Impact of invasion into cervical esophagus for patients with hypopharyngeal squamous cell carcinoma.
The invasion into cervical esophagus (ICE) sometimes could be encountered in patients with hypopharyngeal squamous cell carcinoma (HypoSCC). However, the incidence, predictive factors, and prognostic impact of ICE on the patients with HypoSCC remain unclear. Patient diagnosis with HypoSCC at the National Taiwan University Hospital between January 2007 and December 2018 were reviewed. All patients were classified into two groups: with and without ICE. The curative treatment included upfront laryngectomy or pharyngo-laryngo-esophagectomy (PLE) with adjuvant chemoradiation, or definite organ-sparing chemoradiation. We analyzed 527 HypoSCC patients, 71 (13.47%) with and 456 (86.53%) without ICE. ICE presented more frequently in females (odds ratio (OR) = 3.01, p = 0.03) and posterior pharyngeal wall (OR = 2.34, p = 0.04). The 5-year disease-free survival of patients with and without ICE were 21.7% and 54.1%, respectively (p < 0.0001) and the 5-year overall survival were 13.1% and 53.8%, respectively (p < 0.0001). Among patients with ICE, the disease-free and overall survival of patients with upfront PLE were worse than the patients without upfront PLE (p = 0.21 and p = 0.27, respectively). After multivariant cox analysis, ICE was an independent risk factor for disease-free survival (p < 0.001) and overall survival (p < 0.001). ICE was occasionally present (13.47%) in HypoSCC patients. Unfortunately, the presence of ICE had a significant impact on disease-free and overall survival. For the HypoSCC patients with ICE, organ-sparing chemoradiation should be considered first as upfront PLE had no additional benefit.


Nutritional assessment and management in hospitalised patients: implication for DRG-based reimbursement and health care quality.
Malnutrition is associated with a higher morbidity resulting in an increased need for medical resources and economic expenses. In order to ensure sufficient nutritional care it is mandatory to identify the effect of malnutrition and nutritional care on direct cost and reimbursement. The primary aim of this study was to evaluate the economic effect of a nutritional screening procedure on the identification and coding of malnutrition in the G-DRG system. All G-DRG relevant parameters of 541 consecutive patients at a gastroenterology ward were documented. Moreover, all patients were screened for malnutrition by a dietician according to the subjective global assessment (SGA). Patients were then grouped into the appropriate G-DRG and the effective cost weight (CW) was calculated. Ninety-two of 541 patients (19%) were classified malnourished (SGA B or C). Recognition of malnutrition increase from 4% to 19%. Malnourished patients exhibited a significantly increased length of hospital stay (7.7+/-7 to 11+/-9, P<0.0001). In 26/98 (27%) patients, the coding of malnutrition was considered relevant by grouping and resulted in a rise of DRG benefit. Mean case mix value and patients' complexity and comorbidity level (PCCL) increased after including malnutrition in the codification (CV 1.53+/-2.9 to 1.65+/-2.9, P=0.001 and PCCL 2.69+/-1.4 to 3.47+/-0.82, P<0.0001). The reimbursement increase by 360/malnourished patient or an additional reimbursement of 35280 (8.3% of the total reimbursement for all patients of 423186). Nutritional support in a subgroup of 50 randomly selected patients resulted in additional costs of 10268 . Forty-four of these patients (86%) were classified malnourished (32 SGA B and 12 SGA C). However, the subsequent reimbursement covered only approximately 75% of the expenses (7869), but did not include the potential financial benefits resulting from clinical interventions. Malnourished patients can be detected with a structured assessment and documentation of nutritional status and this is partly reflected in the G-DRG/ICD 10 system. In addition to increasing direct health care reimbursement, nutritional screening and intervention has the potential to improve health care quality.


Photodynamic therapy and Acyclovir in the treatment of recurrent herpes labialis: A controlled randomized clinical trial.
Herpes Simplex Virus Type 1 (HSV-1) is one of the most widespread infections that can effect the orofacial region. Recurrent infection is considered a life-long oral health problem, leading to pain, discomfort, and social restriction due to esthetic features when active. Effective therapies are needed. This study aimed to compare photodynamic therapy (PDT), Topical Acyclovir (AC), and the association of both in the healing process and self-reported symptomologies of HSV-1 recurrences. Patients were randomly assigned into 3 groups (n = 25): PDT (low-power laser, 660 nm, 40 mW, 120 J/cm2, 4.8 J, 120 s per point) and methylene blue (0.005 %) as photosensitizer; AC (5%); PDT + AC.Data concerning lesion size, healing time, and self-reported healing parameters, such as pain, tingling, and edema were taken every day up to complete healing for all studied groups. There was no significant difference in healing time and pain between groups. AC group showed a significant minor reduction of the lesion compared to the AC-PDT group on day 1. Regarding edema and tingling, the comparison of treatments showed a statistical difference only on day 1, where PDT showed better results. With all the limitations of this study, it can be concluded that only on day 1 PDT showed positive effects in the treatment of herpes lesions in comparison to AC.


Construction of an anti-hepatitis B virus preS1 antibody and usefulness of preS1 measurement for chronic hepatitis B patients: Anti-HBV PreS1 antibody.
The preS1 region plays an essential role in hepatitis B virus (HBV) infection. We construct an antibody that binds to preS1 and a measurement system for serum preS1 in chronic HBV-infected patients. Hybridoma clones that produce anti-preS1 antibodies were obtained by the iliac lymph node method. Epitope mapping was conducted, and an enzyme-linked immunosorbent assay (ELISA)-based method was developed. Using this ELISA system, serum preS1 levels were measured in 200 chronic HBV-infected patients. Eight types of hybridomas were obtained, of which antibody 3-55 using amino acids 38-47 as the epitope showed high binding affinity to preS1. Serum preS1 levels measured by ELISA using 3-55 antibody were correlated with HBsAg, HBcrAg and HBV DNA levels. Among HBeAg-negative patients without antiviral therapeutic objective (HBV DNA <3.3 log IU/mL or alanine aminotransferase ≤30 U/L), preS1 was significantly higher in subjects who had progressed to the point of requiring antiviral therapy compared to subjects who had maintained their status for the preceding three years (p<0.01). We constructed an antibody against preS1 and an ELISA system capable of measuring serum preS1 levels. PreS1 may serve as a novel tool to predict the need for antiviral therapy in HBeAg-negative HBV-infected patients.


Preliminary study of contrast-enhanced harmonic endosonography with second-generation contrast agents.
We developed a novel echoendoscope that enables contrast harmonic imaging using ultrasound contrast agents and performed contrast-enhanced harmonic endosonography (EUS) both in vitro and in vivo. An experimental convex-array echoendoscope equipped with a wideband transducer and a specific mode for contrast harmonic imaging was used. A Doppler phantom model was employed in in vitro experiments to determine the optimal mechanical indices for contrast harmonic imaging by the echoendoscope. In the in vivo experiments, the echoendoscope was inserted into the stomachs of dogs. The digestive organs were observed after intravenous infusion of a contrast agent, Definity, using contrast-enhanced harmonic EUS. Two patients, one with pancreatic carcinoma and one with a gastrointestinal stromal tumor (GIST), underwent contrast-enhanced harmonic EUS. In vitro experiments revealed that the optimal mechanical indices were 0.35-0.40 for intermittent imaging and 0.30 or less for real-time imaging. In the in vivo experiments, branching vessels and subsequent homogeneous distribution of the signal in the pancreatic tissue were observed. During clinical application, typical vascular patterns were observed in pancreatic carcinoma and a GIST. Contrast-enhanced harmonic EUS visualized parenchymal perfusion and the fine vascular structure in digestive organs and should be a useful and powerful method for clinical investigations.


Triazolyl phenyl disulfides: 8-Amino-7-oxononanoate synthase inhibitors as potential herbicides.
The chemical validation of a potential herbicide target was investigated with 8-amino-7-oxononanoate synthase (AONS, also known as 7-keto-8-aminopelargonate synthase, KAPAS) and triazolyl phenyl disulfide derivatives in vitro and in vivo. AONS activity was completely inhibited by these synthesized compounds, with an IC50 of 48 to 592μM in vitro. Forty five-day old Arabidopsis thaliana plants were completely killed by representative compound KHG23844 {N-(2-fluorophenyl)-3-(phenyldisulphanyl)-1H-1,2,4-triazole-1-carboxamide} at the application rate of 250gha(-1) of foliar treatment in greenhouse conditions. Foliar application of 1000gha(-1) KHG23844 induced 2.3-fold higher l-alanine accumulation in the treated A. thaliana plants. Foliar supplement of 1mM biotin at 1 and 2days before KHG23844 application effectively recovered the growth inhibition of A. thaliana plant treated with KHG23844. The results strongly suggested that representative compound KHG23844 and its derivatives are potential AONS inhibitors.


Influence of different hypoxia models on metastatic potential of SGC-7901 gastric cancer cells.
Gastric cancers are one of the most common gastrointestinal tumors with proclivity to metastasis. Hypoxia is an important feature in solid tumor microenvironment; accumulating evidence suggests that chronic and repetitive exposure to hypoxia and reoxygenation seems to provide an advantage to tumor growth. However, mechanisms of intermittent hypoxia regulating gastric cancer metastatic potential remain to be elucidated. In the present study, we established the continuous and intermittent gastric cancer hypoxia models, and we compared the effects of these models on gastric cancer cell metastatic potential. Hypoxia-inducible factor-1α (HIF-1α) and hypoxia target protein/genes expression in response to different hypoxia models were analyzed by Western blot, immunofluorescence, and real-time PCR assays. Gastric cancer cell migration and invasion ability were analyzed by wound healing and Boyden chamber assay. Colony formation and tumor spheroid formation assays were used to assess the ability of self-renewal. Stem-related protein OCT4 and HIF-1α expression were also analyzed by confocal immunofluorescence in single tertiary generation spheroid. We demonstrated that the intermittent hypoxia model upregulated expression of both HIF-1α and hypoxia target protein/genes in a time-dependent manner compared with that of SGC-7901 cells cultured under normoxia. Remarkably, HIF-1α protein was more prone to being located in the nucleus of SGC-7901 cells under conditions of intermittent hypoxia. Gastric cancer cells' migration and invasion ability were significantly enhanced after hypoxic culture; moreover, intermittent hypoxia-conditioned SGC-7901 cells exhibited higher invasiveness than the continuous hypoxia-conditioned SGC-7901 cells. Gastric cancer stem/progenitor cell subpopulation was also enlarged which indicated an enhanced self-renewal ability in hypoxic cultured SGC-7901 cells. Our study emphasizes the significance of hypoxia in regulating gastric cancer cell metastasis potential. Compared with continuous hypoxia, intermittent hypoxia is a more effective and potent hypoxic stimulus. These results provide a new insight to investigate the hypoxic microenvironment within solid tumors.


