Late discovery of left atrial appendage occluder device embolization: a case report.
Left atrial appendage (LAA) closure has been well evaluated in the prevention of stroke in patients with atrial fibrillation. Device embolization remains one of the most common complications. To the best of our knowledge, there have been no reports of late discovery of LAA occluder device embolization at 1.5 years after implantation. We describe the case of a 77-year-old man who underwent uneventful LAA closure. Echocardiography performed the next day showed the device in place. The patient was discharged but was then lost to follow-up. 1.5 years later, he was admitted for ischemic stroke. Transesophageal echocardiography showed the absence of the occluder device in the LAA. Computed tomography scan of the abdomen showed the device in the abdominal aorta. Due to the high cardiovascular risk, the device was kept in place and the patient was treated medically. Per-procedural and late device embolization are not uncommon. Review of the literature however showed no report of late discovery of device embolization at 1.5 years. Follow-up echocardiography is mandatory for the detection of endothelialization or embolization.


Natural sucrose esters: Perspectives on the chemical and physiological use of an under investigated chemical class of compounds.
The present review describes the chemistry and physiological properties of the sucrose esters (SEs) obtained from natural or synthetic pathways, with emphasis on those that have aliphatic and phenylpropanoid substituents on their sucrose moiety. Synthesis, extraction and characterization methods for the SEs and NSEs are discussed in terms of synthetic procedures, separation techniques and spectroscopic methods. The physiological properties are discussed taking into account the nature of the substituent groups and their regiochemistry (position and number of substitutions) on the sucrose moiety.


Mechanisms of bone metastasis in prostate cancer: clinical implications.
Prostate cancer shows a strong predilection to spread to the bones. Once prostate tumour cells are engrafted in the skeleton, curative therapy is no longer possible and palliative treatment becomes the only option. Herein, we review the multifactorial mechanisms and complex cellular interactions that take place inside the bone metastatic microenvironment. Emphasis is given to the detection and treatment of the micrometastatic stage of prostate cancer, as well as our recent attempts to target the bone metastasis microenvironment-related survival factors using an anti-survival factor manipulation which can increase the efficacy of anticancer therapies such as androgen ablation therapy and chemotherapy in advanced prostate cancer.


Predictors of the persistence of childhood asthma.
The factors relevant to the prognosis of childhood asthma differ from one population to another. To characterize the course of childhood asthma in the catchment area of our hospital, and to identify prognostic factors for this population. All children given a diagnosis of asthma in the paediatric pulmonology service of a tertiary hospital were followed up for 5 years. Satisfactory control of asthma was achieved in 69 % of cases. The factors identified as associated with poor control were allergy to cats and pollen, a large number of crises in the year prior to diagnosis, and younger age at onset. In our region, childhood asthma has a relatively favourable prognosis. The subsequent course of the disease appears to be determined in childhood. The persistence of symptoms appears to depend to a significant extent on the degree of atopy.


The year in cardiovascular medicine 2021: heart failure and cardiomyopathies.
In the year 2021, the universal definition and classification of heart failure (HF) was published that defines HF as a clinical syndrome with symptoms and/or signs caused by a cardiac abnormality and corroborated by elevated natriuretic peptide levels or objective evidence of cardiogenic congestion. This definition and the classification of HF with reduced ejection fraction (HFrEF), mildly reduced, and HF with preserved ejection fraction (HFpEF) is consistent with the 2021 ESC Guidelines on HF. Among several other new recommendations, these guidelines give a Class I indication for the use of the sodium-glucose co-transporter 2 (SGLT2) inhibitors dapagliflozin and empagliflozin in HFrEF patients. As the first evidence-based treatment for HFpEF, in the EMPEROR-Preserved trial, empagliflozin reduced the composite endpoint of cardiovascular death and HF hospitalizations. Several reports in 2021 have provided novel and detailed analyses of device and medical therapy in HF, especially regarding sacubitril/valsartan, SGLT2 inhibitors, mineralocorticoid receptor antagonists, ferric carboxymaltose, soluble guanylate cyclase activators, and cardiac myosin activators. In patients hospitalized with COVID-19, acute HF and myocardial injury is quite frequent, whereas myocarditis and long-term damage to the heart are rather uncommon.


Self-Reported Versus Objectively Assessed Olfaction and Parkinson's Disease Risk.
Poor olfaction is a prodromal symptom of Parkinson's disease (PD); however, self-reported sense of smell is often dismissed as unreliable. To assess self-reported and objectively assessed sense of smell, independently and jointly, in relation to future risk for PD. We conducted a prospective analysis using data from 2,424 participants, ages 71-82 at baseline, from the Health, Aging, and Body Composition study. Exposures were self-reported poor sense of smell or taste and the objectively measured 12-item Brief Smell Identification Test score. The outcome was incident PD, analyzed using Cox proportional hazard models adjusted for age, sex, race, and cognitive function. After approximately 10 years of follow-up, both self-reported and objectively tested poor sense of smell were independently associated with a higher risk of developing PD: the hazard ratios (95% confidence interval) were 2.8 (1.3, 5.9) and 4.0 (2.1, 7.5), respectively. When analyzed jointly, compared with participants who reported and tested normal, the hazard ratio was 2.2 (1.0, 4.6) for those reported poor sense of smell but tested normal, 3.6 (1.9, 6.9) for reported normal but tested poor, and 7.8 (3.2, 19.4) for both reported and tested poor. We did not find significant interactions between self-reported and objectively tested sense of smell in predicting PD risk. This study provides preliminary evidence that self-reported poor sense of smell or taste should not be simply dismissed as useless in predicting risk of PD. Future studies should confirm our finding and evaluate whether structured questionnaires may further improve the predictability.


How to control the risk of novel surgical procedures.
Novel surgical procedures impose particular problems in addition to the general issues of clinical research [1, 7]. Surgical procedures are usually highly technical and therefore difficult to judge by the institutional ethics committee. The ethics committee has therefore to rely on external experts and a relatively large responsibility remains with the surgeon in charge. There are no generally valid regulations regarding new surgical procedures. At our institution, informed consent by the patient, a detailed risk analysis, testing and training in the anatomy/animal lab are required, and in addition a formation/training visit if know-how is available elsewhere. In emergency situations, if during a procedure circumstances call for a new surgical procedure, all the above preconditions cannot be met. A suggested minimum requirement in such a situation is that the decision for a new procedure is achieved by agreement of two board certified specialists. A problem that has to be solved in the future is how to make the negative experiences with new surgical procedures generally available in order to prevent that the same mistakes are repeated in other institutions.


The fate of fungal periprosthetic joint infection after total knee arthroplasty.
To demonstrate the clinical outcomes of patients with fungal periprosthetic joint infections (PJIs) after two-stage exchange arthroplasty combined with antifungal therapy. We retrospectively reviewed the outcomes of 41 patients with fungal PJIs after primary total knee arthroplasty (TKA) in a single centre from January 1999 to October 2017. During the first stage of resection arthroplasty, antifungal-impregnated cement spacers (AICSs) were implanted in all patients. After systemic antifungal treatment during the interval between the two surgeries, delayed reimplantation as part of a two-stage exchange protocol was performed when patients were clinically stable. We defined treatment success as a well-functioning arthroplasty without any signs of PJI after a minimum follow-up of two years without antimicrobial suppression. Successful treatment was confirmed by repeat negative cultures as well as a return of inflammatory markers to normal levels. The treatment success rate was 63.4% at the final follow-up. Thirty-six of 41 patients (87.8%) met the criteria for second-stage revision after confirmation of complete infection control. The mean prosthesis-free interval was 6.6 months (range, 2.0-30.0 months). During follow-up after two-stage exchange arthroplasty, ten patients (27.7% of 36 patients) unfortunately experienced recurrence or relapse of infection after an average of 31.3 months (range, 2.7-135.6 months). The rate of survivorship free from reinfection was 94.4% at six months, 84.8% at one year, and 73.6% at two years. Cox proportional hazard regression analysis demonstrated that the prosthesis-free interval (HR = 1.016, p = 0.037) and mean length of antifungal treatment (HR = 0.226, p = 0.046) were potential risk factors for failure. Fungal PJIs led to devastating clinical outcomes despite even two-stage revision arthroplasty with the use of AICSs and antifungal medications.


TNF-α up-regulates cellular inhibitor of apoptosis protein 2 (c-IAP2) via c-Jun N-terminal kinase (JNK) pathway in nasopharyngeal carcinoma.
Inhibitor of apoptosis proteins (IAPs) contribute to both tumor progression and tumor metastasis. Here, we show that pro-inflammatory cytokine TNF-α induced the up-regulation of c-IAP2 in the potential metastatic nasopharyngeal carcinoma (NPC) cells in a dose- and time-dependent manner. This up-regulation is tolerant, as the pre-treatment of NPC cells with TNF-α reversed the up-regulation of c-IAP2 induced by TNF-α re-stimulation. TNF-α activated MAKP signals, including ERK, JNK and p38, and NF-κB signal, but only inhibition of JNK signal transduction reversed the induction of c-IAP2, suggesting that JNK signaling contributed to the c-IAP2 induction. The results from in vitro scratch wound-healing assays showed that TNF-α promoted cell invasion, which was reversed by the inhibition of JNK signaling. Taken together, these studies suggested that pro-inflammation cytokine TNF-α may be a promoter for NPC metastasis, and the anti-inflammatory therapy may be of benefit to the prevention of NPC metastasis.


Evolutionary kinematics of spinneret movements for rapid silk thread anchorage in spiders.
Many organisms secrete structural materials from their bodies to enhance protection, foraging or signalling. The function of such secretion products can be further extended by their assembly into complex structures, so-called extended phenotypes, such as shells, nests and biofilms. Understanding the variation in the efficacy of such assembly processes could help to explain why extended phenotypes are common on some lineages and rare in others. Here, I comparatively studied the assembly of sticky silk fibres into thread anchorages by the innate 'printing' behaviour in 92 species of spiders from 45 families, representing the so-far largest comparative study of construction-related motion patterns. I found a global evolutionary trend towards a faster production of silk thread anchorages, in both web builders and hunting spiders. The slowest producers of silk anchors belong to a clade with an ancestral configuration of respiratory organs, suggesting that a major constraint to the evolution of spinning speed is the efficiency of oxygen uptake. Motion patterns were found to contain a high phylogenetic signal, but did not correlate with spinning speeds. These results help to explain the variation in diversity and ecological success among the spider fauna and showcase the value of comparative kinematics in biodiversity studies.


