Patient-reported safety incidents in older patients with long-term conditions: a large cross-sectional study.
Increasing evidence suggests that patient safety is a serious concern for older patients with long-term conditions. Despite this, there is a lack of research on safety incidents encountered by this patient group. In this study, we sought to examine patient reports of safety incidents and factors associated with reports of safety incidents in older patients with long-term conditions. The baseline cross-sectional data from a longitudinal cohort study were analysed. Older patients (n=3378 aged 65 years and over) with a long-term condition registered in general practices were included in the study. The main outcome was patient-reported safety incidents including availability and appropriateness of medical tests and prescription of wrong types or doses of medication. Binary univariate and multivariate logistic regression analyses were undertaken to examine factors associated with patient-reported safety incidents. Safety incidents were reported by 11% of the patients. Four factors were significantly associated with patient-reported safety incidents in multivariate analyses. The experience of multiple long-term conditions (OR=1.09, 95% CI 1.05 to 1.13), a probable diagnosis of depression (OR=1.36, 95% CI 1.06 to 1.74) and greater relational continuity of care (OR=1.28, 95% CI 1.08 to 1.52) were associated with increased odds for patient-reported safety incidents. Perceived greater support and involvement in self-management was associated with lower odds for patient-reported safety incidents (OR=0.95, 95% CI 0.93 to 0.97). We found that older patients with multimorbidity and depression are more likely to report experiences of patient safety incidents. Improving perceived support and involvement of patients in their care may help prevent patient-reported safety incidents.


Pain Management at the End of Life in the Emergency Department: A Narrative Review of the Literature and a Practical Clinical Approach.
Access to pain management is a fundamental human right for all people, including those who are at the end of life (EOL). In end-stage patients, severe and uncontrolled pain is a common cause of admission to the emergency department (ED), and its treatment is challenging due to its complex, often multifactorial genesis. The aim of this narrative review was to identify the available literature on the management of severe EOL pain in the ED. The MEDLINE, SCOPUS, EMBASE, and CENTRAL databases were searched from inception to 1 April 2023 including randomised controlled trials, observational studies, systemic or narrative reviews, case reports, and guidelines on the management of EOL pain in the ED. A total of 532 articles were identified, and 9 articles were included (5 narrative reviews, 2 retrospective studies, and 2 prospective studies). Included studies were heterogeneous on the scales used and recommended for pain assessment and the recommended treatments. No study provided evidence for a better approach for EOL patients with pain in the ED. We provide a narrative summary of the findings and a review of the management of EOL pain in clinical practice, including (i) the identification of the EOL patients and unmet palliative care needs, (ii) a multidimensional, patient-centred assessment of the type and severity of pain, (iii) a multidisciplinary approach to the management of end-of-life pain, including an overview of non-pharmacological and pharmacological techniques; and (iv) the management of special situations, including rapid acute deterioration of chronic pain, breakthrough pain, and sedative palliation.


Effects of exercise training after open heart surgery on quality of life and exercise tolerance in patients with mitral regurgitation or aortic regurgitation.
We conducted a questionnaire survey regarding quality of life (QOL) to evaluate the effects of exercise training on the QOL in patients with valvular heart disease after surgery. This study included 64 consecutive patients who underwent heart surgery. They were divided into two groups: exercise training could (EX(+) group, n = 31) and could not be performed (EX(-) group, n = 33) until 6 months after surgery. To evaluate the QOL and exercise tolerance, we employed "a questionnaire regarding disease and quality of life" developed for Japanese people and cardiopulmonary exercise testing. In our questionnaire survey, the improvement rating (Delta subjective/social index), which was calculated from the difference between the pre-and postoperative values, was greater in the EX(+) group than that in the EX(-) group (4.9 +/- 3.1 versus 1.1 +/- 4.0, P < 0.05). In the changes in exercise tolerance, Delta anaerobic threshold was greater in the EX(+) group (0.79 +/- 0.17 versus -0.02 +/- 0.28, P < 0.01). Moreover, there was a positive correlation between Delta subjective/social index and Delta peak VO(2) (r = 0.62, P < 0.05). We concluded that exercise training for patients after cardiac surgery improves the QOL and exercise tolerance. It is suggested that changes in subjective and social parameters contribute to an exercise training-related improvement in the QOL.


The CagA protein of Helicobacter pylori suppresses the functions of dendritic cell in mice.
CagA protein is the most assessed effecter molecule of Helicobacter pylori. In this report, we demonstrate how CagA protein regulates the functions of dendritic cells (DC) against H. pylori infection. In addition, we found that CagA protein was tyrosine-phosphorylated in DC. The responses to cagA-positive H. pylori in DC were reduced in comparison to those induced by cagA-negative H. pylori. CagA-overexpressing DC also exhibited a decline in the responses against LPS stimulation and the differentiation of CD4(+) T cells toward Th1 type cells compared to wild type DC. In addition, the level of phosphorylated IRF3 decreased in CagA-overexpressing DC stimulated with LPS, indicating that activated SHP-2 suppressed the enzymatic activity of TBK1 and consequently IRF3 phosphorylation. These data suggest that CagA protein negatively regulates the functions of DC via CagA phosphorylation and that cagA-positive H. pylori strains suppress host immune responses resulting in their chronic colonization of the stomach.


[Use of heparin and platelet GPIIbIIIa inhibitor tirofiban for cardiac surgery in patients for suspicion of heparin-induced thrombocytopenia].
In a patient with heparin-induced thrombocytopenia few antithrombotic alternate treatments are proposed for cardiac surgery with or without cardiopulmonary bypass: danaparoid, lepirudine or powerful antiplatelet agent. Recently, the platelet GPIIbIIIa antagonist tirofiban (Aggrastat) was tested in humans. We reported two cases of patients operated upon for cardiac surgery with unfractionnated heparin (UFH) and tirofiban. The first patient underwent an off-pump coronary artery bypass graft and the second one a mitral valvular replacement under cardiopulmonary bypass. Tirofiban was associated with UFH and aprotinine. Postoperative bleeding was in the normal range for the two types of surgeries and haemodynamic tolerance was good. These two case reports support the possibility of secure cardiac surgery under efficient platelet inhibition with tirofiban. The management of cardiac surgery with tirofiban without monitoring of platelet aggregation appeared to be more simple than with the other alternate antithrombotic agents.


Value of Hu antibody determinations in the follow-up of paraneoplastic neurologic syndromes.
The long-term evolution of Hu antibody (Hu-Ab) titers in patients with paraneoplastic neurologic syndromes (PNSs) is not known. Described is the evolution of Hu-Ab titers in 35 patients with PNS with a median follow-up of 32 months (range 6 to 108 months). No correlation was observed between Hu-Ab titers and neurologic outcome, tumor evolution, or type of treatment. Serial Hu-Ab determinations are not useful for monitoring the clinical outcome of patients with PNS.


[Gallbladder Perforation after Transarterial Chemoembolization in a Patient with a Huge Hepatocellular Carcinoma].
Transarterial chemoembolization (TACE) is a common treatment for unresectable hepatocellular carcinoma (HCC). The most common complications after TACE are non-specific symptoms called post-embolization syndrome, such as abdominal pain or fever. Rare complications, such as liver failure, liver abscess, sepsis, pulmonary embolism, cholecystitis, can also occur. On the other hand, gallbladder perforation is quite rare. This paper reports a case of gallbladder perforation following TACE. A 76-year-old male with a single 9-cm-sized HCC underwent TACE. Five days after TACE, he developed persistent right upper quadrant pain and ileus. An abdomen CT scan confirmed gallbladder perforation with bile in the right paracolic gutter and pelvic cavity. Percutaneous transhepatic gallbladder drainage was performed with the intravenous administration of antibiotics. After 1 month, the patient underwent right hemihepatectomy and cholecystectomy. Physicians should consider the possibility of gallbladder perforation, which is a rare complication after TACE, when unexplained abdominal pain persists.


Leukaemogenesis: a postulated mechanism involving tyrosine protein kinase and DNA topoisomerase.
The weight of available evidence suggests that leukaemogenesis is a multi-step, complex process. Since there are different types of leukaemia, it seems likely that a variety of distinct molecular mechanisms are involved, arising from different combinations of genetic defects. It is not therefore surprising that studies at genetic, karyotypic, biochemical, cellular and clinical levels all reveal considerable heterogeneity of abnormalities. An attempt to define associations between abnormalities at these different levels in the myeloid leukaemias, led to a new hypothesis which provides a link between activation of the tyrosine kinase group of oncogenes and two components of multi-step leukaemogenesis: reduced differentiation and the tendency for acquisition of further genetic changes.


Systematic Order-Made Synthesis of Sequence-Defined Polyurethanes with Length, Types, and Topologies.
Polyurethanes are industrially and academically important as soft materials. They are conventionally synthesized by a process based on step-growth polymerization; thus, molecular weight and structural control are impossible. However, the development of a synthetic strategy for polyurethanes remains a big challenge in designing soft materials. Herein, we demonstrate a synthetic methodology for generating polyurethanes with selectable lengths and termini characteristics. The multistep synthetic process offered the systematic synthesis of high-molecular weight, regioregular, and α,ω-urethane telechelics. Various oligomers with order-made repeating units revealed the effective length of the polymer properties. To demonstrate the scope of our methodology, it was also applied to the synthesis of block co-oligomers, three-armed star oligomers, and miktoarm star co-oligomers. Thus, our method allows the synthesis of high-molecular-weight oligomers with complete structural and molecular weight control, which is of enormous value to materials science; particularly the study and application of structure-property relationships in polyurethanes.


Neonatal behavior in full-term small for date.
Fifty newborns, 25 full term SFDs (small for date) and 25 full term AGAs (appropriate for gestational age) were taken up for comparative study of their behavior using BNBAS (Brazelton's neonatal behavior assessment scale). The study revealed that full term SFDs performed significantly poorly on all items under cluster interactive processes compared to their counterparts full term AGAs on day 1. They also showed similar poor performance in clusters of motor processes and organizational processes (State control). Follow up assessment on day 30 revealed significantly better performance in these clusters. However, the performance of SFD babies in all items of cluster of organizational processes (physiological response) was comparable to that of AGA babies in the initial as well as follow up assessments.


