High density lipoprotein free cholesterol and other lipids in coronary heart disease.
The cholesterol and choline-containing phospholipid fractions of high density lipoproteins (HDL) were determined in healthy males and in male patients with coronary heart disease (CHD) to ascertain which HDL parameter or combined parameters possess the greatest discriminative power. The free cholesterol fraction (HDL-fc) was found to be the most significant discriminator between controls and males with CHD, the mean levels (+/- SEM) being 6.6 (+/- 0.9) and 4.4 (+/- 0.6) mg/dl, respectively. Classification of CHD patients and controls using one-variable discriminant function analysis (DFA) yielded an error rate of 27% for plasma HDL-fc. Two-variable DFA using both the HDL esterified cholesterol levels and the HDL-fc levels of controls and patients reduced the error rate to 11%. The results obtained in this study indicate a possible role for HDL-fc as a predictor of CHD risk.


Enzymuria in workers exposed to inorganic mercury.
Urinary excretion of beta-hexosaminidase (NAG = N-acetyl-beta-glucosaminidase) and albumin was examined in 41 chlor-alkali workers exposed to inorganic mercury and 41 age-matched controls. Either U-HG or B-Hg levels for these workers were available dating from the 1960s to the present. Increased U-NAG was seen in workers with a U-Hg today of more than 4 micrograms/mmol creat (about 50 micrograms/l: 35 ug/g creat). Multiple linear regression analysis showed that U-NAG was correlated to U-Hg and integrated dose but not to the present B-Hg level. No albuminuria (detection limit 12.5 mg/l) was found in any of the subjects. In a longitudinal study, no decrease in U-NAG levels was seen in 15 chlor-alkali workers after their vacation (means = 20d). In five workers followed for ten months after a short exposure period, no definite time trend could be seen. The results show that there is a slight effect on renal tubules even at rather low levels of exposure to mercury vapour. The clinical significance of the enzymuria levels found here is, however, debatable.


Introduction to the antibiotic and antiviral compounds themed collection.
Guest editors Michael J. Sofia and Xuechen Li introduce the themed collection on antibiotic and antiviral compounds.


Number and shape of tears in aphakic retinal detachment: its relationship with different surgical techniques of cataract extraction.
An analysis is made of retinal detachments which occurred in patients operated upon for cataract with different surgical techniques, as well as the degree of operating experience of the surgeons. The main clinical features of the detachments are recorded such as number, shape, localization of retinal tears, type and extension. The different surgical techniques are explained and a statistical comparison of the incidence of detachments is set up.


Efficacy and safety of lenalidomide treatment in multiple myeloma (MM) patients--Report of the Polish Myeloma Group.
The aim of the multi-centre retrospective study was to evaluate the efficacy and safety of lenalidomide (LEN) therapy in patients with resistant or relapsed multiple myeloma (MM) as well as in patients with stable disease (LEN used due to neurological complications). The primary endpoint of this study was an overall response rate (ORR). The secondary endpoints were as follows: time to progression (TTP), overall survival (OS) and the safety of drug use. Data were collected in 19 centres of the Polish Multiple Myeloma Study Group. The study group consisted of 306 subjects: 153 females and 153 males. In 115 patients (38.8%, group A), a resistant myeloma was diagnosed; in 135 (44.1%, group B) a relapse, and in 56 (18.3%, group C) a stable disease were stated. In 92.8% of patients, LEN+DEX combination was used; in remaining group, LEN monotherapy or a combination therapy LEN+bortezomib or LEN+bendamustine and other were used. In the entire study group, ORR was 75.5% (including 12.4% patients achieving complete remission [CR] or stringent CR [sCR]). Median time to progression (TTP) was 20 months. Median overall survival (OS) was 33.3 months. The regression model for "treatment response" was on the borderline of statistical significance (p=0.07), however the number of LEN treatment cycles ≥ 6 (R(2)=17.2%), baseline LDH level (R(2)=1.1%) and no ASCT use (R(2)=1.7%) where the factors most affecting treatment response achievement. The regression model for dependant variable--"overall survival"--was statistically significant (p=0.0000004). Factors with the most impact on OS were as follows: number of LEN cycles treatment ≥ 6 (R(2)=16.7%), treatment response achievement (R(2)=6.9%), β-2-microglobulin (β-2-M) level (R(2)=4.8%), renal function (R(2)=3.0%) and lack of 3/4 grade adverse events (R(2)=1.4%). LEN is an effective and safe therapeutic option, even in intensively treated resistant and relapsed MM patients, as well as in patients with stable disease and previous treatment-induced neurological complications. In particular, the number of LEN treatment cycles ≥ 6 was the factor which affected treatment response achievement the most, together with an important impact on OS.


Toxic psychosis: an unusual presentation of propranolol intoxication.
Timely diagnosis of acute propranolol intoxication requires a high index of suspicion and a knowledge of the multiple ways in which these patients may present to the emergency department. We report a case of severe propranolol intoxication that presented as an acute psychotic episode preceding cardiovascular decompensation and seizures by several hours. Though acute reversible psychosis has been appreciated after initiating or increasing propranolol dosage therapeutically, this association has not been reported in the literature regarding beta blocker overdose or intoxication. Propranolol psychosis and several other pertinent aspects of this case are discussed.


Benchmarking algorithms for pathway activity transformation of single-cell RNA-seq data.
Biological pathway analysis provides new insights for cell clustering and functional annotation from single-cell RNA sequencing (scRNA-seq) data. Many pathway analysis algorithms have been developed to transform gene-level scRNA-seq data into functional gene sets representing pathways or biological processes. Here, we collected seven widely-used pathway activity transformation algorithms and 32 available datasets based on 16 scRNA-seq techniques. We proposed a comprehensive framework to evaluate their accuracy, stability and scalability. The assessment of scRNA-seq preprocessing showed that cell filtering had the less impact on scRNA-seq pathway analysis, while data normalization of sctransform and scran had a consistent well impact across all tools. We found that Pagoda2 yielded the best overall performance with the highest accuracy, scalability, and stability. Meanwhile, the tool PLAGE exhibited the highest stability, as well as moderate accuracy and scalability.


Arteriovenous fistula after superficial temporal artery biopsy.
Arteriovenous fistula of the superficial temporal artery is quite rare. If it occurs, it is most often caused by trauma to the temporal region where the artery is very superficial to the skin. We present the first reported case of an arteriovenous fistula after temporal artery biopsy and review the literature on the pathophysiology, diagnosis, and treatment of arteriovenous fistula.


Endoscopic Release of Master Knot of Henry.
A post-traumatic partial tear of the flexor hallucis longus tendon at the master knot of Henry and the resultant fibrosis of the knot can result in pain at the medial foot arch or posteromedial ankle pain with trigger hallux. Open debridement of the master knot of Henry is indicated if the symptoms do not improve with nonoperative treatment. The open procedure requires extensive soft-tissue dissection because the master knot of Henry is a deep structure. Endoscopic release of the master knot of Henry is an alternative to the open procedure and has the advantage of less surgical trauma and potential for less chance of recurrence of fibrosis of the master knot of Henry.


Improving urban sustainability and resilience with the optimal arrangement of water-energy-food related practices.
Water-, energy-, and food (WEF) related practices, such as low impact development (LID), residential solar panels, and rooftop urban agriculture, have been applied to improve urban sustainability and resilience under climate change and urbanization. However, most practices require space. This requirement may result in competition for land. In addition, not all newly built practices benefit the environment from the life cycle perspective. Therefore, this study aims to develop a systematic WEF-related practice planning method to improve urban sustainability and resilience in a limited space. The core method is a multi-objective optimization model that considers the performance and environmental impacts of the selected practices. The assessment was conducted in a densely populated area in Taipei, the capital city of Taiwan, to describe the planning processes and demonstrate the feasibility of the methods. In the Taipei case, five goals were defined: the supply of WEF, the sponge city development target, and the greenhouse gas reduction target. The optimal results of the multi-objective optimization model indicated the closeness of the optimal implementation of WEF-related practices to achieving the goals. The results showed that the optimal arrangement of WEF-related practices could provide water supply benefits and was favorable for developing a sponge city. According to the sensitivities, to achieve urban sustainability and resilience, the priorities in order of importance are as follows: establish a rainwater harvesting system for buildings, encourage the implementation of rooftop photovoltaic systems, and improve the materials and processes used solar panel and bioretention cell production. The systematic planning method provides a quantitative assessment and delivers practical cross-sectoral integrated strategies for decision-making.


Teduglutide in pediatric intestinal failure: A position statement of the Italian society of pediatric gastroenterology, hepatology and nutrition (SIGENP).
In recent years, the spectrum of possible treatments for Intestinal Failure (IF)-Short Bowel Syndrome (SBS) has been enriched by the implementation of GLP-2 analogues. In Italy, teduglutide (Ted), an analogue of GLP-2, was approved in January 2021 by the Italian Regulatory Agency for Drugs (AIFA) for IF-SBS patients ≥1 year old. According to the Agency indications, Ted can now be prescribed by regional reference centers, with costs fully charged to the National Health Service. Following pediatric-use approval in our country and in light of scarce evidence in childhood, the pediatric network for IF of the Italian Society for Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) planned to share management methods of Ted in pediatric IF. The main purpose was to identify the best candidates from a cost-effective perspective. Thus, focusing on available literature and on expert opinions, the present position statement provides consensus-based recommendations on the use of Ted for pediatric gastroenterologists and nutritionists treating children with SBS.