Unravelling Atrioventricular Block Risk in Inflammatory Diseases: Systemic Inflammation Acutely Delays Atrioventricular Conduction via a Cytokine-Mediated Inhibition of Connexin43 Expression.
Background Recent data suggest that systemic inflammation can negatively affect atrioventricular conduction, regardless of acute cardiac injury. Indeed, gap-junctions containing connexin43 coupling cardiomyocytes and inflammation-related cells (macrophages) are increasingly recognized as important factors regulating the conduction in the atrioventricular node. The aim of this study was to evaluate the acute impact of systemic inflammatory activation on atrioventricular conduction, and elucidate underlying mechanisms. Methods and Results We analyzed: (1) the PR-interval in patients with inflammatory diseases of different origins during active phase and recovery, and its association with inflammatory markers; (2) the existing correlation between connexin43 expression in the cardiac tissue and peripheral blood mononuclear cells (PBMC), and the changes occurring in patients with inflammatory diseases over time; (3) the acute effects of interleukin(IL)-6 on atrioventricular conduction in an in vivo animal model, and on connexin43 expression in vitro. In patients with elevated C-reactive protein levels, atrioventricular conduction indices are increased, but promptly normalized in association with inflammatory markers reduction, particularly IL-6. In these subjects, connexin43 expression in PBMC, which is correlative of that measured in the cardiac tissue, inversely associated with IL-6 changes. Moreover, direct IL-6 administration increased atrioventricular conduction indices in vivo in a guinea pig model, and IL-6 incubation in both cardiomyocytes and macrophages in culture, significantly reduced connexin43 proteins expression. Conclusions The data evidence that systemic inflammation can acutely worsen atrioventricular conduction, and that IL-6-induced down-regulation of cardiac connexin43 is a mechanistic pathway putatively involved in the process. Though reversible, these alterations could significantly increase the risk of severe atrioventricular blocks during active inflammatory processes.


Anticipatory grief and experience of providing at-home palliative care among informal caregivers of spouses in Croatia: a qualitative study.
In palliative care, caring for spouses suffering from incurable diseases can provoke a range of reactions in informal caregivers that are part of the grieving process, as well as other reactions and ways of coping with a current role, which is often challenging. Anticipatory grief occurs before death and is often present in people who face the eventual loss of a loved one or their own death. This study aimed to gain insight into the anticipatory grief of informal caregivers who are providing at-home palliative care for their ill spouse. Our research questions focus on investigating the meanings caregivers ascribe to the experience of providing palliative care and the impending loss of a spouse. A qualitative study was conducted in Zagreb, Croatia, from April to June of 2021. Eight participants took part in the study. Participants in the study were informal caregivers of a spouse suffering from an incurable, terminal disease that receives at-home palliative care. Data were collected through semi-structured face-to-face interviews. Transcripts were analyzed by interpretive phenomenological analysis. The analysis provided several meanings that represent caregivers' experiences and coping strategies. The caregivers bravely face the challenges of "living with an illness" by maintaining optimism, strong cohesion with their partner and a sense of joint destiny. They tend to repress their own personal needs and feelings while carrying the burden of care. Caregivers tend to stay positive and focus on living in the present by taking an active role in providing care for the ill spouse and family. Anticipatory grief presents emotional, cognitive, and spiritual challenges to spouse caregivers in palliative care. The contribution of this study was to gain insight into the meaning that caregivers ascribe to the experience and challenges they face while providing everyday care for their ill spouse. Confirming prior results, the experiences are generally similar to all caregivers, pointing to the need for substantial improvement in the quality of the support and help from the healthcare workers and other experts who provide palliative care and support for the patients' family members.


Beyond type III Paprosky acetabular defects: are partial pelvic replacements with iliosacral fixation successful?
Supra-acetabular bone loss close beyond the sciatic notch is one of the most challenging defect types for stable anatomical reconstruction in revision arthroplasty. Using reconstruction strategies from tumour orthopaedic surgery, we adapted tricortical trans-iliosacral fixation options for custom-made implants in revision arthroplasty. The aim of the present study was to present the clinical and radiological results of this extraordinary pelvic defect reconstruction. Between 2016 and 2021, 10 patients with a custom-made pelvic construct using tricortical iliosacral fixation (see Fig. 1) were included in the study. Follow-up was 34 (SD 10; range 15-49) months. Postoperatively CT scans evaluating the implant position were performed. Functional outcome and the clinical results were recorded. Implantation was possible as planned in all cases in 236 (SD 64: range 170-378) min. Correct centre of rotation (COR) reconstruction was possible in nine cases. One sacrum screw crossed a neuroforamen in one case without clinical symptoms. During the follow-up period, four further operations were required in two patients. There were no individual implant revisions or aseptic loosening recorded. The Harris Hip Score increased significantly from 27 Pts. to 67 Pts. with a mean improvement of 37 (p < 0.005). EQ-5D developed from 0.562 to 0.725 (p = 0.038) as a clear improvement in quality of life. Custom-made partial pelvis replacement with iliosacral fixation offers a safe solution in "beyond Paprosky type III defects" for hip revision arthroplasty. Due to meticulous planning, precise implantation with good clinical outcome can be achieved. Furthermore, the functional outcome and patient satisfaction increased significantly showing promising early results with a relatively low complication rate.


Diversification of an ancient theme: hydroxynitrile glucosides.
Many plants produce cyanogenic glucosides as part of their chemical defense. They are alpha-hydroxynitrile glucosides, which release toxic hydrogen cyanide (HCN) upon cleavage by endogenous plant beta-glucosidases. In addition to cyanogenic glucosides, several plant species produce beta- and gamma-hydroxynitrile glucosides. These do not release HCN upon hydrolysis by beta-glucosidases and little is known about their biosynthesis and biological significance. We have isolated three beta-hydroxynitrile glucosides, namely (2Z)-2-(beta-D-glucopyranosyloxy)but-2-enenitrile and (2R,3R)- and (2R,3S)-2-methyl-3-(beta-D-glucopyranosyloxy)butanenitrile, from leaves of Ribesuva-crispa. These compounds have not been identified previously. We show that in several species of the genera Ribes, Rhodiola and Lotus, these beta-hydroxynitrile glucosides co-occur with the L-isoleucine-derived hydroxynitrile glucosides, lotaustralin (alpha-hydroxynitrile glucoside), rhodiocyanosides A (gamma-hydroxynitrile glucoside) and D (beta-hydroxynitrile glucoside) and in some cases with sarmentosin (a hydroxylated rhodiocyanoside A). Radiolabelling experiments demonstrated that the hydroxynitrile glucosides in R. uva-crispa and Hordeum vulgare are derived from L-isoleucine and L-leucine, respectively. Metabolite profiling of the natural variation in the content of cyanogenic glucosides and beta- and gamma-hydroxynitrile glucosides in wild accessions of Lotus japonicus in combination with genetic crosses and analyses of the metabolite profile of the F2 population provided evidence that a single recessive genetic trait is most likely responsible for the presence or absence of beta- and gamma-hydroxynitrile glucosides in L. japonicus. Our findings strongly support the notion that the beta- and gamma-hydroxynitrile glucosides are produced by diversification of the cyanogenic glucoside biosynthetic pathway at the level of the nitrile intermediate.


Case report: the sonographic appearance of neonatal herpes simplex encephalitis.
This case report describes the sonographic appearances in a proven case of neonatal Herpes Simplex encephalitis. Both early and late phase appearances are discussed, and are compared with other reports of imaging in similar disease processes. A role for sonography in the management of neonatal Herpes Simplex encephalitis is suggested.


Radiomanometric guides to common bile duct exploration.
The accuracy of operative cholangiograms can be increased by radiomanometry. This study identified 17 patients among 198 studied whose choledocholiths would have likely been missed by routine cholangiography. These are almost invariably small stones the fate of which would be conjectural if left behind. In the present study, if the cholangiogram was negative and the passage pressure within normal limits, calculi were seen only once. If the cholangiogram was positive for choledocholithiasis and the passage pressure elevated, stones were almost invariably found (95 per cent). Such accuracy cannot be expected from either roentgenography alone or determination solely of pressure relationships.


The prognostic significance of proliferative activity in poor histology non-Hodgkin's lymphoma: a flow cytometry study using archival material.
The DNA content and proliferative activity of paraffin-embedded lymph node tissue from 111 patients with poor histology non-Hodgkin's lymphoma were measured by flow cytometry. These patients had been entered into a prospective randomized trial which, to date, has shown no survival difference by treatment arm. Forty-four (40%) samples showed evidence of aneuploidy with three samples having more than one aneuploid population. The aneuploid populations had a bimodal distribution with one group having a DNA index between 1.1-1.3 and the other 1.8-2.2. The incidence of aneuploidy did not correlate with age, stage or survival. In 56 diploid samples the S phase values below 10% had a significantly better survival than those with S phase values above 10% (P less than 0.011). For patients with diffuse large cell histology the corresponding discriminatory S phase value was 19% (P less than 0.009).


Citrus polymethoxylated flavones improve lipid and glucose homeostasis and modulate adipocytokines in fructose-induced insulin resistant hamsters.
The present study was undertaken to determine whether supplementation with polymethoxylated flavones (PMFs) could ameliorate the fructose-induced hypertriglyceridemia and other metabolic abnormalities associated with insulin resistance (IR) in hamsters. Following feeding with the fructose diet, hamsters were supplemented orally with PMF-L or PMF-H (62.5 and 125 mg/kg/day) for 4 weeks. Both PMF-treated groups showed a statistically significant (p<0.05) decrease in serum triglyceride (TG) and cholesterol levels compared to the fructose-fed control group. The fructose control group at the end of the study showed elevated serum insulin and impaired insulin sensitivity (glucose intolerance). On the other hand, PMF-supplemented groups showed a reversal in these metabolic defects, including a decrease in insulin level and an improvement in glucose tolerance. PMF supplementation also reduced TG contents in the liver and heart and was able to regulate adipocytokines by significantly suppressing TNF-alpha, INF-gamma, IL-1beta and IL-6 expression and increasing adiponectin in IR hamsters. The mechanism of PMF on the activation of peroxisome proliferator-activated receptors (PPAR) was also explored. PMF-H supplementation significantly increased PPARalpha and PPARgamma protein expression in the liver. This is the first report of positive effects of PMF on adipocytokine production and on PPAR expression in IR hamsters. This study suggests that PMF can ameliorate hypertriglyceridemia and its anti-diabetic effects may occur as a consequence of adipocytokine regulation and PPARalpha and PPARgamma activation.