[Multiple Resections for Metastases from Colorectal Cancer].
We analyzed to clarify an outcome of multiple resections of metastases from colorectal cancer. Total 7 cases who underwent several resections for metastases from colorectal cancer in Saiseikai Kurihashi Hospital after 2010 were enrolled for analysis. Age of patients at the time of the primary site resection was 67(45-78)year-old, including 4males and 3 females. Patients located at cecum/ascending/sigmoid/rectosigmoid/upper rectum were 1/1/2/2/1 respectively. Metachronous metastases were found in 5 patients. There were 1 patient for Stage I , 2 patients for Stage III a and III b each and all Stage III patients received adjuvant chemotherapy. The resected organs were 9 in lung, 8 in liver, 1 case in lymph node, local site and peritoneum and the median resected sites were 3(2-4)lesions. In 17 months median observation periods after latest resection, 5 cases have not been prolapsed including 3 cases with chemotherapy. Two cases were relapsed with unresectble status. One case died for 24 months and one case is under the chemotherapy for 12 months. Five year survival rate was 75% and 2 year prolapse free rate was 66.7%, since the relatively good prognosis was obtained by multiple resections. The cases that multiple resections with R0 were able to perform for the metastases were analyzed. Although cases which become finally to be unresectable exist, it is suggested that the relatively good prognosis might be obtained by multiple resections for metastases.


Gastrointestinal bezoars.
Of 99 patients with 117 gastrointestinal bezoars, 69 had undergone previous surgery, the most common operation being bilateral truncal vagotomy with pyloroplasty (55 patients). An excessive intake of vegetable fibre was found in 38 patients and poor mastication in 27. Thirty bezoars presented with gastric symptoms and patients had endoscopy as the diagnostic technique; 87 caused symptoms of intestinal obstruction with the diagnosis made by plain abdominal radiography. Medical treatment by enzymic or endoscopic fragmentation was used for 17 of 30 gastric bezoars; surgery was required in the remainder. Intestinal bezoars causing obstruction can be fragmented and 'milked' to the caecum. The stomach should be explored for associated gastric bezoars.


[Chronic obstructive pulmonary disorder (COPD) patients with the syndrome of combined pulmonary fibrosis and emphysema, compared to patients with emphysema alone].
In recent years the syndrome of combined puLmonary fibrosis and emphysema (CPFE) was recognized as a unique disorder. The diagnosis of CPFE is based on the pulmonary findings of High ResoLution Computed Tomography (HRCT) of the Lung. Patients with this entity have reLativeLy preserved lung volumes and spirometry but marked reductions in diffusing capacity on pulmonary function testing. Since dyspnea is the main symptom that limits daily activities in patients with COPD, we wanted to compare the clinical features, exercise tolerance, quality of life and dyspnea of patient with CPFE to patients with emphysema alone. A total of 14 patients with CPFE were compared to 16 patients with COPD and emphysema alone. All patients had HRCT, spirometery, body ptethysmography, CO diffusion capacity, 6 minute walk test, inspiratory muscle strength, measurements of the perception of dyspnea at rest and following effort, and they completed a questionnaire on quality of Life aspects. Patients with CPFE were a littLe younger, had a similar smoking history, had milder airway obstruction, smaller RV and FRC, and more severe reductions in diffusing capacity. They had more dyspnea at rest and following effort, and their exercise tolerance and quality of life were significantly reduced compared to patients with emphysema alone. The group of patients with combined pulmonary fibrosis and emphysema (CPFE), based on the HRCT, is characterized by relatively preserved lung volumes and spirometry but marked reductions in diffusing capacity, exercise tolerance, quality of life and higher perception of dyspnea, compared to patients with emphysema alone.


Irradiation induces increased production of haemopoietic and proinflammatory cytokines in the mouse lung.
To investigate cytokine expression following irradiation of mice, predominantly in lung tissue but also in selected other tissues. Mice of strain ICR were whole-body (unilaterally) exposed to 3-20 Gy of (60)Co gamma-rays. Colony-stimulating activity (CSA) of lung-conditioned media (LCM), and also other non-haemopoietic and haemopoietic organs, and blood serum of mice was assayed using a GM-CFC bioassay. The production of GM-CSF, IL-6 and TNF-alpha protein in LCM and sera was determined by an ELISA method. Greatest CSA was detected in conditioned media from the lungs and was induced in a dose- and time-dependent fashion, peaking at 3-9 days after irradiation with a lethal dose of 9 Gy. Conditioned medium prepared from lungs that had been irradiated with a dose of 9 Gy in vitro did not exhibit an increase in CSA. However, whereas the lung-conditioned medium from irradiated mice was found to produce CSA, sera from normal or irradiated mice did not lead to this effect. A significant increase in CSA in sera was observed in the presence of a suboptimal concentration of IL-3, implying that they comprise the co-stimulatory activity (CoSA). The results showed that radiation exposure increased GM-CSF and TNF-alpha protein levels but did not affect IL-6 production in LCM. In contrast, IL-6 and TNF-alpha protein levels in serum were increased after irradiation but no GM-CSF production could be detected. Whole-body irradiation enhances CSA in lungs as well as in other haemopoietic and non-haemopoietic organs. The increase of CSA correlates with increased levels of haemopoietic and proinflammatory cytokines in lung.


A Novel α2/α4 Subtype-selective Positive Allosteric Modulator of Nicotinic Acetylcholine Receptors Acting from the C-tail of an α Subunit.
Positive allosteric modulators (PAMs) of nicotinic acetylcholine receptors (nAChR) are important therapeutic candidates as well as valuable research tools. We identified a novel type II PAM, (R)-7-bromo-N-(piperidin-3-yl)benzo[b]thiophene-2-carboxamide (Br-PBTC), which both increases activation and reactivates desensitized nAChRs. This compound increases acetylcholine-evoked responses of α2* and α4* nAChRs but is without effect on α3* or α6* nAChRs (* indicates the presence of other nAChR subunits). Br-BPTC acts from the C-terminal extracellular sequences of α4 subunits, which is also a PAM site for steroid hormone estrogens such as 17β-estradiol. Br-PBTC is much more potent than estrogens. Like 17β-estradiol, the non-steroid Br-PBTC only requires one α4 subunit to potentiate nAChR function, and its potentiation is stronger with more α4 subunits. This feature enables Br-BPTC to potentiate activation of (α4β2)(α6β2)β3 but not (α6β2)2β3 nAChRs. Therefore, this compound is potentially useful in vivo for determining functions of different α6* nAChR subtypes. Besides activation, Br-BPTC affects desensitization of nAChRs induced by sustained exposure to agonists. After minutes of exposure to agonists, Br-PBTC reactivated short term desensitized nAChRs that have at least two α4 subunits but not those with only one. Three α4 subunits were required for Br-BPTC to reactivate long term desensitized nAChRs. These data suggest that higher PAM occupancy promotes channel opening more efficiently and overcomes short and long term desensitization. This C-terminal extracellular domain could be a target for developing subtype or state-selective drugs for nAChRs.


Case report: Vulval sebaceous carcinoma: a report of two cases and literature review focus on treatment and survival.
Background: Extraocular sebaceous carcinoma (SC) arising in the vulva is extremely rare that no treatment consensus has been well-defined. Case presentation: We here presented two cases of vulval SC in a 31-year-old and a 62-year-old woman, respectively. Radical wide local excision was performed with free margin and they received no postoperative adjuvant therapy. No evidence of disease was detected after follow-ups for 12 months and 49 months, respectively. A comprehensive literature review of vulval SC was further conducted and other ten cases were included. The mean age was 55.9 years, nine patients were diagnosed with FIGO stage I diseases while the remaining three patients had metastatic lesions at initial diagnosis. Surgery was the mainstay treatment option that 11 (91.7%) underwent surgical resection, of which 5 patients received inguinal lymphadenectomy and 2 patients showed lymph nodes involved. Radiotherapy and chemotherapy were given in 2 and 1 patient, respectively. Two patients experienced recurrence within 1 year after initial therapy. At the final follow-up, ten patients had no evidence of disease, one patient was alive with the disease, and only one died of the disease. Conclusion: Radical wide local excision may be preferred in early-stage vulval SC and utilization of sentinel lymph node sampling should be recommended. Postoperative adjuvant therapy may be spared in patients with negative surgical margin and absence of lymph node involvement. Treatment of vulval SC referring to the guidelines of vulvar cancer should be administered in case of positive margins or metastatic disease.


Innexin expression in electrically coupled motor circuits.
The many roles of innexins, the molecules that form gap junctions in invertebrates, have been explored in numerous species. Here, we present a summary of innexin expression and function in two small, central pattern generating circuits found in crustaceans: the stomatogastric ganglion and the cardiac ganglion. The two ganglia express multiple innexin genes, exhibit varying combinations of symmetrical and rectifying gap junctions, as well as gap junctions within and across different cell types. Past studies have revealed correlations in ion channel and innexin expression in coupled neurons, as well as intriguing functional relationships between ion channel conductances and electrical coupling. Together, these studies suggest a putative role for innexins in correlating activity between coupled neurons at the levels of gene expression and physiological activity during development and in the adult animal.


Influence of age on the clinical presentation of prolactinomas in male patients.
Secreting pituitary adenomas are usually not considered a disease of older people. However, in male patients, prolactin-secreting pituitary tumours occur at a similar frequency throughout the entire life span, giving the opportunity to study in this gender the influence of age on the clinical presentation and response to treatment of these tumours. We conducted a retrospective study including 9 male patients aged >/=60 (range 60-73) years and 10 aged </=30 (range 17-30) years presenting with a prolactinoma in order to compare clinical presentation, results of pituitary function tests, and response to dopamine agonist therapy between older and younger patients. Four of the 9 elderly as well as the 10 younger patients came to medical attention for typical features of male prolactinomas including visual field defect in 5 (2 elderly), headaches in 2 (1 elderly), impotence in 3 (1 elderly), gynaecomastia and/or galactorrhoea in 2, and arrested puberty in 2. The remaining 5 older people presented for other various reasons: symptoms related to cortisol deficiency in 2, lethargy with clinical signs of hypopituitarism in 1, spontaneous multiple vertebral fractures in 1, and incidental discovery of a pituitary mass in 1. Basal prolactin levels (3,051+/-4,151 vs. 3,365 +/- 4,949 microg/l) and mean tumour diameter (30 +/- 16 vs. 25 +/- 13 mm) were similar in old and young patients. Cortisol deficiency was significantly more frequent in the elderly (n = 6) than in the young (n = 1) patients (p 0.02, Fisher's exact test). Secondary hypothyroidism was found in 2 elderly only, but not in young patients. Sixteen patients (8 elderly) received bromocriptine therapy for at least 6 months with a good tolerance. Normalization of the prolactin levels was achieved in 6 older (75%) and 4 younger patients (50%). The presentation of a prolactinoma in the elderly man is very heterogeneous and can be misleading. At the time of diagnosis, hypopituitarism is more frequent among older than younger patients despite a similar tumour size. We found dopamine agonists equally effective in the elderly.