Inhibition of the transport of adenosine, other nucleosides and hypoxanthine in novikoff rat hepatoma cells by methylxanthines, papaverine, N6-cyclohexyladenosine and N6-phenylisopropyladenosine.
Theophylline, caffeine, isobutylmethylxanthine, papaverine, N6-cyclohexyladenosine, N6-allyl-N6-cyclohexyladenosine ( ACHA ) and N6-L-phenylisopropyladenosine (L-PIA) inhibited the transport of adenosine, uridine and hypoxanthine in Novikoff rat hepatoma cells. The IC50 values for the inhibition of uridine transport ranged from 5 microM for ACHA to 3200 microM for caffeine and were inversely proportional to the lipid solubility of the inhibitors. L-PIA and papaverine inhibited uridine influx in a non-competitive manner, having a greater influence on the Michaelis-Menten constant than on maximum velocity, just as observed previously for the inhibition of nucleoside transport by dipyridamole and hypoxanthine. [3H]L-PIA rapidly accumulated in Novikoff cells at 25 degrees to about five times higher levels than present extracellularly. The initial rates of L-PIA uptake were directly proportional to its extracellular concentration between 0.01 and 240 microM and not affected by structurally related analogs, methylxanthines, papaverine, dipyridamole, or 2 mM uridine, but were dependent on temperature. We conclude that L-PIA inhibits nucleoside transport in these cells without being significantly transported by the carrier, that it equilibrates rapidly across the plasma membrane without carrier mediation consistent with its lipophilicity, and that it accumulates concentratively in cells due to partitioning into membrane lipids and binding to intracellular components.


Mal3, the fission yeast EB1 homologue, cooperates with Bub1 spindle checkpoint to prevent monopolar attachment.
Bipolar microtubule attachment is central to genome stability. Here, we investigate the mitotic role of the fission yeast EB1 homologue Mal3. Mal3 shows dynamic inward movement along the spindle, initial emergence at the spindle pole body (SPB) and translocation towards the equatorial plane, followed by sudden disappearance. Deletion of Mal3 results in early mitotic delay, which is dependent on the Bub1, but not the Mad2, spindle checkpoint. Consistently, Bub1, but not Mad2, shows prolonged kinetochore localization. Double mutants between mal3 and a subset of checkpoint mutants, including bub1, bub3, mad3 and mph1, but not mad1 or mad2, show massive chromosome mis-segregation defects. In mal3bub1 mutants, both sister centromeres tend to remain in close proximity to one of the separating SPBs. Further analysis indicates that mis-segregated centromeres are exclusively associated with the mother SPB. Mal3, therefore, has a role in preventing monopolar attachment in cooperation with the Bub1/Bub3/Mad3/Mph1-dependent checkpoint.


[Chronic rhinosinusitis with septal perforation. Differential diagnostic considerations].
Chronic rhinosinusitis together with nasal septal perforation with or without pain of the nasal skeleton and without previous trauma or surgery point toward the possible diagnosis of Wegener's granulomatosis. However, nasal biopsy and serologic testing remain inconclusive in many patients. The otolaryngologist's role in this situation is to initiate, in close cooperation with a rheumatologist, therapy with sulfatrimethoprim, as well as with immunosuppressants if necessary. This helps stabilize the symptomatology and may prevent progressive systemic disease.


Robotic surgery in Hirschsprung disease: a unicentric experience on 31 procedures.
Robotic surgery has been increasingly applied to Hirschsprung patients with encouraging results. We report the results of a 5 year unicentric experience. All consecutive HSCR patients older than 12 months who underwent a surgical procedure with robotic approach between September 2017 and August 2022 were prospectively included. We collected data regarding demographics, extent of aganglionosis, associated anomalies, indications to surgery, and a number of perioperative data such as surgical details, intraoperative and perioperative complications, length of surgery, length of hospital stay, and functional outcome. A total of 28 patients underwent 31 robotic procedures during the study period. Median age at surgery was 82 months. Eleven primary Totally Robotic Soave Pull-Through, 12 redoes, 5 innervative mapping, 2 redundant rectal pouch excision, and 1 Miles' procedures have been performed. Median console time was 145 min. No conversion to either laparoscopy nor to laparotomy was required. Median length of hospital stay was 6 days. Two patients experienced complications requiring reiterative surgery. One patient experienced mild postoperative enterocolitis. Normal continence was achieved by 70% of patients after a median of 16 months postoperatively (80% for primary pull-throughs, 55% for redoes). To conclude, robotic surgery for older HSCR patients proved to be feasible, safe, and effective. Patients with complex surgical requirements seem to benefit most from this promising approach. Provided the economic burden is addressed and solved, robotic surgery will represent an excellent alternative for the surgical treatment of HSCR patients.


Contour-based lung shape analysis in order to tuberculosis detection: modeling and feature description.
Statistical shape analysis of lung is a reliable alternative method for diagnosing pulmonary diseases such as tuberculosis (TB). The 2D contour-based lung shape analysis is investigated and developed using Fourier descriptors (FDs). The proposed 2D lung shape analysis is carried out in threefold: (1) represent the normal and the abnormal (i.e. pulmonary tuberculosis (PTB)) lung shape models using Fourier descriptors modeling (FDM) framework from chest X-ray (CXR) images, (2) estimate and compare the 2D inter-patient lung shape variations for the normal and abnormal lungs by applying principal component analysis (PCA) techniques, and (3) describe the optimal type of contour-based feature vectors to train a classifier in order to detect TB using one publicly available dataset-namely the Montgomery dataset. Since almost all of the previous works in lung shape analysis are content-based analysis, we proposed contour-based lung shape analysis for statistical modeling and feature description of PTB cases. The results show that the proposed approach is able to explain more than 95% of total variations in both of the normal and PTB cases using only 6 and 7 principal component modes for the right and the left lungs, respectively. In case of PTB detection, using 138 lung cases (80 normal and 58 PTB cases), we achieved the accuracy (ACC) and the area under the curve (AUC) of 82.03% and 88.75%, respectively. In comparison with existing state-of-art studies in the same dataset, the proposed approach is a very promising supplement for diagnosis of PTB disease. The method is robust and valuable for application in 2D automatic segmentation, classification, and atlas registration. Moreover, the approach could be used for any kind of pulmonary diseases. Graphical abstract Contour-based lung shape analysis in order to detect tuberculosis: modeling and feature description.


Increasing incidence of diabetes mellitus in Norwegian children 0-14 years of age 1973-1982.
A retrospective technique was used to register all newly diagnosed cases of diabetes mellitus in Norwegian children 0-14 years of age during the ten-year period 1973-1982. A total of 1,914 newly diagnosed cases were detected, from an average population of 932,037 children. The degree of ascertainment was near to 99%. The male incidence exceeded the female incidence by 12% (p less than 0.02). The mean yearly incidence for the ten-year period was 20.5 per 100,000. Comparing the two five-year periods 1973-1977 and 1978-1982, the mean yearly incidence increased from 18.5 to 22.7 per 100,000 (p less than 0.0001). There was a marked geographic variation with the highest incidence in the south-east and lower incidence in the northern part of the country. However, in the northern part of the country, there was a remarkable increase of the annual incidence from the first to the second five-year period (12.9 vs 19.3 per 100,000). The highest numbers of new cases were detected in the months of January and October, and the lowest numbers in May and July. The seasonal pattern was significantly different from a uniform distribution of new cases throughout the year (p less than 0.001). The age-specific incidence increased towards a peak at 12 years for both sexes. In conclusion, Norway has a high and apparently increasing incidence of childhood diabetes. The geographic variation and secular trend present challenging clues for a search of etio-pathogenic factors.


Mycoplasma pneumonia Infection: A Possible Trigger for Immune Thrombocytopenia.
Mycoplasma pneumonia (M. pneumonia) is usually not considered among the several pathogens that induce immune thrombocytopenia (ITP). We report a child with a clinical diagnosis of severe ITP that was associated with M. pneumonia pneumonia, and review the few cases described in the English literature. We suggest that thrombocytopenia associated with M. pneumonia infection may constitute a subset of ITP, although unlike ITP it occurs concomitantly with the infection and tends to be more severe than "classic" ITP. We recommend that prompt specific antibiotic and immune modulating treatment should be initiated in appropriate clinical settings.


Colour matching of isoluminant samples and backgrounds: a model.
A cone-opponent-based vector model is used to derive the activity in the red-green, yellow-blue, and achromatic channels during a sequential asymmetric colour-matching experiment. Forty Munsell samples, simulated under illuminant C, were matched with their appearance under eight test illuminants. The test samples and backgrounds were photometrically isoluminant with each other. According to the model, the orthogonality of the channels is revealed when test illuminants lie along either red-green or yellow blue cardinal axes. The red green and yellow-blue outputs of the channels are described in terms of the hue of the sample. The fact that the three-channel model explains the data in a colour-matching experiment indicates that an early form of colour processing is mediated at a site where the three channels converge, probably the input layer of V1.


Proteasome inhibitor MG132 induces selective apoptosis in glioblastoma cells through inhibition of PI3K/Akt and NFkappaB pathways, mitochondrial dysfunction, and activation of p38-JNK1/2 signaling.
Proteasome inhibitors are emerging as a new class of anticancer agents. In this work, we examined the mechanisms underlying cytotoxicity, selectivity and adjuvant potential of the proteasome inhibitor MG132 in a panel of glioblastoma (GBM) cells (U138MG, C6, U87 and U373) and in normal astrocytes. MG132 markedly inhibited GBM cells growth irrespective of the p53 or PTEN mutational status of the cells whereas astrocytic viability was not affected, suggesting a selective toxicity of MG132 to cancerous glial cells. Mechanistically, MG132 arrested cells in G2/M phase of the cell cycle and increased p21(WAF1) protein immunocontent. Following cell arrest, cells become apoptotic as shown by annexin-V binding, caspase-3 activation, chromatin condensation and formation of sub-G1 apoptotic cells. MG132 promoted mitochondrial depolarization and decreased the mitochondrial antiapoptotic protein bcl-xL; it also induced activation of JNK and p38, and inhibition of NFkappaB and PI3K/Akt survival pathways. Pre-treatment of GBMs with the mitochondrial permeability transition pore inhibitor, bongkrekic acid, or pharmacological inhibitors of JNK1/2 and p38, SP600125 and SB203580, attenuated MG132-induced cell death. Besides its apoptotic effect alone, MG132 also enhanced the antiglioma effect of the chemotherapeutics cisplatin, taxol and doxorubicin in C6 and U138MG cells, indicating an adjuvant/chemosensitizer potential. In summary, MG132 exerted profound and selective toxicity in GBMs, being a potential agent for further testing in animal models of the disease.