Pregnant mare's serum gonadotropin. IV. Induction of premature labor by pregnant mare's serum gonadotropin and its prevention by using clomiphene or indomethacin.
The administration of pregnant mare's serum gonadotropin (PMSG), 30 IU on day 18 of pregnancy, resulted in premature labor in rats. However, this abortifacient efficacy of PMSG was not demonstrable when a simultaneous injection of progesterone, clomiphene, or indomethacin was scheduled, thus suggesting that the action of PMSG is medicated by the estrogen-stimulated release of prostaglandin. The termination of pseudopregnancy in bilaterally hysterectomized rats by PMSG and its reversal by indomethacin revealed that the inhibition of luteal function by PMSG does not require the presence of a uterus.


How much of the female disadvantage in late-life cognition in India can be explained by education and gender inequality.
In social environments characterized by high levels of gender inequality, women fare worse than men in human capital accumulation and health. We examine the association of gender inequality with female disadvantage in late-life cognitive function, using newly available data from Wave 1 (2017-2019) of the Longitudinal Aging Study in India (LASI), representative of the Indian population over the age of 45. We find a substantial female gap in cognition among mid-aged and older adults in India; early life socioeconomic conditions and education explain up to 74 percent of the female disadvantage in cognition, and model predictions suggest that it takes nine years of education on average to overcome this deficit. However, further contextualizing the environment, we find that the level of education at which differences in late-life cognition between women and men become negligible increases with the degree of gender inequality.


Synthesis of γ,γ-Disubstituted Butenolides through a Doubly Vinylogous Organocatalytic Cycloaddition.
A novel organocatalytic approach to γ,γ-disubstituted butenolides is described. It is based on a fully site-selective functionalization of 5-alkylidenefuran-2(5H)-ones via trienamine-mediated [4+2]-cycloaddition with α,β,γ,δ-diunsaturated aldehydes. The developed methodology proceeds with excellent stereocontrol and constitutes a unique example of trienamine chemistry with vinylogous dienophiles. Importantly, the reaction has very broad scope and allows for the introduction of substituents also in the α- or the β-position of the butenolide ring. Usefulness of the products obtained has been confirmed in the intramolecular Stetter reaction leading to polycyclic product.


Low frequency of AIP mutations in patients with young-onset sporadic pituitary macroadenomas.
Mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene cause familial isolated pituitary adenomas (FIPA). AIP mutations have also been found in patients with apparently sporadic pituitary adenomas, particularly in young patients with large adenomas. The aim of this study was to determine the frequency of AIP germline mutations in patients with young-onset sporadic pituitary macroadenomas. The AIP gene was sequenced in 218 Portuguese patients with sporadic pituitary macroadenomas diagnosed before the age of 40 years. Heterozygous rare sequence variants in AIP were identified in 18 (8.3%) patients. However, only four (1.8%) patients had pathogenic or likely pathogenic variants. These consisted of two already known mutations (p.Arg81* and p.Leu115Trpfs*41) and two novel mutations (p.Glu246*, p.Ser53Thrfs*36). All four patients had GH-secreting adenomas diagnosed between the ages of 14 and 25 years. The frequency of AIP pathogenic or likely pathogenic variants in patients under the age of 30 and 18 years was 3.4% and 5.0%, respectively. The frequency of AIP mutations in this cohort was lower than in other studies. Previous reports may have overestimated the contribution of AIP mutations due to the inclusion of genetic variants of uncertain significance. The identification of novel AIP mutations expands the known spectrum of genetic causes of pituitary adenomas and may help understand the role of AIP mutations in the molecular mechanisms underlying pituitary tumorigenesis.


Public perception of epilepsy in dogs is more favorable than in humans.
With the use of YouTube™, this study provides results on both the demographics and public perception for a sample of videos of canine epilepsy. A random sample of 150 videos was collected, the uploader description was recorded, and viewers' comments were coded according to their emotional and informational content. More comments were found to be sympathetic than derogatory, and there were more information-providing than information-seeking comments. The number of sympathetic comments was found to correlate positively with the number of derogatory comments, and the number of information-providing comments correlated positively with the number of information-seeking comments. These findings shed light on the variation in perceptions of seizures in dogs, which are interestingly more sympathetic towards dogs with epilepsy than towards humans with epilepsy. This highlights the potential future use of YouTube in investigating public views as well as in informing and educating.


Highly sensitive α-amanitin sensor based on molecularly imprinted photonic crystals.
α-amanitin is the most toxic amanita in mushrooms with lethal dose to humans around 0.1 mg. Kg-1. Hence, early identification of the poison would improve survival rates and prevent lethal poisoning cases. In this study, molecularly imprinted photonic crystal (MIPC) sensor was prepared by combining molecular imprinting with photonic crystal templates and tested towards the detection of α-amanitin. In this process, synthesized moiety of α-amanitin was utilized as template, dispersed SiO2 colloidal photonic crystal as carrier, methacrylic acid (MAA) as functional monomer, and ethylene glycol dimethacrylate (EDGMA) as crosslinker. The adsorption behavior of MIPC towards α-amanitin in ethanol solution showed shifts in diffraction peaks of MIPC upon binding with α-amanitin molecules. The reflection peak wavelength varied linearly with α-amanitin concentration according to the correlation formula: λ = 15.417c+489.17 (R2 = 0.9985). The recognition process was accompanied by gradual color change in MIPC film. The prepared MIPC sensor possessed wide linear range (10-9-10-3 mg L-1), change in visual color, low detection limit (10-10 mg L-1), short response time (2 min), and good reusability. The MIPC film was then tested towards the detection of α-amanitin in real biological samples (mushroom, urine, and serum) and showed reasonable shift in diffraction peaks and color change upon soaking in solutions spiked with α-amanitin at 10-6 mg L-1 and 10-3 mg L-1, suggesting the suitability of the film for the rapid identification of α-amanitin in complex sample matrices. Overall, the proposed sensor looks promising for the rapid identification of α-amanitin in clinical analysis and food poisoning.


Nutrition Literacy of Middle School Students and Its Influencing Factors: A Cross-Sectional Study in Chongqing, China.
Nutrition literacy plays an important role in children's dietary habits and nutrition. This study aimed to analyse the status of nutrition literacy and its influencing factors amongst middle school students in Chongqing, China. "Nutrition literacy scale for middle school students in Chongqing" was used in 29 districts of Chongqing in September 2020. The scores of nutrition literacy and its' three sub-domains (functional, interactive and critical nutrition literacy) were divided into low and high groups based on their median scores. Binary logistic regression was used to measure the influencing factors of nutrition literacy. A total of 18,660 middle school students were included in this study. The median of nutrition literacy of middle school students was 61.68 (IQR = 14.37). Interactive nutrition literacy had the highest score (median = 70.00, IQR = 20.00), followed by functional nutrition literacy (median = 68.69, IQR = 14.14) and critical nutrition literacy (median = 45.83, IQR = 25.00). Students who were the minority (OR = 0.71, 95% CI = 0.637-0.785), in senior high school (OR = 0.51, 95% CI = 0.477-0.548), in rural areas (OR = 0.85, 95% CI = 0.790-0.911), receiving school meal support from the government (OR = 0.63, 95% CI = 0.591-0.664), with other caregivers' parenting (OR = 0.86, 95% CI = 0.805-0.914), with parents having a low level of education and with an abnormal BMI [thin (OR = 0.91, 95% CI = 0.837-0.990), overweight (OR = 0.87, 95% CI = 0.785-0.968), and obese (OR = 0.83, 95% CI = 0.767-0.902)] presented less probability of being a high level of nutrition literacy. Our results could assist public health authorities in developing strategies of nutrition literacy promotion for references and theoretical foundations.


Recent development of nonviral gene delivery systems with virus-like structures and mechanisms.
The concept of gene therapy includes not only the addition of normal genes to genetically deficient cells, but also the use of transgenes encoding several peptides that function to enhance the capacity of normal cells or to regulate cell differentiation. The application of gene therapy has been widely considered for various diseases, as well as for the field of tissue engineering. To overcome the problems with viral vectors, a broad range of nonviral systems for gene delivery have been developed, including systems composed of cationic lipids (lipoplexes) and cationic polymers (polyplexes). However, most of these systems are still much less efficient than viral vectors, especially for in vivo gene delivery. Paradoxically, to achieve a maximum transgene expression in the targeted cells, there is no question that natural viruses are the most effective nanocarriers. In this article, we highlight the approaches currently being taken to improve nonviral gene delivery systems so that they better replicate the typical structures and mechanisms of viruses, such as DNA (RNA) condensation in the core, surrounding structures with targeting molecules for specific receptors, as well as the toxic and immunogenic problems which should be avoided, with the ultimate goal of bringing these systems into a clinical setting.


Erratum to: Impact of the nitric oxide-donor pentaerythrityl-tetranitrate on perinatal outcome in risk pregnancies: a prospective, randomized, double-blinded trial.
On page 1 "adjusted relative risk (RR)" should be changed to "adjusted odds ratio (OR)". On page 1, 3 and in the table head of table 2 "adjusted RR" should be changed to "adjusted OR". On page 3 "Mantel-Haenszel estimates of relative risk" should be changed to "Mantel-Haenszel estimates of odds ratios". In Table 2, caption b "Mantel-Haenszel estimate of relative risk" should be changed to "Mantel-Haenszel estimate of odds ratio".


Madhuca longifolia Embedded Silver Nanoparticles Attenuate Diethylnitrosamine (DEN)-Induced Renal Cancer via Regulating Oxidative Stress.
Madhuca longifolia has been used for the treatment of renal cancer. Therefore, the current study describes the protective effects of biofabricated silver nanoparticles (MLAg- NPs) using Madhuca longifolia aqueous leaves extract against diethylnitrosamine (DEN) induced Renal Cell Carcinoma (RCC) in rats. Animals were categorized into five groups and treated with doses of silver nanoparticles for 16 weeks. Antineoplastic effect in renal cancer was dose dependent to control the macroscopical variations when compared to DEN induced group. Significant changes were observed in biochemical parameters and dose graded improvement in the level of antioxidants parameters were accountable for its protective nature. Silver nanoparticles in dose dependent manner was effective to modify the raised levels of pro-inflammatory cytokines and inflammatory mediators during renal cancer. Alteration in renal histopathology were also detected in the silver nanoparticles treated group, which show its safety concern. Biofabricated silver nanoparticles (MLAgNPs) using Madhuca longifolia can convey significant chemo-protective effect against renal cancer by suppressing the IL-6, TNF-α and IL-1β by nuclear factor-kappa B (NF-κB) pathway. Our outcomes implicates that biofabricated MLAgNPs exhibited a chemoprotective potential in the prevention and intervention of RCC.


