Fine-needle aspiration of Riedel's disease: report of a case and review of the literature.
The cytomorphological features of a case of Riedel's thyroiditis (Riedel's disease) in a 37-yr-old woman are reviewed. The patient presented with a diffusely enlarged thyroid gland with extension to carotid and jugular vessels bilaterally. A fine-needle aspiration of the right lobe of the thyroid demonstrated moderate cellularity with fragments of fibrous tissue with bland spindle-shaped cells and myofibroblasts. The patient subsequently underwent a bilateral subtotal thyroidectomy with removal of two-thirds of both lobes of the thyroid. A frozen section diagnosis of Riedel's disease was later confirmed on paraffin sections. Here we describe the cytological findings of a case of Riedel's disease and provide some helpful clues in distinguishing it from other forms of thyroiditis such as fibrosing variant of Hashimoto's thyroiditis, subacute thyroiditis, or granulomatous thyroiditis and from malignancy with which it can be confused both clinically and cytologically.


The Effects of Virtual Reality on Preoperative Anxiety in Patients Undergoing Colorectal and Abdominal Wall Surgery: A Randomized Controlled Trial.
The purpose of this study was to investigate the effects of a virtual reality (VR) application on preoperative anxiety (PA) in patients undergoing colorectal and abdominal wall surgery. A prospective, parallel two-armed, randomized controlled trial. Eighty six patients were divided into the control group (n = 43) and in the experimental group (n = 43). The experimental group received a preoperative VR application for 10 minutes. The routine preoperative procedure used at the clinic was used for the patients in the control group. The anxiety level was assessed using the Anxiety Specific to Surgery Questionnaire (ASSQ) and measured with physiological responses to anxiety, such as changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), respiratory rate (RR), and peripheral oxygen saturation (SpO2), before and after the VR application. The VR application reduced PA levels in the experimental group (P < .001) and changes in the SBP (P < .001), DBP (P < .001), HR (P < .001), RR (P = .041) and SpO2(P = .019) values) compared to the levels in the control group. VR applications can reduce psychological and physiological responses to PA in patients undergoing colorectal and abdominal wall surgery.


Phospholipid polymers--synthesis and spectral characteristics.
A new approach has been developed for the study of model and natural biomembranes. This involves the cross-linking of diacetylene groups after ultraviolet irradiation. For the study of model biomembranes, pure phospholipids (phosphatidylcholines) have been synthesized containing diacetylene groups in each acyl chain. The physical properties of these lipids have been examined and the conditions under which they polymerise have been determined. Polymerisation occurs when the lipid is in a crystalline phase, either compressed in KBr, dispersed in water (liposomes) or deposited on a suitable support (multilayers). The resultant polymer contains a conjugated backbone and is coloured. The visible spectrum of the phospholipid polymer is sensitive to its environment. Preliminary experiments show that similar polymerisation can be induced in Acholeplasma laidlawii cells grown on diacetylenic fatty acid.


Postnatal appearance of 5-HT2A receptors on fast flexor and slow extensor rat motor neurons.
Motor neurons to the slowly contracting extensor soleus muscle in behaving rats begin to fire tonically in the 2nd week after birth. In the adult, tonic firing becomes predominant and appears to arise from plateau potentials under monoaminergic control. In the present work, motor neurons to slowly contracting extensor soleus and rapidly contracting extensor digitorum longus, a physiological flexor muscle, were retrogradely labeled with fluorescent dextran and examined for immunoreactivity to 5-HT(2A) receptors in 1 and 2 week old and adult rats. No reactivity was detected at 1 week. At 2 weeks, reactivity was detected on 67% slowly contracting extensor soleus (16 of 24) and 19% extensor digitorum longus (11 of 57) motor neurons. In the adult, the intensity of staining was higher and the percentage of labeled motor neurons 79 for slowly contracting extensor soleus (34 of 43) and 31 for extensor digitorum longus (11 of 35). On slowly contracting extensor soleus motor neurons, labeling appeared more often on soma and dendrites than on dendrites only, whereas on extensor digitorum longus motor neurons, labeling appeared more often on dendrites only. These results are consistent with the hypothesis that serotonergic innervation contributes to the appearance and subsequent increase in tonic firing of rat slowly contracting extensor soleus motor neurons in postnatal development.


Clinical, electrophysiologic, and genetic study of non-dystrophic myotonia in French-Canadians.
Thirty-three French-Canadian families with non-dystrophic myotonia were identified. Fifty subjects were recruited and submitted to a complete clinical, electrophysiologic and genetic evaluation. Thirteen mutations were identified in CLCN1 and five mutations were identified in SCN4A. Onset in the lower extremities, presence of tongue myotonia and transient weakness suggested recessive CLCN1 mutations. Lid myotonia, absence of hypertrophy and exacerbation with cold temperature suggested SCN4A mutations. Pain was not a feature of dominant CLCN1 mutations while it could be seen in the others, more frequently in SCN4A mutations. Warm up phenomenon, hand grip myotonia, percussion myotonia, lid lag and hormonal effects were not distinguishing features. Repetitive nerve stimulation and short exercise test showed either a large (>50%) or mild-moderate (10-50%) decrement with recessive CLCN1 mutations while they showed only mild or no decrement with dominant CLCN1 and SCN4A mutations. The French-Canadian population shows wide phenotypic and genotypic heterogeneity in non-dystrophic myotonias.


Characterization of insulin uptake into subcellular fractions of perfused rat liver using two different iodinated tracers.
The binding and uptake of insulin in perfused rat liver has been investigated with specifically labelled 125I-A14-tyrosyl insulin as a tracer and compared with a commercially available iodo-insulin preparation. The commercial preparation did not show saturation uptake kinetics and the clearance from the perfusate remained low and constant throughout a wide concentration range. A14 labelled insulin showed saturation kinetics and high clearance at low carrier concentration, falling rapidly with increasing carrier concentration and reaching a steady state value of 1 ml/min. These results emphasize the importance of using specifically labelled insulin in physiological and biochemical studies of hepatic insulin metabolism. Perfusion with A14 tyrosine-labelled insulin at 4 degrees C showed apparent saturation with binding to the plasma membrane fraction. Perfusion at 37 degrees C also showed apparent saturation with uptake predominantly to the ligandosome fraction. These results implicate the plasma membrane-ligandosome pathway in the hepatic uptake of insulin at both physiological and pharmacological concentrations of the hormone.


Development of a time-temperature indicator based on Maillard reaction for visually monitoring the freshness of mackerel.
Due to the highly cost-effective and maneuverable property, Maillard reaction-based time-temperature indicators (TTIs) are considered ideal devices for temperature track and quality indication. The objective of this study was to develop a cold-sensitive TTI based on the Maillard reaction reflecting the freshness of chilled seafood. Firstly, the color evolution trends of a series of Maillard reaction-based TTIs were investigated and the xylose-lysine group represented obvious color change. Fourier transform infrared (FTIR) spectroscopy revealed the color change was associated with the formation of CN bond in melanoidin. Simultaneously, the relationships of the color change of TTI with time and temperature were established. The activation energy value (Ea) of TTI was close to that of mackerel. There existed a good relevance (R2 = 0.98) between the color change of TTI and the total volatile basic nitrogen content of mackerel, suggesting this novel TTI might have the potential to monitor the freshness of mackerel.


Transgender adults, gender-affirming hormone therapy and blood pressure: a systematic review.
Gender-affirming hormone therapy (GHT) is utilized by people who are transgender to align their secondary sex characteristics with their gender identity. Data relating to cardiovascular outcomes in this population are limited. We aimed to review the impact of GHT on the blood pressure (BP) of transgender individuals. We searched PubMed/MEDLINE, SCOPUS and Cochrane Library databases for articles published relating to the BP of transgender adults commencing GHT. Methodological quality was assessed via the 'Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group'. Six hundred articles were screened, of which 14 studies were included in this systematic review encompassing 1309 individuals (∼50% transgender men and women) treated with GHT between 1989 and 2019. These articles were all pre-post observational studies without control groups. Mean ages ranged between 23.0-36.7 years (transgender men) and 25.2-34.8 years (transgender women). Interventions were diverse and included oral, transdermal and injectable hormonal preparations with 4 months to 5 years follow-up. Most studies in transgender men did not demonstrate a change in BP, whereas transgender women on GHT demonstrated both increases and decreases in SBP. These studies were heterogenous with significant methodological limitations and only two were determined to have a good quality rating. There is currently insufficient data to advise the impact of GHT on BP in transgender individuals. Better quality research is essential to elucidate whether exogenous sex hormones modulate BP in transgender people and whether this putative alteration infers poorer cardiovascular outcomes.


The Experiences of Individuals with a History of Acute Exacerbations of COPD and Their Thoughts on Death: Empirical Qualitative Research.
The most important problem of chronic obstructive pulmonary disease (COPD) patients is acute exacerbation. Researching this experience and examining its relationship with death is extremely important in patient care. This study was conducted to reveal the experiences of individuals with a history of acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) and their thoughts on death by qualitative empirical research. The study was conducted in a pulmonology clinic between July and September 2022. In-depth face-to-face interviews were conducted with patients in their rooms using a semi-structured form created specifically for the study and used as a data collection tool. With patient consent, interviews were recorded and documented. During the data analysis phase, the Colaizzi method was used. The study was presented in accordance with the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist for qualitative research. The study was completed with 15 patients. A total of 13 of the patients were male and the mean age was 65 years. Patient statements were coded after the interviews and collected under 11 sub-themes. These sub-themes were categorized under the following main themes: recognizing AECOPDs, AECOPD instant experiences, post-AECOPD, and thoughts on death. Patients were able to recognize the symptoms of an AECOPD, that the severity of the symptoms increased during the exacerbation, that they felt regret or anxiety about re-exacerbation, and that all of these factors contributed to their fear of death.


Spontaneous and lymphokine-induced cytotoxic activity of monkey intestinal mucosal lymphocytes.
We determined the capacity of primate (macaque monkey) intestinal mucosal lymphocytes to mediate natural killer cytotoxicity, and characterized the nature of cells mediating this form of cytotoxicity in the intestine. Isolated macaque monkey intestinal mucosal lymphocytes were found to have intermediate levels of spontaneous cytotoxicity against K562 target cells compared to higher values found in lymphocytes of peripheral blood (PBL) and spleen and low values for mesenteric lymph node (MLN) lymphocytes. Intestinal lymphocytes were similar to PBL in having the same range of target cell specificites, in having augmentation of activity by interferon or interleukin 2, and in demonstrating specificity in cold target inhibition studies. Both intestinal and PBL spontaneous cytotoxic function in primates was mediated predominantly by cells bearing antigens cross-reactive with the anti-human monoclonal antibody Leu-11. The percentage of Leu-11+ lymphocytes was significantly lower in isolated intestinal, spleen, and MLN lymphocytes compared to peripheral blood. Furthermore, isolated intestinal lymphocytes differed from PBL in that intestinal Leu-11+ were predominantly Leu-15-, while Leu-11+ PBL were predominantly Leu-15+. These studies demonstrate that the lower spontaneous cytotoxic function of intestinal mucosal lymphocytes compared to PBL is associated with a lower number of effector cells and with effector cells which differ qualitatively in expression of the Leu-15 antigen.


