Factors associated with employment outcome after critical illness: Systematic review, meta-analysis, and meta-regression.
To synthesize data on prevalence and risk factors for return to work (RTW) in ICU survivors. Systematic review and meta-analysis. PUBMED, CINAHL, EMBASE and PsycINFO databases were searched from 2000-Feb 2020. Peer-reviewed articles that included adult ICU survivors and employment outcomes. Two investigators independently reviewed articles following the PRISMA protocol. Pooled prevalence for RTW was calculated. Meta-regression analyses were performed to assess the association between disability policies, temporal factors and RTW following ICU. Twenty-eight studies (N = 8,168) met the inclusion criteria. All studies were scored as 'low risk of bias'. Using meta-analysis, the proportion (95% CI) of RTW following ICU was 29% (0.20,0.42), 59% (0.50,0.70), 56% (0.50,0.62), 63% (0.54,0.72), 58% (0.37,0.91), 58% (0.42,0.81), and 44% (0.25,0.76) at 3, 4-6, 7-12, 13-24, 25-36, 37-48, and 49-60 months, respectively. Time and disability policy support are factors associated with the proportion of ICU survivors who RTW. Through meta-regression, there is a 20% increase (95% CI: 0.06, 0.33) in the proportion of individuals who RTW per year. However, the average rate of increase slows by 4% (-0.07, -0.1) per year. In countries with high support policies, the proportion of RTW is 32% higher compared with countries with low support policies (0.08, 0.24). However, as subsequent years pass, the additional proportion of individuals RTW in high support countries declines (β = -0.06, CI: -0.1, -0.02). Unemployment is common in ICU survivors. Countries with policies that give higher support for disabled workers have a higher RTW proportion to 3 years following ICU admission. However, from 3-5 years, there is a shift to countries with lower support policies having better employment outcomes. Health care policies have an impact on RTW rate in survivors of ICU. Healthcare providers, including nurses, can function as public advocates to facilitate policy change.


Poly(acrylic acid)-cysteine for oral vitamin B12 delivery.
The aim of this study was to investigate the potential of poly(acrylic acid)-cysteine (PAA-cys) solution and microparticles to enhance the transport of vitamin B12 (VB 12) across Caco-2 cell monolayer and rat intestinal mucosa. Thiolated PAA was synthesized by covalent attachment of L-cysteine. Microparticles were prepared by spray-drying and characterized regarding their size, morphology, thiol group content, VB 12 payload and release, swelling behavior, mucoadhesion, permeation-enhancing effect, and cytotoxicity. Particles with a mean diameter of 2.452±2.26 μm, a payload of 1.11±0.72%, and 190.2±8.85 μmol of free thiol groups per gram were prepared. Swelling behavior studies revealed that the stability of thiolated particles was improved compared with unmodified ones. Of the total VB 12 loaded, 95±0.12% was released within 3 h from thiolated particles. PAA-cys particles exhibited 2.24-fold higher mucoadhesive properties compared with unmodified particles. Permeation experiments with Caco-2 cells proved that permeability of VB 12 with PAA-cys solution and particles was 3.8- and 3.6-fold higher than control, respectively, and with rat intestinal mucosa it was 4.8- and 4.4-fold higher than control, respectively. Negligible cytotoxicity was assessed. PAA-cys is a promising excipient for oral delivery of VB 12 as a solution and as microparticles.


[The effectiveness of the use of local antibacterial drugs in the postoperative period in a patient with a neoplasm of the external auditory canal].
This article presents clinical case of external auditory canal osteoma and postoperative management of this patients. In this publication the etiology of this pathology, as well as the clinical manifestations that accompany this pathological condition are described. We present a literature review and our own experience of treatment this group of patients.


The historical record of PAH, PCB, trace metal and fly-ash particle deposition at a remote lake in north-west Scotland.
Sediment cores taken from the deep basin of Loch Coire nan Arr in north-west Scotland were dated using 210Pb calibrated spheroidal carbonaceous particle (SCP) profiles and analysed for trace metals, polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs). These data show that the site is one of the least contaminated by atmospheric pollution in the UK. Peak concentrations of PAHs were found to be equivalent to background values at sites in the English Lake District. The date of concentration maxima for SCP, PCB and some metals were in agreement with previously published polychlorinated dibenzo-p-dioxin/polychlorinated dibenzofuran (PCDD/F) data suggesting long-range industrial sources. The date of individual PAH concentration maxima were earlier, but concomitant with each other, possibly suggesting the influence of a local source. Comparison with remote European mountain lakes shows Loch Coire nan Arr to be one of the least contaminated sites in Europe with respect to PCBs, but more contaminated with respect to PAHs.


The Diagnostic Potential of Circulating Autoantibodies to Amyloid-β in Alzheimer's Disease.
The profile of naturally occurring antibodies to amyloid-β (NAbs-Aβ) is altered in patients with Alzheimer's disease (AD). However, the diagnostic potential of NAbs-Aβ for AD is not clear yet. This study aims to investigate the diagnostic capacities of NAbs-Aβ for AD. A total of 40 AD patients and 40 cognitively normal (CN) controls were enrolled in this study. Levels of NAbs-Aβ were detected by ELISA. The correlations of NAbs-Aβ levels with cognitive function and AD-associated biomarkers were examined by Spearman correlation analysis. Diagnostic abilities of NAbs-Aβ were evaluated by the receiver operating characteristic (ROC) curve analyses. The integrative diagnostic models were established by logistic regression models. We found that NAbs-Aβ7-18 had the highest diagnostic capability (AUC = 0.72) among all single NAbs-Aβ. The combined model (NAbs-Aβ7-18, NAbs-Aβ19-30, and NAbs-Aβ25-36) had a noticeable improvement (AUC = 0.84) in the diagnostic capacity compared with each single NAbs-Aβ. NAbs-Aβs are promising in the diagnosis of AD. Further investigations are needed to confirm the translational potential of this diagnostic strategy.


Influence of temperature and substrate conditions on the omt-1 gene expression of Aspergillus parasiticus in relation to its aflatoxin production.
Most strains of Aspergillus parasiticus are able to produce high concentrations of aflatoxin (AF) B1 and G1 which are among the most potent mutagenic, teratogenic, and carcinogenic mycotoxins. Molecular studies in relation to activity of secondary metabolite gene clusters are crucial to improving food safety. In the present work, reverse transcriptase quantitative PCR (RT-qPCR) was used to monitor the influence of temperature, substrates containing nitrogen and incubation time on the omt-1 gene expression in A. parasiticus. Phenotypic AFB1 and G1 production was also evaluated by high-performance liquid chromatography-mass spectrometry (HPLC-MS). The results demonstrated that temperature (25°C and 30°C) influenced relative expression of omt-1 gene throughout the time (maximum at 25°C) while substrate composition was not affected by it. However, when effect of temperature and substrate was analyzed at each incubation time, significant effects were found. Optimal conditions for biosynthesis of AFB1 and AFG1 were similar, and they were related to changes in temperature and sodium nitrate. The highest AFB1 and G1 production levels were found at 25°C. However, lower AFB1 and G1 values were obtained when A. parasiticus grew on the substrate containing sodium nitrate and there was no production of these AFs at 37°C in any of the conditions tested. In addition, omt-1 gene expression was correlated to AFB1 and G1 syntheses at the different conditions. Use of temperature conditions and sodium nitrate concentrations which limit production of AFs holds potential for preventing AF from entering the food chain.


Spontaneous forward mutation versus reversion frequencies for maize Adh1 in pollen.
Reliable quantitative data on spontaneous, specific gene mutation frequencies in higher plants and animals are few. Detergents include low natural frequencies and difficulty in obtaining in excess of 10(6) scorable organisms or gametophytes. The alcohol dehydrogenase-1 gene (Adh1 gene; ADH enzyme EC 220.127.116.11.), as expressed in pollen grains, is among the exceptionably suitable; much is known about the maize ADHs, Adh1 function is totally dispensible in an aerobic environment and maize pollen is a trinucleate gametophyte which expresses much of its haploid genome, including Adh1. In particular, there have been two recent methodological advances. First, I am able to cytochemically stain pollen, before or after in vitro germination, for the presence of above 5% normal ADH activity. And second, ADH1- pollen grains survive allyl alcohol (C=C-C-OH) vapour concentrations which kill ADH1+ grains; this selection scheme was developed for yeast by Megnet. My genetic resolution is approximately one mutant (Adh1+-->ADH-) per 10(7) chemically selected, viable gametophytes, and one (phenotypic) revertant (Adh1--->ADH+) per 10(8) unselected gatetophytes. In this note, I compare spontaneous forward mutant frequency with previously published revertant frequencies for one naturally occurring and six ethyl methanesulphonate-induced Adhl-deficient (Adh1-) alleles.


Resistant starch from green banana (Musa sp.) attenuates non-alcoholic fat liver accumulation and increases short-chain fatty acids production in high-fat diet-induced obesity in mice.
This study aimed to investigate the effect of resistant starch from green banana (GB) on steatosis and short-chain fatty acid (SCFAs) production in high fat diet-induced obesity in mice. High-fat green banana group (HFB) exhibited lower gains in BM (body mass; -6%; P < 0.01) compared with High-fat diet group (HF). Additionally, HFB mice showed reduction in liver steatosis (-28%, P < 0.01) with reduction of 93% in hepatic triacylglycerol (P < 0.01) compared to HF-diet-fed mice. In addition, the protein abundance of AMPKp/AMPK, HMGCoA-r and FAS were downregulated in livers of HFB mice (P < 0.01), relatively to the HF-diet-fed mice. ABCG8 and ABCG5 were up-regulated in HFB group compared to HF group (P < 0.01). Furthermore, the HFB fed-mice produced the highest amount of SCFAs (p < 0.05) compared to its counterpart HFD. In conclusion, we demonstrated that resistant starch from GB improved metabolic parameters by modulating the expression of key proteins involved in liver lipid metabolism.


Studies of EPR parameters for Mn5+ -doped Li3PO4 and Li3VO4 crystals.
The EPR parameters (zero-field splitting D and g factors g parallel, g perpendicular) of Mn5+ -doped Li3PO4 and Li3VO4 crystals are calculated from the complete high-order perturbation formulas based on a molecular orbital scheme for a 3d2 ion in tetragonal MX4 clusters. These formulas include not only the contribution coming from crystal-field excitations, but also that arising from charge-transfer excitations (which is discarded in crystal field theory). The calculated results are in reasonable agreement with the observed values. The contributions to EPR parameters coming from the charge-transfer excitations are comparable with those arising from the crystal-field excitations. It appears that for a high valence state 3dn ion in crystals, the reasonable explanations of EPR parameters should take the contributions due to both crystal-field and charge-transfer excitations into account.