Insulin-mediated fusion of negatively charged phospholipid vesicles at low pH.
Fusion of negatively charged phospholipid vesicles by bovine insulin was studied. The fusion induced by the hormone was demonstrated by resonance energy transfer, sepharose chromatography, light scattering and electron microscopy. The insulin effect was more effective when the pH was in the range of 3.6 - 3.9. The action of insulin also depends on the phosphatidylcholine: phosphatidic acid molar ratio, and buffer and vesicles concentration. At optimal conditions, half-maximal effect was obtained at 2 X 10(-8)M. The insulin-mediated fusion is non specific. The potential importance of these studies is discussed.


Functional renal collecting ducts from human PSCs.
Collecting ducts in the kidney control the balance of water and electrolytes, as well as pH of the urine to maintain body homeostasis. Shi et al.1 recently reported in Nature Biotechnology a protocol to generate functional collecting duct cells from human pluripotent stem cells.


Malignant triton tumors--complete surgical resection and adjuvant radiotherapy associated with improved survival.
Malignant triton tumors (MTT) are a rare form of peripheral nerve sheath tumors that follows a particularly aggressive course. Given its rarity, only case reports and small series of patients have been published. A Pubmed search was conducted (1966-2009) using the terms "triton tumor," "rhabdomyosarcoma," and "malignant peripheral nerve sheath tumor." The reference lists of retrieved articles were searched. Cases were included when the diagnosis was clear, the patient underwent surgery, and follow-up data were available. Univariate and multivariate analyses were conducted for predictors of positive resection margin, local recurrence/progression, development of metastases, and mortality. A total of 124 cases were included. The overall 5-year survival was 14% and the median time to death was 13 months. The overall local recurrence/progression rate was 50% and the median time to recurrence/progression was 6 months. On multivariate Cox proportional hazards analysis, positive margin status (HR 2.2, P = 0.01), local recurrence/progression (HR 3.1, P = 0.003), and development of metastases (HR 2.6, P = 0.003) were associated with mortality. Adjuvant radiotherapy was associated with improved survival (HR 0.4, P = 0.005). Complete surgical resection and adjuvant radiotherapy should be the cornerstones of treatment for MTT.


A novel route for immobilization of oligonucleotides onto modified silica nanoparticles.
A novel approach for immobilization of probe oligonucleotides that uses zirconium phosphate modified silica nanoparticles is proposed. The surface modification of nanoparticles was carried out in two stages. Initially binding of Zr4+ to the surface of silica nanoparticles and later treated with phosphoric acid for terminal phosphate groups. Oligonucleotide probes modified with amine group at 5'-end were strongly binds to the phosphate terminated silica nanoparticles with imidazole in presence of 0.1 mol L(-1) EDC [N-ethyl-N'-(3-dimethylaminopropyl) carbodiimide], as phosphate groups are more reactive towards amine group. Various studies, i.e., synthesis of silica nanoparticles, their surface modification, probe immobilization, measurement of hybridization and effect of bovine serum albumin (BSA) were carried out during optimization of reaction conditions. The significant reduction in the background signal was observed by treating the probe modified silica nanoparticles with bovine serum albumin prior to hybridization. The probe modified silica nanoparticles were retained their properties and the hybridization was induced by exposure of single-stranded DNA (ssDNA) containing silica nanoparticles to the complementary DNA in solution. The decrease in the fluorescence signal for one mismatch and three mismatch was observed upon hybridization of probe with target DNAs, while there was no response for the random target ssDNA under the same experimental conditions. The intensity of fluorescence signal was linear to the concentration of target DNA ranging from 3.9 x 10(-9) to 3.0 x 10(-6)mol L(-1). A detection limit of 1.22 x 10(-9) mol L(-1) of oligonucleotides can be estimated. The proposed hybridization assay is simple and possesses good analytical characteristics and it can provide an effective and efficient route in the development of DNA biosensors and biochips.


Prophylactic role of oral L-arginine on histological and contractile changes in a rat chronic bladder injury model.
The effect of L-arginine on bladder tissue structure and function in a rat bladder injury model were investigated. 24 male Sprague-Dawley rats were used. The control group received a regular diet. The L-arginine group received oral L-arginine (1 g/day). The protamine sulfate (PS) group received intravesical PS every 48 h (0.5 ml, 5 mg/ml). L-arginine was administered to the PS+L-arginine group in addition to PS. At the end of 1 week, bladder tissues were processed for histological and functional studies. The PS group revealed urothelial damage with glycosaminoglycan layer irregularity and mast cell infiltration which was not evident in the PS+L-arginine group. 120 mM potassium and electrical field stimulation (EFS)-induced contractions in the PS group were significantly lower than in other groups, whereas carbachol-induced contractions were not significantly different. Relaxation responses of precontracted strips to EFS and isoproterenol did not reveal a significant decrease in the PS group, whereas L-arginine significantly enhanced these responses in PS-treated animals. Intravesical PS causes urothelial damage and inflammation that is associated with significant changes in rat bladder tissue contractility. Oral L-arginine treatment is found to prevent these histological and contractile alterations. Our findings may indicate the nitric oxide-cGMP pathway as a possible therapeutic target in various bladder diseases associated with urothelial damage.


Characterization of the 5' regulatory region of the human sodium-dependent multivitamin transporter, hSMVT.
We cloned and functionally characterized the 5' regulatory region of the human sodium-dependent multivitamin transporter (hSMVT) gene, a remarkably versatile carrier responsible for uptake of biotin, pantothenic acid and lipoate. Two potential transcriptional start sites were determined by 5'-RACE and found to be at -4603, and -4303. Two distinct promoters (P1 and P2) were identified. Both putative promoter sequences were TATA-less, CAAT-less, contained highly GC-rich sites, and had multiple putative regulatory cis-elements (e.g., AP1, AP2, C/EBP, SP1, NF1, and GATA). The activities of the putative promoters were confirmed using a firefly luciferase reporter gene assay system following transient transfection into three cultured human cell lines: Caco-2, HEK293, and vascular smooth muscle cells. The minimal region required for basal activity of the hSMVT promoter was also determined by generating a series of deletion constructs and found to be encoded by a sequence between -5846 to -5313 for P1 and between -4417 to -4244 for P2 relative to the translation initiation codon. These results demonstrate the first molecular characterization of the regulatory region of this important human gene.


The impact of gender on long-term mortality in patients with multivessel disease after primary percutaneous coronary intervention.
Gender and complete revascularisation are known to affect mortality. The objective of this study was to analyse a gender difference in mortality with respect to complete revascularisation for multivessel disease after primary percutaneous coronary intervention (PPCI) in ST-elevation myocardial infarction (STEMI) patients. In a prospective consecutive cohort of 1472 patients presenting with STEMI for PPCI, between January 2006 and January 2010, 832 patients with multivessel disease were analysed. The primary outcome was long-term mortality. Median follow-up was 3.3 ± 1.2 years. Complete revascularisation was performed less in females than in males (30 vs. 38 %; p = 0.04). At PPCI, women (27 %, n = 221) were ± 10 years older (p = 0.001), had more hypertension, renal failure and symptoms of heart failure (all p < 0.01). Cumulative long-term mortality with incomplete revascularisation was higher in females (F: 30 vs. M: 15 %, p = 0.01). After adjustment for baseline characteristics, complete revascularisation (0.84; 95 % CI 0.54-1.32) and gender (1.11; 95 % CI 0.73-1.69) lost significance. Also the gender-by-complete revascularisation interaction was not significant at long term. In women, age under 60 years independently predicted higher mortality (HR 10.09; 95 % CI 3.08-33.08; p < 0.001). In STEMI patients with multivessel disease at PPCI, women under the age of 60 years had higher mortality, but in women older than 60 years comorbidity impacted the outcome of revascularisation strategy in the long term.


Short-term effects of three chest physiotherapy regimens in patients hospitalized for pulmonary exacerbations of cystic fibrosis: a cross-over randomized study.
The aim of our study was to compare the short-term efficacy of three different chest physiotherapy (CPT) regimens (PD, postural drainage; PEP, positive expiratory pressure physiotherapy; HFCC, high-frequency chest compression physiotherapy) on patients with cystic fibrosis (CF) hospitalized for an acute pulmonary exacerbation. Sixteen patients with CF, 8 males, 8 females, aged 15-27 years (mean, 20.3 +/- 4), met the inclusion criteria: 1) age over 14 years; 2) mild or moderate airway obstruction; 3) sputum volume > 30 mL/day; 4) being proficient in PD and PEP CPT. Patients at admission had (mean +/- SD) forced volume in 1 second (FEV1) 52.2 +/- 21.9 percent predicted; Shwachman-Kulczycki clinical score 65.1 +/- 11 points; Chrispin-Norman chest radiography score 18.6 +/- 4.3 points. The three CPT regimens and a control-treatment (CONT) were administered in a random sequence, each patient receiving each treatment twice a day (in 50 minute sessions) for 2 consecutive days. During CONT and for 30 minutes after each session only spontaneous coughing was allowed. Wet and dry weight of sputum were recorded during the 50-minute sessions and 30 minutes afterward. Lung function was measured before and 30 minutes after each session. For each treatment a score was given by the patient for efficacy, and by both the patient and the physiotherapist for tolerance. Wet and dry weights of sputum collected during the sessions were greater for all CPT regimens than for CONT (P < 0.001, P < 0.0001). No significant differences between the three CPT regimens for both wet and dry weights were found when the number of coughs was taken into account.(ABSTRACT TRUNCATED AT 250 WORDS)


Fibrous hamartoma of infancy with bone destruction of the tibia: A case report.
Fibrous hamartoma of infancy (FHI) is a rare disease of infancy with unknown etiology. The disease mainly involves soft tissue, has no specific clinical manifestations, and is difficult to diagnose. At present, the diagnosis is mainly confirmed by histopathological examination, and the main treatment is surgical resection of the pathological tissue, which is prone to recurrence. A five-month-old female patient was admitted to our hospital with swelling in the right calf. Two biopsies were performed in our hospital and another hospital, respectively, confirming the diagnosis as fibrous hamartoma. After exclusion of surgical contraindications, resection was performed with clear margins of 1 cm. Radiographic examination showed tumor recurrence more than four months after the operation, and surgery was performed again to extend the resection margins to 1.5 cm. The patient is recovering well, and after a follow-up of 36 mo, shows no signs of recurrence. Our case report demonstrates that FHI should be considered in the differential diagnosis for a lower extremity mass with bone destruction. For FHI with bone destruction and unclear boundaries, excision margins of 1.5 cm could be superior to margins of 1 cm.