Mucin production in metastatic papillary carcinoma of the thyroid.
Although textbooks often state that demonstration of mucin in a metastatic carcinoma excludes the possibility of a thyroidal primary tumor, mucin recently has been reported in various types of thyroid carcinoma, particularly medullary carcinoma. The presence of mucin in papillary carcinoma has not been extensively studied, even though this tumor not uncommonly presents with lymph node metastasis. We stained 40 lymph nodes containing metastatic papillary carcinoma of the thyroid for mucin. Mucin was demonstrable by mucicarmine stain in the colloid, luminal borders, and cytoplasm in 18 (45%), 9 (22.5%), and 7 (17.5%) cases respectively; 17 cases (42.5%) were completely negative. With alcian blue staining, mucin was seen in 9 (22.5%), 9 (22.5%), and 7 (17.5%) cases; 25 cases (62.5%) were negative. Most of the cytoplasmic vacuoles were target-like, with a peripheral rim of sulfated acid mucin and a central core of neutral mucin. The psammoma bodies stained consistently with mucicarmine, alcian blue, and periodic acid-Schiff. We conclude that papillary carcinoma of the thyroid should be included in the differential diagnoses for a mucin-producing metastatic carcinoma.


68Ga-EMP-100 PET/CT-a novel ligand for visualizing c-MET expression in metastatic renal cell carcinoma-first in-human biodistribution and imaging results.
68Ga-EMP-100 is a novel positron emission tomography (PET) ligand that directly targets tumoral c-MET expression. Upregulation of the receptor tyrosin kinase c-MET in renal cell carcinoma (RCC) is correlated with overall survival in metastatic disease (mRCC). Clinicopathological staging of c-MET expression could improve patient management prior to systemic therapy with for instance inhibitors targeting c-MET such as cabozantinib. We present the first in-human data of 68Ga-EMP-100 in mRCC patients evaluating uptake characteristics in metastases and primary RCC. Twelve patients with mRCC prior to anticipated cabozantinib therapy underwent 68Ga-EMP-100 PET/CT imaging. We compared the biodistribution in normal organs and tumor uptake of mRCC lesions by standard uptake value (SUVmean) and SUVmax measurements. Additionally, metastatic sites on PET were compared to contrast-enhanced computed tomography (CT) and the respective, quantitative PET parameters were assessed and then compared inter- and intra-individually. Overall, 87 tumor lesions were analyzed. Of these, 68/87 (79.3%) were visually rated c-MET-positive comprising a median SUVmax of 4.35 and SUVmean of 2.52. Comparing different tumor sites, the highest uptake intensity was found in tumor burden at the primary site (SUVmax 9.05 (4.86-29.16)), followed by bone metastases (SUVmax 5.56 (0.97-15.85)), and lymph node metastases (SUVmax 3.90 (2.13-6.28)) and visceral metastases (SUVmax 3.82 (0.11-16.18)). The occurrence of visually PET-negative lesions (20.7%) was distributed heterogeneously on an intra- and inter-individual level; the largest proportion of PET-negative metastatic lesions were lung and liver metastases. The highest physiological 68Ga-EMP-100 accumulation besides the urinary bladder content was seen in the kidneys, followed by moderate uptake in the liver and the spleen, whereas significantly lower uptake intensity was observed in the pancreas and the intestines. Targeting c-MET expression, 68Ga-EMP-100 shows distinctly elevated uptake in mRCC patients with partially high inter- and intra-individual differences comprising both c-MET-positive and c-MET-negative lesions. Our first clinical results warrant further systemic studies investigating the clinical use of 68Ga-EMP-100 as a biomarker in mRCC patients.


Photostable Organic Two-photon Dyes with Ultrahigh Brightness for Long-term Fluorescence Imaging.
Developing photostable two-photon dyes with high brightness and negligible photocytotoxicity is of key importance in fluorescence imaging but remains a huge challenge. Here, a two-photon dye with ultrahigh brightness and photostability is demonstrated for high-performance long-term two-photon fluorescence imaging. By terminated donor engineering, the designed DBD shows a higher two-photon absorption cross-section (δ, 418 GM vs 329 GM) and photoluminescence quantum yield (ΦPL , 62.74% vs 54.63%) than its counterpart DBA. As a consequence, two-photon fluorescence brightness (δ×ΦPL ) of DBD exhibits a 10-folded enhancement (262 GM vs 19 GM) in comparison with typical Coumarin 307 dye. More importantly, DBD displays ultrahigh photostability and negligible photobleaching under 10 min femtosecond laser irradiation, which stands in marked contrast to Coumarin 307. Furthermore, femtosecond transient absorption spectroscopy ascribes this ultrahigh photostability and negligible photobleaching to the inefficient intersystem crossing. With these merits, DBD can be used long-term two-photon fluorescence imaging in vitro.


Regulation of human microsomal epoxide hydrolase gene (EPHX1) expression by the transcription factor GATA-4.
Microsomal epoxide hydrolase (mEH) is a bifunctional protein that plays a crucial role in the metabolism of numerous xenobiotics as well as in mediating the hepatic sodium-dependent uptake of bile acids that are involved in numerous physiological processes including the regulation of cholesterol metabolism. The transcription factors and nuclear receptors that control the constitutive and inducible expression of the mEH gene (EPHX1), however, have not been described. To characterize these factors, a series of 5'-deletion constructs have been transfected into human liver-derived HepG2 cells as well as non-hepatic HeLa cells. Promoter activity analysis indicated the presence of a positive regulatory element in the -80/-70 bp region. Sequence analysis revealed a putative GATA site at -79/-74 bp as well as an additional site at -31/-26 bp. Electrophoretic mobility shift assays with an anti-GATA-4 antibody confirmed that GATA-4 bound to these two sites with a dissociation constant of 1.56 nM (-79 site) and 0.65 nM (-31 site). Coexpression of GATA-4 stimulated EPHX1 promoter activity up to 7.5-fold in a dose-dependent manner. Endogenous EPHX1 message in HepG2 cells was also significantly increased by overexpression of GATA-4. Mutating the -79 element resulted in a 65% loss of promoter activity, while mutating the -31 element had no effect on basal activity but greatly reduced the response to additional GATA-4. In HeLa cells, which do not express GATA-4, EPHX1 activity was negligible; however, activity could be reconstituted by the addition of exogenous GATA-4. These results demonstrate that GATA-4 plays a critical role in regulating EPHX1 expression.


Rumen microbial community and milk quality in Holstein lactating cows fed olive oil pomace as part in a sustainable feeding strategy.
The use of alternative feed ingredients from the Agro-industry could be an efficient tool to improve the sustainability of dairy cow production. Since the richness in polyphenols, olive oil pomace (OOP), produced during olive oil milling, seems a promising by-product to ameliorate milk's nutritional value. The aim of this study was to test the use of OOP produced by means of a new technology (biphasic with stone deprivation) in dairy cow feeding strategy to evaluate the effect on animal performances, rumen microbiota, biohydrogenation processes and milk quality by a multidisciplinary approach. Forty multiparous Italian-Friesian dairy cows, at middle lactation, were randomly allotted into two homogenous groups and fed respectively a commercial diet (CON) and the experimental diet (OOPD) obtained by adding OOP to CON as partial replacement of maize silage. The two diets were formulated to be isoproteic and isoenergetic. The same diets were tested also in an in vitro trial aimed to evaluate their rumen degradability (% DEG). The dietary supplementation with OOP did not affect DM intake, rumen % DEG and milk production. The milk's nutritional quality was improved by increasing several important functional fatty acids (FAs; i.e., linoleic acid, conjugated linoleic acid, oleic acid, vaccenic acid). This finding was related to a decrease in rumen liquor biohydrogenation rate of unsaturated FAs. The stochiometric relation between volatile FA production in the rumen and methanogenesis suggested that OOP lowers the methane potential production (CON = 0.050 mol/L vs OOPD = 0.024 mol/L, SEM = 0.005, P = 0.0011). Rumen microbiota and fungi community did not be strongly altered by OOP dietary inclusion because few bacteria were affected at the genus level only. Particularly, Acetobacter, Prevotellaceae_UCG-004, Prevotellaceae_UCG-001, Eubacterium coprostanoligenes, Lachnospira, Acetitomaulatum, Lachnospiraceae_NK3A20 group were more abundant with OOPD condition (P < 0.05). Data reported in this study confirm that the use of OOP in dairy cow feeding can be an interesting strategy to improve milk nutritional quality increasing functional FA content without compromising the rumen degradability of the diet or causing strong perturbation of rumen ecosystem and maintaining animal performances.


Suspension Concentrate crop protection formulation design and performance for low spray volume and UAS spray application.
Unmanned aerial systems (UAS) are providing interesting disruptive solutions for spray application of crop protection products with very-low spray volumes (VLV) down to 8 L/ha that offer improved sustainability through reduced water volumes and reduced soil compaction. However, the efficacy of products can be reduced by the significantly lower crop/plant spray coverage and formulation designs that can compensate for this are highly important here. Suspension Concentrate (SC) formulations designed for VLV use containing and delivering low dose rates (g/ha) of organosilicone alkoxylate high-spreading surfactants were found to result in leaf coverage of VLVs comparable to those observed at higher spray volumes. High spreading was observed on textured leaf surfaces containing sub-micron sized epicuticular wax crystals. Greenhouse fungal disease studies showed enhanced efficacy with these SC formulations compared to standard SC formulations without these additives and maintained the observed increase in efficacy when applied at VLV. Alternatively, SC formulations without high spreading formulants but containing uptake promoting nonionic surfactants showed enhanced cuticle penetration through isolated cuticles at VLV in comparison to higher spray volumes, with coffee-ring spray deposit microstructures present at VLVs. Similarly, greenhouse studies showed enhanced efficacy that was maintained at VLV relative to SCs without these additives. At VLVs, SC formulations applied at relatively low dose rates (g/ha) of formulants (adjuvants) enhancing spreading on the leaf surface and/or uptake of the active ingredient(s) maintained good spreading, uptake and biological efficacy in greenhouse studies overcoming the coverage limitations of SC formulations without these additives. This result is unexpected considering the low dose rate of adjuvants used. © 2023 Bayer AG. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Editorial: The Role of Computational Models to Uncover the Cognitive Mechanisms Underpinning Disruptive Mood Dysregulation Disorder.
Computational models mimic important concepts inherent to brain function and the relationships among these concepts in a mathematical form.1 These models offer a suitable approach to quantitatively explore properties of complex systems across levels of investigation. Therefore, these models may be well suited to linking molecular, cellular, circuits, cognition, and behavior in psychiatry.2 Although some progress has been made in applying such models for understanding other mental disorders,2,3 their role in uncovering the cognitive mechanisms underpinning disruptive mood dysregulation disorder (DMDD) has not previously been explored in the medical literature. In fact, very little is known about the neurocognitive correlates of DMDD in children.