[Examination of psychic effects of a new analgesic agent of the cyclohexanols series. A contribution to a possible psychic dependence potential of tramadol (author's transl)].
A double-blind trial was performed with 30 male students of the University of Düsseldorf. The volunteers were divided at random into two groups containing 15 subjects each. One group received 1-(m-methoxyphenyl)-2-(dimethylaminomethyl)-cyclohexan-1-ol (tramadol; Tramal), and the other placebo. The latter served as the controls. On three occasions at regular intervals in the course of one week the volunteers were questioned on the basis of Janke and Debus's "Eigenschaftswörterliste" (EWL) (attribution word list). The interviews were carried out 1 h after the injection (1 ampoule 100 mg i.m.). The results in the sense of any euphoretic or dysphoretic effects are discussed.


Peptic Ulcer Disease and Helicobacter pylori Infection in Different Siberian Ethnicities.
The high prevalence of Helicobacter pylori (H. pylori) infection in eastern Siberia is consistently established. In the same geographic area, however, fragmentary information is available on the epidemiology of the peptic ulcer disease (PUD). To assess the prevalence of H. pylori infection (including CagA status) and PUD in different eastern Siberian ethnicities. An endoscopy population of 3149 eastern Siberian dyspeptic patients was considered [1727 Europoids and 1422 Mongoloids (Evenks = 792; Khakases = 630)]. H. pylori status was assessed by urease test and/or serum anti-H. pylori IgG and/or histology. CagA status was serologically assessed (anti-CagA antibodies). All the Siberian ethnicities featured high rates of H. pylori infection (Europoids = 87.1%, Evenks = 88.6%, Khakases = 85.4%). Among the 1504 H. pylori-positive Europoids, the prevalence of CagA-positive status (68.7%) was significantly higher than that featured by the 1240 H. pylori-positive Mongoloid ethnicities (46.9%; p < .001 for both comparisons). Peptic ulcer disease significantly prevailed among Europoids (prevalence among Europoid Evenks and Khakases: 8.9% and 8.3%, respectively; prevalence among Mongoloid Evenks and Khakases = 1.0% and 4.4%, respectively). eastern Siberian populations feature consistent high rates of H. pylori infection, but different prevalence of peptic ulcer disease. In particular, Europoids featured a prevalence of both CagA-positive status and peptic ulcer disease significantly higher than that of the Mongoloid ethnicities. These results suggest that both environmental factors (coexisting with the H. pylori infection) and host-related variables modulate the clinicopathological expression of the H. pylori -associated gastric diseases.


Analysis of Cases of Neonatal Appendicitis from a Tertiary Care Unit.
To compare the clinical characteristics and prognosis of neonatal appendicitis (NA) alone and neonatal appendicitis with neonatal necrotizing enterocolitis (NEC) to improve the early recognition and diagnosis rate for this type of disease. Cases of appendicitis proved by operation and pathology younger than 28 d old in the authors hospital from 1990 to 2021 were retrospectively analyzed. According to whether combine with NEC, the cases were divided into two groups, analyzes the clinical characteristics. A total of 48 patients were enrolled, 15 cases in the NA group and 33 cases in the NEC with NA group. The age of onset, time from onset of symptoms to surgical intervention were both earlier in the NEC with NA group (p < 0.05). The preoperative white blood cells (WBC) and platelets (PLT) in the NA group were higher (p < 0.05). NEC with NA was more likely to be complicated with neonatal pneumonia and sepsis before surgery (p < 0.05). The main clinical symptom of NA was abdominal distension, while the other was bloody stool. The positive rate of ultrasound was high before the operation. The perforation rate of the appendix was very high (NA 100% vs. NEC 57.6%). In the NA group, 100% underwent appendectomy and 78.8% in the NEC with NA group underwent terminal ileostomy and appendectomy. The incidence of neonatal appendicitis is low. It is easily misdiagnosed as NEC. The perforation rate is very high, it is recommended to operate as soon as possible, and the prognosis is good.


Reproducibility of Accelerometer and Posture-derived Measures of Physical Activity.
The present study estimated the long-term reproducibility of accelerometer-based measures over 6 months in adults and the implications for statistical power, and attenuation in regression coefficients for future activity-disease studies. We used data from 914 adults in the Interactive Diet and Activity Tracking in AARP study. Participants wore an activPAL 3 (AP) and an ActiGraph GT3X (AG) twice, 6 months apart. AP measures included time spent sitting or lying, standing, and stepping, whereas AG measures included time spent in sedentary, light, and moderate-to-vigorous physical activity (PA). Reproducibility of each metric and implications for epidemiological studies were determined based on intraclass correlation coefficients (ICC; 95% confidence interval). The ICC values for AP estimates were 0.58 (95% confidence interval, 0.53-0.63) for sitting, 0.62 (0.57-0.67) for standing, and 0.57 (0.51-0.62) for stepping. The ICC values for AG were 0.56 (0.50-0.61) for sedentary, 0.54 (0.49-0.60) for light PA, and 0.58 (0.52-0.63) for moderate-to-vigorous PA. Modeling showed that increasing the number of replicate administrations to two or three resulted in the most noticeable increases in ICC values, statistical power, and reductions in attenuation coefficients. For example, administering the AP twice reduced within-subject variability by half and resulted in an increase in the ICC associated with sitting time from 0.58 to 0.74. Similar comparisons for AG and measure of sedentary time resulted in an increase in ICC values from 0.56 to 0.72. Increasing the number of replicate administrations from one to two reduced the attenuation in activity-outcome associations from 40% to 25%. Accelerometer-based classifications of activity are moderately stable over time, but there is considerable within-subject variability that needs to be considered when estimating usual activity in future studies.


Plasma concentrations of vitamin D metabolites during puberty of diabetic children.
Plasma concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D and vitamin D binding protein were determined in 87 serum samples from 46 Type 1 (insulin-dependent) diabetic children and adolescents at the various stages of puberty. The results were compared with data similarly obtained from healthy pubertal children. The diabetic patients had lower mean 1,25-dihydroxyvitamin D concentrations (p less than 0.05) and higher molar ratios of 24,25-dihydroxyvitamin D to 25-hydroxyvitamin D (p less than 0.05) than their healthy counter parts. In contrast to the reference group, the diabetic patients failed to attain the increase in 1,25-dihydroxyvitamin D normally seen during the pubertal stages of maximal growth velocity. The mean plasma levels of vitamin-D binding protein did not differ between the two groups, and a calculated 'free' 1,25-dihydroxyvitamin D value followed a pattern similar to that of total 1,25-dihydroxyvitamin D throughout puberty for both groups. The results suggest that the regulatory mechanisms of the vitamin D endocrine system are altered in diabetic children at puberty, resulting in a relative decrease in 1,25-dihydroxyvitamin D plasma concentration and increased 24,25-dihydroxyvitamin D levels.


Inhibitory effect of fluoride on the secretion of insulin.
The oral administration of sodium fluoride (NaF) (40 mumol/100 body weight [bw]) to fasting rats produced an immediate fall in insulin levels and the consequent increase in glycemia. These phenomena were observed with plasma fluoride concentrations 5-15 microM. Glycemia and insulin returned to normal levels within 4-5 hours, together with the washing out of fluoride from plasma and soft tissues. The insulin secretion of isolated Langerhans islets, perifused with solutions containing 5, 10, or 20 microM fluoride, was found to be significantly inhibited as a function of fluoride levels, both with basal and stimulatory concentrations of glucose. One hour after the intake of 60 mg of NaF, fasting human volunteers showed increased fluoride (5-15 microM) together with a significant fall of plasma insulin levels.


Gender and burden differences in family caregivers of patients affected by ten rare diseases.
Gender differences in caregiving may determine social and/or health inequalities among family caregivers (FCs). This study aimed to analyse gender specific differences of burden and quality of life (QoL) in FCs belonging to ten different rare diseases (RD). Burden levels and QoL data, derived from a sample of 210 FCs of RD patients, were analysed by student t-test, Anova and Kruskal-Wallis followed by multiple comparisons and evaluation of factors, including sex, by correlation and multiple regression analyses. FCs caring for Prader Willi, X-fragile, mucopolysaccharidosis and epidermolysis bullosa patients showed significant higher levels of burden as compared to other RDs. Burden is related to FC's QoL and can be down modulated by the reduction of the number of hours/week devoted to care and by the improvement of patient's QoL. No gender-specific burden differences were observed among all FCs. However, female FCs devoted to care significant more numerous hours/week than men and perceived more emotional/physical burden and poorer psychological health than males. Women, who are more frequently early retired from work, not occupied or homemakers than men, suffered more burden as compared to men in the same conditions. This study showed gender specific differences in RD caregiving, which are important for planning personalized health prevention policies.


Evaluation of molecularity of rate-limiting step of pore formation by antimicrobial peptides studied using mitochondria as a biosensor.
Toxic agents, derived from bee or hornet venoms and from fungi - melittin, mastoparan, and alamethicin are able to permeabilize biological membranes. We studied the initial steps of pore formation by these peptides in rat liver mitochondria preparations (RLM) generating transmembrane potential (ΔΨ). RLM has been used as a potassium transmembrane current (PTC) sensor. The PTC induced in RLM depends linearly on the degree of steady-state activation of RLM respiration. The concentration order of such activation by melittin in a "potassium" incubation medium containing 6mM Mg(2+) was 2.01±0.15. In the case of mastoparan, the reaction order was 1.83±0.23. The first steady-state phase of activation of RLM respiration by alamethicin was not detected in "Tris" incubation medium; it appeared only after addition of KCl. The order of the reaction limiting such activation was 1.92±0.07. It is suggested that PTC in this phase is determined by the channels with the lowest degree of oligomerization formed by "dimers". The ratio of equally active membrane concentrations of peptides obviously reflects the ratio of average lifetimes (ALT) for corresponding "dimers" (alamethicin and melittin, 38.5; mastoparan and melittin, 0.32). It is concluded that the results of this investigation may be useful for comparative testing of perspective pharmaceuticals.


Solid recommendations from soft numbers: the test/treatment decision.
The authors review the probability threshold approach to test/treatment decisions developed by Pauker and Kassirer, emphasizing that certain aspects of the nature of medical decisions call for a new approach. The utility threshold approach, while maintaining all the advantages of threshold methods in general, brings improvements. It diminishes the need to accurately assess one of the decision's parameters: the patient's utility for the outcome states. For a simple case of one disease with three outcome states (cured, diseased, dead) and one test, three utility thresholds are derived. The treat/no treat threshold, denoted by u, separates the utility space in two. If the patient's value for the diseased state is greater than u, the analyst can feel confident in recommending the patient forego treatment. Similar interpretations are developed for u1, the no treatment/test utility threshold (the value u must take, given a positive test result, for the patient to be indifferent between foregoing and receiving treatment), and u2, the test/treatment utility threshold (the value u must take, given a negative test result, for the patient to be indifferent between foregoing and receiving treatment.