Swallowing Preparation and Execution: Insights from a Delayed-Response Functional Magnetic Resonance Imaging (fMRI) Study.
The present study sought to elucidate the functional contributions of sub-regions of the swallowing neural network in swallowing preparation and swallowing motor execution. Seven healthy volunteers participated in a delayed-response, go, no-go functional magnetic resonance imaging study involving four semi-randomly ordered activation tasks: (i) "prepare to swallow," (ii) "voluntary saliva swallow," (iii) "do not prepare to swallow," and (iv) "do not swallow." Results indicated that brain activation was significantly greater during swallowing preparation, than during swallowing execution, within the rostral and intermediate anterior cingulate cortex bilaterally, premotor cortex (left > right hemisphere), pericentral cortex (left > right hemisphere), and within several subcortical nuclei including the bilateral thalamus, caudate, and putamen. In contrast, activation within the bilateral insula and the left dorsolateral pericentral cortex was significantly greater in relation to swallowing execution, compared with swallowing preparation. Still other regions, including a more inferior ventrolateral pericentral area, and adjoining Brodmann area 43 bilaterally, and the supplementary motor area, were activated in relation to both swallowing preparation and execution. These findings support the view that the preparation, and subsequent execution, of swallowing are mediated by a cascading pattern of activity within the sub-regions of the bilateral swallowing neural network.


Submicroscopic anatomy of photoreceptors in the female scale insect Eupulvinaria hydrangeae (Homopteres, Coccideae).
The submicroscopic anatomy of the eye in female Eupulvinaria is described. This scale insect has no compound eyes but simple pericerebral eyes composed of one pair of ocelli. The ocelli, located dorsolaterally to the brain, are of rhabdomeric type. They are situated in the subepidermal region underneath the basement membrane of the epidermis. Each ocellus consists of a cup made of a layer of numerous pigmented cells enclosing a few photoreceptive cells. The cuticular lens is facing the opening of the pigment-cup, while the optic nerve is emerging from the bottom of the cup. Pigmented cells show characteristic pigment granules. They are linked to each other by interdigitations or by desmosomes junctions. Both dendrites and cell body of the photoreceptor cell lie inside the eyecup, while the axon lies outside. The dendritic processes consist of large shaft-shaped rhabdomeres with microvilli extending perpendicular to the direction of the shaft. These microvilli are enveloped by digitiform cytoplasmic extensions of pigmented cells. These latter strands are free of pigment granules but contain microtubules orientated to the centre of the cup.


Bacterial contamination of endoscopist and assistant face visors during gastrointestinal endoscopy: a pilot study.
During the COVID-19 pandemic, health workers' facial exposure to pathogens has been brought into focus. In this study, we aimed to determine the occurrence and degree of facial contamination to both endoscopists and their assistants during endoscopic procedures to help inform future safety measures. Non-sterile visors worn by endoscopist, assistant and room control visors from 50 procedures were swabbed post procedure for culture. Procedure type, therapy, duration and evidence of visible visor contamination were recorded. After 48-hour incubation, all bacterial colonies were identified using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. Organisms were classified into skin/environmental, oronasal and enteric. A total of 104 visors were available for assessment (93 staff; 11 control). In worn visors, skin/environmental flora were isolated from 70, oronasal flora from 8, and enteric flora from 3 with an average colony count of >9.5. Notably, bacteria of enteric origin (Escherichia coli and Enterobacter cloacae) were isolated from three worn visors. In room control, skin/environmental flora were isolated from seven and oronasal flora from one with average colony count of five. No room control visors grew enteric flora. Overall, 9.1% room control and 10.8% worn visors were contaminated with organisms that could possibly have originated from patients. However, enteric flora were only obtained from worn visors. No visors were visibly contaminated. This pilot study demonstrates risk of contamination to faces of endoscopists and assistants. Larger studies are required to determine degree of risk and to give guidance on facial protection during gastrointestinal endoscopy.


[Endovascular management of arteriovenous malformations].
Management of high-flow arteriovenous malformation remain often problematic. Complete eradication of the nidus is the only potential cure, but this, however, is often difficult if not impossible. Frequently, a multidisciplinary approach is required. In these article, techniques and results of the endovascular management of MAV are discussed.


Healthcare regulation in the UK (part one).
Since New Labour came to power in the United Kingdom in 1997, health care and the National Health Service in particular have never strayed far from the top of the political agenda with the Government promising a more patient-centred health service and greater accountability for both hospitals and individual healthcare practitioners.


Suture extrusion in small arteries and veins.
One longitudinally orientated microsuture was implanted in the femoral artery and vein of 40 rats and harvested at 4 different time intervals (2, 8, 12, 18 weeks). The tissue section containing the most luminal portion of suture loop was chosen and submitted for analysis. Two parameters, one estimating the suture location in the vessel wall relative to the internal elastic lamina (IEL) and a second, estimating the magnitude of the intimal response at the suture site were addressed. Average suture location changed significantly over time. The suture tended to be exteriorized or extruded from its once luminal location within the intima to a position located within the adventitia. Veins exhibited a greater incidence of suture extrusion than arteries. The maximum magnitude of the intimal cellular response occurred in the 2 week time interval. Significant decreases (p less than 0.05) in the thickness of the intima was observed in each subsequent time interval for both arteries and veins. The results of this experiment indicate that the cellular response and reparative processes occurring in small arteries and veins modifies the luminal papillary projection and extrudes nylon suture material.


Meaningful use's benefits and burdens for US family physicians.
The federal meaningful use (MU) program was aimed at improving adoption and use of electronic health records, but practicing physicians have criticized it. This study was aimed at quantifying the benefits (ie, usefulness) and burdens (ie, workload) of the MU program for practicing family physicians. An interdisciplinary national panel of experts (physicians and engineers) identified the work associated with MU criteria during patient encounters. They conducted a national survey to assess each criterion's level of patient benefit and compliance burden. In 2015, 480 US family physicians responded to the survey. Their demographics were comparable to US norms. Eighteen of 31 MU criteria were perceived as useful for more than half of patient encounters, with 13 of those being useful for more than two-thirds. Thirteen criteria were useful for less than half of patient encounters. Four useful criteria were reported as having a high compliance burden. There was high variability in physicians' perceived benefits and burdens of MU criteria. MU Stage 1 criteria, which are more related to basic/routine care, were perceived as beneficial by most physicians. Stage 2 criteria, which are more related to complex and population care, were perceived as less beneficial and more burdensome to comply with. MU was discontinued, but the merit-based incentive payment system within the Medicare Access and CHIP Reauthorization Act of 2015 adopted its criteria. For many physicians, MU created a significant practice burden without clear benefits to patient care. This study suggests that policymakers should not assess MU in aggregate, but as individual criteria for open discussion.


Retinopathy of Prematurity Screening Examination and Changes in Vital Signs.
Dilation and examination during retinopathy of prematurity (ROP) screening can cause systemic complications and even life-threatening adverse events (AEs). The main objective of this study is to assess the prevalence and significance of AEs and changes in vital signs during ROP screenings, and to correlate birth weight, gestational age, and length of exam as possible predictors of these changes. This is a prospective, observational study that includes 1,360 screening exams from 680 premature infants in two neonatal intensive care units. Systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate, and oxygen saturation were monitored from the time that dilating drops were administered until 4 hours after the examination was completed. Any clinical deterioration or complication was documented. Of 1,360 infant screening exams, 153 (11%) screening exams resulted in at least one change in vital sign that alerted the monitor. There was one serious AE requiring bag valve mask resuscitation 30 minutes after dilating drops were placed. Gestational age, birth weight, and length of ROP exam were not significant predictors of AEs. There were statistically significant changes when comparing pre- and post-vital signs following dilation and funduscopy exam. Although ROP screening exams are essential for at-risk neonates, mydriatic drops and retinal exams can result in changes to vital signs and AEs. It is important to closely monitor neonates during these examinations. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:458-463.].


Inhaled Drug Therapy 2016: The Year in Review.
Some recent salient publications related to inhaled drug therapy are discussed. Unexpectedly, a 2.5-μg once-daily dose of tiotropium (Respimat) had greater efficacy than the 5.0-μg daily dose. Occurrence of a reverse dose response serves to caution us that administering more drug is not always beneficial. Small-airway inflammation contributes to pathogenesis of asthma, especially severe asthma. However, there is no conclusive evidence that the use of small-particle aerosols to target small airways improves clinical outcomes in controlled clinical trials. Clinical outcomes of patients with symptomatic asthma have been better in "real-life" studies when fine-particle aerosols were compared with conventional (large-particle) aerosols. In subjects with COPD, the FLAME study indicates that a long-acting antimuscarinic agent/long-acting β-agonist combination was superior to an inhaled corticosteroid/long-acting β-agonist combination in preventing exacerbations. Another study in children with asthma and adults with asthma or COPD showed that peak inhalation flow must be considered in the context of the dry powder inhaler resistance. Investigators from the United Kingdom have shown modest success in replacing the defective cystic fibrosis transmembrane regulator gene in subjects with cystic fibrosis with a plasmid encoding the normal cystic fibrosis transmembrane regulator gene packaged within a non-viral vector. Also, inhaled antibiotics in patients with non-cystic fibrosis bronchiectasis and inhaled interferon-γ in patients with idiopathic pulmonary fibrosis have shown encouraging results but are investigational at this time. Compared to combustion cigarettes, use of e-cigarettes reduces exposure to carcinogens and volatile organic compounds. However, high levels of benzaldehyde in the vapor from cherry-flavored cigarettes raise concerns about the safety of some food flavorings in e-cigarettes.