Reducing methane emissions and the methanogen population in the rumen of Tibetan sheep by dietary supplementation with coconut oil.
The objective was to evaluate the effect of dietary coconut oil on methane (CH(4)) emissions and the microbial community in Tibetan sheep. Twelve animals were assigned to receive either a control diet (oaten hay) or a mixture diet containing concentrate (maize meal), in which coconut oil was supplemented at 12 g/day or not for a period of 4 weeks. CH(4) emissions were measured by using the 'tunnel' technique, and microbial communities were examined using quantitative real-time PCR. Daily CH(4) production for the control and forage-to-concentrate ratio of 6:4 was 17.8 and 15.3 g, respectively. Coconut oil was particularly effective at reducing CH(4) emissions from Tibetan sheep. The inclusion of coconut oil for the control decreased CH(4) production (in grams per day) by 61.2%. In addition, there was a positive correlation between the number of methanogens and the daily CH(4) production (R = 0.95, P < 0.001). Oaten hay diet containing maize meal (6:4) plus coconut oil supplemented at 12 g/day decreases the number of methanogens by 77% and a decreases in the ruminal fungal population (85-95%) and Fibrobacter succinogenes (50-98%) but an increase in Ruminococcus flavefaciens (25-70%). The results from our experiment suggest that adding coconut oil to the diet can reduce CH(4) emissions in Tibetan sheep and that these reductions persist for at least the 4-week feeding period.


PURL: Time to stop glucosamine and chondroitin for knee OA?
Prior studies provided conflicting results regarding the efficacy of these medications. This study offers evidence for discontinuing them.


Aberrant lipid metabolism in cancer cells - the role of oncolipid-activated signaling.
Metabolic activity of malignant cells is very different from that of their nontransformed equivalents, which establishes metabolic reprogramming as an important hallmark of every transformed cell. In particular, the current arena of research in this field aims to understand the regulatory effect of oncogenic signaling on metabolic rewiring in transformed cells in order to exploit this for therapeutic benefit. Alterations in lipid metabolism are one of the main aspects of metabolic rewiring of transformed cells. Up-regulation of several lipogenic enzymes has been reported to be a characteristic of various cancer types. Lysophosphatidic acid (LPA), a simple byproduct of the lipid biosynthesis pathway, has gained immense importance due to its elevated level in several cancers and associated growth-promoting activity. Importantly, a current study revealed its role in increased de novo lipid synthesis through up-regulation of sterol regulatory element-binding protein 1, a master regulator of lipid metabolism. This review summarizes the recent insights in the field of oncolipid LPA-mediated signaling in regard to lipid metabolism in cancers. Future work in this domain is required to understand the up-regulation of the de novo synthesis pathway and the role of its end products in malignant cells. This will open a new arena of research toward the development of specific metabolic inhibitors that can add to the pre-existing chemotherapeutics in order to increase the efficacy of clinical output in cancer patients.


Identification and characterization of U1 small nuclear RNA genes from two crustacean isopod species.
Four different units containing three variants of the U1 snRNA gene have been identified in the genome of Asellus aquaticus and only one unit has been identified in the genome of Proasellus coxalis. All four identified U1 snRNA genes can be folded according to the proper secondary structure and possess the functionally useful conserved sequences. Moreover, in the 3 flanking regions, all genes present both the 3 box, a conserved sequence required for 3 processing of mature snRNA, and a polyadenylation signal which is unusual for these genes. The PCR products were used as probes in fluorescent in-situ hybridization (FISH) experiments to locate them on chromosomes of A. aquaticus and P. coxalis.


Aerobic and lung performance in premature children with and without chronic lung disease of prematurity.
This study intended to identify pulmonary and exercise-related effects of chronic lung disease of infancy (CLD) versus prematurity (PRE) without CLD in children 5 to 7 years old who were born prematurely (24-30 weeks of gestation) with very low and extremely low birthweight of 500 to 1500 g (VLBW, ELBW). Seventeen CLD and 14 PRE were compared with 24 term controls (CON). The premature children had no overt manifestations of a neuromuscular disease. Pulmonary function at rest and following exercise, and aerobic exercise performance were measured. Peak [latin capital V with dot above]O2 and maximal aerobic power were not different among the groups, but O2 uptake at a given mechanical power was higher in the CLD than in PRE and in CON (P < 0.05). At rest, forced vital capacity was significantly lower in CLD than in PRE (P < 0.05) and CON (P < 0.0005), and FEV1 and FEF25-75 were lower in CLD than CON (P < 0.0005 and P < 0.005, respectively). Exercise-induced bronchoconstriction (EIB) was more prevalent among the 2 premature groups (P < 0.05). Our children 5 to 7 years old born at VLBW or ELBW, with or without CLD, have some degree of pulmonary dysfunction at rest and following exercise and a higher prevalence of EIB with no reduction in maximal aerobic exercise performance. The findings suggest that the pulmonary limitations are associated with low birthweight even in the absence of CLD. The higher O2 uptake at a given mechanical power in the CLD group may cause early fatigability during prolonged exercise, even when aerobic performance is normal.


Bilingualism as a risk factor for false reports of stuttering in the Early Childhood Longitudinal Study (ECLS-K:2011).
Bilingualism has historically been claimed to be a risk factor for developmental stuttering. The Early Childhood Longitudinal Study, Kindergarten Class of 2010-11 (ECLS-K:2011) ostensibly contains evidence to test that claim. We analyze data from monolingual and bilingual children in Kindergarten through fifth grade in the ECLS-K:2011. The prevalence, male/female ratio, and onset and recovery of reported stuttering in the ECLS are inconsistent with widely-accepted clinical reports of stuttering. We argue that the reported figures may be misleading. We discuss some factors that may inflate the reported prevalence, including a lack of awareness of the difference between stuttering vs. normal disfluencies, and the informal usage of the word "stuttering" on the part of teachers and parents to describe typical disfluencies.


[Treatment of prostate cancer using high-intensity focused ultrasound, literature review.]
The treatment of prostatecancer has recently been questioned because ofthe adverse effects it causes may out weigh the benefitsin many patients, so, it has increased interest in active surveillance for low-risk diseases and tissue preservation with focal therapy, thereby reducing the burden on medical care and side effects that may occur after radical prostatectomy and radiation therapy. provide updated information on the treatment of prostate cancer with high intensity focused ultrasound therapy. Bibliographic reviewstudy and systematic analysis of 27 scientific articlesfound in the Medline, Scielo and PubMed databases, whose publication dates correspond to the last 5 years.The search criteria used consisted of terms: prostatic neoplasms, ablation techniques, high-intensity focused ultrasound ablation. Focal therapy is a therapeutic option forlow-risk prostate cancer, clinical studies report a 75% cancer-free survival, 99% cancer-specific survival and 96% metastasis-free survival, the prostate antigen is maintained at values lower than 0.1 ng/ml in long-term controls, while the adverse effects of surgery such as incontinence and sexual impotence are rare. HIFU is a less invasive option for the treatment of low-risk prostate cancer, with oncological results similar to radiotherapy and radical prostatectomy.


Dexfenfluramine, fluoxetine, and weight loss among female carbohydrate cravers.
The consumption of excess calories as carbohydrates (CHO)-rich, protein-poor snacks characterizes the overeating of obese CHO cravers, premenstrual women, patients with Seasonal Affective Disorder, and former smokers. This specific appetite for CHOs may involve brain serotonin, as the synthesis and release of this neurotransmitter can increase following consumption of CHO-rich foods. To examine whether weight loss produced by serotoninergic drugs involves a selective reduction in CHO intake, obese females who consumed at least 30% of their daily calories from CHO-rich snacks were treated with dexfenfluramine ([DF] 15 mg b.i.d.); fluoxetine ([FL] 20 mg t.i.d.); or placebo (PL) for 12 weeks. Weekly weight loss for 25 of 29 PL completers was 0.22 kg +/- 0.06 (mean +/- SEM); for 21 of 28 DF completers, 0.56 +/- 0.08 kg; and for 18 of 30 FL completers, 0.58 +/- 0.09 kg (PL < DF = FL; p = .039). Seven FL subjects, 2 PL subjects, and 1 DF subject withdrew from the study due to side effects; other withdrawals were due to intercurrent illness or personal problems. Prior to treatment, subjects consumed over 40% of their daily CHO intake from snacks. Both of the drugs selectively decreased CHO snack intake (p < 0.05); DF, but not FL, also decreased meal CHO intake (p < .025). These results suggest that weight loss following treatment with serotoninergic drugs may relate to a selective decrease in CHO appetite.


Effect of head positioning on intracranial blood flow velocities in acute ischemic stroke: a pilot study.
Current nursing practice for the care of patients with ischemic stroke advocates routine elevation of the head of the bed (HOB) to 30 degrees. Evidence supporting this practice is lacking, and it may reflect inappropriate generalization of findings from studies conducted primarily on traumatic brain injury patients with associated increased intracranial pressure to the ischemic stroke population. We used a repeated measures design to conduct a pilot study of the effect of three HOB positions on middle cerebral artery mean flow velocities (MCA-MFV) in patients with acute ischemic stroke. Transcranial Doppler (TCD) sonography was used to measure MCA-MFV. Eleven patients were enrolled in the study; the mean age of the sample was 60 years, and the mean National Institutes of Health Stroke Scale score was 8.7. On average, a 9.2% increase in MCA-MFV was measured when the HOB was lowered to 15 degrees from the 30 degrees elevation standard (p = .02); MCA-MFV increased on average by 3.9% when the HOB was again lowered from the 15 degrees position to the 0 degrees (flat) position (p = not significant). Mean arterial pressure, heart rate, and pulse pressure remained stable without significant change throughout the positioning intervention and measurement period. The overall increase in MCA-MFV achieved from lowering the HOB position from 30 degrees to a flat position was 13.1% (p = .054). Our findings from this small sample suggest that patients with acute ischemic stroke may benefit from lower HOB positions, in particular flat positioning, to promote an increase in flow to ischemic brain tissue that may ultimately reduce brain infarct volume.