Looking harder. Not-for-profit hospitals use Sarbanes-Oxley to strengthen their boards' financial accountability.
The Sarbanes-Oxley Act is intended to improve corporations' financial accountability, but boards of not-for-profit hospitals are taking their own cues from its provisions.


Current Treatment Management of Aneurysmal Subarachnoid Hemorrhage with Prevailing Trends and Results in Tanzania: A Single-Center Experience at Muhimbili Orthopedic and Neurosurgery Institute.
In Africa, no cerebral aneurysm treatment guidelines exist. Epidemiology, management, and outcomes after aneurysmal subarachnoid hemorrhage (aSAH) remain poorly understood, with many underdiagnosed cases. Muhimbili Orthopaedic and Neurosurgery Institute (MOI) is the only neurosurgical referral center in Tanzania. The aim of this study is to describe the current aSAH management with regional outcomes and limitations. Patients with aSAH confirmed by computed tomography/magnetic resonance angiography between February 2019 and June 2021 were retrospectively studied. The analyzed parameters included demographics, clinical/radiologic characteristics, injury characteristics, and the modified Rankin Scale (mRS) score. In total, 22 patients, with a female/male ratio of 1.4 and a median age of 54 years (interquartile range [IQR], 47.2-63 years) harboring 24 aneurysms were analyzed. Thirteen patients (59.1%) paid out of pocket. The median distance traveled by patients was 537 km (IQR, 34.7-635 km). The median time between admission and treatment was 12 days (IQR, 3.2-39 days). The most common symptoms were headache (n = 20; 90.9%) and high blood pressure (n = 10; 45.4%). Nine patients (40.9%) had Fisher grade 1 and 12 (54.5%) World Federation of Neurosurgical Societies grade I. The most common aneurysms were of the middle cerebral artery (7/29.2%). Fourteen patients (63.6%) underwent clipping; of those, only 4 (28.6%) were operated on within 72 hours. Mortality was 62.5% in the nonsurgical group. Among clipped patients, 78.6% showed favorable outcomes, with no mortality. Endovascular treatment is not available in Tanzania. To our best knowledge, this is the first study highlighting aSAH management in Tanzania, with its assets and shortcomings. Our data show pertinent differences among international treatment guidelines, with the resultant outcomes, such as high preoperative mortality resulting from delayed/postponed treatment. Regional difficult circumstances notwithstanding, our long-term goal is to significantly improve the overall management of aSAH in Tanzania.


Goniometry and linear assessments to monitor movement outcomes: are they reliable tools in burn survivors?
Despite common use and theoretical construct validity, goniometry is not reported to be reliable for the measurement of burn-affected joint range of motion. Similarly, a number of simple objective measures commonly used to document hand mobility have eluded this rigour. This study aimed to examine the within sessions of intra-rater and inter-rater reliability of active joint range of motion measurement in patients with burns. Intra-rater reliability: One physical therapist (PT) recorded duplicate measurements on each burn-affected joint after a 5-min interval in a subset of patients (n=21). Inter-rater reliability: Four qualified PTs took part in repeated measures testing of 45 patients on the same day. Intra-rater reliability was excellent with intraclass correlation coefficients (ICCs>.99) and 95% confidence intervals (CIs)=.99-1.0. Inter-rater reliability was also excellent with ICCs>.94 (95% CIs=.90-.99). The minimum detectable change using goniometry at the ankle was > or =5 degrees and for all other joints tested was > or =9 degrees. For linear hand measures a change of >1cm and thumb opposition > or =1/2 of one scale point indicated measurable difference. This study demonstrated excellent intra-rater and inter-rater reliability and measurement of clinically relevant change for all measurements when applied with a standardised protocol. Therefore, assessing joint range of motion (ROM) with a goniometer or hand movement with linear or scale measurements can provide accurate, objective measures in the burns population.


In situ Formed Implants, Based on PLGA and Eudragit Blends, for Novel Florfenicol Controlled Release Formulations.
Drug controlled release technologies (DCRTs) represent an opportunity for designing new therapies. Main objectives are dose number optimization and secondary effects reduction to improve the level of patient/client acceptance. The present work studies DCRTs based in blended polymeric implants for single dose and long-term therapies of florfenicol (FF), a broad spectrum antibiotic. Polymers used were PLGA and Eudragit E100/S100 types. Eudragit/PLGA and FF/PLGA ratios were the main studied factors in terms of encapsulation efficiencies (EEs) and drug release profiles. In addition, morphological and physicochemical characterization were carried out. EEs were of 50-100% depending on formulation composition, and the FF releasing rate was increased or diminished when E100 or S100 were added, respectively. PLGA hydrolytic cleavage products possibly affect Eudragit solubility and matrix stability. Different mathematical models were used for better understanding and simulating release processes. Implants maintained the antimicrobial activity against Pseudomonas aeruginosa up to 12 days on agar plates. The developed DCRTs represents a suitable alternative for florfenicol long-term therapies.


Position of the human X inactivation center on Xq.
In three women with a 46,XXq- chromosome constitution, the length of the deletion was expressed as the ratio of the remaining part of Xq to Xp c' over a + b. In one of them (KH) this ratio was 0.33, in another (GE) 0.59, and in the third (AP) the ratio fell between these values. The break in KH is more or less on the border of the Q-dark proximal region. A comparison with relevant X-autosomal translocations indicates that the X inactivation center lies near, but not at the border of, the Q-dark and the adjoining bright region (c and d).


Ultrasound-guided continuous radiofrequency ablation of the suprascapular nerve for chronic shoulder pain secondary to osteoarthritis: a retrospective cohort study.
The objective of this study is to retrospectively evaluate the use of ultrasound-guided continuous radiofrequency (CRF) lesioning of the suprascapular nerve for treating chronic shoulder pain, due to osteoarthritis. We describe a modified distal and selective ablation technique in the spinoglenoid notch, with motor and sensory stimulation, which protects the motor branch of the nerve from ablation. A retrospective analysis was performed of patients, who underwent ultrasound-guided CRF lesioning of the suprascapular nerve from October 2013 to January 2020. During the procedure, the CRF electrode is placed in the spinoglenoid notch, at the distal suprascapular nerve capsular branch. Motor and sensory stimulations are used to confirm the position. CRF lesioning is applied up to three times, at 3 different points, for 1 min each time, at 80° C. In total, 127 first CRF suprascapular nerve lesioning procedures were performed on 101 patients with chronic shoulder pain secondary to osteoarthritis. One hundred nineteen diagnostic ultrasound-guided suprascapular nerve corticosteroid injections were performed prior to ablation. Mean pre-injection Visual Analogue Scale pain score (VAS) was 8.3, with post-injection VAS score of 4.4 at 24 h and 4.5 at 2 weeks. Mean pre-CRF lesioning VAS pain score was 7.7 with post-CRF lesioning VAS score of 4.4 at 24 h and 4.5 at 2 weeks. Ultrasound-guided CRF lesioning of the suprascapular nerve in the spinoglenoid notch is a safe treatment for chronic osteoarthritic shoulder pain, with repeat treatments infrequently required. It is associated with significant improvement in VAS pain scores. • Ultrasound-guided continuous radiofrequency lesioning of the suprascapular nerve in the spinoglenoid notch is a safe treatment for chronic shoulder pain in degenerative disease, with repeat treatments infrequently required. • The procedure is performed under ultrasound guidance, without the use of ionising radiation.


The association between human papillomavirus infection and female lung cancer: A population-based cohort study.
Lung cancer is the leading cause of cancer deaths among Taiwanese women. Human papillomavirus (HPV) has been detected in lung cancer tissues. The aim of this study was to investigate the association between HPV infection and lung cancer among the Taiwanese women. The analytical data were collected from the longitudinal health insurance databases (LHID 2005 and 2010) of the National Health Insurance Research Database (NHIRD). The study participants were 30 years and older and included 24,162 individuals who were identified with HPV infection from 2001 to 2004 and 1,026,986 uninfected individuals. Lung cancer incidence among infected and uninfected individuals was compared using the univariate and multivariate regression models. Among the total participants, 24,162 individuals were diagnosed with HPV. After adjusting for age, gender, low income, residential area, and comorbidity, the risk of lung cancer was higher in women (hazard ratio [HR] 1.263, 95% CI 1.015-1.571), while all cancer risks were high in both men and women with corresponding hazard ratios (HR) of 1.161 (95% CI 1.083-1.245) and HR 1.240 (95% CI 1.154-1.331), respectively. This study showed a significant increase in lung cancer risk among Taiwanese women who were exposed to HPV infection.


[Optimization of the purification of human plasma fibronectin by double affinity chromatography using gelatin and heparin Trisacryl LS].
The authors described an optimized method of preparation to obtain pure human plasma fibronectin. The new performances related to the chromatographic and concentration steps, where the saving of time is about 40% and the lyophilization step where the saving of energy is also about 40%. The final product is without any less of either physical and biological activities. The size of the columns, the volumes of the chromatographic supports (gelatin and heparin-Trisacryl LS) and the quantity of the treated plasma are very much important and also the quantities of the final product are very increased.


Procedural characteristics and outcomes following chronic total occlusion coronary intervention: pooled analysis from 5 registries.
Recent improvements in clinical skills, technology, and hardware have resulted in improved success rates with chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We performed a study level pooled analysis from the five largest registries of percutaneous coronary intervention (PCI) of CTO. We conducted pooled analysis of 9500 patients in registries and data on procedural characteristics, technical success, and MACCE was collected. A total of 9500 patients were included in the analysis. Mean age was 65.4 years with previous CABG in 24.8%, reattempt procedure in 24.8% and mean JCTO score was 2.2. Final wiring strategy in hybrid algorithm-based registries was AWE in 40.8-58%, Retrograde in 24-35%, ADR in 16-25% and in Expert JCTO and EURO CTO was AWE in 72-75% and retrograde in 25-28%. Technical success was achieved in 87.8%. In hospital MACCE was 2.5% (95% CI: 1.8- 3.4%), mortality 0.44% (95% CI: 0.23-0.84%), stroke 0.2% (95% CI: 0.1-0.3%); myocardial infraction 1.6% (95% CI: 1.1-2.2%); and cardiac tamponade 0.8% (95% CI: 0.5 to 1.3%). CTO PCI is currently performed with high technical success rates and low complication rates in experienced hands utilizing various techniques.