Chemokine receptors and stromal cells in the homing and homeostasis of chronic lymphocytic leukemia B cells.
Chronic lymphocytic leukemia (CLL) is a disease characterized by an accumulation, of mature, functionally incompetent B lymphocytes in the blood, secondary lymphoid tissues, and marrow. Lymphocyte trafficking and homing to specialized microenvironments is an active process that depends on the sequential engagement of adhesion molecules and activation through chemokine receptors. CLL B cells express functional CXCR3, CXCR4, and CXCR5 chemokine receptors that can direct leukemia cell chemotaxis in vitro. Marrow stromal cells, blood-derived "nurse-like cells", and extramedullary stromal cells of mesenchymal origin secrete high amounts of stromal cell-derived factor-1 (SDF-1) and thereby can attract CLL B cells via CXCR4. In vitro, CLL cells are rescued from apoptosis by cell-cell contact with such cells. Moreover, we found that the capacity of these cells to protect leukemia cells from apoptosis in vitro is mediated, at least in part, by the SDF-1 chemokine. Taken together, these findings suggest that chemokines and their receptors on CLL B cells can govern the homing and survival of leukemia B cells in vivo and therefore may contribute to their noted resistance to chemotherapy-induced apoptosis. Conceivably, CXCR4, and possibly other chemokine receptors, may represent a novel target for the development of effective treatment of this disease.


Comparison between K-nearest-neighbor approaches for conditional entropy estimation: Application to the assessment of the cardiac control in amyotrophic lateral sclerosis patients.
The study evaluates the k-nearest-neighbor (KNN) strategy for the assessment of complexity of the cardiac neural control from spontaneous fluctuations of heart period (HP). Two different procedures were assessed: i) the KNN estimation of the conditional entropy (CE) proposed by Porta et al; ii) the KNN estimation of mutual information proposed by Kozachenko-Leonenko, refined by Kraskov-Stögbauer-Grassberger and here adapted for the CE estimation. The two procedures were compared over HP variability recordings obtained at rest in supine position and during head-up tilt (HUT) in amyotrophic lateral sclerosis patients and healthy subjects. We found that the indexes derived from the two procedures were significantly correlated and both methods were able to detect the effect of HUT on HP complexity within the same group and distinguish the two populations within the same experimental condition. We recommend the use of the KNN strategy to quantify the dynamical complexity of cardiac neural control in addition to more traditional approaches.


Aldosterone, catecholamines, and CK-BB as biochemical markers in hypertensive intracerebral hemorrhage.
The author measured blood concentrations of aldosterone, epinephrine, norepinephrine, and creatine kinase isozyme (brain type) (CK-BB) in 65 patients with hypertensive intracerebral hemorrhage. The purpose of this study was to evaluate these measurements in determining the severity of acute cerebral damage in such patients. There were 42 males and 23 females ranging in age from 30 to 93 years. Their clinical status was classified as mild or severe on the basis of neurological grading. In the mild group, plasma aldosterone increased slightly at the onset of disease, while the other markers showed no change. In contrast, the severe group showed elevation of all markers on admission, with a gradual return to normal by day 3 to day 7 of hospitalization. Analysis of the data by hematoma site revealed that aldosterone levels increased in patients with thalamic hemorrhage; epinephrine and norepinephrine concentrations were high in those with pontine hemorrhage; and CK-BB levels were elevated in cases of thalamic and cerebellar hemorrhage. It was also noted that patients in whom all four markers were increased tended to have poor outcomes.


Highly Cross-Linked Polyethylene Reduces Osteolysis Incidence and Wear-Related Reoperation Rate in Cementless Total Hip Arthroplasty Compared With Conventional Polyethylene at a Mean 12-Year Follow-Up.
A number of studies on total hip arthroplasty have compared highly cross-linked polyethylene (HXLPE) with conventional polyethylene (CPE) liners beyond 10 years. However, the impact of HXLPE on the wear-related reoperation rate is unclear. The purpose of this study was to evaluate the clinical advantage of using a single manufacturer's HXLPE in terms of reducing the reoperation rate. The study was a follow-up retrospective cohort study over a mean of 12 years that examined patients aged 45-70 years with cementless total hip arthroplasty using a 26-mm-diameter cobalt-chromium head. Sixty-seven patients (79 hips; HXLPE group = 41 hips, CPE group = 38 hips) were evaluated for a minimum 10-year follow-up. Kaplan-Meier survival analysis was performed, with wear-related reoperations and radiographic osteolysis serving as the end points. The polyethylene wear rate was also assessed. The mean 12-year follow-up rates of survivorship that were evaluated using wear-related reoperations as the end point were 100% and 91.4% in the HXLPE and CPE groups, respectively (P = .007), and the mean 12-year follow-up rates of survivorship with osteolysis as the end point were 100% and 36.2%, respectively (P < .001). Compared with the CPE group, the HXLPE group presented a significantly reduced wear rate (HXLPE group, 0.035 mm/y; CPE group, 0.118 mm/y). A unique strength of this study is that we assessed a single manufacturer's HXLPE while keeping most other implant parameters uniform. This study reveals the clinical advantage of using a single manufacturer's HXLPE in terms of a reduced wear-related reoperation rate at a mean 12-year follow-up.


Lesion-remote metabolic changes after neocortical cold injury in rats.
Lesion-remote metabolic changes were examined 1-7 days after neocortical cold injury using tissue ATP, glucose and lactate bioluminescent imaging, pH-dependent fluoroscopy and cerebral protein synthesis (CPS) autoradiography. One day after lesioning an alkaline pH shift (0.35 +/- 0.19 units above contralateral) was noticed in the lesion-remote cortex, the underlying white matter, the striatum, hippocampus and thalamus, which slowly resolved within 7 days and probably reflected the spread of vasogenic edema. Closely associated with the pH shift, elevations in tissue glucose and lactate levels were found, which reached maximum levels after 3 days (7.4 +/- 2.4 vs 4.2 +/- 1.2 micromol/g glucose, 6.6 +/- 2.3 vs 2.1 +/- 0.6 micromol/g lactate) but, in contrast to the alkalosis, remained elevated after 1 week. Thus, neocortical trauma is associated with long-lasting metabolic changes, which are intimately linked with the distribution of post-traumatic alkalosis.


Physical functioning and mindfulness skills training in chronic pain: a systematic review.
The importance of improved physical function as a primary outcome in the treatment of chronic pain is widely accepted. There have been limited attempts to assess the effects mindfulness skills training (MST) has on objective outcomes in chronic pain care. This systematic review evaluated published reports of original randomized controlled trials that described physical function outcomes after MST in the chronic pain population and met methodological quality according to a list of predefined criteria. PRISMA criteria were used to identify and select studies, and assess their eligibility for inclusion. The established guidelines for best practice of systematic reviews were followed to report the results. Of the 2,818 articles identified from the original search of four electronic databases, inclusionary criteria were met by 15 studies published as of August 10, 2015, totaling 1,199 patients. All included studies used self-report measures of physical function, and only two studies also employed performance-based measures of function. There were wide variations in how physical function was conceptualized and measured. Although the quality of the studies was rated as high, there was inconclusive evidence for improvement in physical function assessed by self-report due to contradiction in individual study findings and the measures used to assess function. Strong evidence for lack of improvement in physical function assessed via performance-based measures was found. This review draws attention to the importance of having a unified approach to how physical function is conceptualized and assessed, as well as the importance of using quality performance-based measures in addition to subjective self-reports that appropriately assess the physical function construct within MSTs for chronic pain.


Little Evidence of Zika Virus Infection in Wild Long-Tailed Macaques, Peninsular Malaysia.
We tested a sample of 234 wild long-tailed macaques (Macaca fascicularis) trapped in Peninsular Malaysia in 2009, 2010, and 2016 for Zika virus RNA and antibodies. None were positive for RNA, and only 1.3% were seropositive for neutralizing antibodies. Long-tailed macaques are unlikely to be reservoirs for Zika virus in Malaysia.


Differential Transcriptome Responses to Aflatoxin B₁ in the Cecal Tonsil of Susceptible and Resistant Turkeys.
The nearly-ubiquitous food and feed-borne mycotoxin aflatoxin B₁ (AFB₁) is carcinogenic and mutagenic, posing a food safety threat to humans and animals. One of the most susceptible animal species known and thus a good model for characterizing toxicological pathways, is the domesticated turkey (DT), a condition likely due, at least in part, to deficient hepatic AFB₁-detoxifying alpha-class glutathione S-transferases (GSTAs). Conversely, wild turkeys (Eastern wild, EW) are relatively resistant to the hepatotoxic, hepatocarcinogenic and immunosuppressive effects of AFB₁ owing to functional gene expression and presence of functional hepatic GSTAs. This study was designed to compare the responses in gene expression in the gastrointestinal tract between DT (susceptible phenotype) and EW (resistant phenotype) following dietary AFB₁ challenge (320 ppb for 14 days); specifically in cecal tonsil which functions in both nutrient absorption and gut immunity. RNAseq and gene expression analysis revealed significant differential gene expression in AFB₁-treated animals compared to control-fed domestic and wild birds and in within-treatment comparisons between bird types. Significantly upregulated expression of the primary hepatic AFB₁-activating P450 (CYP1A5) as well as transcriptional changes in tight junction proteins were observed in AFB₁-treated birds. Numerous pro-inflammatory cytokines, TGF-β and EGF were significantly down regulated by AFB₁ treatment in DT birds and pathway analysis suggested suppression of enteroendocrine cells. Conversely, AFB₁ treatment modified significantly fewer unique genes in EW birds; among these were genes involved in lipid synthesis and metabolism and immune response. This is the first investigation of the effects of AFB₁ on the turkey gastro-intestinal tract. Results suggest that in addition to the hepatic transcriptome, animal resistance to this mycotoxin occurs in organ systems outside the liver, specifically as a refractory gastrointestinal tract.