ETV2 primes hematoendothelial gene enhancers prior to hematoendothelial fate commitment.
Mechanisms underlying distinct specification, commitment, and differentiation phases of cell fate determination remain undefined due to difficulties capturing these processes. Here, we interrogate the activity of ETV2, a transcription factor necessary and sufficient for hematoendothelial differentiation, within isolated fate intermediates. We observe transcriptional upregulation of Etv2 and opening of ETV2-binding sites, indicating new ETV2 binding, in a common cardiac-hematoendothelial progenitor population. Accessible ETV2-binding sites are active at the Etv2 locus but not at other hematoendothelial regulator genes. Hematoendothelial commitment coincides with the activation of a small repertoire of previously accessible ETV2-binding sites at hematoendothelial regulators. Hematoendothelial differentiation accompanies activation of a large repertoire of new ETV2-binding sites and upregulation of hematopoietic and endothelial gene regulatory networks. This work distinguishes specification, commitment, and sublineage differentiation phases of ETV2-dependent transcription and suggests that the shift from ETV2 binding to ETV2-bound enhancer activation, not ETV2 binding to target enhancers, drives hematoendothelial fate commitment.


Two cases of systemic lupus erythematosus complicated by hydronephrosis and unique small structures observed in the glomerular basement membrane.
We report two cases having a similar clinical profile of systemic lupus erythematosus (SLE) complicated by hydronephrosis that developed concurrently with a similar pathological recognition of numerous unique microspherical and microtubular structures in the glomerular basement membrane (GBM). Case 1 refers to a 29-year-old woman with SLE. An increase in the level of proteinuria had been triggered by hydronephrosis. The pathological findings of the kidney revealed "bubbling" of the GBM, microspherical and microtubular structures in the GBM, and a suspicion of podocytic infolding into the GBM. Case 2 refers to a 46-year-old woman with SLE complicated with hydronephrosis. The level of proteinuria had increased, which was followed by renal biopsy. Similar pathological findings detected in Case 1 were also recognized in Case 2. The renal disorder of the two cases exhibited pathological abnormality atypical of lupus nephritis. Histopathological abnormality similar to that detected in the two cases has rarely been reported until recently. The pathogenesis of the GBM lesions of the two cases has not yet been elucidated, but we believe that there is a possibility the persistent mild autoimmune disorder and the concurrence of an obstructive state of the urinary tract may facilitate the occurrence of the pathological abnormality, because the clinical feature of the two cases are conspicuously similar to each other.


The role of bromocriptine-QR in the management of type 2 diabetes expert panel recommendations.
To review available data on the efficacy and safety of bromocriptine-QR (BQR) and to consider its role in the management of Type 2 diabetes mellitus (T2DM). Published literature reporting the efficacy and safety of BQR in the treatment of T2DM was reviewed, including peer-reviewed abstracts and poster presentations. BQR is an oral hypoglycemic agent with a novel mechanism of action that appears to involve enhancement of morning central nervous system (CNS) dopaminergic activity, resulting in improved insulin sensitivity and reduced hepatic glucose output. Adjunctive treatment with BQR in the dosing range of 1.6 to 4.8 mg/d may result in a mean (95% confidence interval [CI]) reduction in glycated hemoglobin (A1c) levels of 0.69% (0.97%, 0.41%). Treatment with BQR appears to be associated with minimal intrinsic risk of hypoglycemia, and does not appear to be associated with clinically significant adverse effects on weight, triglycerides, free fatty acids, or blood pressure. The favorable cardiovascular risk profile of BQR suggests that it may be useful in the treatment of patients with T2DM with a history of cardiovascular disease (CVD) or who have significant risk factors for CVD. However, knowledge of the efficacy and safety of BQR is limited by the relatively small clinical trials database. As a result, there is currently insufficient information on the safety and efficacy of adjunctive BQR in T2DM patients being treated with several common diabetes regimens (e.g., thiazolidinediones, insulin).


Physiological limits to exercise performance in the heat.
Exercise in the heat results in major alterations in cardiovascular, thermoregulatory, metabolic and neuromuscular function. Hyperthermia appears to be the key determinant of exercise performance in the heat. Thus, strategies that attenuate the rise in core temperature contribute to enhanced exercise performance. These include heat acclimatization, pre-exercise cooling and fluid ingestion which have all been shown to result in reduced physiological and psychophysical strain during exercise in the heat and improved performance.


Simple balance and mobility tests can assess falls risk when cognition is impaired.
To examine the ability of the Romberg test and the original untimed version of the Get-Up-and-Go test (GUG) to elders at risk for falls. At baseline and two annual follow-up visits, nurses administered the Romberg and GUG tests to 358 primary care patients aged 65+ years. Logistic regression models examined cross-sectional and longitudinal associations between abnormal balance tests and self-reported falls over the preceding year. Models were adjusted for age, sex, education and self-rated health (and, in the longitudinal models, for baseline falls), and the Mini-Mental State Examination (MMSE) as a measure of cognitive status. In cross-sectional analyses, falls reported at baseline were significantly associated with concurrently abnormal Romberg and GUG tests, after adjustment for covariates. In longitudinal analyses, abnormal GUG remained significantly associated with future falls, adjusting for covariates. Among those with low MMSE, GUG remained a significant predictor of future falls. Both balance tests were associated with low MMSE among those reporting no falls. Simple balance tests can help assess falls risk, particularly in cognitively impaired elderly who have elevated falls risk and might not accurately recall previous falls.


A multicenter real-world evidence study in the Swiss treatment landscape of chronic myeloid leukemia.
The real-world experience of Swiss chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs) is largely unknown, in particular with regard to achievement of response per European Leukemia Net (ELN) criteria and adherence to ELN recommendations. This was a retrospective, non-interventional, multicenter chart review of patients with newly diagnosed CML who had received first-line TKI and were solely treated with TKIs between 2010 and 2015, with a minimum follow-up of 18 months, at six Swiss hospitals. Effectiveness was evaluated according to ELN 2013 milestone achievements at 3, 6, 12 and 18 months, and at last follow-up. Data from 63 patients (56% men; median age at diagnosis 55 years) were collected (first-line imatinib [n = 27], nilotinib [n = 27], dasatinib [n = 8], or ponatinib [n = 1]). TKI switches (49 times) and dosing changes (165 times) due to intolerance or insufficient response were frequent. Compared with patients receiving first-line imatinib, a higher proportion of patients receiving first-line nilotinib or dasatinib achieved optimal response at all timepoints, irrespective of subsequent TKI therapy, and a higher proportion of patients treated with first-line nilotinib and dasatinib reached deep molecular response (BCR-ABL1IS ≤ 0.01%) at 18 months (42 and 38%, respectively, versus 27%). Patients who received nilotinib or dasatinib switched therapies less frequently than patients treated with imatinib, irrespective of subsequent TKI therapy. Although patient numbers were small, this real-world evidence study with patients with CML confirms that ELN guidelines are generally implemented in Swiss clinical practice, with a large proportion of patients achieving ELN 2013 milestones. While TKI use involved all inhibitors approved at the time of the study, an unexpectedly high number of TKI therapy switches suggests a clear difference in TKI use between registration trials and clinical practice.


The Value of Real-Time Shear Wave Elastography before and after Rehabilitation of Upper Limb Spasm in Stroke Patients.
Our goal was to evaluate the efficacy of muscle spasm before and after rehabilitation by comparing shear wave propagation velocity (SWV) and Young's modulus (YM) in the normal and spastic biceps brachii in stroke patients. A study of 60 stroke patients with upper limb spasm was performed; these patients were admitted from April 2018 to September 2019. The modified Ashworth scale (MAS) scores of the spastic biceps brachii before and after rehabilitation treatment were compared. SWV and YM on the spastic and normal biceps brachii before rehabilitation treatment, SWV and YM on the spastic and normal biceps brachii after rehabilitation treatment, and SWV and YM on the spastic biceps brachii before and after rehabilitation treatment were compared. Whether SWV and YM on the spastic biceps brachii are related to MAS was compared. There was a statistically significant difference in SWV and YM between the normal and spastic biceps brachii before (P < 0.01) and after (P < 0.05) the rehabilitation treatment. There was no statistically significant difference in SWV and YM in the normal biceps brachii before and after the rehabilitation treatment (P > 0.05). There was a statistically significant difference in SWV and YM in the spastic biceps brachii before and after the rehabilitation treatment (P < 0.01). SWV and FM of the spastic biceps brachii are correlated with MAS before and after rehabilitation treatment, and the correlation coefficient for SWV was 0.563 and 0.605 for YM (P < 0.05). SWE can be used as a means of assessment before and after rehabilitation treatment.