Nitrosative stress induced by homocysteine thiolactone drives vascular cognitive impairments via GTP cyclohydrolase 1 S-nitrosylation in vivo.
s: Hyperhomocysteinemia (HHcy) is one of risk factors for vascular cognitive impairment (VCI). GTP cyclohydrolase 1 (GCH1) deficiency is critical to oxidative stress in vascular dysfunction. The aim of this study was designed to examine whether HHcy induces VCI through GCH1 S-nitrosylation, a redox-related post-translational modification of cysteine. The VCI model was induced by feeding mice homocysteine thiolactone (HTL) for 16 consecutive weeks. The cognitive functions were evaluated by step-down avoidance test, passive avoidance step-through task test, and Morris water maze (MWM) test. Protein S-nitrosylation was assayed using a biotin-switch method. In cell-free system, nitric oxide (NO) donor induced GCH1 protein S-nitrosylation and decreased GCH1 activity. In endothelial cells, HTL increased GCH1 S-nitrosylation, reduced tetrahydrobiopterin, and induced oxidative stress, which were attenuated by N-acetyl-cysteine, L-N6-1-Iminoethyl-lysine, mutant of GCH1 cysteine 141 to alanine (MT-GCH1) or gene deletion of inducible NO synthase (iNOS). Further, HTL incubation or iNOS overexpression promoted endothelial cellular senescence, but abolished by exogenous expression of MT-GCH1 or pharmacological approaches including N-acetyl-cysteine, L-sepiapterin, and tempol. In wildtype mice, long-term administration of HTL induced GCH1 S-nitrosylation and vascular stiffness, decreased cerebral blood flow, and damaged the cognitive functions. However, these abnormalities induced by HTL administration were rescued by enforced expression of MT-GCH1 or gene knockout of iNOS. In human subjects, GCH1 S-nitrosylation was increased and cognitive functions were impaired in patients with HHcy. The iNOS-mediated nitrosative stress induced by HTL drives GCH1 S-nitrosylation to induce cerebral vascular stiffness and cognitive impairments.


Migration of intraocular silicone into the cerebral ventricles.
To report a case in which silicone oil in the eye migrated into the cerebral ventricles and the subarachnoid space. Observational case report. A 62-year-old woman presented with proliferative diabetic retinopathy and tractive retinal detachment in her left eye. Par plana vitrectomy and injection of 5,000-centistoke-viscosity silicone oil were performed. Intraocular pressure was elevated after the operation and poorly controlled for 4 months. Eight months after the first operation, the patient felt dizzy. Computed tomography (CT), magnetic resonance imaging (MRI), and optical coherence tomography (OCT) scanning were performed. The CT imaging, MRI, and OCT showed silicone oils migrated into the sella cistena superioris and the cerebral ventricles. Follow-up examination was continued. Although silicone oil migrating into the ventricles is unusual, we suggest that every patient undergoing silicone oil tamponade with poorly controlled high intraocular pressure and optic disk atrophy should be carefully evaluated.


Severe copper deficiency anemia caused by zinc supplement use.
Copper deficiency is an uncommon condition primarily affecting the hematologic and neurologic systems. We report a unique case of severe anemia in a patient with copper deficiency caused by zinc supplement use.


Laser-induced thermal desorption facilitates postsource decay of peptide ions.
We investigated the thermal mechanism involved in laser desorption/ionization (LDI) of thermally labile molecules from the flat surfaces of amorphous Si (a-Si) and crystalline Si (c-Si). a-Si was selected for this study because of its thermal property, such as low thermal conductivity; thus, it was predicted to be highly susceptible to laser-induced surface heating. By virtue of lack of surface nanostructures, the flat surfaces offer a simple model system to focus on the thermal mechanism, avoiding other effects, including possible non-thermal contributions that can arise from the physical existence of surface nanostructures. For the energetics study, the internal energies of substituted benzylpyridinium ions produced by LDI on the bare and coated surfaces of a-Si and c-Si were obtained using the survival yield method. The results, including LDI thresholds, ion yields, and internal energies all suggested that the LDI mechanism would be indeed thermal, which is most likely promoted by thermal desorption caused by laser-induced surface heating. In addition, the LDI process driven by laser-induced thermal desorption (LITD) was also found to be capable of depositing an excessive internal energy in resulting LDI ions, which underwent a dissociation. It exhibited the essentially same features as in postsource decay (PSD) in MALDI-TOF/TOF mass spectrometry. We report that the LDI process by LITD offers not only a way of intact ionization but also a facile means for PSD of peptide ions, which this work demonstrates is well suited to peptide sequencing using TOF/TOF mass spectrometry.


Cancer detection rates following enrolment in a disease management programme for type 2 diabetes.
Recent prospective studies found an elevated cancer risk shortly after diabetes diagnosis, and this was probably due to increased ascertainment. This study investigated whether site-specific cancer risks are also raised following enrolment in a disease management programme for type 2 diabetes mellitus (DMP-DM2). We linked records from a DMP-DM2 to population cancer registry data. The study period was from June 2003 to December 2009. Standardised incidence ratios (SIRs) were calculated for time intervals following DMP enrolment using the cancer incidence rates of the general source population. Additionally, Poisson regression with natural splines was used to assess time-dependent cancer incidence by diabetes duration. There were 2,034 first invasive cancer cases identified over 163,738 person-years of follow-up. Pancreatic cancer risk was significantly increased mainly in the first year after enrolment (SIR 1.62); the increment was only seen for patients in whom diabetes had been diagnosed less than 1 year before DMP-DM2 enrolment. Risk of endometrial cancer was similarly raised in the first year after DMP-DM2 enrolment among individuals newly diagnosed with diabetes but decreased rapidly thereafter. There was no time dependence in the incidence of cancers of the liver, lung, colon, breast and prostate. Enrolment in a DMP-DM2 did not appear to induce ascertainment bias for most cancers. Cancer risks were initially increased, especially for pancreatic cancer, potentially as a result of reverse causality. Ascertainment bias and time-dependent incidence of cancer appear to be less of a problem in settings using DMP-like structures for the study of the association between diabetes duration, glucose-lowering medication and cancer incidence.


Evaluation of the Association of Endometrial Thickness, Insulin Resistance, and Menstrual Patterns in Adolescent Females with Polycystic Ovarian Syndrome.
To evaluate endometrial stripe (EMS) thickness and its association with menstrual pattern and insulin resistance in adolescent females with or at risk for polycystic ovarian syndrome (PCOS) METHODS: This was a retrospective case-control study of adolescent females ranging between 12 and 21 years old evaluated in the Adolescent Gynecology & Endocrinology Clinic (AGEC) at a tertiary children's hospital between 2017 and 2021. Transabdominal pelvic ultrasound (US) was obtained for evaluation of PCOS or acute pelvic pain. Unadjusted comparisons were performed between imaging measurements in the PCOS and control (girls without PCOS with acute pelvic pain) groups, as well as analysis of the PCOS group adjusted for age, body mass index, race, and biochemical values. This study was approved by the Institutional Review Board. In our study, 54 subjects met the inclusion criteria for the PCOS group and 42 for the control group. EMS thickness was thinner in the PCOS group than in the control (0.55 ± 0.31 cm vs 0.70 ± 0.23 cm; P < .001). There was no difference in EMS thickness in the PCOS group when stratified by intermenstrual interval, insulin resistance, and other biochemical factors. Our findings support recommendations by the 2018 International Guidelines to avoid use of US for the establishment of PCOS diagnosis in adolescents. These results highlight the unique pathophysiology of adolescent PCOS in contrast to PCOS in adult women. Further large-scale prospective studies are needed to understand the role of EMS thickness as a prognostic marker in adolescent PCOS.


Patient perceptions of physical health and bipolar symptoms: The intersection of mental and physical health.
Affective symptoms and medical comorbidities have a negative impact on the course of bipolar disorder. The aim of this analysis was to examine how the perceptions of physical health and functioning in individuals with bipolar disorder relate to their mood symptoms. We analyzed longitudinal data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) on the physical subscales of the Short Form Health Survey (SF-36) (physical functioning, role limitations due to physical problems, bodily pain, and general health). Participants' perception of their overall physical health predicted severity of mania/hypomania, depression, and life satisfaction at concurrent and future visits. Perceptions of role limitations due to physical health problems predicted depressive symptoms and poor life satisfaction. Worse bodily pain predicted symptoms of mania/hypomania. Reports of specific or concrete physical limitations in daily life showed no associations with psychiatric symptoms at concurrent assessments, but did predict worse course of illness one year later. SF-36 scores showed significant, but small associations with the presence of medical comorbidities. Perceptions of physical health and quality of life were self-report, potentially lending themselves to transient negative biases, particularly among depressed participants. Additionally, the SF-36 was selected as a generic, widely used measure; as a result, it was not specific to the illness burden of bipolar disorder. Overall, broad perceptions of poor physical health were associated with worse course of illness over the 24 months of the study. Though further research is warranted, changes in subjective physical health related quality of life, even independent of objective health changes, may offer important insight into global wellbeing and be targets of psychotherapy treatment.


A case of isolated pure trigeminal motor neuropathy.
Isolated trigeminal neuropathy after cranial trauma is exceptional. A 40-year-old woman was found to have unilateral trigeminal motor paralysis with muscle atrophy, unaccompanied by sensory involvement and without affecting other cranial nerves. She developed this deficit immediately after head trauma.


Social diversity and access to healthcare in Europe: how does European Union's legislation prevent from discrimination in healthcare?
Social diversity can affect healthcare outcomes in situations when access to healthcare is limited for specific groups. Although the principle of equality is one of the central topics on the agenda of the European Union (EU), its scope in the field of healthcare, however, is relatively unexplored. The aim of this study is to identify and systematically analyze primary and secondary legislation of the EU Institutions that concern the issue of access to healthcare for various minority groups. In our research, we have concentrated on three features of diversity: a) gender identity and sexual orientation, b) race and ethnicity, and c) religion or belief. For the purpose of this analysis, we conducted a search of database Eur-Lex, the official website of European Union law and other public documents of the European Union, based on specific keywords accompanied by review of secondary literature. Relevant documents were examined with regard to the research topic. Our search covered documents that were in force between 13 December 2007 and 31 July 2019. Generally, the EU legal system prohibits discrimination on grounds of religion or belief, racial or ethnic origin, sex, and sexual orientation. However, with regard to the issue of non-discrimination in access to healthcare EU secondary law provides protection against discrimination only on the grounds of racial or ethnic origin and sex. The issue of discrimination in healthcare on the grounds of religion or belief, gender identity and sexual orientation is not specifically addressed under EU secondary law. The absence of regulations regarding non-discrimination in the EU secondary law in the area of healthcare may result from the division of competences between the European Union and the Member States. Reluctance of the Member States to adopt comprehensive antidiscrimination regulations leads to a situation, in which protection in access to healthcare primarily depends on national regulations. Our study shows that EU antidiscriminatory law with regard to access to healthcare is fragmentary. Prohibition of discrimination of the level of European binding law does not fully encompass all aspects of social diversity.


Relationship Between Myocardial Injury and Expression of PGC-1α and Its Coactivators in Chronic Keshan Disease.
Keshan disease (KD) is a mitochondrial cardiomyopathy. The present study explored the roles of peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), the key regulator of mitochondrial structure and function, and its coactivators in myocardial injury in chronic KD. Furthermore, the usefulness of these molecules in the diagnosis of chronic KD was assessed. In the present case-control study, 43 patients with chronic KD and 30 healthy individuals living in KD endemic areas were included. The myocardial injury indicators and mRNA expression levels of PGC-1α, nuclear respiratory factor 1 (NRF1), PPARα, and estrogen-related receptor alpha (ERRα) in peripheral blood were examined. It was found that the levels of atrial natriuretic peptide, creatine kinase, and lactate dehydrogenase (LDH) were higher in patients with chronic KD, when compared to controls, while the level of bradykinin was lower. Furthermore, the PGC-1α, NRF1 and PPARα mRNA levels were higher in patients with KD. The area under the receiver operating characteristic curve and the optimal diagnostic threshold of LDH was 0.937 and 304.0 U/L, respectively. It is noteworthy that the area under the combined receiver operating characteristic curve was larger, when compared to that for LDH detection alone (Z=2.055, P=0.0399). The area under the curve for the "LDH+PPARα" combination was 0.984, with 96.7% sensitivity and 93.0% specificity. The combined detection of LDH and the expression of PPARα can be performed to diagnose the chronic KD.