[Insulin binding to erythrocytes in chronic glucocorticoid deficiency--investigation before and during replacement therapy].
The effect of chronic glucocorticoid deficiency on insulin binding to erythrocyte was evaluated in 2 cases of ACTH deficiency, 2 of Sheehan's syndrome and a case of Addison's disease before and after the replacement therapy with cortisone acetate. 75 gram oral glucose tolerance test (OGTT) was also performed. Mean fasting plasma glucose (FPG) and insulin (FIRI) before (70.2 mg/dl, 3.6 microU/ml) and after (75.4 mg/dl, 7.8 microU/ml) therapy were significantly lower than those in normal control (97.0 mg/dl, 12.0 microU/ml). The ratio of FIRI/FPG before and after treatment were also significantly lower than that in control subjects. Glucose areas during OGTT before and after treatment were not different from that in control subjects. However, insulin area before treatment was significantly lower than that in control group. There were significant increases in FIRI/FPG and insulin area, but not in FPG and glucose area before and after treatment. Insulin binding to erythrocytes before treatment (11.9 +/- 1.1%, mean +/- SD) was greater than that in normal subjects (7.7 +/- 1.9%, n = 19, p less than 0.05). It was significantly decreased and normalized to 7.8 +/- 2.0% by the treatment. Analysis of binding parameters revealed the increases in receptor concentration at high affinity site (R1) and in average affinity at empty site by average affinity profile (Ke) before treatment in comparison with control subjects. There was no significant difference in binding parameters after treatment and in control group. High R1 or low R2 observed before treatment was significantly decreased or increased after treatment, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Attenuation-Corrected Estimators of Reliability.
The estimates of reliability are usually attenuated and deflated because the item-score correlation ( ρ g X , Rit) embedded in the most widely used estimators is affected by several sources of mechanical error in the estimation. Empirical examples show that, in some types of datasets, the estimates by traditional alpha may be deflated by 0.40-0.60 units of reliability and those by maximal reliability by 0.40 units of reliability. This article proposes a new kind of estimator of correlation: attenuation-corrected correlation (R AC ): the proportion of observed correlation with the maximal possible correlation reachable by the given item and score. By replacing ρ g X with R AC in known formulas of estimators of reliability, we get attenuation-corrected alpha, theta, omega, and maximal reliability which all belong to a family of so-called deflation-corrected estimators of reliability.


Hematological variations in healthy participants exposed 2 h to propylene glycol ethers under controlled conditions.
Glycol ethers are solvents used in a plethora of occupational and household products exposing the users to potential toxic effects. Several glycol ethers derived from ethylene glycol induce hematological toxicity, such as anemia in workers. The exposure effects on blood cells of glycol ethers derived from propylene glycol are unknown in humans. The aim of our study was to evaluate blood parameters indicative of red blood cell (RBC) hemolysis and oxidative stress in participants exposed to propylene glycol (propylene glycol monobutyl ether (PGBE) and propylene glycol monomethyl ether (PGME)), two extensively used propylene glycol derivatives worldwide. Seventeen participants were exposed 2 h in a control inhalation exposure chamber to low PGME (35 ppm) and PGBE (15 ppm) air concentrations. Blood was regularly collected before, during (15, 30, 60, and 120 min), and 60 min after exposure for RBC and oxidative stress analyses. Urine was also collected for clinical effects related to hemolysis. Under the study conditions, our results showed that the blood parameters such as RBCs, hemoglobin concentration, and white blood cells tended to increase in response to PGME and PGBE exposures. These results raise questions about the possible effects in people regularly exposed to higher concentrations, such as workers.


Pushing the limits of high-resolution functional MRI using a simple high-density multi-element coil design.
Recent studies have shown that functional MRI (fMRI) can be sensitive to the laminar and columnar organization of the cortex based on differences in the spatial and temporal characteristics of the blood oxygenation level-dependent (BOLD) signal originating from the macrovasculature and the neuronal-specific microvasculature. Human fMRI studies at this scale of the cortical architecture, however, are very rare because the high spatial/temporal resolution required to explore these properties of the BOLD signal are limited by the signal-to-noise ratio. Here, we show that it is possible to detect BOLD signal changes at an isotropic spatial resolution as high as 0.55 mm at 7 T using a high-density multi-element surface coil with minimal electronics, which allows close proximity to the head. The coil comprises of very small, 1 × 2-cm(2) , elements arranged in four flexible modules of four elements each (16-channel) that can be positioned within 1 mm from the head. As a result of this proximity, tissue losses were five-fold greater than coil losses and sufficient to exclude preamplifier decoupling. When compared with a standard 16-channel head coil, the BOLD sensitivity was approximately 2.2-fold higher for a high spatial/temporal resolution (1 mm isotropic/0.4 s), multi-slice, echo planar acquisition, and approximately three- and six-fold higher for three-dimensional echo planar images acquired with isotropic resolutions of 0.7 and 0.55 mm, respectively. Improvements in parallel imaging performance (geometry factor) were up to around 1.5-fold with increasing acceleration factor, and improvements in fMRI detectability (temporal signal-to-noise ratio) were up to around four-fold depending on the distance to the coil. Although deeper lying structures may not benefit from the design, most fMRI questions pertain to the neocortex which lies within approximately 4 cm from the surface. These results suggest that the resolution of fMRI (at 7 T) can approximate levels that are closer to the spatial/temporal scale of the fundamental functional organization of the human cortex using a simple high-density coil design for high sensitivity.


Postnatal development of onset transient responses in macaque V1 AND V2 neurons.
Vision of newborn infants is limited by immaturities in their visual brain. In adult primates, the transient onset discharges of visual cortical neurons are thought to be intimately involved with capturing the rapid succession of brief images in visual scenes. Here we sought to determine the responsiveness and quality of transient responses in individual neurons of the primary visual cortex (V1) and visual area 2 (V2) of infant monkeys. We show that the transient component of neuronal firing to 640-ms stationary gratings was as robust and as reliable as in adults only 2 wk after birth, whereas the sustained component was more sluggish in infants than in adults. Thus the cortical circuitry supporting onset transient responses is functionally mature near birth, and our findings predict that neonates, known for their "impoverished vision," are capable of initiating relatively mature fixating eye movements and of performing in detection of simple objects far better than traditionally thought.


Dietary intervention prior to pregnancy reverses metabolic programming in male offspring of obese rats.
Obesity involving women of reproductive years is increasing dramatically in both developing and developed nations. Maternal obesity and accompanying high energy obesogenic dietary (MO) intake prior to and throughout pregnancy and lactation program offspring physiological systems predisposing to altered carbohydrate and lipid metabolism. Whether maternal obesity-induced programming outcomes are reversible by altered dietary intake commencing before conception remains an unanswered question of physiological and clinical importance. We induced pre-pregnancy maternal obesity by feeding female rats with a high fat diet from weaning to breeding 90 days later and through pregnancy and lactation. A dietary intervention group (DINT) of MO females was transferred to normal chow 1 month before mating. Controls received normal chow throughout. Male offspring were studied. Offspring birth weights were similar. At postnatal day 21 fat mass, serum triglycerides, leptin and insulin were elevated in MO offspring and were normalized by DINT. At postnatal day 120 serum glucose, insulin and homeostasis model assessment (HOMA) were increased in MO offspring; glucose was restored, and HOMA partially reversed to normal by DINT. At postnatal day 150 fat mass was increased in MO and partially reversed in DINT. At postnatal day 150, fat cell size was increased by MO. DINT partially reversed these differences in fat cell size. We believe this is the first study showing reversibility of adverse metabolic effects of maternal obesity on offspring metabolic phenotype, and that outcomes and reversibility vary by tissue affected.


Management of "Atypical Endocervical Cells" Compared to "Atypical Glandular Cells".
To assess adherence to management guidelines based on the terminology used to describe atypical glandular cells (AGC) on cytology reports. We analyzed AGC pathology reports from Hartford Hospital, 2004-2007, and identified cases of AGC with the terminology atypical glandular cells or atypical endocervical cells (AEC). We calculated rates of clinical evaluations based on the terminology used to describe the AGC. Statistical analysis was performed using the χ test. Seventy-eight reports contained the terminology AEC and 97 reports contained the terminology AGC. The rate of histologic sampling in women with AEC was lower than in women with AGC (52.6% vs 83.5%; p < .01). Similarly, the rate of comprehensive evaluations was lower (33.3% vs 71.1%; p < .01). Fewer endocervical curettages (47.4% vs 77.3%; p < .01) and fewer endometrial biopsies in women 35 years or older were performed (26.9% vs 69.1%; p < .01) in women with AEC than in women with AGC. Women with AGC reports containing the term AEC were managed less optimally than those with AGC. These results suggest that the terminology used to describe the finding of atypical glandular cells may influence the clinical evaluation. Clinicians may not recognize AEC as AGCs. Ours results suggest that the terminology atypical endocervical cells should be avoided or accompanied by the terminology atypical glandular cells.


The Fat Kidney.
The purpose of this review is to summarize the current evidence on the role of obesity in the development and progression of chronic kidney disease and the current evidence on nutritional, pharmacological, and surgical strategies for the management of individuals with obesity and chronic kidney disease. Obesity can hurt the kidney via direct pathways, through the production of pro-inflammatory adipocytokines, and indirectly due to systemic complications of obesity, including type 2 diabetes mellitus and hypertension. In particular, obesity can damage the kidney through alterations in renal hemodynamics resulting in glomerular hyperfiltration, proteinuria and, finally, impairment in glomerular filtratation rate. Several strategies are available for weight loss and maintenance, such as the modification of lifestyle (diet and physical activity), anti-obesity drugs, and surgery therapy, but there are no clinical practice guidelines to manage subjects with obesity and chronic kidney disease. Obesity is an independent risk factor for the progression of chronic kidney disease. In subjects with obesity, weight loss can slow down the progression of renal failure with a significant reduction in proteinuria and improvement in glomerular filtratation rate. Specifically, in the management of subjects with obesity and chronic renal disease, it has been shown that bariatric surgery can prevent the decline in renal function, while further clinical studies are needed to evaluate the efficacy and safety on the kidney of weight reducing agents and the very low-calorie ketogenic diet.


Nasal Swab as Preferred Clinical Specimen for COVID-19 Testing in Children.
The first pediatric study demonstrating significantly higher positivity rate of nasal (mid-turbinate) swab testing over oropharyngeal swab testing in detecting SARS-CoV-2 (Fisher exact test 0.046, Cohen K 0.43, confidence interval 95%, 0.014-0.855). Benefits might include lower collection-related hazard for healthcare workers. We recommend it as preferred choice for swab-based SARS-CoV-2 testing in children.


[Removal of a foreign metallic body with a magnet].
Foreign bodies in the human body are frequent and can be very hard to identify. Over the years it has been shown that removal could be done by magnetic force if the foreign body is magnetic. We present two stories where a foreign body was removed from a leg and abdomen respectively, with magnetic force. Removal of metallic foreign bodies with magnetic force is a fast, inexpensive and almost atraumatic procedure, which can minimize the use of anaesthetics and probably the use of X-ray.