Probiotic Bacillus subtilis contributes to the modulation of gut microbiota and blood metabolic profile of hosts.
Probiotic Bacillus subtilis has beneficial efficacy on host's health. The microbiota-gut-blood system (MGBS) plays a crucial role in maintaining the homeostasis of hosts. However, the mechanism by which the probiotic B. subtilis positively acts on the MGBS of hosts remains unclear. Herein, we used an interspecies animal model to explore the causal associations between this bacterium and the micro-ecology balance and circulatory homeostasis of hosts. Results showed that the body weight of hosts significantly increased after probiotic B. subtilis supplementation (P < 0.05). Enterococcus was found to be the most important microbial marker causing the intergroup differences observed herein, and its relative abundance remarkably increased after B. subtilis supplementation. In addition, the supplementation of B. subtilis induced significant alterations in the levels of circulating metabolites, such as serine, arginine, adenine, uric acid, and pyridoxal (P < 0.05), indicating that B. subtilis modulated the metabolic profile of blood circulation in the host. The metabolisms of amino acids, purine, and vitamin B were the primary pathways modulated by B. subtilis. In conclusion, probiotic B. subtilis substantially introduced subtle but positive changes in the host's gut microbiome, and it promoted the physiological activity of the host by modulating circulating metabolites. The study provides a theoretical reference for the application of probiotic B. subtilis to improve the health state of specific populations.


Low-temperature hydrothermally grown 100 μm vertically well-aligned ultralong and ultradense ZnO nanorod arrays with improved PL property.
The hydrothermal synthesis of ZnO nanorods (NRs) has been investigated using ammonium hydroxide and polyethyleneimine as additives to the conventional nitrate based synthesis route, to obtain thin-films of well-aligned, ultradense and ultralong nanostructures. ZnO NRs longer than 60 μm were obtained in a one-cycle growth run and rod lengths ~ 100 μm by a two-cycle growth. The lengths of the rods were distributed uniformly across the substrate in all samples and highly dense NR arrays were observed. These conditions were obtained by a careful review of the nucleation and growth kinetics for this material system, such that the supersaturation of the solution was only relieved by precipitation on and in the presence of crystalline ZnO, and by the exploitation of a second growth phase due to the chelating behave of PEI and the products of HMTA. Also, the growth behavior was correlated to the solution pH values. The structural and optical data were found to be supportive of the growth conditions. The photoluminescence (PL) spectra from as-grown ultralong ZnO NRs exhibited a strong broad (580-625 nm) visible emission peak. However, annealing in a forming gas atmosphere at 623K (350°C) revealed a PL spectrum with a significantly decreased visible emission and an increased near band gap UV emission at 379 nm. Thus, the mechanisms associated with ammonium hydroxide and PEI addition provide a simple route for synthesizing ultralong and dense arrays of ZnO NRs at low temperature i.e. 368K (95°C).


Polysomnographic parameters in first-degree relatives of unipolar probands.
We present polysomnographic data for psychiatrically asymptomatic first-degree relatives of unipolar depressed probands. Relatives were classified by proband rapid eye movement (REM) latency (reduced/nonreduced) and by personal REM latency (reduced/nonreduced). Reduced REM latency relatives, whether defined by the proband or by their own REM latency, had polysomnographic alterations consistent with those found in depressed patients, although none of these relatives was depressed at assessment. Reduced REM latency relatives with a history of unipolar depression were compared to reduced REM latency relatives with no history of depression. Virtually no polysomnographic differences were found. Polysomnographic alterations may be stable antecedents of the onset of depression.


Grasping frequent subgraph mining for bioinformatics applications.
Searching for interesting common subgraphs in graph data is a well-studied problem in data mining. Subgraph mining techniques focus on the discovery of patterns in graphs that exhibit a specific network structure that is deemed interesting within these data sets. The definition of which subgraphs are interesting and which are not is highly dependent on the application. These techniques have seen numerous applications and are able to tackle a range of biological research questions, spanning from the detection of common substructures in sets of biomolecular compounds, to the discovery of network motifs in large-scale molecular interaction networks. Thus far, information about the bioinformatics application of subgraph mining remains scattered over heterogeneous literature. In this review, we provide an introduction to subgraph mining for life scientists. We give an overview of various subgraph mining algorithms from a bioinformatics perspective and present several of their potential biomedical applications.


Application of carbon and hydrogen stable isotope analyses to detect exogenous citric acid in Japanese apricot liqueur.
Japanese apricot liqueur manufacturers are required to control the quality and authenticity of their liqueur products. Citric acid made from corn is the main acidulant used in commercial liqueurs. In this study, we conducted spiking experiments and carbon and hydrogen stable isotope analyses to detect exogenous citric acid used as an acidulant in Japanese apricot liqueurs. Our results showed that the δ13C values detected exogenous citric acid originating from C4 plants but not from C3 plants. The δ2H values of citric acid decreased as the amount of citric acid added increased, whether the citric acid originated from C3 or C4 plants. Commercial liqueurs with declared added acidulant provided higher δ13C values and lower δ2H values than did authentic liqueurs and commercial liqueurs with no declared added acidulant. Carbon and hydrogen stable isotope analyses are suitable as routine methods for detecting exogenous citric acid in Japanese apricot liqueur.


Tle4 controls both developmental acquisition and early post-natal maturation of corticothalamic projection neuron identity.
Identities of distinct neuron subtypes are specified during embryonic development, then maintained during post-natal maturation. In cerebral cortex, mechanisms controlling early acquisition of neuron-subtype identities have become increasingly understood. However, mechanisms controlling neuron-subtype identity stability during post-natal maturation are largely unexplored. We identify that Tle4 is required for both early acquisition and post-natal stability of corticothalamic neuron-subtype identity. Embryonically, Tle4 promotes acquisition of corticothalamic identity and blocks emergence of core characteristics of subcerebral/corticospinal projection neuron identity, including gene expression and connectivity. During the first post-natal week, when corticothalamic innervation is ongoing, Tle4 is required to stabilize corticothalamic neuron identity, limiting interference from differentiation programs of developmentally related neuron classes. We identify a deacetylation-based epigenetic mechanism by which TLE4 controls Fezf2 expression level by corticothalamic neurons. This contributes to distinction of cortical output subtypes and ensures identity stability for appropriate maturation of corticothalamic neurons.


A prospective 10 year audit of a single Irish centre's experience of retroperitoneal lymph node dissection for metastatic testis cancer.
Retro-peritoneal lymph node dissection (RPLND) following chemotherapy is critical in advanced germ cell tumours with residual retro-peritoneal masses. Post-chemotherapy RPLND is more extensive, may require adjacent organ resection and has higher morbidity. The study aim was to analyse patient demographics, clinical stage, surgical procedures and cure rates following RPLND. An RPLND database (1994-2005) was analysed prospectively for demographics, pre/post-RPLND staging, chemotherapy regimen, cure, follow-up and early/late morbidity and mortality. 73 patients were identified (range 17-49 median 25.7). The mean hospital stay was 14.3 days (range 6-50). Clinical stage at presentation was; IV (16), III (19), II (27), I (11) and prior to RPLND was IV (12), III (6), II (55), I (0). Eleven patients with stage I disease progressed prior to RPLND. Seventy-one patients received cisplatin-based chemotherapy with partial response (49), minimal response (14), no response (7), disease progression (3) and 13 patients required salvage chemotherapy. RPLND was bilateral (26), unilateral (36) and suprahilar (11) with nerve sparing in 10. Other major procedures included nephrectomy (22), aortic graft (1), ureterectomy (1) and caval dissection (1). RPLND histology was mature teratoma (MT) (37), fibrosis/necrosis (26), NSGCT (6), seminoma (1), mixed NSGCT/teratoma (1), sarcoma (1) and mixed seminoma/teratoma (1). Early (n = 26) and late (n = 13) morbidity was significant but expected. There was no mortality. Ninety-five per cent had complete remission following RPLND (mean follow-up 30 months). One patient is deceased following relapse. The decision to perform post-chemotherapy RPLND depends on the possibility of viable tumour or teratoma and surgical morbidity. Appropriate case selection and timely intervention in an experienced centre permits optimum outcome.


l-3-n-Butylphthalide ameliorates beta-amyloid-induced neuronal toxicity in cultured neuronal cells.
l-3-n-Butylphthalide (l-NBP), as an anti-cerebral ischemia agent, has been shown to have therapeutic effects on learning and memory deficits induced by chronic cerebral hypoperfusion and Abeta intracerebroventricular infusion in rats. In the present study, we investigated the neuroprotective effects of l-NBP on beta-amyloid (Abeta)25-35-induced neuronal death/apoptosis and potential mechanisms in rat hippocampal neurons and human neuroblastoma SH-SY5Y cells. Abeta25-35 significantly reduced cell viability and increased the number of apoptotic-like cells, indicating that Abeta25-35-induced neurotoxicity. In addition, tau protein hyperphosphorylation was found to increase after Abeta exposure. All of these phenotypes induced by Abeta25-35 were markedly reversed by l-NBP. Pretreatment with l-NBP prior to Abeta25-35 exposure significantly elevated cell viability, and reduced Abeta25-35-induced nuclear fragmentation and early apoptosis. Furthermore, immunoreactivity for hyperphosphorylation tau protein was significantly decreased by l-NBP treatment. Our results suggest that l-NBP may protect neurons against Abeta-induced neurotoxicity via inhibiting tau protein hyperphosphorylation.