Activatable Mn2+-Armed nanoagonist augments antitumor immunity in colorectal cancer: A NIR-II Photonic neoadjuvant paradigm.
Postoperative recurrence frequently occurs in patients with colorectal cancer (CRC) due to residual microtumors and host cellular immune dysfunction, leading to major setbacks in clinical outcomes and CRC staging. As an increasingly prevalent therapeutic option for CRC patients, neoadjuvant chemoradiotherapy bears unmet challenges of limited tumor targeting and common side effects of gastrointestinal reaction and radiodermatitis. It is highly desirable to develop neoadjuvant treatment paradigms that impart both tumor-targeting accuracy and protection against recurrence of resectable CRC. Here we report a versatile photo-regulated nanoagonist of plasmonic gold blackbody (AuPB) with a polydopamine (PDA) coating carrying manganese ion (Mn2+) payloads (AuPB@PDA/Mn). When armed with second near-infrared (NIR-II) light, AuPB@PDA/Mn with broad-band localized surface plasmon resonance generates local hyperthermia and discharges Mn2+ ions, which evidently amplify the effects of immunogenic cell death in tumor cells and activate the cyclic GMP-AMP synthase/stimulator of interferon genes pathway in dendritic cells (DCs), hence potentiating the maturation of DC and the secretion of type I interferon in a synergistic way. Matured DCs undertake the task of tumor antigen presentation as the crosstalk to adaptive immunity. As such, the administration of AuPB@PDA/Mn coupled with NIR-II laser irradiation has eminently augmented the infiltration of CD8+ T cells as well as the development of memory CD8+ T cells in colorectal tumor models, substantiating enhanced immunomodulatory efficacy against primary and recurrent CRC. Our strategy highlights the potency of an integrated NIR-II photothermal and immunoregulatory modality by photo-activate delivery of Mn2+ ions, as a neoadjuvant paradigm for presurgical tumor debulking and against postoperative tumor recurrence.


Overall survival is similar between women who seek care at one or more institutions after diagnosis of operable breast cancer in the community.
As breast cancer diagnoses increase, so does the number of patients who are critically evaluating hospital attributes to determine where to receive their treatment. Evidence suggests that complex surgeries have better outcomes in high volume academic centers. Whether clinical outcomes of women diagnosed with operable breast cancer, who are treated by multiple disciplines including non-complex surgical approaches, differ for those received all or part of their treatment at their community cancer center is unclear. We hypothesize that the clinical outcomes do not differ for those who received all or part of their care at their community cancer center. Our aim is to analyze data from the National Cancer Database (NCDB) to assess the clinical characteristics and outcomes of patients who received all their treatment at community cancer center when compared with those who had part or all of their care elsewhere. A cohort of 162,803 women diagnosed at a community cancer center with an operable breast cancer (clinical stage I - III) between 2005 and 2014 from the NCDB was evaluated. Demographics, cancer-specific characteristics and overall survival differences between patients who stay at or leave their home institution for breast cancer treatment were compared. Within this cohort, patients treated at multiple institutions were younger, traveled further from home for their care, and were more likely to have no comorbidities (p < 0.001). Overall survival adjusted for demographics and cancer stage and subtype did not differ based on treatment at one or multiple institutions. The decision for patients to undergo breast cancer treatment in a different institution after being diagnosed in a community center does not appear to impact overall survival.


Ischemic Stroke Severity and Mortality in Patients With and Without Atrial Fibrillation.
Background Our objective was to investigate stroke severity and subsequent rate of mortality among patients with and without atrial fibrillation (AF). Contemporary data on stroke severity and prognosis in patients with AF are lacking. Methods and Results First-time ischemic stroke patients from the Danish Stroke Registry (January 2005-December 2016) were included in an observational study. Patients with AF were matched 1:1 by sex, age, calendar year, and CHA2DS2-VASc score with patients without AF. Stroke severity was determined by the Scandinavian Stroke Scale (0-58 points). The rate of death was estimated by Kaplan-Meier plots and multivariable Cox regression. Among 86 458 identified patients with stroke, 17 205 had AF. After matching, 14 662 patients with AF and 14 662 patients without AF were included (51.8% women; median age, 79.6 years [25th-75th percentile, 71.8-86.0]). More patients with AF had very severe stroke (0-14 points) than patients without AF (13.7% versus 7.9%, P<0.01). The absolute rates of 30-day and 1-year mortality were significantly higher for patients with AF (12.1% and 28.4%, respectively) versus patients without AF (8.7% and 21.8%, respectively). This held true in adjusted models for 30-day mortality (hazard ratio [HR], 1.40 [95% CI, 1.30-1.51]). However, this association became nonsignificant when additionally adjusting for stroke severity (HR, 1.10 [95% CI, 1.00-1.23]). AF was associated with a higher rate of 1-year mortality (HR, 1.39 [95% CI, 1.32-1.46]), although it was mediated by stroke severity (HR, 1.15 [95% CI, 1.09-1.23], model including stroke severity). Conclusions In a contemporary nationwide cohort of patients with ischemic stroke, patients with AF had more severe strokes and higher mortality than patients without AF. The difference in mortality was mainly driven by stroke severity.


[The differential diagnosis of cochlear, retrocochlear and central hearing disorders, and the limitations of conventional audiometry (author's transl)].
A review is made of the difficulties of audiometric diagnosis resulting from inadequate anatomical, physiological and pathological knowledge of the auditory system and from discrepancies in audiometric technique. Even with a broad battery of tests there is in 20-40% of cases an inconsistent audiometric pattern, which differs from the expected and typical cochlear eighth nerve, brain stem and cortical responses. These are demonstrated in presbyacusis, Meniere's disease, acoustic tumours, brainstem disorders and temporal lobe disease.


Ventral and incisional hernia: the cost of comorbidities and complications.
Ventral and incisional hernia repair (VIHR) is among the most frequently performed abdominal operations with significant incidence of postoperative complications and readmissions. Payers are targeting increased "value" of care through improved outcomes and reduced costs. Cost data in clinically relevant terms is still rare. This study aims to identify hospital costs associated with clinically relevant factors in order to facilitate strategies by surgeons to enhance the value of VIHR. An IRB-approved retrospective review of VIHRs performed at the University of Kentucky from April 2009 through September 2013 was conducted. NSQIP clinical data and hospital cost data were matched. Operating room (ORC), total encounter (TEC), and 90-day postdischarge (90PDC) hospital costs were analyzed relative to clinical variables using non-parametric tests. In total 385 patients that underwent VIHR during the time period were included in the analyses. Considering all VIHRs, median [interquartile range (IQR)] ORC was $6900 ($5600-$10,000); TEC was $10,700 ($7500-$18,600); and 90PDC was $0 ($0-$800). Compared to all VIHRs, ASA Class ≥ 3 was associated with increased ORC and TEC (p < .001), and 90PDC (p < .01). Preoperative open wound was associated with increased ORC and TEC (p < .001). Numerous operative variables were associated with both increased ORC and TEC. Wound Class > 1 was associated with increased ORC and TEC (p < .001) and 90PDC (p < .01). Inpatient occurrence of any complication was associated with increased TEC and 90PDC (p < .001). ASA Class ≥ 3, Wound Class > 1, open abdominal wound, and postoperative complications significantly increase costs. Although the hospital encounter represents the majority of the cost associated with VIHR, additional costs are incurred during the 90-day postoperative period. An appreciation of global costs is essential in developing alternative payment models for hernia in order to provide the greatest value in hernia care.


Correction: Patterns of Protein Evolution in Cytochrome c Oxidase 1 (COI) from the Class Arachnida.
[This corrects the article DOI: 10.1371/journal.pone.0135053.].


Loss of SDHB Elevates Catecholamine Synthesis and Secretion Depending on ROS Production and HIF Stabilization.
Germline mutations in genes encoding succinate dehydrogenase subunits are associated with the development of familial pheochromocytomas and paragangliomas [hereditary paraganglioma/pheochromocytoma syndrome (HPPS)]. In particular, a mutation in succinate dehydrogenase subunit B (SDHB) is highly associated with abdominal paraganglioma and subsequent distant metastasis (malignant paraganglioma), indicating the importance of SDHB genetic testing. The discovery of HPPS suggests an association among genetic mitochondrial defects, tumor development, and catecholamine oversecretion. To investigate this association, we transfected pheochromocytoma cells (PC12) with SDHB-specific siRNA. SDHB silencing virtually abolished complex II activity, demonstrating the utility of this in vitro model for investigating the pseudo-hypoxic drive hypothesis. Lack of complex II activity resulting from RNA interference of SDHB increased tyrosine hydroxylase (TH; the rate-limiting enzyme in catecholamine biosynthesis) activity and catecholamine secretion. Reduced apoptosis was observed accompanied by Bcl-2 accumulation in PC12 cells, consistent with the phenotypes of paragangliomas with SDHB mutations. In addition, SDHB silencing increased reactive oxygen species (ROS) production and nuclear HIF1α stabilization under normoxic conditions. Furthermore, phenotypes induced by complex II activity knockdown were abolished by pretreatment with N-acetyl cysteine (an ROS scavenger) and by prior HIF1α knockdown, indicating an ROS- and HIF1α-dependent mechanism. Our results indicate that increased ROS may act as signal transduction messengers that induce HIF1α stabilization and may be necessary for the pseudo-hypoxic states observed in our experimental model. To our knowledge, this is the first study demonstrating that pseudo-hypoxic states resulting from SDHB knockdown are associated with increased TH activity and catecholamine oversecretion.


Use of the barium enema in the diagnosis of necrotizing enterocolitis.
Necrotizing enterocolitis (NEC) is associated with considerable morbidity and mortality in infants. The diagnosis relies heavily upon radiographic and clinical features. Failure to accurately diagnose NEC is associated with a risk of complications and death, however overdiagnosis also causes both morbidity and mortality as well as excessive medical costs. This report documents the use of barium enema to evaluate suspected clinical or radiographic NEC in 31 premature infants with ambiguous clinical and radiographic signs. The enema was normal in 26 infants and no treatment for NEC was given. Only one of these infants developed signs of NEC subsequent to the examination. Five infants had radiographic evidence of colitis including small ulcerations, spasm, intramural extravasation of barium and mucosal irregularity. Two of the five positive cases are pathologically documented. The barium enema can represent a significant improvement in the specificity of the diagnosis of NEC. Its greatest value is in the exclusion of NEC in ambiguous cases.