IOL prediction: an evaluation of preoperatively determined intraocular lens power accuracy.
A retrospective survey of 612 eyes that had undergone cataract extraction and IOL implantation was undertaken to evaluate the accuracy of ultrasound biometry combined with keratometry using the SRK regression formula, for the preoperative prediction of intraocular lens powers. A mean error of +0.35 dioptre sphere (DS) (SD +/- 0.98) was found for the series overall, with a significant (P less than 0.005) difference between the distribution of postoperative refractive errors using the S.R.K. formula for IOL prediction and the use of a standard lens of 19.5 DS. The consistency of results was tested for those patients with greater or less than normal axial length. Linear regression analysis showed no correlation between axial length and postoperative refractive error and therefore does not support the adjustment of predicted IOL powers by a factor based on axial length. Statistically significant differences were found between surgeons' results, supporting the practice of A-constant modification for individual surgeons.


Quality control in the production of fluoridated food grade salt.
Fluoridated food grade salt has been manufactured in Switzerland for 50 years. Since correct dosing is important not only for effective caries prophylaxis but also in order to guarantee food safety, the production of fluoridated salt must be accurately monitored. The authorities do not impose any specific requirements as regards the purity of the fluoride compounds that are used, nor the homogeneity or dosing accuracy that should be attained during the manufacture of fluoridated salt. The quality requirements to be observed and the means by which these standards are to be ensured must largely be determined by the producer himself as part of the "self-monitoring" that is stipulated by the law. Depending on whether fluoridated salt is manufactured in a continuous or discontinuous process and on whether the fluoride is added as a solution or in solid form, a plant-specific testing plan must be drawn up for the implementation of quality monitoring. On the basis of statutory requirements, a food manufacturer must subject all the processes which he carries out to a risk analysis (HACCP study). Monitoring of the dosing of fluoride must be classified as a Critical Control Point (CCP). Three well-established testing methods which have been validated in ring tests are available to determine the fluoride content in food grade salt (a potentiometric, an ion-chromatographic and a photometric method). In practice, the potentiometric method has proven to be a simple, accurate and comparably low-priced process and is widely used.


Rise in prostate-specific antigen in men with untreated low-grade prostate cancer is slower during spring-summer.
To test the hypothesis that the rate of rise in prostate-specific antigen (PSA) is slower during the spring-summer than during the rest of the year, we used PSA data from a prospective single-arm cohort study of men who had been followed to characterize a watchful observation protocol with selective delayed intervention for clinically localized, low-to-intermediate grade prostate adenocarcinoma. The rate of PSA increase was calculated as the visit-to-visit slope of log (PSA) against time, from 1 calendar-quarter visit to the next. The nonparametric Friedman test confirmed differences in rate of PSA rise among the calendar quarters (P = 0.041). Post hoc analysis showed the rate of PSA increase during Q2 was significantly slower than in each one of the other calendar quarters (Q1 versus Q2, P = 0.025; Q3 versus Q2, P = 0.002; Q4 versus Q2, P = 0.013), with no differences among quarters Q1, Q3, and Q4. These results are consistent with the vitamin D hypothesis that the higher 25-hydroxyvitamin D levels associated with spring and summer have a desirable effect on prostate biology. The therapeutic implication is that vitamin D supplementation in the range of 2000 IU/d, a dose comparable to the effect of summer, can benefit men monitored for rising PSA.


Minimal pigment: a new type of oculocutaneous albinism.
Minimal pigment, a new type of oculocutaneous albinism (OCA), is described. At birth, affected individuals had no skin or eye pigment, and white hair and blue irides, but minimal amounts of pigment developed in the iris during the first decade of life. They had no measurable hairbulb tyrosinase activity. A characteristic and unusual pattern of parental activity was found in each of three families studied, with one parent having normal and the other parent having abnormally low tyrosinase activity. The melanocyte ultrastructure was normal and variations in premelanosomal pigmentation correlated with tyrosinase activity. This clinical and biochemical pattern has not been seen in any of the previously described types of OCA. The biochemical defect in minimal pigment OCA is unknown.


[Analysis of clinical and laboratory characteristics and survival with hairy cell leukemia].
To explore the clinical and laboratory characteristics and survival of Chinese patients with hairy cell leukemia (HCL). A total of 30 HCL patients from August 1990 to March 2012 were retrospectively analyzed. There were 22 cases with classical HCL (HCL-C) and 8 with variant HCL (HCL-V). Splenomegaly was the most common physical finding. Leukocytosis was found in all cases of HCL-V. But pancytopenia only accounted for 36.4% (8/22) in HCL-C. And 3/5 of HCL-V had abnormal chromosome karyotypes. Ribosomal-lamellae complexes (RLC) were found only in about 3/12 of HCL cases. Chemotherapy regimens including purine nucleoside analogues achieved a better complete remission (CR) rate than other regimens (3/4 vs 1/18, P = 0.012) in HCL-C. The median follow-up period was 27 (1 - 142) months. There was no follow-up loss. Eleven cases progressed and 6 died. The median overall survival (OS) was not reached. And the 1, 3, 6-year OS rates were 84%, 78% and 58% respectively. The median progression-free survival (PFS) was (63 ± 24) months and the 1, 2, 5-year PFS rates were 86%, 72% and 44% respectively. The median PFS of HCL-V was significant shorter than HCL-C ((23 ± 3) vs (78 ± 12) months, P = 0.014). In HCL-C group, fever (P = 0.038) and anemia (P = 0.000) at diagnosis were poor prognostic factors. But purine nucleoside analogues made no significant difference in PFS. Pancytopenia is infrequent in Chinese HCL patients. And classical RLC is rare under electron microscope. Purine nucleoside analogues may achieve a better CR rate, but fail to improve PFS rate. As compared with HCL-C, HCL-V is common with genetic abnormalities and has a worse prognosis with a shorter PFS.


The intermembrane space of mitochondria.
Mitochondria contain two aqueous compartments: the matrix and the intermembrane space. Whereas many of the biologic functions of the matrix were well characterized in the past, it became clear very recently that the intermembrane space plays a pivotal role in the coordination of mitochondrial activities with other cellular processes. These activities include the exchange of proteins, lipids, or metal ions between the matrix and the cytosol, the regulated initiation of apoptotic cascades, signalling pathways that regulate respiration and metabolic functions, the prevention of reactive oxygen species produced by the respiratory chain, or the control of mitochondrial morphogenesis. We focus on the different biologic functions of the intermembrane space and discuss the relevance of this fascinating compartment for cellular physiology and human health.


LncRNA PAXIP1-AS1 fosters the pathogenesis of pulmonary arterial hypertension via ETS1/WIPF1/RhoA axis.
Pulmonary arterial hypertension (PAH) is a life-threatening disease featured with elevated pulmonary vascular resistance and progressive pulmonary vascular remodelling. It has been demonstrated that lncRNA PAXIP1-AS1 could influence the transcriptome in PAH. However, the exact molecular mechanism of PAXIP1-AS1 in PAH pathogenesis remains largely unknown. In this study, in vivo rat PAH model was established by monocrotaline (MCT) induction and hypoxia was used to induce in vitro PAH model using human pulmonary artery smooth muscle cells (hPASMCs). Histological examinations including H&E, Masson's trichrome staining and immunohistochemistry were subjected to evaluate the pathological changes of lung tissues. Expression patterns of PAXIP1-AS1 and RhoA were assessed using qRT-PCR and Western blotting, respectively. CCK-8, BrdU assay and immunofluorescence of Ki67 were performed to measure the cell proliferation. Wound healing and transwell assays were employed to evaluate the capacity of cell migration. Dual-luciferase reporter assay, co-immunoprecipitation, RIP and CHIP assays were employed to verify the PAXIP1-AS1/ETS1/WIPF1/RhoA regulatory network. It was found that the expression of PAXIP1-AS1 and RhoA was remarkably higher in both lung tissues and serum of MCT-induced PAH rats, as well as in hypoxia-induced hPASMCs. PAXIP1-AS1 knockdown remarkably suppressed hypoxia-induced cell viability and migration of hPASMCs. PAXIP1-AS1 positively regulated WIPF1 via recruiting transcriptional factor ETS1, of which knockdown reversed PAXIP1-AS1-mediated biological functions. Co-immunoprecipitation validated the WIPF1/RhoA interaction. In vivo experiments further revealed the role of PAXIP1-AS1 in PAH pathogenesis. In summary, lncRNA PAXIP1-AS1 promoted cell viability and migration of hPASMCs via ETS1/WIPF1/RhoA, which might provide a potential therapeutic target for PAH treatment.


Current body composition measurement techniques.
The current article reviews the most innovative and precise, available methods for quantification of in-vivo human body composition. Body composition measurement methods are continuously being perfected. Ongoing efforts involve multisegmental and multifrequency bioelectrical impedance analysis, quantitative magnetic resonance for total body water, fat, and lean tissue measurements, imaging to further define ectopic fat depots. Available techniques allow for the measurement of fat, fat-free mass, bone mineral content, total body water, extracellular water, total adipose tissue and its subdepots (visceral, subcutaneous, and intermuscular), skeletal muscle, select organs, and ectopic fat depots. There is an ongoing need for methods that yield information on metabolic and biological functions. Based on the wide range of measurable properties, analytical methods and known body composition models, clinicians, and scientists can quantify a number of body components and with longitudinal assessment, can track changes in health and disease with implications for understanding efficacy of nutritional and clinical interventions, diagnosis, prevention, and treatment in clinical settings. With the greater need to understand precursors of health risk beginning prior to conception, a gap exists in appropriate in-vivo measurement methods with application beginning during gestation, that is, fetal development.


[Growth of neurites and formation of connections in cultures of pteropodial mollusc neurons].
Dissociated neurons from the brain of pteropodial mollusc were cultivated in a 25% Leibovitz medium containing 2% of calf serum. Neurite outgrowth was observed in 1-30% of the neurons. It was maximum during the first 3 days. Neurite length reached 300 microns. Membrane potential of neurons was 40-60 mV; they generated single spikes or bursts of impulses. Intercellular connections were tested on the 3-4th days in 70 pairs of neurons with neurites overlapped. Electrical connections between the cells were observed in 20% of the pairs tested, and in 6% of pairs stimulation of one of the neurons evoked an inhibitory postsynaptic potential in the other.


[Mitochondrial ND5 as the causative gene of Leight syndrome].
To report a Chinese Han family with two patients of Leigh syndrome (LS) and to scan the mutation in mitochondrial DNA(mtDNA). The clinical features and the laboratory findings were summarized. Mitochondrial DNA chip and direct sequencing were performed to detect the mutation in entire mtDNA. Failure of thrive, psychomotor retardation, hypotonia and weakness, cerebellar ataxia, and seizure were the main manifestations of the family. Brain magnetic resonance imaging (MRI) showed lesions at midbrain, periaqueductal gray matter, dentate nuclei of cerebellar and thalami. The levels of lactic acid and pyruvate were mildly abnormal. The mutation of ND5*13513 G to A was identified in the LS family. Patients with ND5*13513 G to A mutation may have a characteristic clinical course and ND5 *13513 G to A might be a preferential candidate mutation of Leigh syndrome.