Mucin-hypersecreting bile duct neoplasm characterized by clinicopathological resemblance to intraductal papillary mucinous neoplasm (IPMN) of the pancreas.
Although intraductal papillary mucinous neoplasm (IPMN) of the pancreas is acceptable as a distinct disease entity, the concept of mucin-secreting biliary tumors has not been fully established. We describe herein a case of mucin secreting biliary neoplasm. Imaging revealed a cystic lesion 2 cm in diameter at the left lateral segment of the liver. Duodenal endoscopy revealed mucin secretion through an enlarged papilla of Vater. On the cholangiogram, the cystic lesion communicated with bile duct, and large filling defects caused by mucin were observed in the dilated common bile duct. This lesion was diagnosed as a mucin-secreting bile duct tumor. Left and caudate lobectomy of the liver with extrahepatic bile duct resection and reconstruction was performed according to the possibility of the tumor's malignant behavior. Histological examination of the specimen revealed biliary cystic wall was covered by micropapillary neoplastic epithelium with mucin secretion lacking stromal invasion nor ovarian-like stroma. The patient has remained well with no evidence of recurrence for 38 months since her operation. It is only recently that the term "intraductal papillary mucinous neoplasm (IPMN)," which is accepted as a distinct disease entity of the pancreas, has begun to be used for mucin-secreting bile duct tumor. This case also seemed to be intraductal papillary neoplasm with prominent cystic dilatation of the bile duct.


High Output Heart Failure in Multiple Myeloma: Pathogenetic Considerations.
The high output heart failure is a clinical condition in which the systemic congestion is associated to a high output state, and it can be observed in a non-negligible percentage of hematological diseases, particularly in multiple myeloma, a condition in which the risk of adverse cardiovascular events may increase, with a worse prognosis for patients. For this reason, though an accurate literature search, we provided in this review a complete overview of different pathogenetic mechanisms responsible for high output heart failure in multiple myeloma. Indeed, this clinical finding is present in the 8% of multiple myeloma patients, and it may be caused by artero-venous shunts, enhanced angiogenesis, glutamminolysis, hyperammonemia and hemorheological alterations with increase in plasma viscosity. The high output heart failure in multiple myeloma is associated with significant morbidity and mortality, emphasizing the need for a multidisciplinary approach.


Three-dimensional-two-dimensional mixed display system using integral imaging with an active pinhole array on a liquid crystal panel.
A display system that simultaneously displays two-dimensional (2D) and three-dimensional (3D) images using a pinhole array on a liquid crystal (LC) panel is proposed. Using the transparent structure of the LC panel, the system can generate or eliminate pinholes electrically and can display a 3D image in a selectable specific area of the display panel, while 2D images are displayed on the rest of the screen. An analysis showing the advantages and limitations of the proposed system is provided. Finally, the proposed principle is proven by experimental results.


Erratum: Tips and tricks and clinical outcome of cryopreserved human amniotic membrane application for the management of medication- related osteonecrosis of the jaw (MRONJ): A pilot study.
[This corrects the article DOI: 10.3389/fbioe.2022.936074.].


Time, pattern, and outcome of medulloblastoma relapse and their association with tumour biology at diagnosis and therapy: a multicentre cohort study.
Disease relapse occurs in around 30% of children with medulloblastoma, and is almost universally fatal. We aimed to establish whether the clinical and molecular characteristics of the disease at diagnosis are associated with the nature of relapse and subsequent disease course, and whether these associations could inform clinical management. In this multicentre cohort study we comprehensively surveyed the clinical features of medulloblastoma relapse (time to relapse, pattern of relapse, time from relapse to death, and overall outcome) in centrally reviewed patients who relapsed following standard upfront therapies, from 16 UK Children's Cancer and Leukaemia Group institutions and four collaborating centres. We compared these relapse-associated features with clinical and molecular features at diagnosis, including established and recently described molecular features, prognostic factors, and treatment at diagnosis and relapse. 247 patients (175 [71%] boys and 72 [29%] girls) with medulloblastoma relapse (median year of diagnosis 2000 [IQR 1995-2006]) were included in this study. 17 patients were later excluded from further analyses because they did not meet the age and treatment criteria for inclusion. Patients who received upfront craniospinal irradiation (irradiated group; 178 [72%] patients) had a more prolonged time to relapse compared with patients who did not receive upfront craniospinal irradiation (non-irradiated group; 52 [21%] patients; p<0·0001). In the non-irradiated group, craniospinal irradiation at relapse (hazard ratio [HR] 0·27, 95% CI 0·11-0·68) and desmoplastic/nodular histology (0·23, 0·07-0·77) were associated with prolonged time to death after relapse, MYC amplification was associated with a reduced overall survival (23·52, 4·85-114·05), and re-resection at relapse was associated with longer overall survival (0·17, 0·05-0·57). In the irradiated group, patients with MBGroup3 tumours relapsed significantly more quickly than did patients with MBGroup4 tumours (median 1·34 [0·99-1·89] years vs 2·04 [1·39-3·42 years; p=0·0043). Distant disease was prevalent in patients with MBGroup3 (23 [92%] of 25 patients) and MBGroup4 (56 [90%] of 62 patients) tumour relapses. Patients with distantly-relapsed MBGroup3 and MBGroup4 displayed both nodular and diffuse patterns of disease whereas isolated nodular relapses were rare in distantly-relapsed MBSHH (1 [8%] of 12 distantly-relapsed MBSHH were nodular alone compared with 26 [34%] of 77 distantly-relapsed MBGroup3 and MBGroup4). In MBGroup3 and MBGroup4, nodular disease was associated with a prolonged survival after relapse (HR 0·42, 0·21-0·81). Investigation of second-generation MBGroup3 and MBGroup4 molecular subtypes refined our understanding of heterogeneous relapse characteristics. Subtype VIII had prolonged time to relapse and subtype II had a rapid time from relapse to death. Subtypes II, III, and VIII developed a significantly higher incidence of distant disease at relapse whereas subtypes V and VII did not (equivalent rates to diagnosis). This study suggests that the nature and outcome of medulloblastoma relapse are biology and therapy-dependent, providing translational opportunities for improved disease management through biology-directed disease surveillance, post-relapse prognostication, and risk-stratified selection of second-line treatment strategies. Cancer Research UK, Action Medical Research, The Tom Grahame Trust, The JGW Patterson Foundation, Star for Harris, The Institute of Child Health - Newcastle University - Institute of Child Health High-Risk Childhood Brain Tumour Network (co-funded by The Brain Tumour Charity, Great Ormond Street Children's Charity, and Children with Cancer UK).


Hepatitis C virus core antigen assay: can we think beyond convention in resource limited settings?
Hepatitis C virus infects over 15 million patients from India and 2.86 million from Brazil. Detection of anti-hepatitis C virus antibodies has limited sensitivity during acute phase: the pre-seroconversion window period. Hepatitis C virus-RNA detection techniques are used to overcome this shortfall, but are costly and unavailable widely in developing countries. Estimation of hepatitis C virus core-antigen, a protein with highly conserved sequence, by enzyme-immunoassays is an economic and simpler alternative to RNA detection. This study was conducted in Delhi, involving 300 acute and chronic liver disease patients, tested for anti-hepatitis C virus 3rd-generation ELISA, hepatitis C virus core-antigen-ELISA and hepatitis C virus-RNA reverse transcription-polymerase chain reaction. Among the acute patients, hepatitis C virus core-antigen assay could identify 13 out of 14 pre-seroconversion window period cases and 6 out of 8 seroconverted cases, with a pre-seroconversion window period sensitivity of 92.9% and specificity of 100%. In hepatitis C virus core-antigen-positive cases, the viral load was in the range of 4900 to 1.46×10(6)IU/mL, whereas in hepatitis C virus core-antigen-negative cases, the range of viral load was 100-4500IU/mL. The cost of the hepatitis C virus core-antigen-ELISA was estimated around 3-4 times lesser than the in-house reverse transcription-polymerase chain reaction and 9-10 times lesser than the United States Food and Drug Administration approved reverse transcription-polymerase chain reaction. With a good sensitivity and specificity in the acute phase of infection, hepatitis C virus core-antigen-ELISA can thus be a useful alternative in the developing nations.


Morphologic association between microglia and senile plaque amyloid in Alzheimer's disease.
Alzheimer senile plaques are comprised of extracellular deposits of beta-amyloid. The cell type responsible for the secretion of this amyloid, however, is unknown. In the present study, compact amyloid 'stars' and the cellular elements directly apposed to them were examined at the ultrastructural level. In many cases, amyloid fibrils were closely interdigitated with the plasma membrane of cells with dark cytoplasm, dense bodies and distinctive nuclei. These cells were morphologically identified as microglia, the resident macrophages of the brain. Previous work has described an identical morphologic association between macrophages and several types of systemic and cerebral amyloidoses. Taken together, these data suggest that beta-amyloid may be secreted by microglia.