Vitamin D Status Does Not Affect Disability Progression of Patients with Multiple Sclerosis over Three Year Follow-Up.
The risk of developing multiple sclerosis (MS) as well as MS disease activity is associated with vitamin D (25(OH)D) status. The relationship between the main functional disability hallmark of MS, disability progression, and 25(OH)D status is less well established though, especially not in MS patients with progressive disease. This retrospective follow-up study included 554 MS patients with a serum baseline 25(OH)D level and Expanded Disability Status Scale (EDSS) with a minimum follow-up of three years. Logistic regressions were performed to assess the effect of baseline 25(OH)D status on relapse rate. Repeated measures linear regression analyses were performed to assess the effect on disability and disability progression. Baseline deseasonalized 25(OH)D status was associated with subsequent relapse risk (yes/no), but only in the younger MS patients (≤ 37.5 years; OR = 0.872, per 10 nmol/L 25(OH)D, p = 0.041). Baseline 25(OH)D status was not significantly associated with either disability or disability progression, irrespective of MS phenotype. Within the physiological range, 25(OH)D status is just significantly associated with the occurrence of relapses in younger MS patients, but is not associated with disability or disability progression over three years follow-up. Whether high dose supplementation to supra physiological 25(OH)D levels prevents disability progression in MS should become clear from long term follow-up of supplementation studies.


A novel automatic flow-batch extraction induced by emulsion breaking platform for on-line copper determination in edible oil samples by atomic absorption spectrometry.
A novel automatic flow-batch platform coupled with atomic spectrometry for on-line acidic extraction induced by emulsion breaking with heating (FB-EIEBH) for metal determination in edible oils (corn, sunflower and olive oil), was developed for the first time. The proposed system was demonstrated for copper determination in conjunction with flame atomic absorption spectrometry. The extraction of metal is accomplished after the oil emulsification with an aqueous solution consisted of Triton X-114 and nitric acid, in an on-line programmed manner. All the main parameters affecting the extraction procedure, such as oil dilution, type and concentration of surfactant and nitric acid as well as temperature and time for the emulsion breaking and phase separation, have been investigated and optimized. A mixture of oil/xylene at 10:2 proportion was found to be appropriate to use in the flow manifold. Optimum conditions were verified employing 8.0 mL of oil sample, 990 μL of extractant solution containing 10.0% m/v Triton X-114 and 10.0% v/v HNO3. Emulsion breaking and phases separation were completed at temperature 90 °C, and time 300 s. The detection and quantification limit for copper determination was found to be 5.8 μg L-1 and 19.3 μg L-1, employing aqueous standards, which are proved to produce similar performance characteristics with oil-based standards. Recovery tests were executed by appropriate additions of oil-based standard solution of copper and the recoveries ranged between 94.2 and 102.4%.


The Joint Committee for Traceability in Laboratory Medicine (JCTLM) - its history and operation.
The Joint Committee for Traceability in Laboratory Medicine (JCTLM) was formed to bring together the sciences of metrology, laboratory medicine and laboratory quality management. The aim of this collaboration is to support worldwide comparability and equivalence of measurement results in clinical laboratories for the purpose of improving healthcare. The JCTLM has its origins in the activities of international metrology treaty organizations, professional societies and federations devoted to improving measurement quality in physical, chemical and medical sciences. The three founding organizations, the International Committee for Weights and Measures (CIPM), the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and the International Laboratory Accreditation Cooperation (ILAC) are the leaders of this activity. The main service of the JCTLM is a web-based database with a list of reference materials, reference methods and reference measurement services meeting appropriate international standards. This database allows manufacturers to select references for assay traceability and provides support for suppliers of these services. As of mid 2015 the database lists 295 reference materials for 162 analytes, 170 reference measurement procedures for 79 analytes and 130 reference measurement services for 39 analytes. There remains a need for the development and implementation of metrological traceability in many areas of laboratory medicine and the JCTLM will continue to promote these activities into the future.


Dietary glycemic index and glycemic load, and breast cancer risk: a case-control study.
Certain types of carbohydrates increase glucose and insulin levels to a greater extent than others. In turn, insulin may raise levels of insulin-like growth factors, which may influence breast cancer risk. We analyzed the effect of type and amount of carbohydrates on breast cancer risk, using the glycemic index and the glycemic load measures in a large case-control study conducted in Italy. Cases were 2,569 women with incident, histologically-confirmed breast cancer interviewed between 1991 and 1994. Controls were 2588 women admitted to the same hospital network for a variety of acute, non-neoplastic conditions. Average daily glycemic index and glycemic load were calculated from a validated 78-item food frequency questionnaire. Direct associations with breast cancer risk emerged for glycemic index (odds ratio, OR for highest vs. lowest quintile = 1.4; P for trend <0.01) and glycemic load (OR = 1.3; P < 0.01). High glycemic index foods, such as white bread, increased the risk of breast cancer (OR = 1.3) while the intake of pasta, a medium glycemic index food, seemed to have no influence (OR = 1.0). Findings were consistent across different strata of menopausal status, alcohol intake, and physical activity level. This study supports the hypothesis of moderate, direct associations between glycemic index or glycemic load and breast cancer risk and, consequently, a possible role of hyperinsulinemia/insulin resistance in breast cancer development.


A novel phenolphthalein-based fluorescent chemosensor for pyrophosphate detection via an Al3+ displacement approach in real samples and living cells.
Herein, we report a new phenolphthalein appended Schiff base (PASB) as reversible fluorescent sensor for the detection of pyrophosphate (PPi) ions through the metal displacement mechanism. PASB showed sensing exclusively toward Al3+ ions in DMF/H2O (v/v = 1/4, pH 5.5) solution, which resulted in a significant fluorescence enhancement at 540 nm. The 1: 2 binding stoichiometry for the complex formation between PASB and Al3+ was confirmed by Job's plot and mass spectroscopic studies. Moreover, a solution of the in situ formed PASB-Al3+ complex displayed a high selectivity to PPi. The addition of PPi to PASB-Al3+ ensemble significantly quenched its fluorescence. Thus, a dual response was established based on "Off-On-Off" strategy for detection of both Al3+ and PPi. The detection limit is 5.86 nM and 26 nM for Al3+ and PPi, respectively. On this basis, we use PASB to detect Al3+ in food samples. Furthermore, PASB was successfully applicable to detect Al3+ and PPi for intracellular imaging in Human liver cancer cells.


Comparison of nonbronchoscopic bronchoalveolar lavage to open lung biopsy for the bacteriologic diagnosis of pulmonary infections in mechanically ventilated patients.
We compared nonbronchoscopic bronchoalveolar lavage (NB-BAL) with open lung biopsy to determine the etiological diagnosis of lung infiltrates in patients requiring mechanical ventilation. NB-BAL was performed via a cuffed reusable 7F catheter generally used for right heart catheterization (BAL-C). In 13 patients, BAL-C and open lung biopsy were performed in the same lobe immediately after death when the ventilator was still functioning. No organism was cultured from BAL-C cultures when histopathologic examination of the lung showed no pneumonia and lung culture isolated no organism. Among the 10 positive BAL-C cultures, lung biopsy showed histologic pneumonia in 9 cases. Among these 9 pneumonia cases, 14 organisms were isolated in lung cultures and BAL-C correctly identified the causative agent in 13 cases. BAL-C appears to be an effective and safe procedure in the diagnosis of pulmonary infections in patients under mechanical ventilation who have previously received antibiotic therapy.


Smart hyaluronidase-actived theranostic micelles for dual-modal imaging guided photodynamic therapy.
We here report smart hyaluronidase-actived theranostic nanoparticles based on hyaluronic acid (HA) coupled with chlorin e6 (Ce6) via adipic dihydrazide (ADH) forming HA-ADH-Ce6 conjugates and self-assembling into HACE NPs. The resulting nanoparticles showed stable nano-structure in aqueous condition with uniform size distribution and can be actively disassembled in the presence of hyaluronidase (over-expressed in tumor cells), exhibiting hyaluronidase-responsive "OFF/ON" behavior of fluorescence signal. The HACE NPs were rapidly taken up to human lung cancer cells A549 via CD44 (the HA receptor on the surface of tumor cells) receptor mediated endocytosis. Upon laser irradiation, the HACE NPs realized good near-infrared fluorescence imaging and photoacoustic imaging in the tumor bearing mice, which showed 5-fold higher fluorescence intensity and 3-fold higher photoacoustic (PA) intensity than free Ce6, respectively. In addition, under low dose of laser power, the HACE NPs presented more effective photodynamic therapy to suppression of tumor growth than free Ce6 in vitro and in vivo. Overall, these results suggest that the well-defined HACE NPs is a biocompatible theranostic nanoplatform for in vivo dual-modal tumor imaging and phototherapy simultaneously.


Complex nontuberculous mycobacterial cervicofacial lymphadenitis: What is the optimal approach?
Assess the role of combined antimicrobial and surgical therapy for difficult-to-treat nontuberculous mycobacteria (NTM) lesions of the head and neck in children. Retrospective cohort. Retrospective review of pediatric head and neck NTM lesions at a tertiary children's hospital from 1999 to 2012. Seventy-one children were diagnosed with NTM lesions. Age of presentation ranged between 7 and 204 months of age. Most patients (62%) had multiple lesions. Treatments included incision and drainage, curettage, antibiotics, excision, and any combination of surgery and antibiotics. Upon initial presentation, the most common treatment was surgical excision alone (n = 34) with a high complication rate (50%). In 18 cases, patients were initially treated with a combination of antibiotics and surgical excision due to the extent or location of the lesion(s). Complication rate in these patients was also high (67%). The most common complications in surgically excised NTM lesions included temporary or persistent facial nerve dysfunction (24.6%), poor wound healing/scarring (10.8%), and Frey's syndrome (6.2%). Surgical excision with or without medical therapy for NTM cervicofacial lymphadenitis in high-risk regions commonly resulted in marginal mandibular nerve dysfunction (24.6%). Postoperative facial nerve weakness generally resolved within a year. High rates of complications and a lack of proven best approaches suggest tailoring the approach to address the potential risks in that particular patient based on location and severity. 4 Laryngoscope, 126:1677-1680, 2016.