Predictors of Intervention Success in a Sports-Based Program for Adolescents at Risk of Juvenile Delinquency.
To prevent juvenile delinquency, there is growing interest in the use of sports-based interventions. To date, there is little empirical research that provides insights into for whom, how, and when sports-based crime prevention programs are most effective. Therefore, the current study assessed which youth, coach, and context factors were predictive of change in risk factors and protective factors for delinquency in a sports-based crime prevention program for at-risk adolescents. Participants ( N = 155) and their teachers filled in questionnaires about risk and protective factors for delinquency at the start of the intervention and 13 months later. In addition, the coaches and participants filled in questionnaires about the predictors of intervention success. The youths showed significant improvements over the course of the intervention. Various youth, coach, and context factors (e.g., the type of education of youth and the sociomoral climate at the sports club) were associated to change in the outcome variables.


Superficial and peripheral dose in compensator-based FFF beam IMRT.
Flattening filter-free (FFF) beams produce higher dose rates. Combined with compensator-based intensity modulated radiotherapy (IMRT) techniques, the dose delivery for each beam can be much shorter compared to the flattened beam MLC-based or flattened beam compensator-based IMRT. This 'snap shot' IMRT delivery is beneficial to patients for tumor motion management. Due to softer energy, superficial doses in FFF beam treatment are usually higher than those from flattened beams. Due to no flattening filter, thus less photon scattering, peripheral doses are usually lower in FFF beam treatment. However, in compensator-based IMRT using FFF beams, the compensator is in the beam pathway. Does it introduce beam hardening effects and scattering such that the superficial dose is lower and peripheral dose is higher compared to FFF beam MLC-based IMRT? This study applied Monte Carlo techniques to investigate the superficial and peripheral doses in compensator-based IMRT using FFF beams and compared it to the MLC-based IMRT using FFF beams and flattened beams. Besides varying thicknesses of brass slabs to simulate varying thicknesses of compensators, a simple cone-shaped compensator was simulated to mimic a clinical application. The dose distribution in water phantom by the cone-shaped compensator was then simulated by multiple MLC-defined FFF and flattened beams with varying apertures. After normalization to the maximum dose, Dmax, the superficial and peripheral doses were compared between the FFF beam compensator-based IMRT and FFF/flattened beam MLC-based IMRT. The superficial dose at the central 0.5 mm depth was about 1% (of Dmax) lower in the compensator-based 6 MV FFF (6FFF) IMRT compared to the MLC-based 6FFF IMRT, and about 8% higher than the flattened 6 MV MLC-based IMRT dose. At 8 cm off-axis at depth of central maximum dose, dmax, the peripheral dose between the 6FFF and flattened 6 MV MLC demonstrated similar doses, while the compensator dose was about 1% (of Dmax) higher. Compensators reduce the superficial doses slightly compared to open FFF beams, but increases the peripheral doses due to scatter in the compensator.


DISMS2: A flexible algorithm for direct proteome- wide distance calculation of LC-MS/MS runs.
The classification of samples on a molecular level has manifold applications, from patient classification regarding cancer treatment to phylogenetics for identifying evolutionary relationships between species. Modern methods employ the alignment of DNA or amino acid sequences, mostly not genome-wide but only on selected parts of the genome. Recently proteomics-based approaches have become popular. An established method for the identification of peptides and proteins is liquid chromatography-tandem mass spectrometry (LC-MS/MS). First, protein sequences from MS/MS spectra are identified by means of database searches, given samples with known genome-wide sequence information, then sequence based methods are applied. Alternatively, de novo peptide sequencing algorithms annotate MS/MS spectra and deduce peptide/protein information without a database. A newer approach independent of additional information is to directly compare unidentified tandem mass spectra. The challenge then is to compute the distance between pairwise MS/MS runs consisting of thousands of spectra. We present DISMS2, a new algorithm to calculate proteome-wide distances directly from MS/MS data, extending the algorithm compareMS2, an approach that also uses a spectral comparison pipeline. Our new more flexible algorithm, DISMS2, allows for the choice of the spectrum distance measure and includes different spectra preprocessing and filtering steps that can be tailored to specific situations by parameter optimization. DISMS2 performs well for samples from species with and without database annotation and thus has clear advantages over methods that are purely based on database search.


Reconstitution and Substrate Specificity of the Radical S-Adenosyl-methionine Thiazole C-Methyltransferase in Thiomuracin Biosynthesis.
Thiomuracin is a thiopeptide antibiotic with potent activity toward Gram-positive drug-resistant bacteria. Thiomuracin is biosynthesized from a precursor peptide, TbtA, by a complex array of posttranslational modifications. One of several intriguing transformations is the C-methylation of thiazole, occurring at an unactivated sp2 carbon. Herein, we report the in vitro reconstitution of TbtI, the responsible radical S-adenosyl-methionine (rSAM) C-methyltransferase, which catalyzes the formation of 5-methylthiazole at a single site. Our studies demonstrate that a linear hexazole-bearing intermediate of TbtA is a substrate for TbtI whereas macrocyclized thiomuracin GZ is not. In determining the minimal substrate for TbtI, we found that the enzyme is functional when most of the leader peptide has been removed. The in vitro reconstitution of TbtI, a class C rSAM methyltransferase, further adds to the chemical versatility of rSAM enzymes, and informs on the complexity of thiomuracin biosynthesis.


A Case of Actinomycosis of the Nasopharynx.
Actinomycosis is a progressive granulomatous infection caused by the bacteria Actinomyces israelii. Classically, the three most common clinical forms are cervicofacial, thoracic, and abdominopelvic. On the contrary, nasopharyngeal actinomycosis is considered to be a rare clinical disease, and its occurrence is extremely low. The infection can take place without any preceding infection or on immunocompromised status. A 25-year-old male with no previous medical history presented with persistent nasal congestion and rhinorrhea. A nasal endoscopy examination revealed an unclearly demarcated nasopharyngeal mass, and a complete microbiology and pathology analysis showed actinomycetes colonies. After two weeks of oral Augmentin therapy, the patient's illness was completely eradicated. Diagnosis of nasopharyngeal actinomycosis is exceptionally crucial, and with early treatment of appropriate antibiotic therapy, the prognosis is excellent. Careful follow-up after adequate treatment as the possibility of frequent relapse is common.


Assessing equine anxiety-related parameters using an isolation test in combination with a questionnaire survey.
The aim of the study was to determine parameters reflecting equine anxiety trait by comparing results obtained in a behavior test and an anxiety score assessed by familiar caretakers in response to a questionnaire. In the behavior test, horses were individually led into a novel room by their caretakers and loosely tethered to decrease excessive movement using the common cross-tying technique with two leads and breakable plastic cords. The horses initially remained with their caretaker for 2 min; the caretaker then left and the subject animal was left alone for 2 min. The latency to break the plastic cords, heart rate, the number of steps and pawings were recorded. When the horses were left alone, most parameters changed significantly and some showed sexual differences. A correlation analysis revealed that anxiety score assessed by caretakers showed a negative correlation with the latency to break the plastic cord and a positive correlation with heart rate only when horses were isolated. These two were suggested feasible parameters for assessing the anxiety trait of unfamiliar horses. Both the behavioral results and the anxiety scores also indicated that females were more anxious than males. Our results suggest that it would be a useful strategy for assessing other temperament traits as well to combine behavior tests with a questionnaire survey.


Serum redox markers in uncomplicated type 2 diabetes mellitus accompanied with abnormal iron levels.
This study aimed at evaluating the serum redox status in type 2 diabetes mellitus (T2DM) accompanied with an imbalance in iron concentrations. Diabetic patients were grouped according to serum iron levels [normal (DNFe), low (DLFe), and high (DHFe)], and their clinical and redox parameters [total sulfhydryl groups (tSH), uric acid (UA), and total bilirubin (tBILI) as non-enzymatic antioxidants, and malondialdehyde (MDA) and advanced oxidation products of proteins (AOPP) as markers of oxidative stress] were determined. Glucose and HbA1c levels in the T2DM patients did not differ in function of serum iron. T2DM was associated with reduced tSH levels. In the diabetic patients, tSH, UA, and tBILI negatively correlated with MDA, as well as HbA1c with UA. Accordingly, AOPP and MDA were higher in the diabetic groups compared to the controls. The reduced antioxidant capacity was particularly pronounced in the DLFe group, which was further characterized by lower levels of UA and tBILI compared to the other groups. Subsequently, the level of MDA in the DLFe group was higher compared to the DNFe and DHFe groups. The positive correlation between serum iron levels and the antioxidants UA and tBILI, in conjunction with the negative correlation between serum iron levels and the markers of oxidative stress in the diabetic patients, corroborated the indication that comparatively higher level of oxidative stress is present when T2DM coexists with decreased iron levels. T2DM-associated redox imbalance is characterized by a decrease in serum total sulfhydryl groups and low serum iron-associated reduction in uric acid and total bilirubin levels, accompanied by increased oxidative stress markers. The relatively noninvasive and simple determination of these parameters may be of considerable interest in monitoring the pathophysiological processes in T2DM patients, and may provide useful insights into the effects of potential therapeutic or nutritional interventions.


Prediction of human dietary δ15N intake from standardised food records: validity and precision of single meal and 24-h diet data.
Natural stable isotope ratios (δ15N) of humans can be used for nutritional analyses and dietary reconstruction of modern and historic individuals and populations. Information about an individual's metabolic state can be obtained by comparison of tissue and dietary δ15N. Different methods have been used to estimate dietary δ15N in the past; however, the validity of such predictions has not been compared to experimental values. For a total of 56 meals and 21 samples of 24-h diets, predicted and experimental δ15N values were compared. The δ15N values were predicted from self-recorded food intake and compared with experimental δ15N values. Predicted and experimental δ15N values were in good agreement for meals and preparations (r = 0.89, p < .001) as well as for the 24-h diets (r = 0.76, p < .001). Dietary δ15N was mainly determined by the amount of fish, whereas the contribution of meat to dietary δ15N values was less pronounced. Prediction of human dietary δ15N values using standardised food records and representative δ15N data sets yields reliable data for dietary δ15N intake. A differentiated analysis of the primary protein sources is necessary when relating the proportion of animal-derived protein in the diet by δ15N analysis.