Antagonism between high pressure and anesthetics in the thermal phase-transition of dipalmitoyl phosphatidylcholine bilayer.
The antagonizing action of hydrostatic pressure against anesthesia is well known. The present study was undertaken to quantitate the effects of hydrostatic pressure and anesthetics upon the phase-transition temperature of dipalmitoyl phosphatidylcholine vesicles. The drugs used to anesthetize the phospholipid vesicles included an inhalation anesthetic, halothane, a dissociable local anesthetic, lidocaine and an undissociable local anesthetic, benzyl alcohol. All anesthetics decreased the phase-transition temperature dose-dependently. In the case of lidocaine, the depression was pH dependent and only uncharged molecules were effective. The application of hydrostatic pressure increased the phase-transition temperature both in the presence and the absence of anesthetics. The temperature-pressure relationship was linear over the entire pressure range studied up to 340 bars. Through the use of Clapeyron-Clausius equation, the volume change accompanying the phase-transition of the membrane was calculated to be 27.0 cm3/mol. Although the anesthetics decreased the phase-transition temperature, the molar volume change accompanying the phase-transition was not altered. The anesthetics displaced the temperature-pressure lines parallel to each other. The mole fraction of the anesthetics in the liquid crystalline membrane, calculated from the van't Hoff equation, was independent of pressure. This implies that pressure does not displace the anesthetics from the liquid membrane, and the partition of these agents remains constant. The volume change of the anesthetized phospholipid membranes is entirely dependent upon the phase-transition and not on the space occupied by the anesthetics.


Fecal transplant for recurrent Clostridium difficile infection.
Clostridium difficile infection (CDI) results in clinical manifestations ranging from mild diarrhea to life-threatening pseudomembranous colitis. Infection is most often initiated by antimicrobial therapy which causes an imbalance in normal colonic microflora. The pathogenesis of C. difficile is predominantly controlled by the production of its two cytotoxins, A and B, which damage the intestinal mucosa. In recent years a nationwide increase in the rate of CDI has been noted as well as an increase in mortality, reduced initial response to antimicrobials, extended resolution time, and increased rates of recurrence. Traditional treatment includes administration of antimicrobials. Fecal microbiota transplant (FMT) is an alternative therapy for CDI that is effective and promising in multiple CDI relapse patients. This paper will provide an overview of CDI epidemiology, pathogenesis, diagnosis, and treatment, and explore the case of a 53-year-old woman suffering from her sixth episode of CDI.


Boosted spatial charge carrier separation of binary ZnFe2O4/S-g-C3N4 heterojunction for visible-light-driven photocatalytic activity and antimicrobial performance.
A potential method for removing toxins from contaminated wastewater, especially organic pollutants, is photo-catalysis. Here, a simple technique for producing zinc ferrite nanoparticles (ZnFe2O4 NPS) with varying quantities of sulphur doped graphitic carbon nitride nanocomposites (ZnFe2O4/S-g-C3N4 NCs) has been described. Then, using X-ray diffraction (XRD), TEM, EDX, XPS, photocurrent response, EIS, and Fourier Transform Infrared spectroscopy (FT-IR), the photo-catalytic activity of the produced nanoparticles (NPs) and nanocomposites (NCs) was examined and evaluated. The photo-catalytic activity of ZnFe2O4/S-g-C3N4 NCs was compared to a model pollutant dye, methylene blue, while degradation was evaluated spectrophotometrically (MB). Solar light has been used through irradiation as a source of lighting. The photocatalytic behaviour of the ZnFe2O4/S-g-C3N4 NCs photocatalyst was superior to that of genuine ZnFe2O4 and S-g-C3N4, which was attributed to synergic effects at the ZnFe2O4/S-g-C3N4 interconnection. Antimicrobial activity of ZnFe2O4/S-g-C3N4 against Gram-positive and Gram-negative bacteria under visible light was performed. In addition, these ZnFe2O4/S-g-C3N4 NCs show a lot of promise as an antibacterial agent.


Damage control hip disarticulation: two-stage operation with index creation of a large medial flap for the septic hip.
Although rarely performed, hip disarticulation (HD) is usually used for the patient with a non-viable leg who is also in extremis. HD was first used for trauma and infection; however, the technique was perfected during the age of hindquarter amputation for osteosarcomas. The operation performed by most surgeons today is still based on the oncological principles of high vessel control and ligation. When this approach has been used in the overwhelmingly infected or mangled extremity, it has resulted in high mortality rates. During the last 20 years, the concept of damage control operation has been embraced by emergency surgeons in all fields. We sought to extrapolate this concept and to apply it to the non-viable lower extremity. We describe a new concept of damage control HD, review the technique and discuss our consecutive series of nine patients who underwent the procedure for trauma or necrotizing infection without flap dehiscence or mortality. All patients survived to hospital discharge. At time of discharge or at follow-up, six of the nine patients were able to transfer to a wheelchair. Proper disarticulations for infection need to address these two operative and postoperative issues: damage control debridement with creation of sufficient flap size and thorough postoperative wound care.Level IV.


Hyaluronic acid-paclitaxel conjugate inhibits growth of human squamous cell carcinomas of the head and neck via a hyaluronic acid-mediated mechanism.
Chemotherapeutic regimens incorporating taxanes significantly improve outcomes for patients with squamous cell carcinomas of the head and neck (SCCHN). However, treatment with taxanes is limited by toxicities, including bone marrow suppression and peripheral neuropathies. We proposed that conjugating taxanes to targeting carrier molecules would increase antitumor efficacy and decrease toxicity. The cell surface proteoglycan, CD44, is expressed on most SCCHNs, and we hypothesized that it is an attractive candidate for targeted therapy via its natural ligand, hyaluronic acid (HA). We determined whether HA-paclitaxel conjugates were able to decrease tumor growth and improve survival in orthotopic nude mouse human SCCHN xenograft models. HA-paclitaxel concentration-dependent growth inhibition of human SCCHN cell lines OSC-19 and HN5 in vitro, very similarly to free paclitaxel treatment. Tumor cell uptake of FITC-labeled HA-paclitaxel was significantly blocked with free HA, indicating the dependence of uptake on CD44. HA-paclitaxel administered intravenously once per week for three weeks at 120 mg/kg paclitaxel equivalents, far above the paclitaxel maximum tolerated dose, exerted superior tumor growth control to that of paclitaxel in both orthotopic OSC-19-luciferase and HN5 xenograft models in vivo. Mouse survival following HA-paclitaxel administration was prolonged compared with that of controls in mice implanted with either of these xenografts. Mice treated with HA-paclitaxel displayed increased TUNEL(+) cells in tumor tissue, as well as markedly reduced microvessel density compared to those treated with free paclitaxel. No acute histopathological changes were observed in mice treated with HA-paclitaxel. Thus, we conclude that HA-paclitaxel effectively inhibits tumor growth in human SCCHN xenografts via an HA-mediated mechanism and this conjugate should be considered for further preclinical development for this disease.


The effect of giving information in advance on the clinical training of medical students.
To study whether or not giving written information in advance influences patients' willingness to participate in the clinical training of medical students. Dermatology surgery at a university hospital. Prior to the visit, patients were randomly allocated either to receive a letter about medical education (the experiment group), or not to receive a letter (the control group). The willingness of patients to participate in clinical training. There was no difference between the 2 groups regarding their willingness to participate. Almost all patients perceived the provided information as good or rather good, but some patients, especially in the control group, did not feel free to refuse to participate. The present written-information-in-advance strategy seems to prevent patients from feeling forced to participate, without having any negative influence on their inclination to participate.


Effect of manganese exposure on MPTP neurotoxicities.
We used a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model to evaluate whether manganese (Mn) exposure can affect MPTP-induced neurotoxicity. We randomly assigned adult male C57BL/6 mice (n=5-7 per group) the following treatments: SO, Mn(-) x MPTP(-); MO, Mn(+) x MPTP(-); SM, Mn(-) x MPTP(+); MM, Mn(+) x MPTP(+). Mn (MnCl(2).4H(2)O) was administered intraperitoneally at a dose of 2 mg/kg daily for 3 weeks. MPTP was then administered intraperitoneally at a dose of 30 mg/kg daily for 5 days in the SM and MM groups. Seven days after the last MPTP injection, the animals were sacrificed. Blood Mn levels were elevated in the Mn-exposed groups. Striatal Mn levels were not influenced by Mn treatment alone, however, they were decreased following MPTP. Tyrosine hydroxylase (TH)-immunoreactive (ir) neurons in the substantia nigra pars compacta (SNpc) were decreased significantly in the MPTP-exposed groups. Densities of TH- and dopamine transporter (DAT)-ir axon terminals in the caudate-putamen (CPU) were also decreased in the MPTP-treated groups. Furthermore, glial fibrillary acidic protein (GFAP)-ir astrocytes increased in the CPU with MPTP treatment. However, no effects were observed with Mn exposure. Concentrations of dopamine (DA), 3,4-dihydrophenyl acetic acid (DOPAC) and homovanillic acid (HVA) in the corpus striatum were also decreased significantly with MPTP treatment alone, but Mn had no effect. Thus, decreased dopaminergic activities with MPTP led to decreased DA and its metabolites. Significant hypertrophies of GFAP-ir astrocytes in the globus pallidus (GP) were observed in Mn-exposed groups, especially in the MM group. MPTP targeted dopaminergic systems whereas Mn neurotoxicities occurred in the GP. In conclusion, our data suggest that Mn does not potentiate the neurotoxicity of MPTP.