Post-mastectomy radiotherapy: Impact of bolus thickness and irradiation technique on skin dose.
To determine 10 MV IMRT and VMAT based protocols with a daily bolus targeting a skin dose of 45 Gy in order to replace the 6 MV tangential fields with a 5 mm thick bolus on alternate days method for post-mastectomy radiotherapy. We measured the mean surface dose along the chest wall PTV as a function of different bolus thicknesses for sliding window IMRT and VMAT plans. We analyzed surface dose profiles and dose homogeneities and compared them to our standard 6 MV strategy. All measurements were performed on a thorax phantom with Gafchromic films while dosimetric plans were computed using the Acuros XB algorithm (Varian). We obtained the best compromise between measured surface dose (mean dose and homogeneity) and skin toxicity threshold obtained from the literature using a daily 3 mm thick bolus. Mean surface doses were 91.4 ± 2.8% [85.7% - 95.4%] and 92.2 ± 2.3% [85.6% - 95.2%] of the prescribed dose with IMRT and VMAT techniques, respectively. Our standard 6 MV alternate days 5 mm thick bolus leads to 89.0 ± 3.7% [83.6% - 95.5%]. Mean dose differences between measured and TPS results were < 3.2% for depths as low as 2 mm depth. 10 MV IMRT-based protocols with a daily 3 mm thick bolus produce a surface dose comparable to the standard 6 MV 5 mm thick bolus on alternate days method but with an improved surface dose homogeneity. This allows for a better control of skin toxicity and target volume coverage.


Use of low density polyethylene membranes for assessment of genotoxicity of PAHs in the Seine River.
The genotoxicity of river water dissolved contaminants is usually estimated after grab sampling of river water. Water contamination can now be obtained with passive samplers that allow a time-integrated sampling of contaminants. Since it was verified that low density polyethylene membranes (LDPE) accumulate labile hydrophobic compounds, their use was proposed as a passive sampler. This study was designed to test the applicability of passive sampling for combined chemical and genotoxicity measurements. The LDPE extracts were tested with the umu test (TA1535/pSK1002 ± S9) and the Ames assay (TA98, TA100 and YG1041 ± S9). We describe here this new protocol and its application in two field studies on four sites of the Seine River. Field LDPE extracts were negative with the YG1041 and TA100 and weakly positive with the TA98 + S9 and Umu test. Concentrations of labile mutagenic PAHs were higher upstream of Paris than downstream of Paris. Improvement of the method is needed to determine the genotoxicity of low concentrations of labile dissolved organic contaminants.


Effects of fetal bovine serum deprivation in cell cultures on the production of Anticarsia gemmatalis multinucleopolyhedrovirus.
Anticarsia gemmatalis is a pest in South America's soybean crops, which could be controlled by the Multinucleopolyhedrovirus of A. gemmatalis (AgMNPV). Currently, its commercial production is based on infected larvae. However, the possibility of using modified baculoviruses in Integrated Pest Management programs has stimulated an interest to develop alternative multiplication processes. This study evaluated the AgMNPV production in UFL-Ag-286 cells previously deprived Fetal Bovine Serum. Culture media containing 1% FBS during the previous 48 hours achieved a synchronized condition where 90% of cells were found in G0/G1 stage, showing the presence of non-filamentous actin. All characteristics were estimated from cellular viability tests, cell actin detection trials and flow cytometer cell cycle analysis. AgMNPV production was tested by transcript studies and budded viruses (BVs) and occlusion bodies (OBs) yield quantitation. Results showed that the productivity in FBS deprived cells was 9.8 times more in BVs and 3.8 times more in OBs with respect to non-treated cells. UFL-Ag-286 cells previously deprived in FBS shown to be a better host for AgMNPV propagation, increasing the useful for both in vitro bioinsecticide production and applications such as recombinant protein expression or gene delivery.


The 9p21 polymorphism is linked with atrial fibrillation during acute phase of ST-segment elevation myocardial infarction.
The aim of the study was to find whether patients carrying polymorphic allele of the rs10757278 polymorphism from 9p21 locus have changed risk of arrhythmia (atrial fibrillation, AF; sustained ventricular tachycardia or ventricular fibrillation, sVT/VF) during acute phase of myocardial infarction. Retrospective analysis of data collected prospectively from two independent centers was performed. The clinical data were pooled from two independent cardiac registries: (1) the Warsaw ACS genetic registry (STEMI and NSTEMI/UA patients hospitalized in the years 2008-2011; only STEMI patients were analyzed); (2) the Bialystok STEMI genetic registry (STEMI patients hospitalized in years 2001-2005, who survived the first 48 h from hospital admission). Data regarding sVT/VF and AF within first 24 h were analyzed. The patients were genotyped with rs10757278 polymorphism. 1083 patients were included in the analysis; 62 (5.7 %) patients had sVT/VF during acute phase and 78 (7.2 %) patients had AF, 46 (4.2 %) patients had new-onset AF. Minor allele frequency in all patients with AF was significantly different from those without AF (0.40 vs 0.51, p = 0.0096). When only new-onset AF was analyzed, the trend was the same, with significant protective effect in recessive model [OR 0.41 (95 % CI 0.17-0.97), p = 0.025]. The effect was independent of age and GRACE score. No relationship was found between sVT/VF and rs10757278. Patients with STEMI, who survived until hospitalization with polymorphic allele of 9p21 rs10757278 SNP have less AF during acute phase of STEMI. SNP rs10757278 is not linked with sVT/VF in acute phase of STEMI.


Peptide YY (1-36) peptides from phylogenetically ancient fish targeting mammalian neuropeptide Y1 receptors demonstrate potent effects on pancreatic β-cell function, growth and survival.
To investigate the antidiabetic efficacy of enzymatically stable Peptide YY (PYY) peptides from phylogenetically ancient fish. N-terminally stabilized, PYY (1-36) sequences from Amia calva (bowfin), Oncorhynchus mykiss (trout), Petromyzon marinus (sea lamprey) and Scaphirhynchus albus (sturgeon), were synthesized, and both biological actions and antidiabetic therapeutic efficacy were assessed. All fish PYY (1-36) peptides were resistant to dipeptidyl peptidase-4 (DPP-4) degradation and inhibited glucose- and alanine-induced (P < 0.05 to P < 0.001) insulin secretion. In addition, PYY (1-36) peptides imparted significant (P < 0.05 to P < 0.001) β-cell proliferative and anti-apoptotic benefits. Proliferative effects were almost entirely absent in β cells with CRISPR-Cas9-induced knockout of Npyr1. In contrast to human PYY (1-36), the piscine-derived peptides lacked appetite-suppressive actions. Twice-daily administration of sea lamprey PYY (1-36), the superior bioactive peptide, for 21 days significantly (P < 0.05 to P < 0.001) decreased fluid intake, non-fasting glucose and glucagon in streptozotocin (STZ)-induced diabetic mice. In addition, glucose tolerance, insulin sensitivity, pancreatic insulin and glucagon content were significantly improved. Metabolic benefits were linked to positive changes in pancreatic islet morphology as a result of augmented (P < 0.001) proliferation and decreased apoptosis of β cells. Sturgeon PYY (1-36) exerted similar but less impressive effects in STZ mice. These observations reveal, for the first time, that PYY (1-36) peptide sequences from phylogenetically ancient fish replicate the pancreatic β-cell benefits of human PYY (1-36) and have clear potential for the treatment of type 2 diabetes.


Safety, tolerability and pharmacokinetics of AFN-1252 administered as immediate release tablets in healthy subjects.
AFN-1252 is a novel inhibitor of FabI, an essential enzyme in Staphylococcus spp. This study was undertaken to assess the safety, tolerability and pharmacokinetic properties of AFN-1252, following oral administration in an ascending dose trial. This was a double-blind, randomized, placebo-controlled, two-part study. In Part I, single doses (QD) of 100, 200, 300, or 400 mg AFN-1252 were administered. In Part II, subjects received 200, 400, 600, or 800 mg (total daily dose) where 100, 200 and 400-mg doses were given twice in one day. AFN-1252 was well-absorbed with Cmax at 3-4 h when given once per day and 2.5-9 h when dosed twice in a single dosing day. T½ ranged from 8 to 11 h. Total and peak exposures of AFN-1252 increased nonlinearly. Adverse events were primarily mild and resolved promptly. Oral doses of AFN-1252 were safe and well tolerated. AFN-1252 has the potential for once or twice-a-day dosing for treatment of staphylococcal infections.


Soft tissue Burkitt's lymphoma: radiological findings.
An unusual case is reported of a soft tissue mass in the lower extremity, without bone involvement, in an 85-year-old woman; the histopathological diagnosis was Burkitt's lymphoma. Pertinent clinical history, histological examination, and imaging procedures allowed early diagnosis. To our knowledge, the radiological findings in Burkitt's lymphoma with this unusual clinical presentation have not been described previously.


Recurrence of endometrial adenocarcinoma in a prior Bartholin's cyst marsupialization incision.
Endometrial cancer recurrences in surgical incisions are rare and thought to be due to seeding of the area with microscopic disease at the time of original surgery. A 53-year-old woman underwent a dual procedure of a marsupialization of a benign bartholin's cyst with a hysteroscopic dilation and curettage for postmenopausal bleeding and received the diagnosis of endometrial adenocarcinoma. Final pathology from subsequent hysterectomy and staging procedure demonstrated a surgical Stage IB Grade 1 endometrial cancer. An isolated recurrence of disease in her marsupialization scar was discovered 10 months after her staging procedure. This case represents the only described endometrial cancer recurrence in a Bartholin's gland which was contaminated at the time of the original hysteroscopy and dilation and curettage.