Systematic review of the implantation of penile prosthesis in major ambulatory surgery.
Penile prosthesis (PP) implantation is an effective option for erectile dysfunction. Although initially PP surgery was carried out in an inpatient setting, there is a growing trend to implant PP as a major ambulatory surgery (MAS). This study aimed to perform a systematic review of the literature to identify available evidence of the implantation of PP under MAS setting and go carry out a comparison between MAS and inpatient procedures. PubMed, EMBASE, Cochrane Library and MEDES electronic databases and non-indexed supplements for scientific congresses were searched to identify articles related to the surgical implantation of PP in MAS up to February 2021. Key search terms included penile prosthesis, erectile dysfunction, ambulatory surgery, ambulatory care, and surgery. Among 171 publications retrieved (51 PubMed, 73 EMBASE, 3 Cochrane, 2 using MEDES and 42 manual searching), 5 studies were finally selected. There were no significant differences between MAS or inpatient setting in terms of the type of device, surgical approach, or location of reservoir. Complication rates observed in both groups were similar. Implantation of PP in MAS was less expensive than inpatient surgery and was associated with acceptable patient satisfaction rates and adequate pain control. Studies demonstrated that outpatient PP surgery can achieve similar outcomes in terms of safety and satisfaction to implantation of PP in the inpatient setting, while it could reduce costs and improve the efficiency. This research could support decision makers to extend PP surgery into the ambulatory setting.


Assessment of the test-retest reliability of a foot placement accuracy protocol in assisted-living older adults.
This study assessed the test-retest reliability of a foot placement accuracy protocol in a population of assisted-living elderly. The goal was to evaluate the execution of foot placement performance with increasing complexity of the walking condition. Twenty-five elderly participants (5 males, 20 females, 80.4±8.6 years) were assessed by one observer in two sessions with 48 h between the measurements. Participants walked at self-selected pace along a pathway with three different walking conditions composed of two rectangular foam target locations and an obstacle on the walking surface. The main outcome measures were foot placement distance error, intra-class correlation coefficients (ICC), and the smallest detectable difference (SDD). Mean absolute values of the foot placement distance errors were 14.0±4.5 mm for medio-lateral deviation and 27.2±2.1 mm for anterior-posterior deviation, respectively. ICC values for test-retest reliability showed 'fair to good' to 'excellent' reliability across all conditions with values ranging from 0.63 to 0.94. SDD values were between 3.6 and 37.3mm. The protocol showed good reliability for test-retest measurements of foot placement accuracy, thus making this protocol a reliable and location-independent tool to assess performance of foot placement in elderly in assisted-living settings. In the future, measurements with elderly fallers and non-fallers should be conducted to assess validity of the protocol.


Neuropeptides facilitate the desensitization of nicotinic acetylcholine-receptor in frog skeletal muscle endplate.
Substance P and luteinizing hormone-releasing hormone (LHRH), neurotransmitter candidates for peptidergic neurotransmission in peripheral autonomic ganglia, facilitated the desensitization of nicotinic acetylcholine (ACh)-receptor at the skeletal muscle endplate. In the presence of these peptides, the desensitization proceeded with a biphasic time course, i.e. fast and then slow components of desensitization. We suggest that neuropeptides such as substance P and LHRH may regulate the sensitivity of nicotinic ACh-receptors by modulating the process of desensitization.


Enhancing stability and bioaccessibility of chlorogenic acid using complexation with amylopectin: A comprehensive evaluation of complex formation, properties, and characteristics.
Chlorogenic acid (CA) performs numerous bioactivities; however, its usage is currently limited because of low stability and poor bioaccessibility. In this study, a amylopectin-CA complex was formed. FTIR studies confirmed that the new complex formed via hydrogen and CH-π bonding, and was involved with the reorganization of the skeletal α-1,4 glucosidic linkages of amylopectin. DSC and XRD studies suggested that complexation affected starch crystallinity and increased the size of the amorphous region. Under high temperature, complex degradation followed first-order reaction kinetics whereas under low acidity, the complex retained maximum CA content at pH 2.5. In vitro gastrointestinal (GI) digestion studies showed that maximum digestion of the complex took place during the gastric phase (39%). In addition, 81.14% of the retained CA was absorbed after GI digestion. In conclusion, amylopectin complexation may improve the stability of CA during digestion and under various food-processing operations.


Should we use composite outcomes in obstetric clinical prediction models?
Clinical prediction models assist clinicians to estimate the natural course of a condition, and thus facilitate treatment decisions. The development of prediction models is increasingly common in obstetric research. Composite outcomes, whereby multiple outcomes are combined into a single endpoint, are frequently used in obstetric prediction models to increase statistical power when predicting rare events. Although existing literature has reviewed the positives and negatives of using composite outcomes in clinical trials, there has been minimal commentary on the implications of their use in the development and reporting of prognostic models. In this article, we review these issues, in particular, highlighting how unequal individual relationships between predictors and individual component outcomes can result in misleading conclusions, which may result in the omission of important but rare predictors or inappropriately inform clinical decisions to implement an intervention. We propose careful use, or where possible avoidance, of composite outcomes in the development of prognostic models in obstetrics. Methodological standards for developing prognostic models should be updated to standardise and appraise composite outcomes when their use is necessary. We also support previous recommendations to report on the accuracy of key components and inconsistencies among predictor variables.


Novel fixation method of a periprosthetic fracture of the acetabulum using burr holes through the retained cup for locking screw fixation.
The incidence of periprosthetic fractures of the acetabulum associated with a total hip arthroplasty is relatively low but may be increasing. Treatment options depend upon the stability of the prosthesis. In this case, we report an unusual fracture pattern where a large portion of posterior column remained osseointegrated to a displaced uncemented acetabular component and removal of the cup would have resulted in massive structural bone loss and potential pelvic discontinuity. A metal cutting burr was used to create additional screw holes in the cup to allow us to retain the original implant and also obtain fixation of the fracture. The patient had a good outcome at one year with a healed fracture, stable implant, and excellent function. To our knowledge, this technique has not been previously described and offers surgeons an approach to fix these challenging fractures.


Preparation of a cimetidine ion-selective electrode and its application to pharmaceutical analysis.
A novel cimetidine ion-selective electrode is prepared, characterized and used in pharmaceutical analysis. The electrode incorporates PVC-membrane with cimetidine-phospohotungstate ion pair complex. The electrode exhibits a Nernstian response for cimetidine in the concentration range 1.0 x 10(-5)-1.0 x 10(-2) M with a slope of 58+/-1 mV per decade. The limit of detection is 5.0 x 10(-6) M. The electrode displays a good selectivity for cimetidine with respect to a number of common foreign inorganic and organic species. It can be used in the pH range 3.0-5.5. The membrane sensor was successfully applied to the determination of cimetidine in its tablets as well as its recovery from a urine sample.


Phosphatases in the central nervous system of spiders (Arachnida, Araneae).
The central nervous systems of web-building spiders (Araneidae, Agelenidae) and hunting spiders (Lycosidae, Salticidae) were tested for non-specific and specific phosphatases. Acid phosphatase exhibited weakly to moderately positive reactions in the neuronal cell bodies and in the neuropile fibre mass of all species investigated. Alkaline phosphatase could only be demonstrated in the external and internal neural lamellae of the brain and ventral cord of several specimens of the araneid species investigated. Tests for thiamine pyrophosphatase were negative with both the lead and calcium-cobalt methods. Distinctive positive reactions for adenosine triphosphatase were visible in the nervous system of all the species used, being especially strong in the optic ganglia of the hunting spiders. The demonstration of adenosine triphosphatase was only possible when applying the calcium-cobalt method after Padykula and Herman, while the lead method after Wachstein and Meisel did not produce any staining reaction at all. Controls of the histochemical reaction showed that the enzyme was activated by Ca2+ and inhibited by sulphydryl destroying reagents (e.g. PCMB), but was insensitive to ouabain. It could be probably classified as a mitochondrial proton-translocating adenosine triphosphatase.


Phlorofucofuroeckol A inhibits the LPS-stimulated iNOS and COX-2 expressions in macrophages via inhibition of NF-κB, Akt, and p38 MAPK.
We have recently reported that phlorofucofuroeckol A isolated from the edible brown algae Ecklonia stolonifera showed potential antioxidative and anti-inflammatory properties in macrophage stimulated by LPS treatments. In this study, we further investigated the pharmacological characteristic of phlorofucofuroeckol A in regulations of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 through regulatory and signaling pathways using LPS-treated RAW 264.7 cells. Treatment with 20 μM of phlorofucofuroeckol A significantly decreased levels of iNOS and COX-2 mRNA induced by LPS stimulation. As results, levels of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were significantly reduced by treatments of phlorofucofuroeckol A in LPS-stimulated RAW 264.7 cells. Phlorofucofuroeckol A inhibited promoter activities of inflammatory-mediators (iNOS and COX-2) and transcriptional factors (nuclear factor-κB, NF-κB, and AP-1) in LPS-treated RAW 264.7 cells. Moreover, phlorofucofuroeckol A inhibited activation of Akt and p38 MAPK in LPS-treated RAW 264.7 cells. These results indicate that the phlorofucofuroeckol A regulates iNOS and COX-2 expressions through the NF-κB-dependent transcriptional control associated with inhibition of multiple signaling proteins, suggesting potential candidates of phloroglucinol derivatives for treatments of inflammatory diseases.


Fluid Dynamic Assessment of Hypersonic and Guillotine Vitrectomy Probes in Viscoelastic Vitreous Substitutes.
To assess the fluidics of 23-gauge (G) large-port (L) and tear drop-port (TD) hypersonic vitrectomy probes (HVPs) compared with guillotine vitrectomy probes (GVPs) of various calibers (23G, 25G, and 27G) and geometries (single and double blades). Also, to identify the working parameters that provide the best balance between acceleration and flow rate, and, for HVPs, to measure temperature variations in the fluid. We used particle image velocimetry to measure flow fields in balanced salt solution and viscoelastic artificial vitreous. We analyzed acceleration, kinetic energy, and volumetric flux. The parameters considered were vacuum pressure, ultrasound stroke, and cut rate. Temperature measurements were taken using an infrared thermal camera. The flow rate was significantly higher for HVPs than GVPs. With both probes, flow rate and acceleration increased with vacuum pressure. Flow rate depended weakly on the ultrasound stroke or cut rate. In HVPs, the acceleration peaked at a stroke of 30 µm, whereas in GVPs it peaked at a cutting rate of 4000 to 5000 cuts per minute (cpm). The HPV/TD combination generated higher flow rates and lower accelerations than did HPV/L. The increase in temperature was small. Under the present experimental setup and medium, HVPs offered better fluidics compared with GVPs in terms of flow and acceleration; however, the flow structure for HVPs is more complicated and unsteady. The HPV/TD combination produced larger flows than did the HPV/L combination and slightly smaller accelerations. HPVs generated a small temperature increase. In the tested artificial vitreous, HVPs were found to be more efficient in terms of generating lower acceleration for a given flow rate. The slight increase in temperature observed with HVPs is unlikely to be clinically significant.