AFM imaging of milk casein micelles: evidence for structural rearrangement upon acidification.
Milk casein micelles are natural association colloids that we all encounter in everyday life, yet we still lack an accurate description of their internal structure and the interactions that stabilize it. In this letter, we provide for the first time detailed images of intact casein micelles as obtained through atomic force microscopy under liquid conditions close to physiological. The micelles appear as heterogeneous raspberry-like particles, which is consistent with a hierarchical/spongelike structure made of connected 10-40 nm dense casein regions. Upon in situ acidification to pH 5, the micelles decrease in size and lose their surface heterogeneities, indicating that this structure is highly sensitive to variations in mineral content and caseins net charge.


Staphylococcus aureus nasal carriage among healthcare workers in Kisangani, the Democratic Republic of the Congo.
Methicillin-resistant Staphylococcus aureus (MRSA) is a global health concern, but there are few data from Central Africa. The objective of our study was to characterise S. aureus colonisation isolates from healthcare-exposed professionals in the Democratic Republic of the Congo (DRC). Healthcare workers and medical students (n = 380) in Kisangani, DRC were screened for S. aureus nasal carriage in a single-centre cross-sectional study in the University Hospital of Kisangani. The isolates were identified and characterised using phenotypic and genotypic methods. The nasal carriage rate of S. aureus was 16.6 % and 10 out of 63 isolates (15.9 %) were MRSA. We found 28 different spa types. Most MRSA isolates belonged to ST8-spa t1476-SCCmec V. The majority of MRSA were multidrug-resistant to non-beta-lactam antibiotics. Overall, 28.5 % of S. aureus carried Panton-Valentine leucocidin (PVL)-encoding genes (all methicillin-sensitive) and 17.5 % carried toxic shock syndrome toxin-1 (TSST-1)-encoding genes. The finding of MRSA carriage among healthcare workers in a setting with limited access to diagnostic microbiology and appropriate therapy calls for improved education on infection control practices and supports the introduction of surveillance programmes.


Upregulation of CSNK1A1 induced by ITGB5 confers to hepatocellular carcinoma resistance to sorafenib in vivo by disrupting the EPS15/EGFR complex.
Oral multitarget tyrosine kinase inhibitors (TKIs), such as sorafenib, which suppress tumor cell proliferation and tumor angiogenesis, have been approved to treat patients with hepatocellular carcinoma (HCC). Of note, only approximately 30% of patients can benefit from TKIs, and this population usually acquires drug resistance within 6 months. In this study, we intended to explore the mechanism associated with regulating the sensitivity of HCC to TKIs. We revealed that integrin subunit β 5 (ITGB5) is abnormally expressed in HCC and contributes to decreased the sensitivity of HCC to sorafenib. Mechanistically, unbiased mass spectrometry analysis using ITGB5 antibodies revealed that ITGB5 interacts with EPS15 to prevent the degradation of EGFR in HCC cells, which activates AKT-mTOR signaling and the MAPK pathway to reduce the sensitivity of HCC cells to sorafenib. In addition, mass spectrometry analysis showed that CSNK1A1 binds to ITGB5 in HCC cells. Further study indicated that ITGB5 increased the protein level of CSNK1A1 through the EGFR-AKT-mTOR pathway in HCC. Upregulated CSNK1A1 phosphorylates ITGB5 to enhance the interaction between ITGB5 and EPS15 and activate EGFR in HCC cells. Thus, we identified a positive feedback loop between ITGB5-EPS15-EGFR-CSNK1A1 in HCC cells. This finding provides a theoretical basis for the future development of therapeutic strategies to improve the anti-HCC efficacy of sorafenib.


Role of immunoglobulin G3 subclass in dilated cardiomyopathy: results from protein A immunoadsorption.
Immunoadsorption (IA) by anti-immunoglobulin G (anti-IgG) columns that effectively eliminates total IgG, including IgG3 subclass, represents an additional therapeutic approach in dilated cardiomyopathy (DCM). A recent study revealed that IA with protein A columns does not effectively remove IgG3 and does not induce hemodynamic improvement in DCM. Eighteen patients with DCM (left ventricular ejection fraction < or =30%) were included in this case-control study. In all patients, IA with protein A was performed in 4 courses, at 1-month intervals until month 3. Nine patients underwent protein A IA with an improved treatment regimen for IgG3 elimination. Data of these patients were compared retrospectively to existing findings for 9 comparable patients treated by protein A IA with ineffective IgG3 reduction. In both groups, IA induced a comparable reduction of the total IgG level. However, reduction of the IgG3 level was different in the 2 groups (P < .001). Hemodynamics did not significantly change throughout the 3 months in the group with ineffective IgG3 reduction. In contrast, the group with improved IgG3 reduction demonstrated during the first IA course an increase in cardiac index from 2.2 +/- 0.1 to 2.8 +/- 0.2 L min(-1) m(-2) (P < .05). After 3 months before the last IA course, cardiac index was 2.2 +/- 0.1 L min(-1) m(-2) in the group with ineffective IgG3 elimination and 2.8 +/- 0.2 L min(-1) m(-2) in the group with improved IgG3 reduction (P < .01). In the group with ineffective IgG3 reduction, left ventricular ejection fraction increased after 3 months from 21.6 +/- 2% to 24.4 +/- 2% (NS), and from 24.3 +/- 2 to 34.7 +/- 4% in the group with improved IgG3 reduction (P < .05). Autoantibodies belonging to IgG3 may play an important role in cardiac dysfunction of patients with DCM. Protein A IA in conjunction with an improved treatment regimen for IgG3 elimination induces hemodynamic benefit in patients suffering from DCM.


Nutritional effects on vaccination.
Immune-induced cachetic response is an example of a biological opportunity to develop technologies that ensure improved performance in animal agriculture. We have estimated that reduced performance of immune stimulated animals, whether by exposure to conventional environments or through vaccination, results in more than U.S. $500 million in reduced productivity. Nontraditional methods to alleviate the adverse effects of the immune response provide an opportunity for those skilled in the art of vaccinology and immunology to develop new technologies and feeding practices. Too often, biologists are blinded by the limits of their disciplines and rarely venture to the fringe of their field to engage in collaborations that at first glance do not seem logical. The examples of CLA and antigastrointestinal peptides suggest that new opportunities await in ensuring that the cost of the immune response is minimized and that new approaches to animal agriculture await discovery.


Use of the APAAP method in the classification and diagnosis of hematologic disorders.
The APAAP technique is a sensitive and relatively easy immunocytochemical method to perform. It requires only a modest amount of laboratory space and no expensive equipment with the exception of a light microscope. Staining can be performed on peripheral blood and bone marrow films as well as cryostat and paraffin-embedded tissue sections. Prior to staining peripheral blood and bone marrow films as well as cryostat sections, slides can be stored at -70 degrees C, thus allowing for batch processing of specimens. Stained slides can be kept at room temperature for prolonged periods of time without loss of label. Surface or cytoplasmic determinants can be stained with the APAAP method. Because the preparations are usually counterstained, the identification of the labeled cells can be observed and photographed. The APAAP method is a reliable procedure and a significant addition to the routine hematology and histopathology laboratory.


Laser deepithelialization: an adjunct to reduction mammaplasty.
A new use is described for the CO2 laser--that of deepithelialization. Deepithelialization is a technique used in a myriad of plastic surgical procedures. This paper introduces the use of the laser for deepithelialization and illustrates its advantages in 44 consecutive patients undergoing reduction mammaplasty. Advantages are the precise removal of the upper dermis and epidermis--a true deepithelialization--with preservation of the lower dermis and pilosebaceous units. Associated decreased blood loss and more rapid operating time without an increase in complications makes this an attractive adjunctive technique with a wide variety of applications. No adverse effects or contraindications to the use of the CO2 laser for deepithelializing have been found.


A Mössbauer spectroscopic study of the form of iron in iron overload.
There are major differences in the temperature dependence of the Mössbauer spectra of ferritin and haemosiderin extracted from the organs of humans suffering from transfusional iron overload. Iron overload can also occur in animal systems as a result of artificial treatments or dietary factors. None of the animal systems which were investigated in the present study showed evidence in their Mössbauer spectra for the presence of the haemosiderin found in transfusional iron overload in humans. This suggests that the haemosiderin which occurs in the case of human transfusional iron overload may be specific to that situation.


[Effects of alpha-ketoacids therapy on protein metabolism and secondary hyperparathyroidism in predialysis patients].
The effects of alpha-ketoacids (alpha-KA) on azotemia, plasma amino acids concentrations, nitrogen balance, serum Ca, PO4 and iPTH levels in 22 predialysis patients were investigated. The results showed that BUN and serum phosphate levels decreased significantly, plasma essential amino acids levels, nitrogen balance and serum calcium levels were improved after 6-8 weeks of alpha-KA therapy. The serum iPTH levels were reduced markedly three months after alpha-KA treatment and maintained lower ten months later.