Indocyanine green fluorescence imaging in the pregnant cynomolgus macaque: childbearing is supported by a unilateral uterine artery and vein alone?
Uterine blood flow is required for the maintenance of uterine viability in pregnancy and delivery, but it is unknown how many vessels are necessary for maintenance of uterine viability. The objective of this study was to examine whether unilateral uterine vessels provide sufficient nutrition in pregnancy in a cynomolgus macaque and to evaluate hemodynamics of pregnant uterus by indocyanine green (ICG) fluorescence imaging. A cynomolgus macaque with uterine blood flow maintained by the right uterine artery and vein alone was made pregnant. Hemodynamics of the uterus in the third trimester was evaluated by ICG fluorescence imaging. Pregnancy was maintained with the right uterine artery and vein. An appropriate-for-date infant was delivered by Cesarean section. ICG fluorescence imaging showed that the uterine body was imaged from the right side to the center; furthermore, collateral circulation was present from the right uterine artery toward the left uterine artery, with expanded blood flow to the left uterine body. Pregnancy and delivery were achieved in a cynomolgus macaque with a unilateral right uterine artery and vein. Blood flow to the side without the artery was complemented by vascularization of collateral circulation to the uterine artery.


Low-level ganglionated plexus stimulation facilitates atrial fibrillation: in vivo and in vitro studies.
The purpose of the present study was to investigate whether long term low level autonomic activation can form electrophysiological substrate for atrial fibrillation (AF). In 16 anesthetized open-chest dogs, electrodes on the anterior right ganglionated plexuses (GP) and superior left GP allowed 6-h low-level GP stimulation (LL-GPS) inducing a 10% decrease in sinus rate. Similar low-level stimulation (without myocardial capture) was delivered to the myocardium remote from the GP for 6h in another 16 dogs as control group. LL-GPS: a) induced shortening of the atrial effective refractory period and increase of the window of vulnerability for AF; b) significantly increased acetylcholine-regulated potassium current (I(KACh)) at left superior pulmonary vein (LSPV) while reduced the density of L-type calcium current (I(CaL)) at LSPV and both atria, the protein expression of the channel subunit showed a consistent alteration, however both without significant changes in mRNA level. Six-hour LL-GPS induced significant changes in atrial electrophysiology and facilitated the initiation of AF, indicating that long-term low level autonomic activation would form electrophysiological substrate for AF. The underlying mechanism may be associated with a post-transcriptional regulation of increased I(KACh) and decreased I(CaL).


Habituation and within-session changes in motivated responding for food in children.
Within-session decreases in instrumental responding to obtain food, consistent with habituation, have been reliably demonstrated in adults and children. This study tested the hypothesis that within-session decreases in instrumental responding for food are due to habituation rather than satiation. Thirty-eight 8-12-year-old children performed a computer-based operant task to earn points toward access to potato chips for 20 min, and for chocolate candies for the final 6 min of the session. Portion size of the food reinforcer (75 kcal vs 225 kcal) and food consumption (consumption/no consumption). There was no difference in the rate of response decrease between the two portion size conditions. Both the consumption and non-consumption groups showed response decelerations during the first 20 min, with responses in the consumption group decreasing at a faster rate. When the novel food was presented, participants in all conditions recovered responding. Although satiation may contribute to reductions in motivated responding for food when food is consumed, habituation provides a more complete explanation for the results observed in this study.


Examination of the metabolism of oedematous brain tissue. V. The metabolism of oedematous white matter from rabbit brain.
Glucose and gas metabolism as well as water, sodium, and potassium content of normal and oedematous white matter slices of rabbit brain have been determined. A cutting technique for the preparation of the slices is described. Although the increase of the relative water content in oedematous white matter is much more pronounced than in oedema of the grey matter, we observed only one significant change: the pyruvate production in vitro is about 20% higher in slices prepared from oedematous brain.


Comparative ethanol productivities of different Zymomonas recombinants fermenting oat hull hydrolysate.
Iogen Corporation of Ottawa, Canada, has recently built a 50 t/d biomass-to-ethanol demonstration plant adjacent to its enzyme production facility. Iogen has partnered with the University of Toronto to test the C6/C5 cofermentation performance characteristics of National Renewable Energy Laboratory's metabolically engineered Zymomonas mobilis using its biomass hydrolysates. In this study, the biomass feedstock was an agricultural waste, namely oat hulls, which was hydrolyzed in a proprietary two-stage process involving pretreatment with dilute sulfuric acid at 200-250 degrees C, followed by cellulase hydrolysis. The oat hull hydrolysate (OHH) contained glucose, xylose, and arabinose in a mass ratio of about 8:3:0.5. Fermentation media, prepared from diluted hydrolysate, were nutritionally amended with 2.5 mL/L of corn steep liquor (50% solids) and 1.2 g/L of diammonium phosphate. The estimated cost for large-scale ethanol production using this minimal level of nutrient supplementation was 4.4cents/gal of ethanol. This work examined the growth and fermentation performance of xylose-utilizing, tetracycline-resistant, plasmid-bearing, patented, recombinant Z. mobilis cultures: CP4:pZB5, ZM4:pZB5, 39676:pZB4L, and a hardwood prehydrolysate-adapted variant of 39676:pZB4L (designated as the "adapted" strain). In pH-stat batch fermentations with unconditioned OHH containing 6% (w/v) glucose, 3% xylose, and 0.75% acetic acid, rec Zm ZM4:pZB5 gave the best performance with a fermentation time of 30 h, followed by CP4:pZB5 at 48 h, with corresponding volumetric productivities of 1.4 and 0.89 g/ (L x h), respectively. Based on the available glucose and xylose, the process ethanol yield for both strains was 0.47 g/g (92% conversion efficiency). At 48 h, the process yield for rec Zm 39676:pZB4L and the adapted strain was 0.32 and 0.34 g/g, respectively. None of the test strains was able to ferment arabinose. Acetic acid tolerance appeared to be a major determining factor in cofermentation performance.


Synthesis of glycocluster peptides.
A new type of glycoconjugate mimetic is introduced that combines a glycocluster head group with a peptide part. These 'glycocluster peptides' are designed to serve as mimetics of glycocalyx constituents. A convergent synthetic scheme was followed, consisting of (i) the synthesis of a clustered carbohydrate head group carrying an amino acid at the focal point, and (ii) the solid phase synthesis of the peptide moiety. Finally, peptide coupling on resin furnished two prototype glycocluster peptides, which each exposes three alpha-mannosyl residues in the form of a dendritic wedge, with different conformational features. Extensive purification and NMR studies were necessary to characterize the target compounds and the results of these investigations are reported here together with the synthesis.


The isolation and sequence analysis of two seed-expressed acyl carrier protein genes from Brassica napus.
Genomic Southern blot analysis of Brassica napus DNA indicates that seed-expressed acyl carrier protein (ACP) is encoded by a multigene family of some 35 genes/haploid genome. Two genomic clones encoding B. napus ACP have been isolated and sequenced. The coding sequences of the 2 respective genes were found to be perfectly homologous to 2 distinct B. napus seed-expressed cDNAs and therefore represent seed-expressed forms of ACP. The 2 genomic ACP sequences share 94% homology within their coding sequences. Both genes are interrupted by 3 intervening sequences whose position within the 2 coding sequences is conserved. RNase protection studies were used to map the transcription start site of one of the genes and to provide further evidence that the gene is seed-expressed. The expression of a sub-group of the ACP gene family was found to be developmentally regulated in concert with the storage lipid synthetic phase of seed development. The coding sequence of both B. napus genes are highly homologous (96% and 93% respectively) to a Brassica campestris ACP cDNA sequence, suggesting that they may have evolved from this ancestral gene.


Decreased Central Macular Choriocapillaris Perfusion Correlates With Increased Low Luminance Visual Acuity Deficits.
Correlations between low luminance visual acuity deficits (LLVADs) and central choriocapillaris perfusion deficits were investigated to help explain how increases in LLVAD scores at baseline predict annual growth rates of geographic atrophy (GA). Prospective cross-sectional study. Photopic luminance best-corrected visual acuity (PL-BCVA) and low luminance BCVA (LL-BCVA) were measured using the Early Treatment Diabetic Retinopathy Study chart. LL-BCVA was measured using a 2.0-log unit neutral density filter. LLVADs were calculated as the difference between PL-BCVA and LL-BCVA. Within a fovea-centered 1-mm circle, the percentage of choriocapillaris flow deficits (CC FD%), drusen volume, optical attenuation coefficient (OAC) elevation volume, and outer retinal layer (ORL) thickness were assessed. In all 90 eyes (30 normal eyes; 31 drusen-only eyes; 29 non-foveal GA eyes), significant correlations were found between the central CC FD% and PL-BCVA (r = -0.393, P < .001), LL-BCVA (r = -0.534, P < .001), and the LLVAD (r = 0.439, P < .001). Central cube root (cubrt) drusen volume, cubrt OAC elevation volume, and ORL thickness were correlated with PL-BCVA, LL-BCVA, and LLVADs (all P < .05). Stepwise regression models showed that central cubrt OAC elevation volume and ORL thickness were associated with PL-BCVA (R2 = 0.24, P < .05); central CC FD%, cubrt OAC elevation volume, and ORL thickness were associated with LL-BCVA (R2 = 0.44, P < .01); and central CC FD% and ORL thickness were associated with LLVAD (R2 = 0.24, P < .01). The significant correlations between central CC FD% and LLVAD support the hypothesis that the ability of LLVAD to predict the growth of GA is mediated through a decrease in macular choriocapillaris perfusion.


Skeletal maturation in different anteroposterior and vertical skeletal growth patterns in female subjects.
The aim of the present work was to study the sequence of skeletal maturation in the various anteroposterior and vertical skeletal growth patterns and to detect whether differences existed between them. Cephalograms of 861 growing and adolescent female patients were traced to categorize the subjects into 9 skeletal patterns. Each subject was assigned a skeletal maturational stage. Analysis of variance (ANOVA) followed by Bonferroni test were used to detect differences in the onset of the three growth stages (prepubertal, pubertal and postpubertal) between the 9 groups. The same statistical methods were used to detect differences between the mean ages at the three growth stages within each group. No statistically significant differences were found between the mean ages of pubertal and postpubertal growth stages between the 9 skeletal patterns. However, class III growers had a significantly earlier onset of prepubertal growth (10.25 ± 1.56 years) when compared to that of class II high angle cases (11.11 ± 1.67 years; P < 0.01). Also, significant differences were found between the mean ages at the three growth stages within the groups. A map was created defining the sequence of skeletal maturation for each skeletal growth pattern. This map defines clinically relevant differences in the starting time points and the optimum intervals of growth modification for each skeletal growth pattern.