Treatment of nausea in pregnancy: a cross-sectional multinational web-based study of pregnant women and new mothers.
The factors related to the treatment of nausea during pregnancy have not yet been investigated in several countries simultaneously. The present study aimed to describe differences in self-reported nausea during pregnancy and the patterns of use for both conventional and herbal medicines across countries. The factors related to nausea and its treatment and the relationships between different self-reported co-morbidities and nausea were also investigated. This cross-sectional study used data collected by a web-based questionnaire distributed between October 2011 and February 2012 in several countries within five regions: Western, Northern, and Eastern Europe, North America, and Australia. Women who were pregnant or had a child less than one year old were eligible to participate. A total of 9113 women were included in the study, whereof 6701 (73.5%) had experienced nausea during pregnancy. Among respondents with nausea, conventional medicines were used by 1201 (17.9%) women and herbal medicines by 556 (8.3%) women. The extent of self-reported nausea and its treatment varied by country. Education, working status, and folic acid use were significantly associated with the use of conventional medicines against nausea. Respondents who had nausea also had a high burden of co-morbidity. The prevalence of nausea was high across all participating countries but its treatment varied, possibly due to cultural differences and differences in attitudes towards medicines. A high degree of co-morbidity was found among respondents with nausea.


18F-fluorodeoxyglucose-positron emission tomography scanning is a useful tool for therapy evaluation of arterial aneurysm in Behçet's disease.
[(18)F]fluorodeoxyglucose-positron emission tomography (FDG-PET) has demonstrated its usefulness in giant cell arteritis, Takayasu's arteritis, and unclassified aortitis. FDG-PET imaging could be more effective than CT-scan or magnetic resonance imaging in detecting the earliest stages of vascular wall inflammation. Data are lacking regarding its accuracy for diagnosis and follow-up of vascular lesions in Behçet's disease. We report the case of a 32-year-old woman with history of Behçet's disease and fever of unknown origin revealing voluminous pulmonary arterial aneurysms. FDG-PET scan revealed a peripheral uptake of pulmonary aneurysms, underlying the inflammatory status of arterial aneurysms wall. Our patient was treated by glucocorticoids and intravenous cyclophosphamide and achieved remission of Behçet's disease. During follow-up, FDG-PET scan enabled to detect an early radiologic therapeutic response after 4 months, while CT angiography remained unchanged. We report the first evidence of usefulness of FDG-PET scan for therapeutic evaluation of arterial aneurysms in Behçet's disease. Further studies are warranted to determine the accuracy of FDG-PET scan in larger cohort of Behçet's disease patients with vascular involvement.


Partial purification and characterization of GDP dissociation stimulator (GDS) for the rho proteins from bovine brain cytosol.
A novel type of regulatory proteins for the rho proteins (rhoA p21 and rhoB p20), ras p21-like small GTP-binding proteins (G proteins), are partially purified from bovine brain cytosol. These regulatory proteins, named rho GDP dissociation stimulator (GDS) 1 and -2, stimulate the dissociation of GDP from rhoA p21 and rhoB p20. rho GDS1 and -2 are inactive for other ras p21/ras p21-like small G proteins including c-Ha-ras p21, smg p21B, and smg p25A. Since we have previously shown that the rate limiting step for the GDP/GTP exchange reaction of the rho proteins is the dissociation of GDP from these proteins, the present results suggest that rho GDS1 and -2 stimulate the GDP/GTP exchange reaction of the rho proteins. rho GDS1 and -2 are distinct from the GAP- and GDI-types of regulatory proteins for the rho proteins previously purified from bovine brain cytosol. rho GAP stimulates the GTPase activity of the rho proteins and rho GDI inhibits the GDP/GTP exchange reaction of the rho proteins. The present results together with these earlier observations indicate that the rho proteins are regulated by at least three different types of regulatory proteins, GDS, GDI, and GAP.


Measuring the quality of antibiotic prescribing for upper respiratory infections and bronchitis in 5 US health plans.
To develop and test the validity of a quality-of-care performance measure that examines antibiotic prescribing rates in children diagnosed as having upper respiratory infection (URI) or bronchitis. The measure developed examines the annual rate of antibiotic prescribing to children aged 3 months to 18 years with an episode of URI or bronchitis. Administrative data from 5 US health plans were used to identify episodes of URI or bronchitis using International Classification of Diseases, Ninth Revision, codes 460, 465, 466, and 490. Pharmacy data (National Drug Codes) were used to determine whether antibiotics were prescribed for the URI or bronchitis episode. Medical record abstractions were performed on a random sample of 465 cases to assess percentage agreement with pharmacy claims data for antibiotic prescribing. For the 84,166 children and adolescents aged 3 months to 18 years who had at least 1 episode of URI or bronchitis during the measurement year, 31% received antibiotics. Prescribing rates for URI and/or bronchitis varied widely among the 5 participating health plans (2%-75%; P < .001). Inappropriate antibiotic prescribing occurred most frequently for bronchitis episodes, with 4 of 5 health plans prescribing antibiotics in 60% of such cases (range, 60%-80%). Percentage agreement between administrative and medical records data for antibiotic prescribing was 88%. This quality measure is feasible to implement at the health plan level and validly assesses antibiotic prescribing rates using administrative data. Improvements in adhering to judicious use guidelines for antibiotic prescribing in children with URI and bronchitis are warranted.


Standardized categorical reporting of cytopathology results: the strengths and weaknesses of a constantly evolving and expanding system.
Since the success of the Bethesda nomenclature system in standardizing Pap smear results, there has been growing interest in adopting Bethesda-like standardized categorical formats in areas of nongynecologic cytopathology. Standardized categorical reporting may have several advantages over descriptive reporting, in enhancing cytopathologist-clinician communication and inter-institutional exchange of information, providing better guidance for treatment planning, and facilitating statistical analysis for research purposes or quality control studies. On the other hand, descriptive reporting may be more effective as a tool of communication between cytopathologists, may better express the uncertainty of the observer in diagnostically difficult and equivocal cases and may better serve the purposes of training and continuing education of cytopathologists. Future studies on the pros and cons of the different reporting systems used in cytopathology may provide further insight on these issues. The most problematic areas need to be identified and optimal solutions decided. Despite the ongoing debate on the optimal reporting format in cytopathology, there is general agreement on the need for high quality cytology reports (whether descriptive or standardized) in terms of their diagnostic accuracy, clarity and clinical value.


Staff interaction with vocally disruptive demented patients compared with demented controls.
This study addressed the effect of social isolation on vocally disruptive demented patients (V); the results center on the amount of time patients spent in interactions, and the differences in type and time of staff-patient interaction (IA), compared to controls (C). Semi-structured observations were collected (1100 hours) for 37 vocally disruptive patients and 37 controls, all residents of psychogeriatric wards. Quantitative analysis revealed a low frequency of interactions, elicited mainly for procedural matters and short duration of most interaction episodes. Multiple regression analysis showed a significant difference in the type of interaction: there was more correction of undesired behaviour for vocally disruptive patients than for controls. The results show that social isolation is part of the institutionalized demented patients' life. The dominance of short interaction episodes could contribute to overstimulation. The only significant difference found was the frequency of corrective interactions in the group of vocally disruptive patients. We conclude that this is not the cause of their behaviour, but it may reinforce it. Other factors that might cause and maintain this behaviour require investigation.


The wheat TaGI1, involved in photoperiodic flowering, encodes an Arabidopsis GI ortholog.
Wheat (Triticum aestivum L.) is an important crop and requires long day and short night to flower. To study the molecular mechanism of photoperiodic regulation of flowering in this species, we isolated a wheat TaGI1 gene, an ortholog of GIGANTEA (GI) in Arabidopsis. RNA blot hybridization revealed that TaGI1 is expressed in leaves in a rhythmic manner under long day and short day conditions and its rhythmic expression is regulated by photoperiods and circadian clocks. Further study demonstrated that the TaGI1 rhythmic expression in the leaves of seedlings is initiated by photoperiods, implying that TaGI1 does not show circadian regulation until after being entrained in a light/dark cycle. Interestingly, TaGI1 mRNA was detected in adaxial epidermal cells right above the vascular bundles of leaves, suggesting that the localization of TaGI1 transcripts in leaves may function to regulate flowering in response to photoperiods. Since overexpression of TaGI1 altered flowering time in wild type and complemented the gi mutant in Arabidopsis, it confirmed that TaGI1 is an ortholog of GI in Arabidopsis.


Polymorphism of p16 INK4A and cyclin D1 in adenocarcinomas of the upper gastrointestinal tract.
We investigated the prevalence of single nucleotide polymorphisms in the p16 gene (C540G) and the cyclin D1 gene (G870A), both known to regulate function in G1 arrest and therefore, may play an important role in carcinogenesis. Using PCR based restriction fragment length polymorphism and single strand conformational polymorphism, we determined single nucleotide exchanges in the p16 and cyclin D1 genes among 56 esophageal adenocarcinomas (ADC) arising in Barrett's esophagus, 95 cardiac gastric ADC, and in 191 distal gastric ADC. The allelic frequencies were compared to a control group of 253 healthy blood donors. The C/G genotype of p16 was identified in 10.4% of esophageal carcinomas, 13.3% of cardiac carcinomas, and in 14.1% of gastric carcinomas, compared to 17.4% in the healthy control group. All other cases showed the C/C wildtype, as no homozygous G/G nucleotide exchange was detected in the group of cancer patients or in the control group. In esophageal cancer, cyclin D1 G/G genotype was found 28.6%, A/G in 46.4%, and A/A in 25.0%. In cardiac carcinoma, frequency of cyclin D1 genotype was 27.4% for G/G, 57.9% for A/G, and 14.7% for AA. In distal gastric carcinoma, both homozygous genotypes (G/G and A/A) had a frequency of 15.2% each, while the heterozygous A/G genotype occurred in 69.6% of patients. The control group displayed 24.9% G/G, 53.8% A/G, and 21.3% A/A genotype. Our results show that frequencies of p16 or cyclin D1 polymorphisms in gastric and esophageal ADC do not differ significantly from the healthy control group. Therefore, these polymorphisms are unlikely to be associated with risk of ADC of the upper gastrointestinal tract.


Sociality in molerats : Metabolic scaling and the role of risk sensitivity.
The foraging behaviour and diets of the various bathyergid molerat species are reviewed briefly, and inferences are drawn concerning their dietary specialisation. A simple model has been constructed which investigates the risks of unproductive foraging by specialist feeders as a function of resource dispersion characteristics and group size. The model suggests that the principal benefit of group foraging is a reduction in foraging risk, rather than increased resource procurement per se. Meeting the energetic costs of non-workers in social groups necessitates a reduction of the total energetic expenditure of the colony. This is achieved by reducing body size, huddling in the nest, and scaling mass-specific resting metabolic rate virtually independent of mass.