Antithymocyte globulin induction therapy adjusted for immunologic risk after heart transplantation.
The efficacy of antithymocyte globulin (ATG) induction in the therapy of immunologically low- and high-risk patients after heart transplantation is not known. All patients who received ATG induction from January 2000 through January 2010 were divided into two groups based on the risk of rejection. A higher-risk group (age younger than 60 years, multiparous females, African Americans, panel-reactive antibody >10%, or positive cross-match) received ATG (1.5 mg/kg) for 7 days (ATG7), and the remaining lower-risk group received ATG for 5 days (ATG5), all followed by calcineurin inhibitor, mycophenolate, and prednisone. Endomyocardial biopsies were performed based a standard protocol for up to 3 years after heart transplantation, and for suspected rejection. Of 253 heart transplant recipients, 87 received ATG5 and 166 ATG7. Absolute lymphocyte count <200 per microliter was achieved within 10 days in 88% of ATG5 and 86% of ATG7. Baseline creatinine was 1.3 ± 0.8 pre-transplantation, 1.8 ± 0.9 post-transplantation, and 1.0 ± 0.4 mg/dL at discharge (mean ± standard deviation [SD]; P < .001, compared with pre-transplantation). Of 3667 biopsies, 33 (0.90%) had ≥3A/2R cellular rejection (CR). Of 3599 biopsies, 16 (0.44%) had definite antibody-mediated rejection (AMR). At 5 years, freedom from ≥3A/2R CR (94% ± 2.8% vs 83% ± 7.7%; P = .31) and freedom from AMR (95% ± 2.4% vs 90% ± 6.4%; P = .98) were similar between ATG5 and ATG7, respectively. Survival for ATG5 and ATG7 was comparable at one year (94% ± 2.5% vs 93% ± 2.0%), and at 8 years (61% ± 6.9% and 61% ± 4.7%; P = .88). At 5 years, ATG5 and ATG7 were similar in freedom from cytomegalovirus (CMV) infection (92.3% vs 94.3%; P = not significant [NS]), freedom from pneumonia (83.8% vs 82.1%; P = NS), and in rate of malignancy (excluding skin cancer; 8.0% vs 6.0%; P = NS). ATG induction therapy (prospectively dose-adjusted for immunologic risk) in low- and high-risk patients results in excellent and equivalent short- and long-term survival rates, with a low incidence of CR and AMR. The use of ATG does not increase rates of CMV infection with appropriate prophylaxis. ATG may benefit renal function by delaying calcineurin inhibitor exposure, and may have a role in the prevention of AMR.


Use of additive solutions and pathogen inactivation treatment of platelet components in a regional blood center: impact on patient outcomes and component utilization during a 3-year period.
The Etablissement Français du Sang Alsace (EFS Alsace) successively implemented universal use of platelet additive solutions (PASs) and pathogen inactivation (PI) for platelet components (PCs). To assess the impact of these changes, EFS Alsace evaluated PC use, red blood cell (RBC) component use, and transfusion-related adverse events after implementation of these new technologies. EFS Alsace prospectively collects data on production, distribution, and response to transfusion of all blood components with greater than 99.5% data acquisition. Adverse events attributed to platelet (PLT) transfusions were collected through a mandatory, active hemovigilance program. A retrospective review of prospectively collected data was conducted covering three periods: 1) apheresis and whole blood-derived PCs in plasma, 2) apheresis and whole blood-derived PCs with PAS, and 3) PCs prepared with PI and PAS. Data on component utilization were analyzed for all patients receiving PCs in each period and for the subset of hematology-oncology patients to evaluate PC use in an intensely transfused population. Values for all continuous variables were summarized as mean and standard deviation, median, and range. Approximately 2000 patients received PCs in each period. PLT and RBC use per patient was not increased after PI (analysis of variance, F = 1.9 and 2.9, respectively) and the incidence of acute transfusion reactions was significantly reduced (p < 0.001). Universal use of PI was implemented without impacting component use, as indicated by total dose of PLTs per patient, and outcomes to transfusion were improved.


High-level extracellular production of alkaline polygalacturonate lyase in Bacillus subtilis with optimized regulatory elements.
The present work aims to construct a robust recombinant Bacillus subtilis to achieve secretory production of alkaline polygalacturonate lyase (PGL). First, 6 signal peptides (amyX, bpr, vpr, yvgO, wapA and nprE) were screened with a semi-rational approach and comparatively investigated their effects on the production of PGL. The signal peptide bpr directed efficient PGL secretory expression and increased PGL titer to 313.7 U mL(-1). By optimizing and applying strong promoter P43 and Shine-Dalgarno sequence, higher titer of 446.3 U mL(-1) PGL was achieved. Finally, the capacity of the recombinant B. subtilis WB43CB was evaluated with a fed-batch strategy in 3 L fermentor. The PGL titer reached 632.6 U mL(-1) with a productivity of 17.6 U mL(-1) h(-1), which was the highest secretory production of PGL by the B. subtilis system. The recombinant B. subtilis strain WB43CB constructed in the present work has great potential in production of alkaline PGL.


The brain landscape of the two-hit model of posttraumatic stress disorder.
The neurophysiological mechanisms underlying the development of posttraumatic stress disorder (PTSD) are poorly understood. Here we test a proposal that PTSD symptoms reflect fixed, highly correlated neural networks resulting from massive engagement of sensory inputs and the sequential involvement of those projections to limbic areas. Three-tesla functional magnetic resonance imaging (fMRI) data were acquired at rest in 15 veterans diagnosed with PTSD and 21 healthy control veterans from which zero-lag cross correlations between 50 brain areas (N = 1,225 pairs) were computed and analyzed. The brain areas were assigned to tiers based on the neurocircuitry of successively converging sensory pathways proposed by Jones and Powell (Jones EG, Powell TP. Brain 93: 793-820, 1970). The primary analyses assessed normalized proportional differences in cross correlation strength within and across tiers in veterans with PTSD and control veterans. Compared with control veterans, cross correlation strength was higher in veterans with PTSD, within and across tiers of areas involved in processing sensory inputs, and systematically increased from sensory processing areas to limbic areas. The functional relevance of this hypercorrelation was further documented by the finding that the severity of self-reported PTSD symptomatology was positively associated with higher neural correlations.NEW & NOTEWORTHY The neurophysiological mechanisms underlying the development of PTSD are poorly understood. Here we document that massive engagement of sensory modalities during trauma exposure leads to fixed, hypercorrelated frontal, parietal, temporal, and limbic networks, reflecting the successive integration of salient sensory inputs along the framework of Jones and Powell.


Two Laparotomy Surgeries to Achieve Hemostasis After Kidney Transplantation in a Patient With Frailty: A Case Report.
The assessment of frailty before and after kidney transplantation is becoming more important in the aging population. It is recommended to recognize the post-transplant risks and establish a treatment strategy. We report the case of a patient who underwent 2 laparotomy hemostasis procedures due to frailty after kidney transplantation. A 72-year-old woman presented with end-stage renal failure due to an unknown primary disease. She was also found to be frail when assessed using the physical frailty phenotype. She underwent ABO-incompatible kidney transplantation from her husband at the end of March 2020. On the first postoperative day, re-operation for hematoma evacuation was performed. The bleeding point could not be identified at that time. Progression of anemia was observed on the sixth postoperative day, and computed tomography showed no obvious bleeding. Subsequently, the renal allograft started functioning immediately, without rejection. However, emergency laparotomy for hematoma removal was performed on the 22nd postoperative day. Bleeding had occurred from the anastomotic region of the renal allograft artery and the external iliac artery. Her serum creatinine levels and renal function remained stable one month after surgery. We encountered a case of living-donor kidney transplantation in a frail older woman who underwent 2 laparotomies due to hemorrhage. Perioperative risk management is necessary for patients with a high risk of postoperative bleeding. To ensure a good outcome, preoperative and postoperative rehabilitation is important for patients with frailty.


Determining the effect of cardiac blood volume on accuracy of uptake rate constants by simulation.
Objective. There is great interest in better understanding coronary microvascular disease using mouse models. Typical quantification requires dynamic imaging to estimate the rate constantK1of the tracer moving from the blood into the myocardium. In addition toK1, it is also desirable to determine blood volume fractionV, which if known allows for more accurate fitting ofK1. Our previously published kinetic modeling software did not consider the effect ofV. To ensure a better fit of experimental data to the model for myocardialμSPECT imaging, in this work we updated our kinetic modeling software to include a blood volume fractionV, which adds a fraction of the arterial activity concentration into the tissue concentration.Approach. The tissue and blood time-activity curves (TACs) used for fit input were generated using ideal equations with known values in MATLAB. This allowed post-fit results to be compared to known values to determine fit errors. Parameters that were varied in generating the TACs included blood volume fraction (0, 0.05, 0.1, 0.2 and 0.3),K1(0.5, 1.5, 2.5 ml min-1g-1), frame length (1, 2, 5, 10, 15, 20 s), FWHM of the input Gaussian (10, 20, 40 s), and time of the injection peak relative to frame duration. Blood volume-fraction results have low error when blood volume is lowest, but results worsen as frame length andK1increase.Main results. We demonstrated that blood volume can be accurately determined, and also show how fit accuracy varies across TACs with different input properties.Significance. This information allows for robust use of the fitting algorithm and aids in understanding fit performance when used in animal studies.


Hyperthyroidism association with SLE, lessons from real-life data--A case-control study.
Despite the frequently encountered association between thyroid disease and systemic lupus erythematosus (SLE) is well known, it is of surprise that only several reports compromised of small population size support this observation. To investigate the association of comorbid SLE and hyperthyroidism. Using the database of the largest health maintenance organization (HMO) in Israel, the Clalit Health Services, we searched for the co-existence of SLE and hyperthyroidism. Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of hyperthyroidism in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study included 5018 patients with SLE and 25,090 age- and sex- matched controls. The prevalence of hyperthyroidism in patients with SLE was increased compared with the prevalence in controls (2.59% and 0.91%, respectively, p < 0.001). In a multivariate analysis, SLE was associated with hyperthyroidism (odds ratio 2.52, 95% confidence interval 2.028-3.137). Patients with SLE have a greater prevalence of hyperthyroidism than matched controls. Therefore, physicians treating patients with SLE should be aware of this possibility of this thyroid dysfunction.


The role of home medication storage location in increasing medication adherence for middle-aged and older adults.
Over 50% of US adults do not take their prescriptions as prescribed, which is responsible for 33%-69% of hospital admissions and 125,000 deaths annually. Given the higher prevalence of prescription drug use among middle-aged and older adult populations, promoting medication adherence is of particular importance with these age groups. Two speculated facilitators of medication adherence are home medication storage location and the use of digital health devices. Our objective was to use survey data to investigate the associations between medication storage location and medication adherence among adults 40 years and older. Additionally, we aimed to report preliminary findings about the associations between use of devices and medication adherence in this same population. We conducted primary analysis of data sampled from a home medication management survey deployed in November 2021 (n = 580). We conducted exploratory analyses by way of chi2 tests and creation of bivariate logistic regression models. The most commonly used storage locations by our sample were nightstand drawers (27%), kitchen cabinets (25%), and atop bedroom nightstands (23%). Several medication storage locations were significantly associated with decreased odds of having ever forgotten to take a medication, including kitchen drawers, in refrigerators, atop bedroom nightstands, in nightstand drawers, and backpacks, purses, or bags. Two home medication storage locations were significantly associated with increased odds of having ever forgotten to take a medication: kitchen cabinets and bathroom vanities. Further, most (94%) survey respondents indicated they would be receptive to guidance about where to store their medications. Given that some home medication storage locations are associated with adherence, an intervention to guide storage location selection may support increased adherence, especially with high receptivity expressed for such guidance. Increased adherence may also accrue from device usage paired with optimized home medication storage location. We plan to investigate that further, as well as how new device designs can incorporate contextual cues related to location to promote medication adherence more effectively in middle aged and older adults.