A case of coccidioidomycosis in Australia.
We report what we believe to be the first case of coccidioidomycosis to be diagnosed within Australia, and emphasize the dangers of handling Coccidioides immitis in the laboratory.


Physical and genetic map of Enterococcus faecium ATCC19434 and demonstration of intra- and interspecific genomic diversity in enterococci.
A physical map of the Enterococcus faecium ATCC19434 chromosome was constructed by NotI, I-CeuI and Sse8387I. The chromosome was a circular DNA of 2600 kb in size, and contained six rRNA operons (rrn). The locations and orientations of the six rrn operons and 24 different determinants were mapped. Genomes of three additional E. faecium strains were also analyzed by I-CeuI digestion, and the genome sizes were found to vary from 2550 to 2995 kb. We further investigated the genome sizes and number of rrn operons in four E. faecalis, one E. avium, and one E. durans strains. The genome sizes were larger than E. faecium: 3000-3250 kb in E. faecalis, 3445 kb in E. avium, and 3070 kb in E. durans. E. avium and E. durans contained six rrn operons as in E. faecium, but all the E. faecalis strains possessed four rrn operons.


Catastrophic cerebral antiphospholipid syndrome presenting as cerebral infarction with haemorrhagic transformation after sudden withdrawal of warfarin in a patient with primary antiphospholipid syndrome.
Catastrophic antiphospholipid syndrome (APS) is caused by thrombotic vascular occlusions that affect both small and large vessels, producing ischaemia in the affected organs. The "catastrophic" variant of the antiphospholipid syndrome (cAPS) develops over a short period of time. Although patients with cAPS represent <1% of all patients with APS, they are usually life threatening with a 50% mortality rate. A strong association with concomitant infection is thought to act as the main trigger of microthromboses in cAPS. Several theories have been proposed to explain these physiopathological features. Some of them suggest the possibility of molecular mimicry between components of infectious microorganisms and natural anticoagulants, which might be involved in the production of cross-reacting antiphospholipid antibodies. We present a case of catastrophic cerebral APS characterised by massive temporal lobe infarction and subsequent haemorrhagic transformation after sudden withdrawal of warfarin.


Prescribing trends of proton pump inhibitors, antipsychotics and benzodiazepines of medicare part d providers.
Proton pump inhibitors, benzodiazepines, and antipsychotics are considered potentially inappropriate medications in older adults according to the American Geriatric Society Beers Criteria, and deprescribing algorithms have been developed to guide use of these drug classes. The objective of this study was to describe the number of beneficiaries prescribed these medications, provider specialty and regional trends in prescribing, and the aggregate costs for these claims in Medicare Part D. This was a retrospective cross-sectional study using publicly available Medicare Provider Utilization and Payment Data: Part D Prescriber data for years 2013-2019. Descriptive statistics and the Cochrane-Armitage test were used to summarize the trends. Overall, 30.1%, 25.6%, 4.6% of Medicare Part D beneficiaries had a proton pump inhibitor, benzodiazepine, and antipsychotic claim in 2013, respectively. These rates decreased to 27.5%, 17.5%, 4.1% in 2019 (p-value < 0.0001). However, the number of standardized 30-day claims increased from 63 million in 2013 to 84 million in 2019 for proton pump inhibitors, remained steady for benzodiazepines and slightly increased (10 million to 13 million) for antipsychotics. Total aggregate costs decreased by almost $1.5 billion for proton pump inhibitor, $100 million for benzodiazepine, and $700 million for antipsychotic from 2013 to 2019 (p-value < 0.0001). Almost 93% of gastroenterologists prescribed a proton pump inhibitor, and 60% of psychiatrists prescribed benzodiazepines and antipsychotics all seven years. The Other region had the highest percentage of providers prescribing all three classes and the highest number of standardized 30-day benzodiazepine claims. The overall rate of use of proton pump inhibitors, benzodiazepines, and antipsychotics decreased from 2013-2019 among Medicare Part D beneficiaries. Despite the increase in raw number of standardized 30-day claims, the costs decreased which is likely due to generics made available. These prescribing trends may aid in identifying and targeting potential deprescribing interventions.


Two-day oral desensitization to trimethoprim-sulfamethoxazole in HIV-infected patients.
To establish whether an outpatient, 2-day oral desensitization protocol would be both safe and effective in HIV-infected patients with previous trimethoprim-sulfamethoxazole (TMP-SMX) intolerance. A single center trial of TMP-SMX desensitization in HIV-infected patients with prior TMP-SMX hypersensitivity reactions. HIV-infected patients with CD4 lymphocyte counts < 250 x 10(6)/l cells or CD4% < 20% with previous non-life-threatening hypersensitivity reactions to TMP-SMX were eligible. The desensitization protocol utilized 40 graduated doses over 36 h; the first 28 doses (7.5 h) of the protocol were given in an outpatient clinic with the remaining doses taken at home. Twenty-seven (60%) of the 45 subjects completed the protocol and were subsequently maintained on daily TMP-SMX without adverse reactions (mean follow-up, 9 months; range, 4-16 months). Patients with CD4 counts < 100 x 10(6)/l cells were just as likely as patients with higher CD4 counts to tolerate the desensitization. No patient required hospitalization for treatment of an adverse reaction. Oral desensitization to TMP-SMX in HIV-infected patients is a useful option in the management of patients with advanced HIV disease and prior intolerance to TMP-SMX.


Plasma sphingolipids and risk of cardiovascular diseases: a large-scale lipidomic analysis.
Sphingolipids are a diverse class of lipids with various roles in cell functions and subclasses such as ceramides have been associated with cardiovascular diseases (CVD) in previous studies. We aimed to measure molecularly-distinct sphingolipids via a large-scale lipidomic analysis and expand the literature to an Asian population. We performed a lipidomics evaluation of 79 molecularly distinct sphingolipids in the plasma of 2627 ethnically-Chinese Singaporeans. During a mean follow-up of 12.9 years, we documented 152 cases of major CVD (non-fatal myocardial infarction, stroke and cardiovascular death). Total ceramide concentrations were not associated with CVD risk [hazard ratio (HR), 0.99; 95% CI 0.81-1.21], but higher circulating total monohexosylceramides (HR, 1.22; 95% CI 1.03, 1.45), total long-chain sphingolipids (C16-C18) (HR, 1.22; 95% CI 1.02, 1.45) and total 18:1 sphingolipids (HR, 1.21; 95% CI 1.01, 1.46) were associated with higher CVD risk after adjusting for conventional CVD risk factors. Our results do not support the hypothesis that higher ceramide concentrations are linked to higher CVD risk, but suggest that other classes of sphingolipids may affect CVD risk.


Early antibiotic treatment of pseudomonas aeruginosa colonisation in cystic fibrosis: a critical review of the literature.
To assess the evidence supporting early antibiotic treatment in asymptomatic cystic fibrosis (CF) patients colonised by Pseudomonas aeruginosa (PA). We carried out a computerised (Medline, Embase) and hand search of journals for suitable publications. All English-language clinical studies regarding the efficacy of early antibiotic treatment on PA colonisation in asymptomatic patients were considered. Each eligible publications fitting these criteria were assessed for the following outcome measures: frequency of positive PA cultures; serum level of precipitating antibodies; lung function; survival; number of hospitalisations; adverse effects and resistance to antibiotics. Of the 11 studies eventually considered, 3 were randomised-2 versus placebo- and 8 were cohort studies-2 of which had historical controls. Overall, 309 patients (population range 7-91 patients) were recruited. There was a high variability between the individual studies for age, outcome measures, duration of follow-up (1 to 44 months) and treatment (three studies used only aerosol tobramycin, one colistin, four aerosol colistin plus oral ciprofloxacin, one used intravenous treatment and two miscellaneous therapy). An overall evaluation indicated that early antibiotic treatment can reduce the number of positive cultures and the anti-PA antibody titre. In one study, FEV1 was better in the treated group (oral ciprofloxacin and nebulised colistin) than in historical controls, while in one placebo-controlled trial, no effect on lung function was shown after 1 year of tobramycin inhalation. Collateral effects and bacterial resistance were not increased. The short follow-up did not allow definite conclusions with regard to the long-term progression of respiratory insufficiency or survival. Evidence was found that antibiotic treatment can reduce the rate of positive cultures and of anti-PA antibody titres in asymptomatic CF patients with newly isolated PA. Different therapeutic options have not been directly compared: a multi-centre comparative study needs to be carried out.


A TD-DFT study of the excited dissociative electronic states of the DNA nucleobases bound to Li.
In this work, the first and second dissociative potential curves of adenineLi+ (ADLi+), guanineLi+ (GUALi+), cytosineLi+(CYTLi+), and thymineLi+ (THYLi+) complexes, related to the dissociation of their LiO and LiN bonds, have been calculated in the gas phase and water, separately. For this purpose, the fifteen excited potential curves, in order of increasing energy, were calculated for each complex and the dissociative potential curves were distinguished from them considering the conical intersection points. The time-dependent density functional theory (TD-DFT) method employing the M06-2X functional was used for the calculations. It was observed that the electron transfer from the DNA base to the Li+ took place during the dissociation of complexes in the gas phase. The electrostatic field of water blocked this charge transfer and led to the excited DNA base and Li+ in its ground state. The vertical excitation energy for the desorption of the Li fragment as a neutral and cation species from the DNA bases was determined. The effect of the interaction site of Li+ on the dissociative potential curves was also investigated.


Arthroscopic Assisted Anterior Cruciate Ligament Tibial Spine Avulsion Reduction and Cortical Button Fixation.
Tibial spine avulsion fractures, or tibial eminence fractures, are intra-articular knee injuries that affect the bony attachment of the anterior cruciate ligament (ACL). It is commonly seen in children and adolescents aged 8 to 15 years old and can be caused by noncontact pivot shift injuries or by traumatic hyperextension knee injuries, as seen in adult ACL patients. A thorough history and physical exam is important in these patients alongside proper imaging that will confirm the diagnosis of a tibial spine avulsion. Proper imaging may also demonstrate other associated conditions or injuries to the cartilage, meniscus, or ligamentous structures. Following diagnosis, treatment can be both nonoperative versus operative, depending upon the degree of displacement and reducibility of the fragment, as well as other concomitant injuries. For nondisplaced or minimally displaced, and reducible injuries, the patient can be immobilized in full extension for several weeks. For displaced fragments that are unable to be reduced by closed methods, open reduction internal fixation or arthroscopic fixation is recommended. In this Technical Note, we describe an arthroscopy-assisted reduction and internal fixation with suture tape through 2 transtibial tunnels with a cortical suture button fixation technique.