Engineering of an endogenous hydrogen sulfide responsive smart agent for photoacoustic imaging-guided combination of photothermal therapy and chemotherapy for colon cancer.
Photothermal therapy can be synergistically combined with chemotherapy to improve the therapeutic effect for colon cancer. However, conventional therapeutic agents have side effects in normal tissues, limiting their application. To reduce these side effects, a smart agent (Cur@HKUST-1@PVP) whose functionality is triggered by the high content of endogenous hydrogen sulfide in colon tumors was engineered for photoacoustic imaging-guided combination of photothermal therapy and chemotherapy for colon tumors. After reacting with hydrogen sulfide, Cur@HKUST-1@PVP simultaneously generates CuS and releases curcumin. The generated CuS serves as an imaging agent for both photothermal therapy and photoacoustic imaging, while the released curcumin is used for chemotherapy. In vivo photoacoustic imaging experiments demonstrated that Cur@HKUST-1@PVP can be used for selectively imaging colon cancer tumors. In vivo experiments in mice for treatment suggested that the endogenous hydrogen sulfide-activated combination of photothermal therapy and chemotherapy has a better treatment effect that photothermal therapy or chemotherapy treatment alone. The endogenous hydrogen sulfide-activated Cur@HKUST-1@PVP agent developed herein shows great potential for the accurate diagnosis and effective treatment of colon cancer.


The Single-Molecule Approach to Membrane Protein Stoichiometry.
The advent of techniques for imaging solitary fluorescent molecules has made possible many new kinds of biological experiments. Here, we describe the application of single-molecule imaging to the problem of subunit stoichiometry in membrane proteins. A membrane protein of unknown stoichiometry, prestin, is coupled to the fluorescent enhanced green fluorescent protein (eGFP) and synthesized in the human embryonic kidney (HEK) cell line. We prepare adherent membrane fragments containing prestin-eGFP by osmotic lysis. The molecules are then exposed to continuous low-level excitation until their fluorescence reaches background levels. Their fluorescence decreases in discrete equal-amplitude steps, consistent with the photobleaching of single fluorophores. We count the number of steps required to photobleach each molecule. The molecular stoichiometry is then deduced using a binomial model.


Lack of pharmacist-physician communication associated with nimesulide-induced oligohydramnios during pregnancy.
The consequences of medication errors can be serious, especially in pregnant women. When decision-making is critical, physician-pharmacist communication has the potential to improve patient safety. In this report, we describe the case of a pregnant woman who developed oligohydramnios after taking nimesulide for neuropathic pain. The drug was improperly prescribed by a family physician and mistakenly dispensed by a community pharmacist. Oligohydramnios was observed during ultrasound examination and an iatrogenic cause was suspected. This case is presented to raise awareness that patient safety is threatened because of a lack of physician-pharmacist communication, especially for pregnant patients. Healthcare professionals are continually at-risk for making errors at work. Effective inter-professional communication should be an organisational tool to prevent adverse events for pregnant women.


Sustained vascular endothelial growth factor delivery enhances angiogenesis and perfusion in ischemic hind limb.
We hypothesized that sustained delivery of vascular endothelial growth factor (VEGF) using a polymer [85:15 poly(lactide-co-glycolide) (PLG)] would enhance angiogenesis and improve perfusion of ischemic tissue. C57BL/6J mice (n = 20/group) underwent unilateral hind limb ischemia surgery and were randomized to groups of no scaffold implantation (0-Implant), unloaded scaffold implantation (Empty-PLG), or implantation of scaffolds incorporating 3 microg of VEGF165 (PLG-VEGF). Endpoints included laser Doppler perfusion imaging (LDPI, ischemic/nonischemic limb, %), local vessel counts, immunohistochemistry for CD31, and alpha-smooth muscle actin. In vitro release kinetics of VEGF from PLG was also measured. PLG-VEGF resulted in improved lower extremity perfusion vs. controls as measured by LDPI% at 7, 14, 21, and 28 days (p < 0.05). PLG-VEGF was associated with significantly greater percentage of vessels staining for CD31 and alpha-smooth muscle actin compared to the Empty-PLG or 0-Implant (p < 0.05 for both). The PLG-VEGF scaffolds resulted in sustained VEGF delivery, improved tissue perfusion, greater capillary density, and more mature vasculature compared to the controls. The sustained-release PLG polymer vehicle is a promising delivery system for therapeutic neovascularization applications.


Prostate cancer screening practices of African-American and non-African-American US primary care physicians: a cross-sectional survey.
We explored whether African-American (AA) primary care physicians (PCPs) have different prostate cancer screening practices compared to non-AA PCPs, after adjustment for potential confounding factors such as the proportion of AA patients in PCP practices. We used SAS/SUDAAN to compare weighted responses from AA PCPs (n = 604) with those from non-AA PCPs (n = 647) in the 2007-2008 National Survey of Primary Care Physician Practices Regarding Prostate Cancer Screening. We used multivariate logistic regression to calculate the weighted odds ratios (OR) and 95% confidence intervals (CI). We found that AA PCPs had higher odds of working in practices with above-the-median (≥ 21%) proportions of AA male patients (OR, 9.02; 95% CI: 5.85-13.91). A higher proportion of AA PCPs (53.5%; 95% CI: 49.5-57.4) reported an above-the-median proportion (≥ 91%) of PSA testing during health maintenance exams as compared to non-AA PCPs (39.4%; 95% CI: 35.5-43.4; P < 0.0002). After adjusting for the proportion of AA patients and other factors, we found that AA PCPs had higher odds of using PSA tests to screen men (OR, 1.74; 95% CI: 1.11-2.73). This study quantifies the magnitude of the differences reported in previous focus group studies. Our results may be helpful in hypothesis generation and in planning future research studies.


Covid-19 associated Guillain-Barré syndrome: A series of a relatively uncommon neurological complication.
The COVID-19 pandemic has turned the world topsy turvy since its emergence and has claimed innumerable lives worldwide. Neurological manifestations of the disease have raised several eyebrows around the world among which Guillain-Barré syndrome (GBS) deserve special mention. Although majority of the cases of the coronavirus disease 2019 (COVID-19) present with respiratory symptoms, extrapulmonary manifestations are being increasingly reported. We conducted this study to analyze detailed clinical presentations and outcome in a series of eight cases (n = 8) with COVID-19 associated GBS. An observational prospective study was conducted among patients with post-infectious/para-infectious GBS. 8 patients were subclassified into acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN) and acute motor and sensory axonal neuropathy (AMSAN) as per electrodiagnostic criteria and were followed up from admission to 6 months post discharge, to obtain a comprehensive clinical profile and outcome in these patients. The diagnosis of GBS was confirmed as per Asbury criteria, supported by electrodiagnostic features in nerve conduction velocity test. Among the series of 8 patients, 3 were diagnosed as AIDP, 3 had AMAN and the remaining 2 patients had AMSAN. 3 patients of GBS were afebrile and were diagnosed as COVID-19 after a positive assay on routine screening. Cerebro-spinal fluid analysis for SARS-Cov-2 RT-PCR and serum anti-ganglioside antibodies were negative in all the patients. GBS in patients with COVID-19 should be differentiated from critical illness neuropathy and myopathy. Early diagnosis is important as it is associated with poor outcome and prolonged invasive ventilation.


The year in cardiovascular medicine 2021: interventional cardiology.
Since last year's report in the European Heart Journal, we have witnessed substantial progress in all aspects of interventional cardiology. Of note, the practice of interventional cardiology took place amidst successive waves of the COVID-19 pandemic, which continues to be a major burden for all healthcare professionals around the globe. In our yearly review, we shall revisit the developments in percutaneous coronary intervention (PCI), structural heart interventions, and adjunctive pharmacotherapy.


Long-term outcome in severe traumatic brain injury is significantly influenced by brainstem involvement.
To study the 1-year-outcome of 32 survivors of severe traumatic brain injury with respect to the impact of brainstem injury. Retrospective clinical study performed in a university hospital. Thirty-two 1-year-survivors (15 with brainstem injury present) of severe traumatic brain injury were investigated for neurological function, activities of daily living, need for care and professional ability. Visual impairment, spasticity, co-ordination deficits and organic psychosis were more frequent in the group harbouring brainstem lesions. Professional ability was worse among these patients. Brainstem involvement in survivors of severe traumatic brain injury conveys a negative impact on long-term outcome.


Removal of p-nitrophenol from simulated sewage using MgCo-3D hydrotalcite nanospheres: capability and mechanism.
4-Nitrophenol (4-NP) is an organic pollutant found in the wastewater discharged from coking and petrochemical industries, and it is highly toxic, persistent, and bioaccumulative. 4-NP is difficult to degrade and causes serious damage to human health and the ecological environment. In this study, MgCo-3D hydrotalcite nanospheres were synthesized via the hot solvent method using ZIF-67 as a template for 4-NP removal from wastewater. The composition and structure of MgCo-3D hydrotalcite nanospheres were characterized via X-ray diffraction (XRD), Scanning electron microscope (SEM), Transmission Electron Microscope (TEM), Fourier-transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), Energy Dispersive Spectroscopy (EDS), and BET analyses. The maximum adsorption capacity was 131.59 mg g-1 under the optimized conditions (pH = 7, t = 298 K, C 0 = 50 mg L-1, dose = 0.4 g L-1). The adsorption obeyed the Langmuir, Redlich-Peterson and Sips models and pseudo-second-order kinetics, and the adsorption activation energy was 29.4 kJ mol-1, indicating a monolayer physical adsorption phenomenon. The adsorption of 4-NP on the MgCo-3D hydrotalcite nanospheres mainly involved hydrogen bonding and electrostatic interactions. The nanospheres were regenerated using the hot-air purging method. After five adsorption-desorption cycles, the adsorption capacity reached 107.6 mg g-1, indicating the good regeneration performance of the MgCo-3D hydrotalcite nanospheres.