Rare case of a strangulated intercostal flank hernia following open nephrectomy: A case report and review of literature.
Flank incisions may be associated with incisional flank hernias, which may progress to incarceration and strangulation. Compromised integrity of the abdominal and intercostal musculature due to previous surgery may be associated with herniation of abdominal contents into the intercostal space. There have been six previously reported cases of herniation into the intercostal space after a flank incision for a surgical procedure. This case highlights the clinical picture associated with an emergent strangulated hernia and highlights the critical steps in its management. We present a case of a 79-year-old adult man with multiple comorbidities presenting with a strangulated flank hernia secondary to an intercostal incision for a right-sided open nephrectomy. The strangulated hernia required emergent intervention including right-sided hemi-colectomy with ileostomy and mucous fistula. Abdominal incisional hernias are rare and therefore easily overlooked, but may result in significant morbidity or even death in the patient.. The diagnosis can be made with a thorough clinical examination and ultrasound or computed topographical investigation. Once a hernia has become incarcerated, emergent surgical management is necessary to avoid strangulation and small bowel obstruction. Urgent diagnosis and treatment of this extremely rare hernia is paramount especially in the setting of strangulation.


Parametric assessment of household's food intake, agricultural practices and health in rural South West, Nigeria.
Food intake and health are important component of agriculture. The contribution of these duo have a lot to say about the productivity of farmers in the nations of the world. The results presented here relied on data collected on households' food intake nutrition and health profile through multistage random sampling of 420 households selected from the Southwest, Nigeria using well-structured questionnaires. Descriptive statistics (percentage, frequency, mean) and inferential statistics (Logistic regression and Negative Binomial). The result shows that the farmers were ageing, given an average of (53 ± 11.44 years). The Logistic regression model of the effect of farming households food intake on health showed that gender of the households' head, marital states of the head, household food security and knowledge of nutrition significantly reduced the probability of reporting good health while the educational year(s) of the farmers, total cost of health and consumption of fruit increased it. In addition, the Negative Binomial Regression model, employed in the assessment of the effect of farming households' nutrition on health indicated that gender, marital status, and consumption of milk and total cost of health significantly increased day(s) incapacitated while the year(s) of education reduced it. It was therefore concluded that diversity of food intake among the farmers was low. Ageing, education and large household size among others, were also identified as major problem among the rural farmers. It was however recommended that considerable investment in human capital should be encouraged since food diversity and nutrition education enhances households' food intake and health status.


Does Mobile Internet Use Affect the Loneliness of Older Chinese Adults? An Instrumental Variable Quantile Analysis.
Based on the 2018 China Family Panel Studies (CFPS) data, we empirically analyze the effect, heterogeneity, quantile differences and influencing mechanisms of mobile Internet use on loneliness in the elderly. The study found that the loneliness of the elderly who used mobile Internet was 33.1% lower than that of the elderly who did not use the mobile Internet The study also passed the robustness test. There is heterogeneity in the effect of mobile Internet use on loneliness among the elderly of different ages, educational levels and marital status. Among them, the use of mobile Internet has a significant alleviating effect on the loneliness of the 60-70-year-old elderly, those of junior high school education level and below, and the elderly with a partner. The quantile regression analysis showed that the elderly group with a high level of loneliness benefited more from the use of mobile Internet. Mediation analysis further showed that mobile Internet use can improve parent-child relationship, increase offline interactions with children, and reduce children's tangible support, which we interpret as a potential mechanism for mobile Internet use to alleviate loneliness in the elderly.


Confirmation of enhanced expression of heme oxygenase-1 gene induced by ultrasound and its mechanism: analysis by cDNA microarray system, real-time quantitative PCR, and Western blotting.
The present study was undertaken to reconfirm heme oxygenase-1 (HO-1) induction by ultrasound, and elucidate the mechanism by which this occurs. After exposure of human lymphoma U937 cells to 1 MHz continuous ultrasound (US), gene profiling by using cDNA microarray analysis, cell viability by using the trypan blue dye exclusion test, mRNA expression by using real-time quantitative polymerase chain reaction, and protein expression by using Western blotting were examined. As an indicator of cavitation, hydroxyl radical formation was studied by using electron paramagnetic resonance-spin trapping. The cDNA microarray analysis reconfirmed HO-1 induction in human lymphoma U937 cells after exposure to US, and further identified one upregulated and two downregulated genes. When U937 cells were exposed to US for 1 min, HO-1 induction, as examined by real-time quantitative polymerase chain reaction and Western blotting, was observed at intensities higher than the cavitational threshold. When a potent antioxidant, N-acetyl-L-cysteine, was added to the culture medium before or after sonication, the induction was attenuated, indicating that reactive oxygen species are involved in HO-1 induction. A decrease in mitochondrial membrane potential and generation of superoxide anion radicals were also observed in the cells exposed to US. We used a cDNA microarray system to confirm upregulation of the HO-1 gene and to discover new genes that respond to ultrasonic cavitation. Increased intracellular oxidative stress secondary to the sonomechanical effects arising from ultrasonic cavitation is suggested to be the mechanism of enhancement of HO-1 expression.


Congenital abnormalities in Japanese patients with Menkes disease.
Menkes disease (MNK) is an X-linked recessive disorder. Incidence of live-born infants with MNK is 2.8 per million live births in Japan. The aim of this study was to observe congenital malformations (CMs) in MNK patients. Subjects comprised 35 Japanese male patients with classical MNK who received copper histidine treatment. Patient clinical data were obtained anonymously from medical records or medical record summaries by pediatrician's retrospective review through a survey. We observed 21 different CMs in 14 patients. Eight of these had a single CM, while six had multiple CMs. The most frequent CM was higher arched palate with other CMs found in five patients. There was no relationship between CMs and mutations in the ATP7A gene. Using Mann-Whitney U tests, age at death was also significantly lower in MNK patients with CMs (P<0.05), compared to those without CMs, even though there was no significant difference of age onset, age at diagnosis and age at start of treatment with copper histidine between both groups of patients. Sudden death occurred in three MNK patients with CMs only: two with congenital heart disease, and one with microphallus.


Purification and characterisation of lignin peroxidase from Pycnoporus sanguineus MTCC-137.
Extracellular secretion of lignin peroxidase from Pycnoporus sanguineus MTCC-137 in the liquid culture growth medium amended with lignin containing natural sources has been shown. The maximum secretion of lignin peroxidase has been found in the presence of saw dust. The enzyme has been purified to homogeneity from the culture filtrate of the fungus using ultrafiltration and anion exchange chromatography on DEAE-cellulose. The purified lignin peroxidase gave a single protein band in sodium dodecylsulphate polyacrylamide gel electrophoresis corresponding to the molecular mass 40 kDa. The K(m)(, kcat) and k(cat)/K(m) values of the enzyme using veratryl alcohol and H2O2 as the substrate were 61 microM, 2.13 s(-1), 3.5 x 10(4) M(-1) s(-1) and 71 microM, 2.13 s(-1), 3.0 x 10(4) M(-1) s(-1) respectively at the optimum pH of 2.5. The temperature optimum of the enzyme was 25 degrees C.


Gut microbiome and prostate cancer.
The gut microbiome is linked to several diseases such as Alzheimer's disease, rheumatoid arthritis, and colon cancer. The gut microbiome is also associated with the modulation of immune function, resulting in a different response to immune checkpoint therapy. The gut microbiome differs according to lifestyle, diet, sex, race, genetic background, and country. Lifestyle, especially diet, plays an important role in the development and progression of prostate cancer. Recent studies have revealed a connection between the gut microbiome and prostate cancer. A high-fat diet causes gut dysbiosis and gut bacterial metabolites, such as short-chain fatty acids and phospholipids that enter systemic circulation result in promoting prostate cancer growth. Additionally, the gut microbiota can serve as a source of testosterone, which affects prostate cancer progression. Men with castration-resistant prostate cancer have an increased abundance of gut bacteria with androgenic functions. Men with high-risk prostate cancer share a specific gut microbial profile and profiling gut microbiota could be a potentially effective tool to screen men with high-risk prostate cancer. Lifestyle modifications can improve the gut microbiome. Furthermore, altering the gut microbiome using prebiotic or probiotic interventions may prevent or delay prostate cancer development. Further study into the "Gut-Prostate Axis" would help in the discovery of new strategies for the prevention, screening, and treatment of prostate cancer.


Ethylenediurea offers moderate protection against ozone-induced rice yield loss under high ozone pollution.
Tropospheric ozone (O3) is the main phytotoxic air pollutant threatening food security, while ethylenediurea (EDU) can effectively mitigate O3-induced crop yield loss. EDU's mode of action, however, remains unclear, and the underlying physiological mechanisms of mitigating O3-induced crop yield loss are poorly understood. We cultivated hybrid rice seedlings under two O3 treatments (NF, nonfiltered ambient air; and NF60, ambient air plus 60 ppb O3) and sprayed foliage with 0 or 450 ppm EDU every ten days and determine photosynthesis-related traits, biomass indicators, and yield components. We found that EDU significantly increased the leaf nitrogen (N) allocation to photosynthesis (NP) and the grain N accumulation, while the grain N accumulation was positively correlated with NP and root biomass. EDU significantly increased the rice yield mainly by increasing the individual grain weight rather than the number of panicles and grains. While EDU protected from yield loss, the degree of protection was only 31% under NF60 treatment, thus EDU was unable to offer complete protection under high O3 pollution. These results will be conducive to a better understanding of the EDU protection mechanism and better application of EDU under high O3 pollution in the future.


Dismantling cognitive-behavioral group therapy for social phobia.
The efficacy of Heimberg's (1991) Cognitive-Behavioral Group Therapy (CBGT) [Unpublished manuscript] for social phobia has been demonstrated in several studies in recent years. However, little is known about the mechanisms underlying the treatment's success. In order to determine whether the cognitive restructuring component of CBGT is essential, this study compared CBGT to an exposure-based treatment without formal cognitive restructuring. A wait-list control was also included. In general, Ss in the active treatment conditions improved and control Ss did not improve on a variety of self-report, clinician, and behavioral measures. Limited evidence indicated that Ss in the non-cognitive treatment may have made somewhat greater gains on some measures. Although CBGT Ss reported more improvement than exposure-alone Ss in subjective anxiety during an individualized behavioral test at posttreatment, this difference disappeared at 6-month follow-up. Surprisingly, CBGT was less effective than in previous controlled trials, and possible reasons for this are discussed. Implications of the results for cognitive theory and cognitive-behavioral therapy for social phobia are addressed.