Design of the dual stone locating system on an extracorporeal shock wave lithotriptor.
Extracorporeal Shock Wave Lithotriptors are very popular for the treatment of urinary stones all over the world. They depend basically upon either X-ray fluoroscopy or ultrasound scans to detect the stones before therapy begins. To increase the effectiveness of treatment this study took advantage of both X-ray and ultrasound to develop a dual stone locating system with image processing modules. Its functions include the initial stone locating mode with stone detection by fluorescent images and the follow-up automatic stone tracking mode made by constant ultrasound scanning. The authors have integrated both apparatus and present the operating principles for both modes. The system used two in vitro experiments to justify its abilities of stone location in all procedures.


Reactive oxygen species in the elongation zone of maize leaves are necessary for leaf extension.
The production and role of reactive oxygen species (ROS) in the expanding zone of maize (Zea mays) leaf blades were investigated. ROS release along the leaf blade was evaluated by embedding intact seedlings in 2',7'-dichlorofluorescein-containing agar and examining the distribution of 2',7'-dichlorofluorescein fluorescence along leaf 4, which was exposed by removing the outer leaves before embedding the seedling. Fluorescence was high in the expanding region, becoming practically non-detectable beyond 65 mm from the ligule, indicating high ROS production in the expansion zone. Segments obtained from the elongation zone of leaf 4 were used to assess the role of ROS in leaf elongation. The distribution of cerium perhydroxide deposits in electron micrographs indicated hydrogen peroxide (H(2)O(2)) presence in the apoplast. 2',7'-Dichlorofluorescein fluorescence and apoplastic H(2)O(2) accumulation were inhibited with diphenyleneiodonium (DPI), which also inhibited O*(2)(-) generation, suggesting a flavin-containing enzyme activity such as NADPH oxidase was involved in ROS production. Segments from the elongation zone incubated in water grew 8% in 2 h. KI treatments, which scavenged H(2)O(2) but did not inhibit O*(2)(-) production, did not modify growth. DPI significantly inhibited segment elongation, and the addition of H(2)O(2) (50 or 500 microM) to the incubation medium partially reverted the inhibition caused by DPI. These results indicate that a certain concentration of H(2)O(2) is necessary for leaf elongation, but it could not be distinguished whether H(2)O(2), or other ROS, are the actual active agents.


Dose-intensity of a four-drug chemotherapy regimen with or without recombinant human granulocyte-macrophage colony-stimulating factor in extensive-stage small-cell lung cancer: a multicenter randomized phase III study.
We investigated whether a high-dose chemotherapy regimen of cyclophosphamide 1,800 mg/m2, 4'-epidoxorubicin 60 mg/m2, etoposide 330 mg/m2, and cisplatin 120 mg/m2 given monthly for four cycles with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) support (5 micrograms/kg daily for 10 days) could improve the survival of patients with extensive-stage small-cell lung cancer (SCLC) compared with a standard-dose regimen (cyclophosphamide 1,200 mg/m2, 4'-epidoxorubicin 40 mg/m2, etoposide 225 mg/m2, and cisplatin 100 mg/m2) given monthly for six cycles. Planned cumulative doses of the drugs were the same in both treatment arms except for cisplatin (which was 80% in the higher-dose plus rhGM-CSF group). At the time of the preplanned interim analysis, 125 patients, 60 in the standard-dose group and 65 in the higher-dose plus rhGM-CSF group, had entered the study; 116 were eligible, 55 in the standard-dose group and 61 in the higher-dose group. All patients were included in the analyses. The cumulative doses of each drug actually delivered were significantly higher in the standard-dose group. No difference in response rates was observed between the two groups. There were significantly greater hematologic toxicities, documented infections, and transfusions of RBCs and platelets in the higher-dose plus rhGM-CSF group. Patients in this group proved to have a shorter survival duration and a shorter time to relapse than patients in the standard-dose group (median overall survival: standard-dose, 10.8 months; higher-dose, 8.9 months; log-rank test with adjustment for prognostic variables, P = .0005; respective probabilities of relapse at 1 year, 77 +/- 0.6 and 96 +/- 2.2; log-rank test, P = .013). A 50% increase in dose-intensity for this four-drug regimen could not be achieved with GM-CSF due to excessive toxicity in patients with extensive-stage SCLC.


Investigations of Alkaline and Enzymatic Membrane Cleaning of Ultrafiltration Membranes Fouled by Thermomechanical Pulping Process Water.
The pulp and paper industry is one of the most important industrial sectors worldwide, and has considerable potential for the sustainable fractionation of lignocellulosic biomass to provide valuable compounds. Ultrafiltration (UF) is a suitable separation technique for the profitable production of hemicelluloses from process water from thermomechanical pulping (ThMP), but is limited by membrane fouling. Improvements in cleaning protocols and new alternative cleaning agents are required to ensure a long membrane lifetime, and thus a sustainable process. This study, therefore, focuses on the cleaning of polymeric UF membranes after the filtration of ThMP process water, comparing alkaline with enzymatic cleaning agents. The aim was to develop a cleaning procedure that is efficient under mild conditions, resulting in a lower environmental impact. It was not possible to restore the initial permeability of the membrane when cleaning the membrane with enzymes alone, but the permeability was restored when using a two-step cleaning process with enzymes in the first step and an alkaline cleaning agent in the second step. Scanning electron microscopy gave a deeper inside into the cleaning efficiency. Attenuated total reflectance Fourier-transform infrared spectroscopy analysis confirmed that not only polysaccharides, but also extractives are adsorbed onto the membrane surface.


Ultrastructural distribution of lectin-binding sites in the glomerular wall of streptozotocin-induced diabetic rats.
Since carbohydrates-containing molecules are known to be preferentially altered in diabetes mellitus and that major functional and morphological alterations do occur during diabetes in the renal tissue, we revealed in the present study various lectin-binding sites in the glomerular wall of control and long-term diabetic animals. Lectin-binding sites specific to N-acetyl-galactosamine, N-acetyl-glucosamine, sialic acid, galactose and fucose were revealed using the appropriate lectin and the lectin-gold complex at the electron microscope level. Differences in intensity of labeling as well as in distribution were detected for several lectin-binding sites particularly in the glomerular basement membrane, reflecting the presence of additional glycoconjugates and changes in the molecular organization of the basement membrane components during diabetes. Alterations in the glycocomponents and the glycoproteins of the glomerular basement membrane as well as non-enzymatic glycosylation of the basement membrane components have been described in diabetes, going along with our present results. The alteration in the distribution of some lectin-binding sites gives support to modifications in the three dimensional organization of some glycoproteins which could occur in diabetes. Since the glomerular wall is actively involved in blood filtration, these changes may either induce, or result from, the loss in selective permeability and the massive proteinuria occurring during diabetes.


Isolation of a novel subgroup B feline leukemia virus from a cat infected with FeLV-A.
Proviruses were cloned directly from a cat that developed neurological disorders approximately 28 months after inoculation with a molecularly cloned, minimally pathogenic subgroup A feline leukemia virus (FeLV-A). In addition to FeLV-A proviruses that were nearly identical to the inoculated virus, we detected a subgroup B-like variant in brain, bone marrow, and lymph node that apparently had acquired the major portion of its extracellular envelope gene (gp70) from endogenous FeLV-related sequences. A similar recombinant was also detected, by PCR, at low levels in bone marrow from an early time postinfection (2.5 months). A full-length proviral variant with this recombinant structure cloned from brain tissue encoded a replication-defective virus. A chimera encoding the 5' gag-pol portion of FeLV-A and the 3' env-LTR portion of the defective brain-derived clone was replication-competent and had the extended host range properties of FeLV-B.


Quantification by image analysis of immunocytochemical reactions: application for determination of lysozyme content in individual smeared cells.
The objective of the present study was to develop a cytophotometric technique to quantitate immunocytochemical reactions. Cell antigens were detected after immunophosphatase alkaline staining procedure. The amount of reaction product was quantitated by computerized scanning cytophotometry. The technical conditions (dilution of primary antibody; incubation time of the three antibodies; volume and pH of the enzyme substrate reaction; storage of the slides) required for optimal cytophotometric determination of the reaction product were determined. Under these optimally defined conditions, a linear relationship between cell protein content (lysozyme) and microdensitometric measure of the colored reaction product was found. This method could be used for other cells, antigens, and enzymatic indicators.


[Research on 7.0 T Magnetic Resonance Based Electrical Properties Tomography Based on Bloch-Siegert Shift].
Magnetic resonance based electrical properties tomography (MREPT) is a different method from proton density imaging, Bloch-Siegert shift (BSS) is used in this paper to reconstruct the radiofrequency (RF) field amplitude and calculate the distribution of the permittivity constant. The phase of the RF field is approximated by the phase component of the magnetization intensity, and the conductivity distribution is calculated. In the experiment, Bruker 7.0 T magnetic resonance device was used to image two water models and in vivo Balb/c mice to obtain the image of electrical characteristics. Experimental results show that the Bloch-siegert B1+ image is significantly more efficient than the double-angle B1+ image. The study can provide a reference for selecting appropriate B1 mapping technology for B1 field imaging of electrical characteristics organizations, and provide basic research support for promoting the practical application of magnetic resonance characteristics.


Genetics of the alpha 1,6-dextran response: expression of the QUPC52 idiotype in different inbred and congenic strains of mice.
Antibodies to dextran B512 were raised in various strains of mice and were assayed by a radioimmunoassay procedure. Idiotypic antibodies to the IgA(k) dextran B512 binding myeloma proteins QUPC52 and W3129 of BALB/c origin were prepared in rabbits. After adsorption each antiserum was specific for the immunizing myeloma protein and did not react with hundreds of other myeloma proteins; nonetheless, antibodies to dextran B512 from various strains of mice cross-reacted in these test systems. Of the 2 idiotypes tested, the W3129 idiotype was more universally expressed in different strains of mice. The QUPC52 idiotype was the predominant idiotype in BALB/c anti-dextran B512 antibodies and was found in only a few other inbred strains. Using a battery of congenic and inbred strains, it was shown that the QUPC52 idiotype was controlled by genes linked to the Igh complex locus (chromosome 12) and to the Ig kappa complex locus (chromosome 6). The W3129 idiotype was found in a number of stocks of mice in the genus Mus recently isolated from the wild. The QUPC52 idiotype thus far was found only in inbred mice.