Differential diagnosis of glandular proliferations in the prostate. A conventional and immunohistochemical approach.
A variety of small acinar lesions of the prostate can mimic prostate cancer in punch biopsies and in transurethral resection material. The first part of this review deals with differential diagnostic problems of the central and transition zone, including atypical adenomatous hyperplasia of the prostate, atrophic processes, sclerosing adenosis, basal cell hyperplasia, and low-grade adenocarcinoma. The second part deals with differential diagnostic problems in the peripheral zone: prostatic intraepithelial neoplasia, postatrophic hyperplasia, Cowper's glands, seminal vesicles, and ductal and intraductal carcinoma. Finally, atypical and small acinar proliferations are described. Diagnostic perspectives are discussed. proliferations (ASAP) that cannot be integrated into any of the well-established diagnostic entities [1, 16, 22, 41]. The relevant glandular proliferations of the central, transitional and peripheral zones of the prostate are discussed here with reference to the related carcinomas.


Why did Alfred Blalock and Helen Taussig not receive the nobel prize?
From the 1940s to the 1960s, the number of cardiac surgeons nominated for the Nobel Prize for Physiology or Medicine grew rapidly. These nominations pinpoint major developments ranging from the first closed extracardiac operations to the era of complete intracardiac repair and treatment of congenital heart diseases. The aim of this article is to present the motivations for the numerous Nobel Prize nominations for the cardiac surgeon Alfred Blalock and the pediatric cardiologist Helen B. Taussig, and to show why the Nobel committee finally chose not to award them for the development of the Blalock-Taussig shunt. The authors have gathered and analyzed files on Blalock and Taussig from the Nobel Prize archive for Physiology and Medicine in Solna, Sweden. More than forty scholars, primarily from the United States and Europe, nominated Blalock and Taussig for the Nobel Prize for Physiology or Medicine. Such a strong transatlantic support is rare for nominated surgeons. The authors discuss why the number of Nobel Prize nominations for cardiac surgeons in general reached a climax around the 1950s and formulate open research questions on why relatively few surgeons have received the prestigious prize for the development of surgical procedures.


Real-world survival of Danish patients with HER2-positive metastatic breast cancer.
The purpose was to investigate the treatment flow of patients with HER2-positive metastatic breast cancer (mBC), progression-free survival (PFS) and overall survival (OS) across treatment lines and adherence to guidelines (defined as trastuzumab, pertuzumab and chemotherapy first line, where 85% received vinorelbine as backbone and T-DM1 second line). Furthermore, we identified clinical markers to predict the risk of developing brain metastases. Patients with HER2-positive mBC, diagnosed between 01.01.2014-31.12.2019, registered in the database of the Danish Breast Cancer Group were included in this real-word study. Clinical follow-up was assessed until 01.10.2020 and complete follow-up for overall survival until 01.10.2021. Survival data were analyzed using the Kaplan-Meier method with guidelines adherence analyzed as a time-varying covariate, and the risk of CNS metastasis was estimated by the cumulative incidence function. 631 patients were included. 329 (52%) patients followed the guidelines. The median OS for all patients was 42.3 months (95% Cl, 38.2-48.4), and significantly higher for the patients who followed guidelines; NA (95% CI, 78.2-NA). The median PFS for all patients was 13.4 months (95% Cl, 12.1-14.8), 6.6 (95% Cl, 5.8-7.6) and 5.8 (95% Cl, 4.9-6.9) for first, second and third line of treatment, respectively. Patients with ER-negative mBC had a higher risk of developing brain metastases and patients with high tumor burden had a higher risk of developing brain metastases with an adjusted HR of 0.69 (95% CI, 0.49-0.98), p = 0.047 and 2.69 (95% CI, 1.45-5.00), p = 0.002, respectively. We found that only half of the patients with HER2-positive mBC, received first and second-line treatment according to national guidelines. Patients receiving treatment according to guidelines had a significantly higher median OS compared to patients who did not. We also found that patients with ER-negative disease or high tumor burden had a significantly higher risk of developing brain metastases.


Ossification of the posterior capitellum: description of a new pathology and its radiological appearance.
Boxer elbow and handball goalkeeper elbow are causes of impingement characterized by osteophytes formation at the olecranon and coronoid tip as well as their corresponding fossae. Herein, we present another distinct pathology in these patients: the formation of an exostosis at the posterolateral aspect of the elbow. Between April 2016 and May 2020, 12 athletes with boxer elbow and handball goalkeeper elbow (mean age of 22 years) suffering from elbow pain were enrolled in the present study. Plain radiography, magnetic resonance imaging (MRI), and computer tomography (CT) scans were used to evaluate the bone conformation of the posterolateral aspect of the elbow. Assessment and staging of the ossification was performed by two independent fellowship-trained elbow surgeons. Bone marrow edema of the posterior aspect of the elbow at the origin of the anconeus muscle was initially detected in MRI scans. With the progression of the condition, imaging revealed an ossification posterior to the capitellum with bony bridges. In the advanced stage of the disease, the exostoses was unstable as the ossification had no adherence to the posterior capitellum during surgical excision. Plain radiographs are limited in their ability to detect the condition, whereas MRI and CT scans allow to identify a signal enhancement at the posterolateral aspect of the elbow. In patients without history of elbow trauma, bony irregularities of the posterior aspect of the capitellum may indicate ossification of the posterolateral aspect of the elbow, most likely caused by repetitive hyperextensions.


Nodal skip metastasis is associated with a relatively poor prognosis in thoracic esophageal squamous cell carcinoma.
Nodal skip metastasis (NSM) is common in esophageal carcinoma, even with different lymph node classification criteria. The prognostic impact of NSM in esophageal carcinoma has been unclear. Some studies found no impact on survival and others found a positive impact. This research was to further investigate the incidence of NSM in patients with thoracic esophageal squamous cell carcinoma (ESCC), and assess its prognostic value in thoracic ESCC. We retrospectively analyzed the clinical data of 340 consecutive patients with solitary lymph node metastasis who underwent esophagectomy with three-field lymph node dissection for ESCC at the First Affiliated Hospital of Zhengzhou University from January 2005 to December 2013. The survivals of the patients with NSM or adjacent node metastasis were compared. There were 216 patients with NSM, and 124 patients with adjacent node metastasis. The incidence of NSM in this cohort was 63.5%. No significant difference was found between the patients with NSM and the patients with adjacent node metastasis in age, sex, tumor location, pathologic T stage, histologic grade, tumor length, and the number of resected lymph nodes (all p > 0.05). Patients with NSM had 5-year cumulative survival of 29.2%, which was significantly worse than the 45.6% survival in those with adjacent node metastasis (p < 0.05). In conclusion, NSM is associated with a relatively poor prognosis in thoracic ESCC.


Effect of natalizumab on oxidative damage biomarkers in relapsing-remitting multiple sclerosis.
Natalizumab is a monoclonal antibody used to treat multiple sclerosis. This study sought to determine whether the protective action of natalizumab involved a reduction in oxidative damage. Twenty-two multiple sclerosis patients fulfilling the revised McDonald criteria were assigned to treatment with 300 mg natalizumab intravenously once monthly (infusion every 4 weeks) in accordance with Spanish guidelines. Carbonylated proteins, 8-hydroxy-2'-deoxyguanosine, total glutathione, reduced glutathione, superoxide dismutase, glutathione peroxidase, and myeloperoxidase levels were measured at baseline and after 14 months' treatment, and the antioxidant gap was calculated. Natalizumab prompted a drop in oxidative-damage biomarker levels, together with a reduction both in myeloperoxidase levels and in the myeloperoxidase/neutrophil granulocyte ratio. Interestingly, natalizumab induced nuclear translocation of Nrf2 and a fall in serum vascular cell adhesion molecule-1 levels. These findings suggest that natalizumab has a beneficial effect on oxidative damage found in MS patients.


Muscle deoxygenation during ramp incremental cycle exercise in older adults with type 2 diabetes.
To explore profiles of fractional O2 extraction (using near-infrared spectroscopy) during ramp incremental cycling in older individuals with type 2 diabetes (T2D). Twelve individuals with T2D (mean ± SD, age: 63 ± 3 years) and 12 healthy controls (mean age: 65 ± 3 years) completed a ramp cycling exercise. Rates of muscle deoxygenation (i.e., deoxygenated haemoglobin and myoglobin, Δ[HHb + Mb]) profiles of the vastus lateralis muscle were normalised to 100% of the response, plotted against absolute (W) and relative (%peak) power output (PO) and fitted with a double linear regression model. Peak oxygen uptake (V̇O2peak) was significantly (P < 0.01) reduced in T2D (23.0 ± 4.2 ml.kg-1.min-1) compared with controls (28.3 ± 5.3 ml.kg-1.min-1). The slope of the first linear segment of the model was greater (median (interquartile range)) in T2D (1.06 (1.50)) than controls (0.79 (1.06)) when Δ%[HHb + Mb] was plotted as a function of PO. In addition, the onset of the second linear segment of the Δ%[HHb + Mb]/PO model occurred at a lower exercise intensity in T2D (101 ± 35 W) than controls (140 ± 34 W) and it displayed a near-plateau response in both groups. When the relationship of the Δ%[HHb + Mb] profile was expressed as a function of %PO no differences were observed in any parameters of the double linear model. These findings suggest that older individuals with uncomplicated T2D demonstrate greater fractional oxygen extraction for a given absolute PO compared with older controls. Thus, the reductions in V̇O2peak in older people with T2D are likely influenced by impairments in microvascular O2 delivery.


Binding to alpha-adrenergic receptors: differential pharmacological potencies and binding affinities of benzodioxanes.
We have compared the influence of a series of benzodioxane alpha-adrenergic antagonists on 3H-WB-4101 and 3H-clonidine binding to alpha-receptor sites in the brain and peripheral tissues with their pharmacological properties. The drug specificity of 3H-WB-4101 binding is quite similar in central and peripheral tissues. Pharmacological potencies of benzodioxanes at postsynaptic alpha-receptors in the rat vas deferens correlate with potencies at 3H-WB-4101 but not at 3H-clonidine binding sites. These findings suggest pharmacological effects of these drugs are mediated by "alpha-1 postsynaptic receptors" labeled by 3H-WB-4101. For several benzodioxanes absolute pharmacological potencies at postsynaptic alpha-receptors of the rat vas deferens are substantially less than their potencies at 3H-WB-4101 sites. The potencies of benzodioxane analogues at 3H-clinidine binding sites are similar to their pharmacological potencies at presynaptic autoreceptors in the rat vas deferens.