Resting-state connectivity predicts levodopa-induced dyskinesias in Parkinson's disease.
Levodopa-induced dyskinesias are a common side effect of dopaminergic therapy in PD, but their neural correlates remain poorly understood. This study examines whether dyskinesias are associated with abnormal dopaminergic modulation of resting-state cortico-striatal connectivity. Twelve PD patients with peak-of-dose dyskinesias and 12 patients without dyskinesias were withdrawn from dopaminergic medication. All patients received a single dose of fast-acting soluble levodopa and then underwent resting-state functional magnetic resonance imaging before any dyskinesias emerged. Levodopa-induced modulation of cortico-striatal resting-state connectivity was assessed between the putamen and the following 3 cortical regions of interest: supplementary motor area, primary sensorimotor cortex, and right inferior frontal gyrus. These functional connectivity measures were entered into a linear support vector classifier to predict whether an individual patient would develop dyskinesias after levodopa intake. Linear regression analysis was applied to test which connectivity measures would predict dyskinesia severity. Dopaminergic modulation of resting-state connectivity between the putamen and primary sensorimotor cortex in the most affected hemisphere predicted whether patients would develop dyskinesias with a specificity of 100% and a sensitivity of 91% (P < .0001). Modulation of resting-state connectivity between the supplementary motor area and putamen predicted interindividual differences in dyskinesia severity (R(2) = 0.627, P = .004). Resting-state connectivity between the right inferior frontal gyrus and putamen neither predicted dyskinesia status nor dyskinesia severity. The results corroborate the notion that altered dopaminergic modulation of cortico-striatal connectivity plays a key role in the pathophysiology of dyskinesias in PD.


Prediction of individual response to controlled ovarian hyperstimulation by means of a clomiphene citrate challenge test.
A clomiphene citrate (CC) challenge test was carried out in 114 patients to evaluate the capacity of this test to predict the patient's individual response to controlled ovarian hyperstimulation (COH) performed with a gonadotropin-releasing hormone agonist and human menopausal gonadotrophins (hMG) for in vitro fertilization. The sum of follicle-stimulating hormone measured before and after CC intake, is the parameter that correlated best with subsequent response to COH. The upper limit of the reference value for this parameter, established by considering the CC challenge test performed on 26 patients who became pregnant, was 26.03 mIU/mL. Twenty patients who presented a CC challenge test result above the reference value were compared with patients with a normal test result. For these 20 patients, COH required more hMG and was cancelled in 25% of the cases (instead of 1% in the control group). The number of follicles aspirated, oocytes retrieved, and embryos obtained were on average six times lower than in patients with a CC challenge test result within the reference value, and no pregnancy was obtained. We concluded that CC challenge test provides a reliable individual prognosis for the ovarian response to COH.


Pseudoginsenoside-F11 inhibits methamphetamine-induced behaviors by regulating dopaminergic and GABAergic neurons in the nucleus accumbens.
Although dependence to methamphetamine (METH) is associated with serious psychiatric symptoms and is a global health and social problem, no effective therapeutic approaches have been identified. Pseudoginsenoside-F11 (PF11) is an ocotillol-type saponin that is isolated from Panax quinquefolius (American ginseng) and was shown to have neuroprotective effects to promote learning and memory and to antagonize the pharmacological effects of morphine. Furthermore, PF11 also shows protective effects against METH-induced neurotoxicity in mice. However, the effects of PF11 on METH-induced preference and dopamine (DA) release have not been defined. We investigated the effects of PF11 administration on METH-induced hyperlocomotion and conditioned place preference (CPP) in mice. Subsequently, extracellular DA and gamma-aminobutyric acid (GABA) levels were determined in the nucleus accumbens (NAc) of mice after co-administration of PF11 and METH using in vivo microdialysis analyses. Moreover, the effects of PF11 administration on the μ-opioid neuronal responses, DAMGO (μ-opioid receptor agonist; [D-Ala(2), N-MePhe(4), Gly-ol]-enkephalin)-induced hyperlocomotion and accumbal extracellular DA increase were investigated to elucidate how PF11 inhibits METH-induced dependence by dopaminergic neuronal hyperfunction. Co-administration of PF11 and METH for 6 days attenuated METH-induced locomotor sensitization compared with treatment with METH alone. In the CPP test, PF11 administration also inhibited METH-induced place preference. In vivo microdialysis analyses indicated that co-administration of PF11 and METH for 7 days prevented METH-induced extracellular DA increase in the NAc and repeated PF11 administration with or without METH for 7 days increased extracellular GABA levels in the NAc, whereas single administration of PF11 did not. Furthermore, DAMGO-induced hyperlocomotion and accumbal extracellular DA increase were significantly inhibited by acute PF11 administration. The present data suggest that PF11 inhibits METH-induced hyperlocomotion, preference, and accumbal extracellular DA increase by regulating GABAergic neurons and μ-opioid receptors.


Influence of Residual Water Traces on the Electrochemical Performance of Hydrophobic Ionic Liquids for Magnesium-Containing Electrolytes.
A trace amount of water is typically unavoidable as an impurity in ionic liquids, which is a huge challenge for their application in Mg-ion batteries. Here, we employed molecular sieves of different pore diameters (3, 4, and 5 Å), to effectively remove the trace amounts of water from 1-methyl-1-propylpiperidinium bis(trifluoromethylsulfonyl)imide (MPPip-TFSI) and 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide (BMP-TFSI). Notably, after sieving (water content <1 mg ⋅ L-1 ), new anodic peaks arise that are attributed to the formation of different anion-cation structures induced by minimizing the influence of hydrogen bonds. Furthermore, electrochemical impedance spectroscopy (EIS) reveals that the electrolyte resistance decreases by ∼10 % for MPPip-TFSI and by ∼28 % for BMP-TFSI after sieving. The electrochemical Mg deposition/dissolution is investigated in MPPip-TFSI/tetraglyme (1 : 1)+100 mM Mg(TFSI)2 +10 mM Mg(BH4 )2 using Ag/AgCl and Mg reference electrodes. The presence of a trace amount of water leads to a considerable shift of 0.9 V vs. Mg2+/ Mg in the overpotential of Mg deposition. In contrast, drying of MPPip-TFSI enhances the reversibility of Mg deposition/dissolution and suppresses the passivation of the Mg electrode.


Incorporation of the hexose analogue 2-deoxy-D-galactose into membrane glycoproteins in HepG2 cells.
The incorporation of 2-deoxy-D-galactose into the oligosaccharide moieties of glycoproteins and the consequences of 2-deoxy-D-galactose treatment on the fucosylation of glycoproteins were investigated in the human hepatoma cell line HepG2. Using different methods, it was shown that treatment of HepG2 cells with 2-deoxy-D-galactose leads to an incorporation of 2-deoxy-D-galactose and a decrease of L-fucose incorporation into the oligosaccharides of glycoproteins. The extent of labeling by L-[3H]fucose was determined by removing L-[3H]fucose from labeled cells with the aid of a purified alpha 1,2-fucosidase from Aspergillus niger. Using this method, it was shown that 2-deoxy-D-galactose markedly inhibits alpha 1,2-fucosylation. Measurement of the amount of 2-deoxy-D-galactose incorporated, however, showed that replacement of D-galactose by 2-deoxy-D-galactose does not entirely account for the decrease in alpha 1,2-fucosylation. In addition, a hitherto unreported compensatory increase of alpha 1,3/alpha 1,4-fucosylation was found to occur when alpha-1,2-fucosylation was inhibited by treatment with 2-deoxy-D-galactose.


Mott-Schottky electrocatalyst selectively mediates the sulfur species conversion in lithium-sulfur batteries.
The lithium sulfur (Li-S) battery is an active research area in the field of energy storage systems, but the shuttle effect is a serious obstacle hindering its application. Herein, a CoSe2/CoO Mott-Schottky catalyst is blended with carbon nanotubes (CNTs) and subsequently coated onto a commercial separator as a modifier, whereby the synergy between the high electrocatalytic activity of the CoSe2/CoO heterostructure and high conductivity of the CNTs selectively mediate the conversion of sulfur species. As a result, a cell with a CoSe2/CoO-CNTs modified separator displays a high initial discharge capacity of 1573 and 910 mAh/g at 0.1 and 2C, respectively. Furthermore, a low decay rate of 0.070% per cycle can be obtained over 500 cycles at 2C. The results of this study suggest that the as-prepared CoSe2/CoO-CNTs is an effective modifier that can improve the performance of Li-S batteries for use in next-generation energy storage systems. This study provides fundamental insights into the rational design of Mott-Schottky catalysts for practical high-performance Li-S batteries.


Spectroscopic studies of the interaction between methylene blue-naphthol orange complex and anionic and cationic surfactants.
Initially, the absorbance of MB at 665 nm decreased rapidly with increasing sodium dodecyl sulfate (SDS) concentration, but increased gradually above about 2.3x10(-3) M. However, the absorbance of MB was almost independent of the cetyltrimethylammonium bromide (CTAB) concentration. On the other hand, the absorbance of NpO was affected by addition of CTAB in a similar manner to the change in MB-SDS system, but not by addition of SDS. The absorption band of MB showed a small red-shift and a decrease in intensity upon addition of NpO, while that of NpO showed only the decrease in the intensity upon the addition of MB. These spectral changes were attributed to the formation of complexes between these dyes. The effects of anionic and cationic surfactants on the absorption spectra of mixtures of MB and NpO were also examined. Contrary to the effects on the absorption spectrum of MB and NpO, respectively, the absorbances of MB and NpO in the mixtures were changed with the additions of both anionic and cationic surfactants. The spectral changes were explained by changes in the forms of MB and NpO in the solutions with increasing surfactant concentrations.


A difference-in-differences analysis of the effect of free dental check-ups in Scotland.
The Scottish Government introduced free NHS dental check-ups in April 2006 as a way of encouraging utilisation and improving the oral health of residents. We use data from the British Household Panel Survey (BHPS), a nationally representative data of 117761 individual respondents in the United Kingdom covering the period between 2001 and 2008 to evaluate the impact of this policy on utilisation of NHS dental check-ups in Scotland, using a difference-in-difference approach. Results show that there was a 3-4 percent increase in NHS dental check-up in Scotland, compared to the rest of the UK. Results suggest that a removal of financial barrier to dental check-ups does indeed lead to a modest increase in utilisation, and may have wider implications for the delivery of dental care in Scotland.


