Exogenous Gal-9 treatment will be a new therapeutic strategy against innate immunity-dominated liver tissue damage.