[The acupuncture in 20 patients submitted to placement of endocardial permanent pacemakers (author's transl)].
The Authors report on 20 patients who underwent definitive surgery for placement of artificial pacemaker with utilisation of acupuncture for analgesic purposes. The report in detail on the results obtained with even, in the light of a limited experience, can be considered positive.


Menstrual bleeding from an endometriotic lesion.
We present a case in which endometriotic lesions were observed to be focally hemorrhagic at laparoscopy performed during menstruation. Red vesicular lesions likely represent early disease with intact capacity for hormonally induced menstrual bleeding.


Prophylactic Central Neck Dissection for Clinically Node-Negative Papillary Thyroid Carcinoma.
We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that scrutinized the oncological benefits and postsurgical complications of total thyroidectomy (TT) plus prophylactic central neck dissection (pCND) versus TT alone among clinically node-negative (cN0) papillary thyroid cancer (PTC) patients. We screened five databases from inception to September 4, 2021 and evaluated the risk of bias of the eligible studies. We pooled dichotomous outcomes using the risk ratio (RR) with 95% confidence interval (CI). Overall, we included 5 RCTs with low risk of bias comprising 795 patients (TT plus pCND = 410 and TT alone = 385). With regard to efficacy endpoint, the rate of structural loco-regional recurrence did not significantly differ between both groups (n = 4 RCTs, RR = 0.49, 95% CI [0.19, 1.27], P = .14). With regard to safety endpoints, the rates of hypoparathyroidism (n = 5 RCTs, RR = 1.48, 95% CI [0.73, 2.97], P = .27), recurrent laryngeal nerve injury (n = 5 RCTs, RR = 1.34, 95% CI [0.59, 3.03], P = .48), and bleeding (n = 3 RCTs, RR = 1.75, 95% CI [0.42, 7.26], P = .44) did not significantly differ between both groups. For cN0 PTC patients, there was no significant difference between TT plus pCND and TT alone with regard to the rate of structural loco-regional recurrence or frequency of postsurgical complications. Adaptation of pCND in cN0 PTC patients should be contemplated by taking into consideration the clinical oncological benefits and rate of postsurgical adverse events. 1 Laryngoscope, 132:1320-1328, 2022.


Longitudinal Analysis of Severe Anxiety Symptoms in the Last Year of Life Among Patients With Advanced Cancer: Relationships With Proximity to Death, Burden, and Social Support.
Temporal changes in the prevalence of anxiety disorders/symptoms for patients with cancer at the end of life (EOL) remain unclear. This study was undertaken to describe changes in the prevalence of severe anxiety symptoms and to identify its correlates in the last year of life for patients with cancer. A convenience sample of 325 patients with cancer was followed until death. Severe anxiety symptoms were identified as anxiety subscale scores of 11 or greater on the Hospital Anxiety and Depression Scale. Longitudinal changes in and correlates of severe anxiety symptoms were examined from demographics, disease-related characteristics, disease burden, perceived burden to others, and social support using multivariate logistic regression modeling with generalized estimating equations. The prevalence of severe anxiety symptoms increased as death approached (18.6%, 21.9%, 26.7%, and 33.4% at 181-365, 91-180, 31-90, and 1-30 days before death, respectively). However, after controlling for covariates, this temporal increase was not significant. The prevalence of severe anxiety symptoms was not associated with fixed demographics and disease-related characteristics, except for diagnosis and metastatic status, but was significantly higher in patients with cancer with high physical symptom distress, severe depressive symptoms, high perceived burden to others, and strong perceived social support. Severe anxiety symptoms were not associated with time proximity to death per se but were related to factors modifiable by high-quality EOL care. Clinicians may decrease the likelihood of severe anxiety symptoms at EOL by adequately managing physical and depressive symptoms and lightening perceived burden to others for patients strongly connected with their social network to improve their psychological well-being.


Effects of alcohols on the reactivity and stability of Azotobacter vinelandii hydrogenase.
The effects of alcohols on the reactivity of Azotobacter vinelandii hydrogenase were investigated. Hydrogenase catalyzed H2 oxidation coupled to methylene blue, benzyl viologen, or phenazine methosulfate when in the presence of solvents containing 15 or 40% ethanol or 40% methanol or 2-propanol. In general, the Km's for the electron acceptors were increased substantially by the presence of the alcohols, while the Km for H2 was not altered in a solvent containing 40% ethanol. Calculation of the apparent maximum velocities for H2 oxidation in the presence of alcohols indicated that the maximum velocity was not decreased in most cases. In contrast, the rates of both H2 evolution and isotope exchange by hydrogenase were substantially decreased when solvent containing alcohol. Hydrogenase was inactivated by 100% ethanol with a half-life of 17 s. Hydrogenase from A. vinelandii was stable when stored in alcohol/buffer solvents at 20 degrees C or below. However, the thermal stability of hydrogenase was greatly decreased by inclusion of an alcohol in the solvent. When incubated at 55 degrees C in a solvent containing 40% ethanol, activity decreased in a first-order process with a half-life of 7 min. When incubated at the same temperature in aqueous buffer, no loss of activity was observed over 30 min.


Impact of single-nucleotide polymorphisms at the TP53-binding and responsive promoter region of BCL2 gene in modulating the phenotypic variability of LGMD2C patients.
Apoptosis of skeletal muscle fibers is a well-known event occurring in patients suffering from muscular dystrophies. In this study, we hypothesized that functional polymorphisms in genes involved in the mitochondrial apoptotic pathway might modulate the apoptotic capacity underlying the muscle loss and contributing to intrafamilial and interfamilial variable phenotypes in LGMD2C (Limb Girdle Muscular Dystrophy type 2C) patients sharing the same c.521delT mutation in SGCG gene. Detection of apoptosis was confirmed on muscle biopsies taken from LGMD2C patients using the TUNEL method. We genotyped then ten potentially functional SNPs in TP53, BCL-2 and BAX genes involved in the mitochondrial apoptotic pathway. Potential genotype-dependent Bcl-2 and p53 protein expressed in skeletal muscle was investigated using western blot and ELISA assays. The result showed that muscle cells carrying the TP53-R72R and TP53-16 bp del/del genotypes displayed an increased p53 level which could be more effective in inducing apoptosis by activation of the pro-apoptotic gene expression. In addition, the BCL2-938 AA genotype was associated with increased Bcl-2 protein expression in muscle from LGMD2C patients compared to -938CC genotype, while there was no evidence of significant difference in the BAX haplotype. Our findings suggest that increased Bcl-2 protein expression may counteract pro-apoptotic pathways and thus reduce the muscle loss. To the best of our knowledge, this is a pioneer study evaluating the role of apoptotic BCL-2 and TP53 genes in contributing to the phenotypic manifestation of c.521delT mutation in LGMD2C patients. Larger studies are needed to validate these findings.


Structural characterization of nitrimyoglobin.
Nitrimyoglobin was formed in greater than 94% yield by a simple reaction between excess nitrite and horse heart metmyoglobin at pH 5.5. This dark green pigment was shown by 1H NMR spectroscopy to be a single, pure product with a well defined tertiary structure that is highly similar to the starting myoglobin. Electronic spin states parallel those of myoglobin, although the relaxation times differ. Ligand binding reactions of nitrimyoglobin parallel those of normal myoglobin, but lead to a unique series of UV-visible spectra. In the ferrous state, nitrimyoglobin reversibly binds O2 with half-saturation of sites at an O2 partial pressure of 10.4 +/- 1.4 mm Hg. 1H NMR data indicate that the altered heme of nitrimyoglobin has not undergone reaction at any meso proton position, nor has it been partially saturated to the level of a chlorin. 15N NMR spectra indicate that only a single nitrogen was added to the protein as a nitro group. Extraction of the modified heme from nitrimyoglobin and spectroscopic characterization of the nitriheme by infrared spectroscopy and of the free base porphyrin methyl ester derived from nitriheme by 1H NMR indicate that the modification is regiospecific. The heme in nitrimyoglobin is 3-(trans-2-nitrovinyl)-2,7,12,18-tetramethyl-8-vinylporphyrin-13,1 7-dipropionic acid. In the Fisher nomenclature scheme, the 2-vinyl substituent is the site of modification and has been converted to a nitrovinyl group by substitution of a proton by -NO2.


Idiopathic bladder instability treated by biofeedback.
Biofeedback training has been used to treat 27 female patients suffering from symptoms associated with detrusor instability Re-education to auditory and visual stimuli took place during 4 to 8 one-hour sessions at weekly intervals. Using subjective and objective methods of assessment 81% of the patients were improved following treatment.


Therapeutic Effects of Medication Use on Intermittent Claudication: A Network Meta-analysis.
To systematically evaluate the therapeutic effects of commonly used drugs for the treatment of intermittent claudication in patients with peripheral arterial diseases. We systematically searched bibliographic databases for randomized clinical trials published between 2000 and 2020, through the China National Knowledge Infrastructure, WanFang Data, PubMed, MEDLINE, Embase, and Cochrane library. Included studies focused on therapeutic effects of beraprost, clopidogrel, aspirin, sarpogrelate and cilostazol on treating intermittent claudication. The outcome measures were maximum walking distance, pain-free walking distance, ankle-brachial index, and severe adverse events. The quality of included trials was evaluated by using the bias risk assessment tool recommended by the Cochrane, after extracting data from the literatures. Stata was used to conduct the network meta-analysis. There were 27 randomized control trials included in the study, covering in total 9491 patients. The network meta-analysis results showed that for maximum walking distance, better therapeutic effect was noted in using beraprost, sarpogrelate, and cilostazol. Beraprost, beraprost combined with aspirin, and sarpogrelate were better in improving pain-free walking distance than other drugs. For the ankle-brachial index, cilostazol combined with clopidogrel, sarpogrelate, and beraprost had better therapeutic effects than others. The use of sarpogrelate, beraprost, and aspirin was associated with a lower ratio of severe adverse events than the use of cilostazol and placebo. Among the commonly used drugs for the treatment of intermittent claudication, beraprost and sarpogrelate may have better efficacy in improving the walking distance and ankle-brachial index, with a beneficial effect on cardiovascular and cerebrovascular comorbidities.


Children's Knowledge of Abuse Questionnaires (CKAQ)-Short: Two Brief Ten-Item Measures of Knowledge about Child Sexual Abuse Concepts.
Child-focused sexual abuse prevention programs were developed in the 1970s in response to significant concerns across North America with respect to children being sexually abused. While program evaluations are common, measures to evaluate these programs, most of which are offered to children in elementary schools, are not widely available. This article reviews the key concepts covered in CSA prevention education programs that comprise the constructs used to measure knowledge/attitude gains post-program. Available measures are reviewed and the psychometrics of two new 10-item versions (one for students in grades 1-2; the other for grades 3-6) of the CKAQ-33, a commonly used tool, are presented and psychometrically assessed with a sample of 7646 elementary school students.