Parametrized topological complexity of poset-stratified spaces.
In this paper, parametrized motion planning algorithms for a fiberwise space X → P over a poset P are studied. Such an algorithm assigns paths in a space X decomposed into subspaces with the index set P, that do not cross the boundaries of the separated regions. We compute the parametrized topological complexity of X → P , which is one less than the minimal number of local parametrized motion planning algorithms used for designing non-cross-border robot motions in X.


Modulation of intrinsic inhibitory checkpoints using nano-carriers to unleash NK cell activity.
Natural killer (NK) cells provide a powerful weapon mediating immune defense against viral infections, tumor growth, and metastatic spread. NK cells demonstrate great potential for cancer immunotherapy; they can rapidly and directly kill cancer cells in the absence of MHC-dependent antigen presentation and can initiate a robust immune response in the tumor microenvironment (TME). Nevertheless, current NK cell-based immunotherapies have several drawbacks, such as the requirement for ex vivo expansion of modified NK cells, and low transduction efficiency. Furthermore, to date, no clinical trial has demonstrated a significant benefit for NK-based therapies in patients with advanced solid tumors, mainly due to the suppressive TME. To overcome current obstacles in NK cell-based immunotherapies, we describe here a non-viral lipid nanoparticle-based delivery system that encapsulates small interfering RNAs (siRNAs) to gene silence the key intrinsic inhibitory NK cell molecules, SHP-1, Cbl-b, and c-Cbl. The nanoparticles (NPs) target NK cells in vivo, silence inhibitory checkpoint signaling molecules, and unleash NK cell activity to eliminate tumors. Thus, the novel NP-based system developed here may serve as a powerful tool for future NK cell-based therapeutic approaches.


Privacy and Confidentiality Considerations for Collecting HIV Risk Network Data among Men who Have Sex with Men and Implications for Constructing Valid Risk Networks.
Studies aiming to construct risk networks have historically collected network members' names, demographic characteristics and relational data (i.e., type, strength, duration, frequency of interaction, and HIV-related risk behaviors between the pair). Due to difficulties in constructing risk networks stemming from partner anonymity and the use of nicknames, some studies also collect network members' screen names, phone numbers, physical attributes, and scars/tattoos to assist with entity resolution. In-depth interviews with 20 men who have sex with men and transgender women in Kentucky assessed privacy/confidentiality concerns as well as accuracy/recall issues associated with providing these details. Most preferred providing alters' nicknames/first names only or a first name with the first letter of the last name. Many perceived screen names, phone numbers, and scars/tattoos to be too personal/identifying. Willingness to provide more detailed information varied by relationship type/strength, which could influence the validity of the resulting network.


Malignant lymphoma in Hawaii-Japanese: a retrospective morphologic survey.
A retrospective morphologic survey (1973-1983) of 146 cases of malignant lymphoma among the Hawaii-Japanese (migrant Japanese and their offspring) was conducted to determine whether differences in the incidence and cytologic types of malignant lymphoma exist when compared to those of native Japanese (lifetime residents of Japan). The age-adjusted incidence rates for malignant lymphoma among the Hawaii-Japanese were similar to rates for U.S. whites. However, higher rates for follicular centre cell (FCC) lymphoma with a follicular pattern were observed in the Hawaii-Japanese population when compared with rates for native Japanese. On the basis of the cytologic types of the Lukes-Collins classification, non-Hodgkin's lymphomas among the Hawaii-Japanese resembled those of Western countries, rather than those of Japan. B-cell lymphomas predominated (72 per cent), while T-cell types comprised 23 per cent of cases. Follicular centre cell types were encountered most often (59 per cent), and the small cleaved FCC subtype was the most common (30 per cent). The high degree of follicularity (29 per cent) was at variance with the consistently low rates reported in Japan. This may be explained, in part, by higher rates of nodal lymphomas among the Hawaii-Japanese. Of the T-cell lymphomas, diffuse large cell types (T-cell immunoblastic sarcoma, T-IBS), often with cytologic pleomorphism, were relatively frequently encountered (16 per cent), and comprised 15 per cent of non-Hodgkin's lymphomas; this observation necessitates special clinical and epidemiologic consideration in view of the large Japanese migration to Hawaii from HTLV-I endemic regions of southern Japan. No registered cases of non-Hodgkin's lymphoma or of Hodgkin's disease were documented in Hawaii-Japanese subjects under the age of 15 years. The age-adjusted incidence rates for Hodgkin's disease among the Hawaii-Japanese were similar with those of native Japanese. Nodular sclerosis was the most frequent histologic subtype. The difficulty in distinguishing between Hodgkin's disease and non-Hodgkin's lymphoma, particularly when immunologic cell surface markers are not available, is addressed. Low rates for chronic lymphocytic leukemia among the Hawaii-Japanese were confirmed. Not one well-documented case was identified in the 11-year period surveyed.


The effects of depth of isoflurane anesthesia on the performance of mice in a simple spatial learning task.
Studies on humans and rodents indicate possible long-term cognitive impairment after surgery or general anesthesia. The goal of this study was to evaluate the effect of various anesthetic concentrations on spatial learning in adult mice. The behavior of adult mice in a T-maze was assessed 28 h after anesthesia (control [0%], low [1%], or high [2%] isoflurane concentration). The mice anesthetized with 1% isoflurane had a significantly poorer performance than did the other 2 groups. The performance of the mice anesthetized with 2% isoflurane was not statistically different from that of the control group. Therefore, low, not high, isoflurane concentration impaired spatial learning in mice.


Prospective multicentric validation of a novel prediction model for paroxysmal atrial fibrillation.
The early recognition of paroxysmal atrial fibrillation (pAF) is a major clinical challenge for preventing thromboembolic events. In this prospective and multicentric study we evaluated prediction scores for the presence of pAF, calculated from non-invasive medical history and echocardiographic parameters, in patients with unknown AF status. The 12-parameter score with parameters age, LA diameter, aortic root diameter, LV,ESD, TDI A', heart frequency, sleep apnea, hyperlipidemia, type II diabetes, smoker, ß-blocker, catheter ablation, and the 4-parameter score with parameters age, LA diameter, aortic root diameter and TDI A' were tested. Presence of pAF was verified by continuous electrocardiogram (ECG) monitoring for up to 21 days in 305 patients. The 12-parameter score correctly predicted pAF in all 34 patients, in which pAF was newly detected by ECG monitoring. The 12- and 4-parameter scores showed sensitivities of 100% and 82% (95%-CI 65%, 93%), specificities of 75% (95%-CI 70%, 80%) and 67% (95%-CI 61%, 73%), and areas under the receiver operating characteristic (ROC) curves of 0.84 (95%-CI 0.80, 0.88) and 0.81 (95%-CI 0.74, 0.87). Furthermore, properties of AF episodes and durations of ECG monitoring necessary to detect pAF were analysed. The prediction scores adequately detected pAF using variables readily available during routine cardiac assessment and echocardiography. The model scores, denoted as ECHO-AF scores, represent simple, highly sensitive and non-invasive tools for detecting pAF that can be easily implemented in the clinical practice and might serve as screening test to initiate further diagnostic investigations for validating the presence of pAF. Prospective validation of a novel prediction model for paroxysmal atrial fibrillation based on echocardiography and medical history parameters by long-term Holter ECG.


Evaluation of multifrequency SAR data for estimating tropical above-ground biomass by employing radiative transfer modeling.
The retrieval of the biophysical parameters and subsequent estimation of the above-ground biomass (AGB) of vegetation stands are made possible by the simulation of the extinction and scattering components from the canopy layer using vector radiative transfer (VRT) theory-based scattering models. With the use of such a model, this study aims to evaluate and compare the potential of dual-pol, multi-frequency SAR data for estimating above-ground biomass. The data selected for this work are L-band dual polarized (HH/HV) ALOS-2 data, S-band dual polarized (HH/HV) NovaSAR data, and C-band dual polarized (VV/VH) Sentinel-1 data. The two key biophysical parameters, tree height, and trunk radius are retrieved using the proposed methodology, applying the frequencies independently. A general allometric equation with vegetation-specific coefficients is used to estimate the AGB from the retrieved biophysical parameters. The retrieval results are validated using ground truth measurements collected from the study area. The L-band, with the coefficient of determination ([Formula: see text]) of 0.73 and the root mean square error (RMSE) of 35.90 t/ha, has the best correlation between the modeled and field AGBs, followed by the S-band with an [Formula: see text] of 0.37 and an RMSE of 63.37 t/ha, and the C-band with an [Formula: see text] of 0.25 and an RMSE of 72.32 t/ha. The L-band has yielded improved estimates of AGB in regression analysis as well, with an [Formula: see text] of 0.48 and an RMSE of 50.02 t/ha, compared to the S- and C-bands, which have the [Formula: see text] of 0.12 and 0.03 and the RMSE of 70.98 t/ha and 80.84 t/ha, respectively.


Selective determination of arginine-containing and tyrosine-containing peptides using capillary electrophoresis and laser-induced fluorescence detection.
The use of two different amino acid-selective fluorogenic reagents for the derivatization of peptides is investigated. One such scheme utilizes a selective reaction of benzoin with the guanidine moiety to derivatize arginine residues occurring in a peptide. The second scheme involves the formylation of tyrosine, followed by reaction with 4-methoxy-1,2-phenylenediamine. The use of capillary electrophoresis and laser-induced fluorescence detection allows enhanced efficiencies and sensitivities to be obtained for the separations of either arginine- or tyrosine-containing peptides. A helium-cadmium laser (325 nm) is ideally suited for the laser-based detection system due to a close match of the excitation maxima of derivatized peptides from both reactions. A detection limit of 270 amol is achieved for model arginine-containing peptides, while the detection limit for model tyrosine-containing peptides is measured at 390 amol. Both derivatization reactions are found to be useful for high-sensitivity peptide mapping applications in which only the peptides containing the derivatized amino acids are detected.


Chronic hepatitis B infection: a workshop consensus statement and algorithm.
Here, presented with an evidence-based algorithm, are workshop consensus recommendations on whom to screen for hepatitis B and when to pursue further evaluation and management.