Stargardt disease: linkage to the ABCR gene region on 1p21-p22 in Scandinavian families.
Stargardt disease (STGD) or fundus flavimaculatus (FFM) is one of the most frequent causes of macular degeneration in childhood. The disease is inherited as an autosomal recessive trait and the corresponding gene has been localized to chromosome 1p21-22 and subsequently identified as the ATP-binding cassette transporter (ABCR) gene. To characterize Finnish and Swedish STGD families genetically, with special reference to chromosome region 1p21-22. We performed genetic linkage and haplotype analyses in five families of Finnish and Swedish origin with members affected by STGD or FFM. Evidence for linkage between STGD and the ABCR gene region on chromosome 1p was found with a maximum cumulative two-point lod score for marker D1S188 (Z=4.04, theta=0.001). The affected individuals of all families, including the offspring of a consanguineous family, were found heterozygous for haplotypes spanning the ABCR gene. The results support genetic homogeneity for a STGD/FFM gene defect on chromosome 1p21-22. A variety of haplotypes tightly linked to the ABCR gene region were found among affected individuals which indicate the presence of several independent STGD mutations in the Scandinavian population.


Soft-tissue distraction with a ring external fixator before centralization for radial longitudinal deficiency.
To review the techniques and evaluate the use of soft-tissue distraction with a ringed fixator for radial longitudinal deficiency (RLD) before centralization. Eight extremities in 6 patients with severe RLD were treated with ring fixator distraction followed by centralization. A clinical examination was performed and radiographic data were obtained prospectively and at an average follow-up period of 17 months. The techniques and the early objective (range of motion, position) and radiographic outcome were evaluated. The preoperative ring fixator accomplished an average of 16 mm of distraction and allowed the centralization procedure to be performed effectively and without tension. Clinical alignment was improved markedly. The hand-forearm angle improved from 72 degrees radial to 8 degrees ulnar after surgery. The volar carpal subluxation improved by an average of 6 mm. Precentralization ring fixator distraction allows the performance of a tensionless centralization procedure with good early radiographic and clinical outcome in patients severely affected with RLD. Therapeutic, Level IV.


Development of T cells in SCID mice grafted with fetal thymus from AKR mice or F344 rats.
To examine the development of T cells within an allogeneic or xenogeneic environment, we engrafted the fetal thymus from AKR mice or F344 rats under the kidney capsule of SCID mice (mTG and rTG mice). T lymphopoiesis developed in SCID mice 2 months after transplantation, although the ratio of CD4/CD8 in both experimental groups was different from that of normal control. T cells in mTG mice did not show in vitro proliferation or cytotoxicity against either host-type C.B-17 (H-2d) or donor-type AKR (H-2k) cells, while they exerted potent activities against third-party B10 (H-2b) cells. In contrast, T cells in rTG mice exhibited proliferation against both host-type C.B-17 and donor-type F344 rat cells. Consistently, graft-vs.-host disease symptoms developed in these mice and histological examination showed impressive infiltration of lymphocytes into the skin or into the mucosal layers of the stomach. Activated state of T cells in rTG mice was also evidence by the positive expression of interleukin-2 receptor. Taken together, fetal thymus appears to contain progenitor cells which are sufficient for in vivo reconstitution of T lymphopoiesis, but species-specific environment is important for the induction of tolerance. In mTG mice, V beta 6+ T cells reactive to donor Mlsa determinants and V beta 3+ T cells reactive to host Mlsc determinants were deleted, suggesting that tolerance was regulated mainly by clonal deletion. By contrast, V beta 11+ T cells reactive to Mlsf determinants were not deleted possibly due to the lack of their ligands.


Orthopedic Activity in Field Hospitals Following Earthquakes in Nepal and Haiti : Variability in Injuries Encountered and Collaboration with Local Available Resources Drive Optimal Response.
Field hospitals have been deployed by the Israel Defense Forces (IDF) Medical Corps in numerous disaster events. Two recent deployments were following earthquakes in Haiti in 2010 and in Nepal in 2015. Despite arrival in similar timetables, the mode of operation was different-independently in Haiti and in collaboration with a local hospital in Nepal. The pathology encountered in the two hospitals and the resultant treatment requirements were significantly different between the two events. The purpose of this study was to analyze these differences and their implications for preparation and planning of future deployments. Data were obtained from IDF records and analyzed using SPSS™ software. 1686 patients were treated in Nepal versus 1111 in Haiti. The caseload in Nepal included significantly less earthquake-related injuries (26 vs. 66 %) with 28 % of them sustaining fractures versus 47 % in Haiti. Femoral fractures accounted for 7.9 % of fractures in Nepal versus 26.4 % in Haiti with foot fractures accounting for 23.8 and 6.4 %, respectively. The rate of open fracture was similar at 29.4 % in Nepal and 27.5 % in Haiti. 18.1 % of injured patients in Nepal underwent surgery, and 32.9 % of which was skeletal compared to 32 % surgical cases (58.8 % skeletal) in Haiti. 74.2 % of patients in Nepal and 34.3 % in Haiti were treated for pathology unrelated to the earthquake. The reasons for the variability in activities between the two hospitals include the magnitude of the disaster, the functionality of the local medical system which was relatively preserved in Nepal and destroyed in Haiti and the mode of operation which was independent in Haiti and collaborative with a functioning local hospital in Nepal. Emergency medical teams (EMTs) may encounter variable caseloads despite similar disaster scenarios. Advance knowledge of the magnitude of the disaster, the functionality of the local medical system, and the collaborative possibilities will help in planning and preparing EMTs to function optimally and appropriately. However, as this information will often be unavailable, EMTs should be capable to adapt to unexpected conditions.


Sedation for Rapid Sequence Induction and Intubation of Neurologically Injured Patients.
There are subtle physiologic and pharmacologic principles that should be understood for patients with neurologic injuries. These principles are especially true for managing patients with traumatic brain injuries. Prevention of hypotension and hypoxemia are major goals in the management of these patients. This article discusses the physiology, pitfalls, and pharmacology necessary to skillfully care for this subset of patients with trauma. The principles endorsed in this article are applicable both for patients with traumatic brain injury and those with spinal cord injuries.


Acute transient spinal paralysis and cardiac symptoms following an accidental epidural potassium infusion - a case report.
To describe a case of an accidental epidural potassium infusion leading to an acute transient spinal paralysis and cardiac symptoms and review the literature on that topic. We report the case of an accidental infusion of 900 mg potassium chloride 7.45% (KCl) into the epidural space, which occurred during epidural analgesia in a 74-year-old patient suffering from immobilization due to lumbar back pain as well as from a paralytic Ileus. The event was resulting in vegetative symptoms, such as tachycardia and hypertension accompanied by a motor complete tetraplegia (AIS B) sub C2 with respiratory depression. The endotracheal intubation was necessary. The patient was treated with 40 mg dexamethasone intravenously, as well an epidural lavage with sodium chloride solution 0.9% (NaCl) through the epidural catheter. The neurologic symptoms completely resolved within five days. An elevation of troponin-T values and a reduced left ventricular ejection fraction (LVEF) of 40% accompanied by transient pectanginous pain were documented. An exertional dyspnea remained. A symptom complex with elevated sympathetic nervous system activity up to a stress cardiomyopathy is possible following epidural potassium infusion. Additionally, generalized pain and muscle spasticity evolve and a progressive acute spinal cord injury syndrome can occur within minutes, accompanied by respiratory depression. Treatment consists of early intensive care and the symptomatic therapy of the associated symptoms, leading in most of the reported cases to a good clinical outcome.


Hypotensive anesthesia for total hip arthroplasty: a study of blood loss and organ function (brain, heart, liver, and kidney).
The authors attempted to determine whether hypotensive anesthesia or the method of inducing hypotension has any effect on postoperative brain, liver, or kidney function and myocardial status following total hip arthroplasty. Thirty patients were anesthestized with halothane-nitrous oxide for total hip arthroplasty and randomly assigned to one of three groups. In two groups mean arterial blood pressure was decreased to 50 torr by high inspired concentrations of halothane (n = 90) or sodium nitroprusside (n = 12). In the third group (n = 9) mean blood pressure was maintained within 20% of control. Intraoperative blood losses decreased from 1,183 +/- 172 ml in the normotensive group to 406 +/- 102 ml and 326 +/- 41 ml in the halothane and nitroprusside hypotensive groups, respectively. Neither method of inducing hypotension nor hypertensive technique affected the results of postoperative tests of cerebral, hepatic, or renal function and myocardial status. These tests were performed before anesthesia and operation and at intervals in the postoperative course. In this small group of patients, deliberate hypotension for total hip arthroplasty added no morbidity and significantly shortened operating time, decreased blood loss, and decreased the number of blood transfusions needed.


Prothrombin G20210A and A19911G mutations in Turkish pediatric stroke patients.
Effects of PT A19911G polymorphism in Turkish pediatric stroke patients were investigated. The case-control study included 107 patients with cerebral infarct and 83 healthy unrelated controls. Distribution of PT A19911G and data on the combined effect of PT 19911G and PT 20210A alleles do not indicate that they constitute a risk in this group of patients.


Socioeconomic and environmental factors associated with malaria hotspots in the Nanoro demographic surveillance area, Burkina Faso.
With limited resources and spatio-temporal heterogeneity of malaria in developing countries, it is still difficult to assess the real impact of socioeconomic and environmental factors in order to set up targeted campaigns against malaria at an accurate scale. Our goal was to detect malaria hotspots in rural area and assess the extent to which household socioeconomic status and meteorological recordings may explain the occurrence and evolution of these hotspots. Data on malaria cases from 2010 to 2014 and on socioeconomic and meteorological factors were acquired from four health facilities within the Nanoro demographic surveillance area. Statistical cross correlation was used to quantify the temporal association between weekly malaria incidence and meteorological factors. Local spatial autocorrelation analysis was performed and restricted to each transmission period using Kulldorff's elliptic spatial scan statistic. Univariate and multivariable analysis were used to assess the principal socioeconomic and meteorological determinants of malaria hotspots using a Generalized Estimating Equation (GEE) approach. Rainfall and temperature were positively and significantly associated with malaria incidence, with a lag time of 9 and 14 weeks, respectively. Spatial analysis showed a spatial autocorrelation of malaria incidence and significant hotspots which was relatively stable throughout the study period. Furthermore, low socioeconomic status households were strongly associated with malaria hotspots (aOR = 1.21, 95% confidence interval: 1.03-1.40). These fine-scale findings highlight a relatively stable spatio-temporal pattern of malaria risk and indicate that social and environmental factors play an important role in malaria incidence. Integrating data on these factors into existing malaria struggle tools would help in the development of sustainable bottleneck strategies adapted to the local context for malaria control.