Development of conversion factors to estimate the concentrations of heavy metals in manure-derived digestates.
During biogas production, a residual by-product rich in organic matter, nutrients, and trace elements - called digestate - is generated. Due to the nature of the anaerobic digestion process (i.e., conversion of organic matter into biogas) and the non-digestibility of trace elements, metal concentrations are higher in digestate than initially in the treated feedstock, resulting in a detrimental effect on the environment when directly applied as fertiliser on the soil. This study aims to predict the concentration of heavy metals in digestate through four different process parameters (Biogas yield - M1, Biodegradable fraction - M2, Dry matter - M3 and Power generation - M4) in full-scale biogas plants. For the validation of the process parameters, the predictions were compared against laboratory analyses of feedstocks and digestates samples from mono- and co-digestion processes. The convergence between the conversion factors based on laboratory data and process parameters (CLD and CFA, respectively) ranged in the following order: M3 > M2 > M1 > M4. Based on laboratory analyses, better predictions were obtained for Al, Cr, Cu, Fe, Mn, and Zn employing M3. Moreover, a robust convergence was achieved between the CLD and CFA conversion factors for the mono-digestion process. Further assessment of a diverse range of feedstocks is needed to increase the convergence between the conversion factors based on process parameters and laboratory data, specifically for the co-digestion process M3. The concentrations of Cd, Co, Ni, and Pb elements were below the detection limits, whereas Cr, Cu, and Zn did not exceed the legal threshold limits of the legislations.


Profiling and factors associated with glaucoma diagnostic practice in sub-Saharan Africa-a cross sectional study of Nigerian and Ghanaian optometrists.
Ghana and Nigeria are the two countries in Africa that currently run the Doctor of Optometry (OD) program in sub-Saharan Africa (SSA). Optometrists in these countries are licensed to provide glaucoma care. Despite the clinically relevant practice guidelines for glaucoma, there is no data on the practice patterns for glaucoma eye care in SSA, a region with the highest prevalence of glaucoma. This study aimed to profile glaucoma diagnosis adherence to practice guidelines among optometrists in two neighbouring anglophone countries (Nigeria and Ghana). A web-based cross-sectional survey of practising optometrists was conducted in both countries. Each country data was weighted to reflect the total number of licensed and practising optometrists at the time of this survey. Descriptive analyses were performed against demography and practice factors using survey commands to adjust for sampling weights when estimating confidence intervals (CI) around prevalence estimates. Simple and multiple logistic regression analyses were performed to identify factors associated with glaucoma diagnosis. A total of 493 optometrists (238, 48.3% and 255, 51.7%) from Ghana and Nigeria respectively, responded to the survey-the first to document and compare the glaucoma diagnostic criteria between optometrists in Ghana and Nigeria. More Ghanaian than Nigerian optometrists diagnosed glaucoma and over 90% in both countries reported that they frequently performed either tonometry, visual field testing, or fundus examination during glaucoma diagnosis. Ghanaian optometrists were significantly more likely to diagnose glaucoma than Nigerian optometrists (adjusted odd ratio, AOR = 6.15, 95%CI:1.63-23.15, P = .007). Optometrists who have practiced for more than 10 years (AOR = 7.04; 95%CI:1.74-28.47, P = .006) and private practice optometrists (AOR = 3.33; 95%CI:1.13-9.83, P = .03) were more likely to diagnose glaucoma. The study provides information for evaluating glaucoma assessment for optometrists in both countries. Optometrists in both countries are reasonably well-equipped to diagnose glaucoma and are practicing at an adequate level, but with room for improvement.


Carpal tunnel syndrome. A scientific basis for clinical care.
The series of experimental studies reviewed in this article supports a classification of median nerve compression at the wrist into early, intermediate, advanced, and acute nerve compression. The findings correlate well with experimental studies on the pathophysiology of nerve compression. A patient-specific management approach is recommended based upon the clinical and electrophysiologic findings which can be correlated with previously demonstrated intraneural pathologic changes.


MR-EYE: High-Resolution MRI of the Human Eye and Orbit at Ultrahigh Field (7T).
Ultrahigh-field (7T) MRI provides improved contrast and a signal-to-noise gain compared with lower magnetic field strengths. Here, we demonstrate feasibility and optimization of anatomic imaging of the eye and orbit using a dedicated commercial multichannel transmit and receive eye coil. Optimization of participant setup techniques and MRI sequence parameters allowed for improvements in the image resolution and contrast, and the eye and orbit coverage with minimal susceptibility and motion artifacts in a clinically feasible protocol.


Silence of the transcripts: RNA interference in medicine.
Silencing of gene expression by ribonucleic acid (RNA), known as RNA interference (RNAi), is now recognized as a major means of gene regulation in biology. In this mechanism, small noncoding double-stranded RNA molecules knock down gene expression through a variety of mechanisms that include messenger RNA (mRNA) degradation, inhibition of mRNA translation, or chromatin remodeling. The posttranscriptional mechanism of RNAi has been embraced by researchers as a powerful tool for generating deficient phenotypes without mutating the gene. In parallel, exciting recent results have promised its application in disease therapy. This review aims to summarize the current knowledge in this area and provide a roadmap that may eventually launch RNAi from the research bench to the medicine chest.


The importance of cryptic diversity in the conservation of wide-ranging species: The red-footed tortoise Chelonoidis carbonarius in Colombia.
Wide-ranging species are seldom considered conservation priorities, yet they have the potential to harbour genetically deeply differentiated units across environments or ecological barriers, including some that warrant taxonomic recognition. Documenting such cryptic genetic diversity is especially important for wide-ranging species that are in decline, as they may comprise a set of even more endangered lineages or species with small distributions. However, studies of wide-ranging species, particularly when they cross political borders, are extremely challenging. One approach to overcoming these challenges is to conduct detailed local analyses in combination with less detailed, range-wide studies. We used this approach with the red-footed tortoise (Chelonoidis carbonarius), a threatened species likely to contain cryptic diversity given its vast range and the distinctive ecoregions that it inhabits. Previous single-gene molecular studies indicated the presence of at least five lineages, two of which occur in different ecoregions separated by the Andes within Colombia. We used a comprehensive genomic analysis to test the hypothesis of cryptic diversity within the single jurisdiction of Colombia. We used a combination of restriction-site-associated DNA sequencing and environmental niche modelling to provide three independent lines of evidence that support the presence of important cryptic diversity that may deserve taxonomic recognition: allopatric reproductive isolation, local adaptation and ecological divergence. We also provide a fine-scale genetic map with the distribution of conservation units in Colombia. As we complete ongoing range-wide analyses and make taxonomic adjustments, we recommend that the two lineages in Colombia be treated as separate units for conservation purposes.


Preliminary antimicrobial susceptibility interpretive criteria for cefetamet (Ro 15-8074) and cefteram (Ro 19-5247) disk tests.
Preliminary interpretive zone criteria were calculated for cefetamet (Ro 15-8074) and cefteram (Ro 19-5247) by using 10- and 30-micrograms disks and three possible MIC susceptibility breakpoints. Absolute interpretive agreement between MICs and zone size criteria ranged from 91.8 to 97.2%. Very major errors (false susceptibility) were less than or equal to 1.2% for both cephalosporin disk tests. Morganella morganii strains appeared to produce the highest rates of very major interpretive errors with cefetamet disks.


Incorporation of mitochondrial L-glycerol-3-phosphate dehydrogenase into liposomes; effect of sodium oleate and calcium ions.
FAD-linked L-glycerol-3-phosphate dehydrogenase purified from liver mitochondria of hyperthyroid rats was incorporated into unilamellar phospholipid liposomes. The incorporation influenced both Vmax,app and Km,app values of the enzyme for its substrate, L-glycerol 3-phosphate. The Km,app for the electron acceptor remained unchanged with a simultaneous slight enhancement of the corresponding Vmax,app value. The steady-state fluorescence anisotropies of the fluorescein isothiocyanate and trimethylammoniumdiphenylhexatriene labels were affected by sodium oleate and calcium ions in the case of both solubilized and liposome-incorporated L-glycerol-3-phosphate dehydrogenase. These results indicate that calcium ions cause a significant alteration of the enzyme conformation. Sodium oleate (used as a model of free fatty acids), besides its direct action on the enzyme itself, affects the enzyme indirectly as well, via alteration of the physical properties of the membrane.


Rediscovery of two casts of the historically important 'Proteo-saurus', the first complete ichthyosaur skeleton.
The first complete ichthyosaur skeleton was introduced to the scientific community in 1819 by Sir Everard Home, and given the name Proteosaurus, although the name was subsequently replaced by 'Ichthyosaurus'. The skeleton is from Lyme Regis and was probably collected by Mary Anning as it was in the collection of Colonel Birch. The specimen ultimately ended up in the collection of the Royal College of Surgeons, London, where it was destroyed in a bombing raid during World War II. We have discovered two plaster casts of the specimen, although no record exists of casts ever being made. The casts are at the Peabody Museum, Yale University, USA and the Museum für Naturkunde, Berlin, Germany. Significantly, these verify the accuracy of the published drawing of the specimen, and clarify morphologies of some of the bones. Discrepancies between the drawing and the casts are mainly in the details of the forefins and hindfins. The specimen can be assigned to Ichthyosaurus, but the species cannot be determined. This case illustrates the importance of old casts in museum collections. Additional, yet unrecognized casts of this specimen might exist in the UK or elsewhere.


A NR2E1-interacting peptide of LSD1 inhibits the proliferation of brain tumour initiating cells.
Elimination of brain tumour initiating cells (BTICs) is important for the good prognosis of malignant brain tumour treatment. To develop a novel strategy targeting BTICs, we studied NR2E1(TLX) involved self-renewal mechanism of BTICs and explored the intervention means. NR2E1 and its interacting protein-LSD1 in BTICs were studied by gene interference combined with cell growth, tumour sphere formation, co-immunoprecipitation and chromatin immunoprecipitation assays. NR2E1 interacting peptide of LSD1 was identified by Amide Hydrogen/Deuterium Exchange and Mass Spectrometry (HDX-MS) and analysed by in vitro functional assays. The in vivo function of the peptide was examined with intracranial mouse model by transplanting patient-derived BTICs. We found NR2E1 recruits LSD1, a lysine demethylase, to demethylate mono- and di-methylated histone 3 Lys4 (H3K4me/me2) at the Pten promoter and repress its expression, thereby promoting BTIC proliferation. Using Amide Hydrogen/Deuterium Exchange and Mass Spectrometry (HDX-MS) method, we identified four LSD1 peptides that may interact with NR2E1. One of the peptides, LSD1-197-211 that locates at the LSD1 SWIRM domain, strongly inhibited BTIC proliferation by promoting Pten expression through interfering NR2E1 and LSD1 function. Furthermore, overexpression of this peptide in human BTICs can inhibit intracranial tumour formation. Peptide LSD1-197-211 can repress BTICs by interfering the synergistic function of NR2E1 and LSD1 and may be a promising lead peptide for brain tumour therapy in future.


[Clinically controlled examination of the utilization of adhesive technology with bridgework prosthetics].
The article reports on the re-examination results of bridges which were made on the Bezirkspoliklinik für Stomatologie Schwerin since 1983. In two cross-sectional examinations 1986 54 and 1987 90 adhesive bridges were controlled. The failure rate of the re-examined adhesive bridges in 1987 was 18.9%.