Pelvic neurectomy abolishes the fetus-expulsion reflex and induces dystocia in the rat.
To clarify the origin of dystocia in bilaterally pelvic neurectomized (BPN) rats, the uterine activity during the periparturient period, and reflex straining movements in response to vaginal stimulation and cervical extensibility were monitored. The BPN rat displayed "stretching" movements and the regular continuous uterine activity with a similar onset and intensity to that in control rats (intact, sham-operated or unilateral pelvic neurectomized rats) on days 22 or 23 of gestation, but lacked the "straining" movements which precede each delivery of pups in controls so that parturition was prolonged. Dissection of rats revealed that an unborn fetus was retained in the expanded upper portion of the vaginal cavity. Vaginal distension induced contraction of the abdominal muscles and diaphragm and an inhibition of respiratory movements, resulting in an increase in intraabdominal pressure in urethane-anesthetized control rats. This reflex muscular contraction which reflects the straining movements in normal delivery may be called the fetus-expulsion reflex and does not occur in BPN rats. It differs from the fetus-ejection reflex (Ferguson reflex) which initiates oxytocin release. There was no difference in weight and distensibility of the uterine cervix between sham-operated and operated rats on day 22 of pregnancy. The results suggest that the main abnormality of delivery in BPN rats, a prolongation of the process of delivery, may be due to a lack of the fetus-expulsion reflex which plays a physiologic role in removing a fetus from the upper vaginal cavity against the resistance of the pelvic outlet.


Measurement of (233)U/(234)U ratios in contaminated groundwater using alpha spectrometry.
The uranium isotope (233)U is not usually observed in alpha spectra from environmental samples due to its low natural and fallout abundance. It may be present in samples from sites in the vicinity of nuclear operations such as reactors or fuel reprocessing facilities, radioactive waste disposal sites or sites affected by clandestine nuclear operations. On an alpha spectrum, the two most abundant alpha emissions of (233)U (4.784 MeV, 13.2%; and 4.824 MeV, 84.3%) will overlap with the (234)U doublet peak (4.722 MeV, 28.4%; and 4.775 MeV, 71.4%), if present, resulting in a combined (233+234)U multiplet. A technique for quantifying both (233)U and (234)U from alpha spectra was investigated. A series of groundwater samples were measured both by accelerator mass spectrometry (AMS) to determine (233)U/(234)U atom and activity ratios and by alpha spectrometry in order to establish a reliable (233)U estimation technique using alpha spectra. The Genie™ 2000 Alpha Analysis and Interactive Peak Fitting (IPF) software packages were used and it was found that IPF with identification of three peaks ((234)U minor, combined (234)U major and (233)U minor, and (233)U major) followed by interference correction on the combined peak and a weighted average activity calculation gave satisfactory agreement with the AMS data across the (233)U/(234)U activity ratio range (0.1-20) and (233)U activity range (2-300 mBq) investigated. Correlation between the AMS (233)U and alpha spectrometry (233)U was r(2) = 0.996 (n = 10).


Leishmania infection: painful or painless?
The complex life cycle and immunopathological features underpinning the interaction of Leishmania parasites and their mammalian hosts poses frequent poorly explored and inconclusively resolved questions. The altered nociceptive signals over the course of leishmaniasis remain an intriguing issue for nociceptive and parasitology researchers. Experimental investigations have utilized behavioral, morphological, and neuro-immune approaches in the study of experimental cutaneous leishmaniasis (CL). The data generated indicates new venues for the study of the pathological characteristics of nociceptive processing in this parasitic disease. Leishmania-induced pain may be easily observed in mice and rats. However, nociceptive data is more complex in human investigations, including the occurrence of painless lesions in mucocutaneous and cutaneous leishmaniasis. Data from recent decades indicate that humans can also be affected by pain-related symptoms, often distinct from the region of body infection. The molecular and cellular mechanisms underlying such variable nociceptive states in humans during the course of leishmaniasis are an active area of research. The present article reviews nociception in leishmaniasis, including in experimental models of CL and clinical reports.


Activation of the trace amine-associated receptor 1 prevents relapse to cocaine seeking.
The trace amine-associated receptor 1 (TAAR1) has emerged as a promising target for medication development in addiction because of its ability to regulate dopamine (DA) transmission. We tested in rats the efficacy of RO5203648 and RO5256390, partial and full TAAR1 agonists, respectively, in models of cocaine relapse. Using a model of context-induced relapse, both RO5203648 and RO5256390 dose-dependently suppressed cocaine seeking after a 2-week period of withdrawal from chronic cocaine self-administration. In a model of extinction-reinstatement, RO5203648 completely inhibited cocaine-primed reinstatement of cocaine seeking. At doses that effectively suppressed cocaine seeking neither RO5203648 nor RO5256390 altered responding maintained by a natural reward. Moreover, fast scan cyclic voltammetry data showed that RO5203648 prevented cocaine-induced DA overflow in the nucleus accumbens without altering DA half-life, suggesting that the partial TAAR1 agonist attenuated cocaine-stimulated DA overflow by mechanisms other than direct interference with DA uptake. Collectively, these data provide strong evidence in support of TAAR1 as a neuropharmacological target for the treatment of cocaine addiction.


[Enhanced inhibition of splenic lymphocyte proliferation by 2,3,7,8-tetrachlorodibenzo-p-dioxin in C57B1/10 (Ah+Ah+) mice compared to DBA/2 (AhAh) mice].
In concanavalin A-treated cultures TCDD (10(-8)M) inhibited proliferation of mouse spleen lymphocytes in cells of C57B1/10/mice by 65% and in cells of DBA/2 mice--by 42%. In phytohaemagglutinin-treated cultures of spleen lymphocytes of both strains TCDD produced no significant decrease in incorporation of 3H-thymidine into DNA. These observations indicate that effects of TCDD on lymphocyte proliferation are mediated by pleiotropic activity of Ah gene.


[Determination of the heart minute volume by impedance cardiography: a way to prophylaxis of premature birth? (author's transl)].
30 gravid women between the ages of 18 and 38 years who had gone into premature labour of unknown etiology were examined with respect to cardiac output and various other cardiovascular parameters in the standing, supine and left lateral positions. Measurements were carried out using an impedance-cardiography. A group of 30 women of similar age and duration of pregnancy but not in premature labour was also tested as controls. In the standing position, the test group showed a cardiac output which was 15% less than that of the controls. Statistically this was highly significant (p less than 0.005). No difference was found in the supine and left lateral positions. These results are in agreement with the literature, but with the method used in this study, an invasive, or X-Ray procedure is avoided. The physiology of the cardiovascular system in pregnancy and the means by which premature labour may be prevented, are discussed.


Ground vegetation biocontent and net production in a deciduous woodland.
Biocontent of the above-ground parts of ground vegetation in an alder-birch woodland was between 75 and 581.3 Kcal/m2 (16.05 and 137.70 g/m2). Species peaks did not necessarily coincide with the highest values for total ground vegetation. Ground vegetation litter biocontent was 1848.4 Kcal/m2 at the beginning of the study (April 1966) but rapidly fell to near 700 Kcal/m2 and remained near this level until April 1968. Net production by the above ground parts of the ground vegetation was 1016 Kcal/m2/yr (277.86 g/m2/yr) and 1142 Kcal/m2/year (280.20 g/m2/yr) in 1966-1967 and 1967-1968 respectively, measured as mortality plus net biocontent changes. These estimates were compared with those based on biocontent changes. Ground vegetation net primary production was not much smaller than tree litter fall (circa 1450 Kcal/m2/yr).


Anatomy and evaluation of the lumbosacral plexus.
Although not as common as brachial plexopathies, lumbosacral plexopathies do occasionally occur. Most plexopathies are due to masses that compress or infiltrate the pelvis, traction on the plexus itself from dislocation of the hemipelvis, or ischemia. Diagnosis and evaluation of the lumbosacral plexus may be made using electrodiagnostic testing, MR imaging, or CT scans, in addition to the patient's history, thorough physical examination, and knowledge of the anatomy of the plexus and its associated anatomical structures.


Prion proteins and ECTO-NOX proteins exhibit similar oscillating redox activities.
Both recombinant full-length mouse prion protein expressed in Escherichia coli and native prion protein (PrPsc) from mouse brain exhibited NADH oxidase and protein disulfide-thiol interchange activities similar to those formerly thought to be properties exclusive to the growth-related, cell surface ECTO-NOX proteins. The two activities exhibited the complex 2+3 pattern of oscillations characteristic of ECTO-NOX proteins where the two activities alternate to generate a period length of 24 min. The oscillations were augmented by copper and diminished by addition of the copper chelator bathocuproene. That the activity might be attributable to a contaminating protein was ruled out by experiments where the purified recombinant prion-containing extracts were resolved by SDS-PAGE and the activity was restricted to a single band corresponding to the predicted Mr of the recombinant prion as verified by Western blot analyses.


A method to identify and correct overextended denture borders.
This paper will present a method of correcting a processed denture for overextension and overwaxup in order to give the patient added comfort and the denture added retention.


Management of dentoskeletal deformity due to condylar resorption: literature review.
The aim of this review was to examine all publicly available literature on the current treatments of the dentoskeletal deformity due to condylar resorption and their outcomes and to suggest management guidelines. A systematic review was performed of all literature located on the electronic PubMed database from 1970 to 2012. The search resulted in 21 papers and 210 cases treated from 1991 to 2012. Orthognathic surgery was the most commonly used option (42%) and was sometimes combined with open joint surgery (19%). Stability was observed, respectively, in 57% and 100% of the orthognathic surgery and open joint surgery cases. Condylectomy and reconstruction with chondrocostal graft or temporomandibular joint total joint prosthesis were used in 19% and 10% of all cases of orthognathic surgery and open joint surgery with good results (95% and 100%, respectively). Osteogenic distraction was anecdotic (1%). Nine percent of all cases received conservative treatment. Larger comparative studies are necessary to obtain evidence-based recommendations.


[Studies on the chemical constituents of Rhododendron molle G. Don].
Two physiologically active diterpenoids were isolated from the flower of Chinese azalea (Ericaceae Rhododendron molle G. Don). One of them is a new compound, named rhodomollein-III; its structure has been established as 1 through IR, MS, 1HNMR, 13C NMR, 1H-1H COSY, 1H-1H NOESY, 13C-1H COSY and long-range 13C-1HCOSY. The other one is the known rhodojaponin-III.