The need for tumor surveillance of children and adolescents with cancer predisposition syndromes: a retrospective cohort study in a tertiary-care children's hospital.
Expert recommendations for the management of tumor surveillance in children with a variety of cancer predisposition syndromes (CPS) are available. We aimed (1) at identifying and characterizing children who are affected by a CPS and (2) at comparing current practice and consensus recommendations of the American Association for Cancer Research workshop in 2016. We performed a database search in the hospital information system of the University Children's Hospital for CPS in children, adolescents, and young adults and complemented this by review of electronic patients' charts. Between January 1, 2017, and December 3, 2019, 272 patients with 41 different CPS entities were identified in 20 departments (144 [52.9%] male, 128 [47.1%] female, median age 9.1 years, range, 0.4-27.8). Three (1.1%) patients died of non-malignancy-associated complications of the CPS; 49 (18.0%) patients were diagnosed with malignancy and received regular follow-up. For 209 (95.0%) of the remaining 220 patients, surveillance recommendations were available: 30/220 (13.6%) patients received CPS consultations according to existing consensus recommendations, 22/220 (10.0%) institutional surveillance approaches were not complying with recommendations, 84/220 (38.2%) patients were seen for other reasons, and 84/220 (38.2%) were not routinely cared for. Adherence to recommendations differed extensively among CPS entities. The spectrum of CPS patients at our tertiary-care children's hospital is manifold. For most patients, awareness of cancer risk has to be enhanced and current practice needs to be adapted to consensus recommendations. Offering specialized CPS consultations and establishing education programs for patients, relatives, and physicians may increase adherence to recommendations. • A wide spectrum of rare syndromes manifesting in childhood is associated with an increased cancer risk. • For many of these syndromes, expert recommendations for management and tumor surveillance are available, although based on limited evidence. • Evaluating current practice, our data attest significant shortcomings in tumor surveillance of children and adolescents with CPS even in a tertiary-care children's hospital. • We clearly advocate a systematic and consistent integration of tumor surveillance into daily practice.


Measuring costs and financial benefits in randomized controlled trials.
Economic assessment can be incorporated into clinical trials to evaluate and compare the costs and benefits of different health care programs. In this article the three main types of evaluation are discussed: cost-effectiveness analysis, cost-utility analysis, and cost-benefit analysis. The measurement of direct and indirect costs is described and specific examples are quoted. Full economic analyses are given for the use of naftidrofuryl in the treatment of acute cerebral hemisphere infarction and the use of auranofin in the treatment of rheumatoid arthritis. Economic evaluation is seen to be justified whenever a more expensive treatment is expected to produce greater benefit. Such analyses should consider quality of life and health status, as well as the more easily identifiable outcomes.


Examining the physician's role with assisted living residents.
In response to the rapid growth of the assisted living (AL) residents, this article considers the resulting range of roles, opportunities, and challenges physicians may face as increasing numbers of their older adult patients choose residence in AL facilities. The problem is framed by providing an overview of the AL industry and reviewing AL resident demographics and health status characteristics. The discussion section examines the pervasive involvement of physicians with AL residents, reviews professional position statements on health care in AL, and reviews the emerging AL-focused clinical literature. In conclusion, the paper proposes key elements of a research agenda including establishing baseline physician-AL activity levels, physician collaboration with mid-level practitioners, and exploring physician involvement in chronic care and health promotion in AL.


A disposable electrochemiluminescence device for ultrasensitive monitoring of K562 leukemia cells based on aptamers and ZnO@carbon quantum dots.
We developed a new electrochemiluminescence (ECL) platform for ultrasensitive and selective detection of leukemia cells. In order to construct the platform, the nonporous gold with controllable three-dimensional porosity and good conductivity was used to modify the screen-printed carbon electrode. The carbon quantum dots (CQDs) coated ZnO nanosphere (ZnO@CQDs) were used as good ECL label with low cytotoxicity and good biocompatibility. Structure characterization was obtained by means of transmission electron microscopy and scanning electron microscopy images. The aptamer was used for cell capture and the concanavalin A conjugated ZnO@CQDs was used for selective recognition of the cell surface carbohydrate. The proposed method showed a good analytical performance for the detection of K562 cells ranging from 1.0 × 10(2) to 2.0 × 10(7) cells mL(-1) with a detection limit of 46 cells mL(-1). The as-proposed device has the advantages of high sensitivity, nice specificity and good stability and could offer great promise for sensitive detection of leukemia cells in response to therapy.


Heavy-for-date infants: their backgrounds and relationship with gestational diabetes.
Gestational diabetes (GDM) is closely related to birth weight. Heavy-for-date (HFD) infants, especially those with macrosomia, cause many perinatal complications. This study was performed to examine the backgrounds of HFD infants and to determine such infants' relationship with GDM. Eighty cases of HFD infants who were delivered from 1996 through 1998 were analyzed. The random blood-glucose level was used for screening for GDM. Maternal body weight and the body-mass index before pregnancy and at delivery and the blood glucose level at the second trimester were positively correlated with birth weight. However, only 8.8% of HFD cases were detected by this screening method in the first trimester, and 11.3% of HFD cases were detected in the second trimester and only 1 case of borderline-type was detected by subsequent 75-g OGTT. Maternal obesity is an independent and more important risk factor for HFD infants than glucose intolerance.


Molecular characterization and expression analysis of fibrinogen related protein (FREP) genes of Manila clam (Ruditapes philippinarum) after lipopolysaccharides challenge.
Ruditapes philippinarum has high economic value and is distributed all over the world. Fibrinogen associated protein (FREP) is a type of pattern recognition receptor, participates in the innate immune response to eliminate pathogens after the invasion of pathogenic microorganisms. In this study, three FREP genes (FREP-1, FREP-2, and FREP-3) were identified and characterized from R. philippinarum. The protein sequence of FREPs were highly conserved with those homologous in vertebrates, and FBG domain possessed significantly high structural conservation in polypeptide binding site and Ca2+ binding site. The tissues expression analysis of FREPs in three shell color strains and two population of R. philippinarum were examined, with the highest expression level in gill and hepatopancreas. Besides, FREP genes were demonstrated to be induced by lipopolysaccharides injection, the significantly changes were observed after LPS injected. Our results suggest the involvement of FREPs in response to LPS injection, and it might exert a significant function on the innate immune defense of the Manila clam.


Use of contrast-enhanced computed tomography to detect kidney infarction in dogs.
Kidney infarction is a renovascular disease diagnosed by contrast-enhanced computed tomography (CECT) in humans. To describe the frequency of kidney infarction and to determine the detection of kidney infarction with CECT in dogs. Eight hundred and twenty-six abdominal CECT studies of 826 dogs. A cross-sectional retrospective study. Dogs with abdominal CT scans including CECT were retrospectively retrieved. Kidney infarction was classified into 3 grades based on the extent of infarction relative to total kidney area. The location and number of kidney infarctions in each kidney were expressed as number and percentage. The ability of visualization of kidney infarction in each multiplanar reconstruction (MPR) image plane was evaluated by agreement of 2 observers. The frequency of kidney infarction in dogs was 3.15% (26/826 dogs; 95% CI = 2.05-4.61). Most kidney infarctions were classified as grade 1, or the lesions were less than 25% of the kidney (47/56, 83.93%) and most were detected at the caudal pole of the kidney (31/56, 55.35%) on the sagittal plane. On MPR image planes, the sagittal plane had the highest proportion (34/56, 60.71%) of excellent visual category to detect kidney infarction. The CECT, especially the sagittal plane, is a useful diagnostic tool for the detection of kidney infarction in dogs.


Reversion of the maple syrup urine disease phenotype of impaired branched chain alpha-ketoacid dehydrogenase complex activity in fibroblasts from an affected child.
Branched chain alpha-ketoacid dehydrogenase is a heteroprotein complex of mitochondria and commits the branched chain alpha-ketoacids to their catabolic fate. Inherited nuclear mutations in humans decrease the activity of this complex and result in maple syrup urine disease. Here we demonstrate the restoration of branched chain alpha-ketoacid dehydrogenase activity to fibroblasts from a child with this disorder by transfection with a cDNA for the prebranched chain acyltransferase. Prior to transfection these fibroblasts contained the prebranched chain acyltransferase gene but failed to transcribe the gene and thus lacked the protein. Regulation of the restored complex by phosphorylation mechanisms resembles that of wild-type cells. These results describe a human cell modeling system for testing engineered proteins and support the possibility of gene replacement therapy for this human disorder.


Simulation of all-or-none K+ efflux from yeast provoked by xenobiotics.
In experiments dealing with the effect of xenobiotics upon the efflux of K+ from yeast cells, one should be aware that when this efflux proceeds via an all-or-none process, the K+ being released from the intoxicated cells can again be accumulated into the still unaffected cells. Therefore, the measured net efflux of K+ will be less than the efflux from the intoxicated cells. The difference between these two magnitudes can be minimalized by incubating the cells for only a short period and on applying yeast densities that are not too high. When the cells are permeabilized relatively slowly but ultimately to a great extent, the kinetics of K+ efflux may be quite complicated.


Effect of electric field switching on the electrophoretic mobility of single-stranded DNA molecules in polyacrylamide gels.
We have examined the effects of pulsed electric fields on the separation of single-stranded DNA molecules in polyacrylamide sequencing gels. Using different electric field pulsing regimens, the mobilities of single-stranded DNA molecules can be retarded or increased as compared to conventional electrophoresis. These results indicated that pulsed field techniques can be applied to gel electrophoresis of small single-stranded DNA molecules.


Potential improvement of tumor control probability by induction chemotherapy for advanced nasopharyngeal carcinoma.
To assess the reduction of tumor bulk and improvement of tumor control probability (TCP) by using induction chemotherapy for advanced nasopharyngeal carcinoma (NPC). From February to December 2005, 20 patients with Stage III-IVB NPC were treated with induction-concurrent chemotherapy and intensity-modulated radiotherapy with accelerated fractionation. Combination of cisplatin and 5-fluorouracil was used in the induction phase and single agent Cisplatin in the concurrent phase. All patients were irradiated at 2Gy per fraction, 6 daily fractions per week, to a total dose of 70Gy. Nineteen (95%) patients completed all 3 cycles of induction chemotherapy and 90% had 2 cycles of concurrent chemotherapy. Induction chemotherapy achieved significant down-staging of T-category in 35% of patients (p=0.016) and reduction of gross tumor volume (GTV_P) from 55.6 to 22.9cc (mean 61.4%, p<0.001). Although the mean radiation dose did not show any substantial change, the volume within GTV_P that failed to reach 70Gy was reduced from 10.2% to 3.8% (p=0.017). The estimated local TCP increased from 0.83 to 0.89 (p=0.002). Induction chemotherapy using cisplatin-5-fluorouracil could significantly reduce tumor bulk leading to potential improvement in tumor control.