NLRP3 inflammasomes are involved in the progression of postoperative cognitive dysfunction: from mechanism to treatment.
Postoperative cognitive dysfunction (POCD) involves patient memory and learning decline after surgery. POCD not only presents challenges for postoperative nursing and recovery but may also cause permanent brain damage for patients, including children and the aged, with vulnerable central nervous systems. Its occurrence is mainly influenced by surgical trauma, anesthetics, and the health condition of the patient. There is a lack of imaging and experimental diagnosis; therefore, patients can only be diagnosed by clinical observation, which may underestimate the morbidity, resulting in decreased treatment efficacy. Except for symptomatic support therapy, there is a relative lack of effective drugs specific for the treatment of POCD, because the precise mechanism of POCD remains to be determined. One current hypothesis is that postoperative inflammation promotes the progression of POCD. Accumulating research has indicated that overactivation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasomes contribute to the POCD progression, suggesting that targeting NLRP3 inflammasomes may be an effective therapy to treat POCD. In this review, we summarize recent studies and systematically describe the pathogenesis, treatment progression, and potential treatment options of targeting NLRP3 inflammasomes in POCD patients.


Cryopreservation of dog epididymal spermatozoa by conventional freezing or ultra-rapid freezing with nonpermeable cryoprotectant.
This study was aimed to assess the effectiveness of two methods for cryopreservation of dog epididymal spermatozoa, one by conventional freezing (CF) with shortening both equilibration and cooling times, and the other by ultra-rapid freezing (URF) with nonpermeable cryoprotectant. Sixty epididymides were recovered from thirty orchiectomized adult dogs and the sperm samples were retrieved by retrograde flushing using TCG-EY (tris, citric acid, glucose + 20% egg yolk) extender and then 20 pools were conformed. Each pool was divided into 2 aliquots and then cryopreserved by CF and URF methods respectively. The CF method maintained the cooled-pool samples for 2h (1h without and 1h with 5% glycerol) and then were frozen by liquid nitrogen (LN2) vapors for 2 min. The URF method cryopreserved the cooled-pool samples using TCG-EY+250 mM sucrose, equilibrating during 30 min (5 °C) and submerging 30-μL drops directly in LN2. The results showed that the URF method produced a lower percentage of total and progressive motilities and acrosome integrity (P < 0.05) than the CF method. However, the kinetic variables (curvilinear and straight-line velocities, straightness, linearity, wobble, amplitude of lateral head displacement, and beat-cross frequency) and plasma membrane integrity did not differ (P > 0.05) between both cryopreservation methods. Unlike the URF method, the width, area and perimeter of sperm head were reduced after the CF method (P < 0.05). In conclusion, despite the low motility achieved after the ultra-rapid freezing method, the similar values of kinetic, viability and head morphometric dimensions to those obtained after conventional freezing, suggest that ultra-rapid freezing with sucrose may be a useful alternative for the cryopreservation of canine epididymal sperm.


Intra-operative application of real-time tissue elastography for the diagnosis of liver tumours.
Real-time tissue elastography (RTE) has made it possible to visualize tissue elasticity. The aim of this study was to evaluate the usefulness of RTE for the differential diagnosis of liver tumours during surgical exploration. Fifty-five liver tumours in 44 patients were examined with RTE, concomitant with routine intra-operative ultrasonography. Elasticity images were classified into four types, from type A (even strain) to type D (no strain), according to the distribution and the degree of the strain contrasted with that of the surrounding liver [elasticity type of liver tumour (ETLT)]. We evaluated the consistency of the findings of RTE with the pathological diagnosis as a reference standard. All malignant lesions showed various degrees of strain reduction in the tumour tissue. Twenty-one of 22 hepatocellular carcinomas (HCCs) were classified as type B with a sensitivity of 95.5%, a specificity of 90.9% and an accuracy of 92.7%, while all 24 metastatic adenocarcinomas were classified as either type C or type D with a sensitivity of 100%, a specificity of 80.6% and an accuracy of 89.1%. Application of RTE in surgical exploration provided significant information about the elasticity of liver tumours. RTE, using a new criterion, ETLT, enabled us to distinguish rather accurately between two common malignancies: HCC and metastatic adenocarcinoma.


Impaired coronary circulation in patients with apical hypertrophic cardiomyopathy: noninvasive analysis by transthoracic Doppler echocardiography.
We designed this study to examine the characteristics of coronary circulation in patients with apical hypertrophic cardiomyopathy (ApHCM) using noninvasive transthoracic Doppler echocardiography (TTDE). Recent advances in TTDE have allowed noninvasive assessment of coronary circulation by the measurement of coronary flow velocity (CFV) patterns and coronary flow velocity reserve (CFVR). However, there have been no previous studies evaluating coronary circulation in ApHCM. We analyzed CFV and CFVR in the left anterior descending coronary artery (LAD), and apical wall thickness in the left ventricle, in 10 ApHCM subjects and 10 control subjects. Mean diastolic velocity (MDV) and time from the beginning of diastole to peak velocity (TPV), and CFVR, defined as a ratio of drug-induced hyperemic to basal MDV, were measured. At baseline, MDV was higher, and TPV was longer, in ApHCM subjects than in control subjects (29 +/- 5.7 versus 19 +/- 6.5 cm/sec; p < 0.01 and 5.2 +/- 1.0 versus 3.5 +/- 0.6 msec; p < 0.005, respectively). CFVR in ApHCM subjects was significantly lower than in control subjects (1.9 +/- 0.4 versus 3.1 +/- 0.8; p < 0.005). CFVR and basal MDV in ApHCM subjects showed significant correlations with apical/posterior wall thickness ratio [CFVR; r =-0.84, p < 0.01 and MDV; r = 0.74, p < 0.05, respectively]. Noninvasive coronary flow assessment by TTDE revealed an impaired coronary circulation with reduced CFVR, high MDV at baseline and prolonged TPV. These results suggest that these characteristics of coronary circulation may provide an additional index for the assessment of ApHCM.


Intraoperative ultrasound in breast cancer surgery-from localization of non-palpable tumors to objectively measurable excision.
The utilization of intraoperative ultrasound (IOUS) in breast cancer surgery is a relatively new concept in surgical oncology. Over the last few decades, the field of breast cancer surgery has been striving for a more rational approach, directing its efforts towards removing the tumor entirely yet sparing tissue and structures not infiltrated by tumor cells. Further progress in objectivity and optimization of breast cancer excision is possible if we make the tumor and surrounding tissue visible and measurable in real time, during the course of the operation; IOUS seems to be the optimal solution to this complex requirement. IOUS was introduced into clinical practice as a device for visualization of non-palpable tumors, and compared to wire-guided localization (WGL), IOUS was always at least a viable, or much better alternative, in terms of both precision in identification and resection and for patients' and surgeons' comfort. In recent years, intraoperative ultrasound has been used in the surgery of palpable tumors to optimize resection procedures and overcome the disadvantages of classic palpation guided surgery. The aim of this review is to show the role of IOUS in contemporary breast cancer surgery and its changes over time. A PubMed database comprehensive search was conducted to identify all relevant articles according to assigned key words. Over time, the use of IOUS has been transformed from being the means of localizing non-palpable lesions to an instrument yielding a reduced number of positive resection margins, with a smaller volume of healthy breast tissue excided around tumor, by making the excision of the tumor optimal and objectively measurable.


Treating mannitol in a saturated solution of mannitol: a novel approach to modify mannitol crystals for improved drug delivery to the lungs.
The aim of this study was to evaluate the influence of treatment of a promising dry powder aerosol carrier (mannitol) on the aerosolization performance of salbutamol sulphate (SS) using a novel approach: treating excess commercial carrier particles in a saturated solution of the same carrier. Commercial mannitol (CM) particles were treated with aqueous mannitol supersaturated solutions (20% and 25% w/v), under stirring, (300 rpm) for either 24h or 48 h. The results showed that particle treatment did not alter the polymorphic form of mannitol (β-mannitol); however, all treated mannitol particles demonstrated smoother surface topography and improved aerosolization performance compared to CM in dry powder inhalations. Unlike the concentration of mannitol solution used during treatment, the time of treatment to collect mannitol crystals was an essential key to modify the physical properties of mannitol and its effect on the aerosolization performance. In comparison to mannitol particles treated for 48 h, mannitol particles treated for 24h demonstrated larger size, more elongated-less regular shape, and smoother surfaces. No apparent relationship was obtained between in vitro aerosolisation behavior of SS with either mannitol particle size or shape descriptors. However, despite their larger size and more irregular-less uniformed shape, treated mannitol particles with smoother surfaces generated drug particles with smaller aerodynamic size and are expected to deliver higher amounts of drug to lower airways. The results demonstrated the potential of treating mannitol particles in aqueous solutions of the same material under controlled conditions to produce mannitol particles promising for dry powder inhaler systems. The results suggested that mannitol particle surface texture properties dominate over both particle size and particle shape of mannitol in terms of determining the aerosolization performance of mannitol.


Flow-volume loop changes reflecting respiratory muscle weakness in chronic neuromuscular disorders.
In order to identify the changes in pulmonary function and in the flow-volume loop due to respiratory muscle weakness, two groups of 10 nonsmokers with stable, chronic neuromuscular disease but without respiratory symptoms were studied: one without (Group 1) and one with (Group 2) respiratory muscle weakness as assessed by measurement of maximal static inspiratory and expiratory pressures. In Group 1, pulmonary function was normal except for increased ratio of one-second forced expiratory volume to forced vital capacity and forced expiratory flow at 25 to 75 percent forced vital capacity, which may reflect increased elastic lung recoil. Group 2 had mild volume restriction, appropriate for the degree of respiratory muscle weakness, and reduced inspiratory and expiratory flow rates. Pulmonary function was significantly more disturbed in Group 2 than in Group 1, and correlated well with maximal static inspiratory and expiratory pressures. Analysis of the flow-volume loop configuration revealed that four parameters describing effort-dependent portions were significantly related to maximal static inspiratory pressure and maximal static expiratory pressure. These parameters were peak expiratory flow, the slope of the ascending limb of the maximal expiratory curve, a drop of forced expiratory flow near residual volume, and forced inspiratory flow at 50 percent of vital capacity. A flow-volume loop score obtained from these four parameters was significantly higher in Group 2 than in Group 1 (2.8 +/- 1.03 versus 1.1 +/- 1.37; p less than 0.01). A flow-volume loop score of 2 or more had 80 percent specificity and 90 percent sensitivity in predicting respiratory muscle weakness in these patients with chronic neuromuscular disease. These data suggest that sensitive assessment of the flow-volume loop configuration as part of routine pulmonary function testing may help to suspect and identify respiratory muscle weakness.