Detection of mucopolysaccharidosis type I heterozygotes based on the biochemical characteristics of leukocyte alpha-L-iduronidase.
In the present study, we biochemically characterized the enzyme alpha-L-iduronidase (IDUA) of leukocytes from normal individuals and from mucopolysaccharidosis I (MPS I) heterozygotes, and compared these characteristics to discriminate for inclusion into two different groups. We fluorimetrically measured IDUA activity in leukocytes using 4-methylumbelliferyl-alpha-L-iduronide as an artificial substrate. Optimum pH, Km, Vmax, and thermostability of the enzyme at 50 degrees C were determined. Based on leukocyte IDUA activity, we divided the heterozygotes into two groups, one (group 1) with activity below that detected in controls, and the other with activity similar to that of normal individuals (group 2). The optimum pH for IDUA was 2.7 for normal individuals and 2.6-2.8 for heterozygotes. With respect to Km, there was a difference only between the value for normal IDUA (0.60 mM) and the value for group 2 (0.38 mM), while group 1 showed a statistically similar value (0.49 mM). The Vmax of the reaction was discriminated in the three groups in a highly effective manner. The IDUA of normal individuals had a higher Vmax (60.98 nmoL/h x mg protein) than the enzyme of group 1 heterozygotes (28.66 nmoL/h x mg protein) and the enzyme of group 2 (31.78 nmoL/h x mg protein). When the IDUA from the three groups was pre-incubated at 50 degrees C, we observed that the IDUA of both group 1 and group 2 was significantly more thermostable than the IDUA of normal individuals. Determination of IDUA activity alone is not sufficient to discriminate between MPS I heterozygotes and normal individuals because a considerable overlap occurs between them. Our study showed that leukocyte IDUA from MPS I heterozygotes differed from the normal enzyme in terms of optimum pH, Km, and Vmax of the reaction and thermostability at 50 degrees C. These parameters provide a simple and reliable tool for the detection of carriers for MPS I.


Achalasia treatment in the elderly: is botulinum toxin injection the best option?
Achalasia treatment in elderly patients is a matter of controversy. Botulinum toxin injection has been proposed as the best option in this group of patients as it is a safe procedure. However, concern persists regarding its short-term effect. To analyse the clinical and economic effectiveness of botulinum toxin injection in the treatment of achalasia patients who are elderly. Seventeen consecutive achalasia patients older than 65 years were treated with 80 units of botulinum toxin. Clinical follow-up at 1, 6 and 12 months was performed. Control manometry when symptoms recurred was carried out. Results were compared with those of an historical control group of 16 achalasia patients also older than 65 years and who had been treated with endoscopic dilation. The costs of both procedures were compared. Twenty-nine botulinum toxin injections were performed in the 17 patients of the botulinum toxin group (follow-up, 12-36 months). In the dilation group only two patients had to be retreated (follow-up, 12-108 months). No major complications were observed in either group. The average duration of symptom alleviation was 48 +/- 33 months for endoscopic dilation and 13.8 +/- 9.5 months for botulinum toxin injection. Maintaining a patient free of symptoms cost E348.31 per year for botulinum toxin injection, whilst if endoscopic dilation was chosen the cost was only E117.47 per year. The effect of botulinum toxin injections wanes with time in elderly patients, necessitating repeated injections to keep the patients symptom-free. Due to the required repeated injections this procedure is more expensive than endoscopic dilation.


Synthesis of 4-Deoxy-4-Fluoro-d-Sedoheptulose: A Promising New Sugar to Apply the Principle of Metabolic Trapping.
Fluorinated carbohydrates are important tools for understanding the deregulation of metabolic fluxes and pathways. Fluorinating specific positions within the sugar scaffold can lead to enhanced metabolic stability and subsequent metabolic trapping in cells. This principle has, however, never been applied to study the metabolism of the rare sugars of the pentose phosphate pathway (PPP). In this study, two fluorinated derivatives of d-sedoheptulose were designed and synthesized: 4-deoxy-4-fluoro-d-sedoheptulose (4DFS) and 3-deoxy-3-fluoro-d-sedoheptulose (3DFS). Both sugars are taken up by human fibroblasts but only 4DFS is phosphorylated. Fluorination of d-sedoheptulose at C-4 effectively halts the enzymatic degradation by transaldolase and transketolase. 4DFS thus has a high potential as a new PPP imaging probe based on the principle of metabolic trapping. Therefore, the synthesis of potential radiolabeling precursors for 4DFS for future radiofluorinations with fluorine-18 is presented.


Clinical Challenges in Primary Erythromelalgia: a Real-Life Experience from a Single Center and a Diagnostic-Therapeutic Flow-Chart Proposal.
Primary erythromelalgia (EM) is a rare clinical syndrome characterized by recurrent erythema, burning pain and warmth of the extremities. The symptoms greatly compromise the patients' quality of life leading to severe disability. SCN9A mutations can be the cause of the disease. Dermatologists are often the specialists these patients turn to for assistance. To describe the demographic and clinical characteristics of patients with primary EM, to assess the presence and mutation types in the SCN9A gene, to evaluate the effectiveness of several therapeutic approaches, and to propose a diagnostic algorithm with therapeutic implications. A monocentric retrospective study using the database of patients with a discharge diagnosis of primary EM of our Center. Demographic, clinical, instrumental and laboratory data of patients were reviewed. Eleven female patients (age range 16 to 57) were selected. All patients were affected in both the lower and upper extremities. Follow-up ranged from 2 to 9 years. Four patients had four different heterozygous variants of the SCN9A gene. Two patients, although genetically negative, had a suggestive family history. A variety of medications were tried in all our patients to alleviate symptoms, but their efficacy was variable, partial and/or transitory. The most effective therapies were antihistamines, venlafaxine, and mexiletine. The diagnosis and treatment of EM remain challenging. Patients with this condition display a wide spectrum of clinical manifestations and severity, as well as a paucity of resources and structures to support them. Mutations in the SCN9A gene are not always detected.


[Total Elbow Replacement - Implantation of the Latitude Prosthesis (Tornier)].
Due to technical progress, the indication for total elbow arthroplasty could be expanded in recent years. As a result, the demand regarding functionality and mobility of the replaced joint has risen as well. Elbow arthroplasty has to be considered as technically demanding. Only with detailed knowledge of this surgical procedure and its possible intraoperative pitfalls can one provide the best possible results. In this instructional video we explain the implantation of the Latitude elbow prosthesis (Tornier) putting emphasis on the correct approach as well as implantation of the prosthesis and subsequent wound closure.


Functional changes of apparent diffusion coefficient during visual stimulation investigated by diffusion-weighted gradient-echo fMRI.
The signal source of apparent diffusion coefficient (ADC) changes induced by neural activity is not fully understood. To examine this issue, ADC-fMRI in response to a visual stimulus was obtained in isoflurane-anesthetized cats at 9.4 T. A gradient-echo technique was used for minimizing the coupling between diffusion and background field gradients, which was experimentally confirmed. In the small b-value domain (b=5 and 200 s/mm2), a functional ADC increase was detected at the middle of the visual cortex and at the cortical surface, which was caused mainly by an increase in cerebral blood volume (CBV) and inflow. With higher b-values (b=200 and 1000-1200 s/mm2), a functional ADC decrease was observed in the parenchyma and also at the cortical surface. Within the parenchyma, the ADC decrease responded faster than the BOLD signal, but was not well localized to the middle of visual cortex and almost disappeared when the intravascular signal was removed with a susceptibility contrast agent, suggesting that the decrease in ADC without contrast agent was mostly of vascular origin. At the cortical surface, an average ADC decrease of 0.5% remained after injection of the contrast agent, which may have arisen from a functional reduction of the partial volume of cerebrospinal fluid. Overall, a functional ADC change of tissue origin could not be detected under our experimental conditions.


Paraganglioma of urinary bladder wall.
A classic case of pheochromocytoma of the urinary bladder is presented. The history of headaches and palpitations during micturition is the result of sudden release of catecholamines into the general circulation. The diagnosis using selective arteriography as well as the medical and surgical management are described.


Do age and social relations moderate the relationship between self-rated health and mortality among adult Danes?
It is well established that self-rated health (SRH) predicts mortality even after controlling for a wide range of factors. We explored the extent to which age and social relations (structural and functional) influenced the relationship between SRH and mortality (after 13 years follow-up) in a representative sample of adult Danes (N=6693). After controlling for socioeconomic status, illness, and lifestyle variables, we found that age moderated the SRH-mortality relationship such that it was present for respondents under 55 but absent for respondents over 56. In addition, weaker structural (but not functional) social relations increased mortality directly but neither structural nor functional social relations moderated the SRH-mortality relationship. We discuss the theoretical and practical implications of these findings.


[Mortality in patients with osteolysis of lymphatic origin: a review of the experience with 54 patients and the literature].
Osteolysis of lymphatic origin is a rare disease with a high mortality which is difficult to attribute whether it is due to the disease itself or the therapeutic morbidity. The aim of this study is to review the causes of mortality in our group of patients with osteolysis of lymphatic origin, compared with the group of patients previously reported in the medical literature. We reviewed all patients with osteolysis of lymphatic origin and treated in our department who had died in the last 15 years, and we reviewed all published cases of death with this disease since the 1950's. A total of 57 patients with osteolysis of lymphatic origin had been studied at our institution, of whom three died, two from sepsis, and one from acute respiratory distress syndrome. All of them suffered severe malnutrition from massive lymphatic loss and 2 had bilateral chylothorax. Among the 51 cases reviewed in the literature between 1954 - 2010, 19 had bilateral chylothorax, 15 had right side involvement and only 2 had an exclusive left chylothorax. Eleven patients had complications, such as respiratory distress and pneumonia. Ten of them suffered from pathological fractures, and 10 from chylopericardium and/or chylous ascites. The most common cause of death was respiratory failure in 25 patients, followed by pneumonia and sepsis. The publications do not specify the ultimate cause of respiratory failure. Patients with severe osteolysis of lymphatic origin suffer three main disorders with overlapping comorbidity: the lymphatic malformation of soft tissue, the bone resorption and the chylothorax. While mortality in the first two is exceptional, the mortality of the chylothorax is common, especially when it is bilateral and does not respond to different therapies. Respiratory failure and infection are aggravated by immunosuppression, malnutrition and the non-restrictive use of central catheters. Unlike respiratory failure, which is difficult to control after the failure of medical and surgical treatment, morbidity from infections can be reduced through careful nutritional support, rational antibiotic prophylaxis and a reduction to a minimum in the use of central catheters and total parenteral nutrition.