Intraoperative infusion of S(+)-ketamine enhances post-thoracotomy pain control compared with perioperative parecoxib when used in conjunction with thoracic paravertebral ropivacaine infusion.
The authors explored the use of continuous postoperative subpleural paravertebral ropivacaine alone combined with intraoperative S(+)-ketamine or perioperative parecoxib as a new approach to pain control after major thoracotomy. A randomized study. A single university hospital. Eighty patients underwent elective thoracotomy under general anesthesia. Study patients were assigned to 1 of 3 groups: group K (n = 27) received intraoperative S(+)-ketamine (0.5 mg/kg as a preincisional bolus followed by a continuous infusion 400 μg/kg/h), group P (n = 27) received perioperative parexocib (40 mg before extubation and 12 hours postoperatively), and group C (n = 26) served as the control group. At the end of surgery, all patients received a subpleural paravertebal infusion of ropivacaine. Pain was assessed by visual analog scores and supplemental morphine consumption with PCA up to 48 hours postoperatively. The duration of stay and postoperative functional parameters also were collected. Compared with ropivacaine alone, S(+)-ketamine significantly reduced pain scores at rest and during movement at 4, 12, 24, and 48 hours postoperatively. Moreover, at 24 and 48 hours, pain was less after S(+)-ketamine compared with parexocib. S(+)-ketamine also reduced morphine needs in comparison to placebo at 4, 12, 24, and 48 hours and in comparison to parexocib at 48 hours after thoracotomy. There were no differences in parameters for lung or bowel function, mobilization time, or ICU and hospital stay. In patients with thoracotomy, postoperative paravertebral ropivacaine combined with intraoperative S(+)-ketamine provided better early postoperative pain relief than ropivacaine and perioperative parexocib or ropivacaine alone.


Better survival with statin administration after revascularization therapy in Japanese patients with coronary artery disease: perspectives from the CREDO-Kyoto registry.
The importance of statins in cardiovascular prevention has been demonstrated in various patient subsets. This study aimed to evaluate the effects of statins on long-term outcomes of Japanese patients undergoing their first coronary revascularization. A total of 9,225 patients undergoing their first coronary revascularizations during 2000--2002 were divided into 2 groups according to the use of statins at discharge; patients with acute myocardial infarction were not included. Statins was administered to only 28.5% (n=2,630) of the patients. The median follow-up period was 3.5 years. Patients on statin therapy showed lower all-cause (5.2% vs 10.0%; p<0.0001) and cardiovascular (3.2% vs 6.2%; p<0.0001) mortality than those without statins (n=6,595) by Kaplan-Meier analysis and log-rank test. After adjustment by multivariate analysis according to 29 variables, statin therapy remained as an independent predictor of reduced all-cause (relative risk ratio (RR) 0.71, 95% confidence interval (CI) 0.59-0.86, p=0.0005) and cardiovascular (RR 0.72, 95% CI 0.56-0.91, p=0.0067) mortality. The validity of RR of statin therapy in multivariate analysis was further confirmed by risk adjustment using propensity scores (all-cause mortality: propensity-adjusted RR 0.70, 95% CI 0.58-0.85, p=0.0003; cardiovascular mortality: propensity-adjusted RR 0.70, 95% CI 0.54-0.89, p=0.0038). Statin therapy started at hospital discharge was associated with increased chance of survival in Japanese patients undergoing their first coronary revascularization.


Expression analysis and binding experiments of chemosensory proteins indicate multiple roles in Bombyx mori.
Chemosensory proteins (CSPs) are a family of small soluble proteins that, in addition to the odorant-binding proteins (OBPs), are involved in chemical communication. To understand the physiological function of the 16 known CSPs in the silkworm Bombyx mori, we investigated the expression patterns in different tissues and developmental stages using quantitative real-time RT-PCR (Q-PCR) and Western blot analysis. The results indicated that most CSPs were widely expressed in embryos, larvae, pupae and adults but were developmentally regulated. Such broad spatial and temporal expression was inconsistent with a specific association with chemosensory function. We conclude that CSPs are multifunctional proteins that are involved in diverse cellular processes and that can play non-chemosensory as well as chemosensory roles. Binding experiments revealed different binding characteristics of CSP1 and CSP2, with retinal being the best ligand, suggesting a putative function of these CSPs as carriers.


Effects of benzylisoquinoline alkaloids on the larvae of polyphagous Lepidoptera.
Six benzylisoquinoline alkaloids were fed to the larvae of three polyphagous Lepidoptera species: Hyphantria cunea, Spodoptera eridania, and Lymantria dispar. Exposure of last instar larvae to alkaloid-containing diets over a 24-h period resulted in reduced feeding rates and reduced growth efficiencies. Lymantria dispar larvae reared from eggs on alkaloid diets took longer to reach the fifth instar, attained lower larval weights, and showed reduced survivorship. The benzylisoquinolines tested were not equally effective as toxins or feeding inhibitors. Some produced dramatic effects while others produced no effects. The relative responses of the three caterpillar species to the six alkaloids were similar. Those benzylisoquinolines with a methylene-dioxyphenyl (1,3-benzodioxole) group were consistently the most toxic or repellent while laudanosine, a relatively simple benzylisoquinoline, was generally innocuous. Available host records indicate that benzylisoquinoline-containing plants are avoided by the larvae of these moth species.


The allosteric transition of glycogen phosphorylase.
The crystal structure of R-state glycogen phosphorylase b has been determined at 2.9 A resolution. A comparison of T-state and R-state structures of the enzyme explains its cooperative behaviour on ligand binding and the allosteric regulation of its activity. Communication between catalytic sites of the dimer is provided by a change in packing geometry of two helices linking each site with the subunit interface. Activation by AMP or by phosphorylation results in a quaternary conformational change that switches these two helices into the R-state conformation.


LMTK2-mediated phosphorylation regulates CFTR endocytosis in human airway epithelial cells.
Cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl(-)-selective ion channel expressed in fluid-transporting epithelia. Lemur tyrosine kinase 2 (LMTK2) is a transmembrane protein with serine and threonine but not tyrosine kinase activity. Previous work identified CFTR as an in vitro substrate of LMTK2, suggesting a functional link. Here we demonstrate that LMTK2 co-immunoprecipitates with CFTR and phosphorylates CFTR-Ser(737) in human airway epithelial cells. LMTK2 knockdown or expression of inactive LMTK2 kinase domain increases cell surface density of CFTR by attenuating its endocytosis in human airway epithelial cells. Moreover, LMTK2 knockdown increases Cl(-) secretion mediated by the wild-type and rescued ΔF508-CFTR. Compared with the wild-type CFTR, the phosphorylation-deficient mutant CFTR-S737A shows increased cell surface density and decreased endocytosis. These results demonstrate a novel mechanism of the phospho-dependent inhibitory effect of CFTR-Ser(737) mediated by LMTK2 via endocytosis and inhibition of the cell surface density of CFTR Cl(-) channels. These data indicate that targeting LMTK2 may increase the cell surface density of CFTR Cl(-) channels and improve stability of pharmacologically rescued ΔF508-CFTR in patients with cystic fibrosis.


Health risk estimations and geospatial mapping of trace metals in soil samples around automobile mechanic workshops in Benin city, Nigeria.
This study was carried out to assess the distribution of trace metals in soil samples from selected automobile mechanic workshops (AMWs) in Benin City, spatially map the concentrations and estimate the health risk indices for the exposed populace. Topsoil samples were collected from twenty-one (21) AMWs in Benin City in 3 composites for three months at each station. Soil samples were analyzed for heavy metals (Pb, Cd, Fe, Cu, Ni, Cr, and Zn) using Atomic Absorption Spectrophotometer. The non-carcinogenic risks caused by exposure to the metals were insignificant, characterized by in mean values of hazard quotient (HQ) and hazard index (HI) below one (1) in adults and children. Carcinogenic risk (CR) occurred only in the children exposed to nickel through ingestion; attributable to ingestion. In adults and children, the risks associated with the uptake routes were in the order of ingestion > dermal contact > inhalation. The hazard index (HI) values of heavy metals for children and adults decreased in the order of Pb > Cr > Cd > Cu > Zn > Ni and were all lower than one (1), which indicated that the children and adults were not at non-carcinogenic risk. The contamination factors (CF) of all metals analyzed were lower than one (1), suggesting low contamination. The average CF decreased in the order of Pb (0.3715) > Zn (0.14) > Cu (0.087) > Cr (0.013) > Ni (0.01) > Fe (0.0007). Potential ecological risks of the trace metals in soils of these workshops revealed low pollution of the soils by the metals. Results indicated that the three routes of uptake in adults and children decreased in the order of ingestion > dermal > inhalation. The non-carcinogenic risks posed by metals to the children and adults were insignificant. Ingested nickel however posed potential carcinogenic risk to only the children. The toxicodynamics of heavy metals in the soil profile demonstrated in this study could be a vital information for future studies and decisions on the management of the health and environment of the study area.


Detection of aerosolized Alternaria alternata conidia, hyphae, and fragments by using a novel double-immunostaining technique.
A double-immunostaining halogen immunoassay was developed to identify aerosolized conidia, hyphae, and fragments of Alternaria alternata by using an anti-Alternaria polyclonal antiserum, while, simultaneously, allergy to these components was concurrently determined by using human immunoglobulin E antibodies.


The function and regulatory network of WhiB and WhiB-like protein from comparative genomics and systems biology perspectives.
whi genes, named after the mutations turning Streptomyces coelicolor colonies into white, exist largely in Actinomyces and Mycobacterium. whiB genes, a subclass of whi, involve in wide range of events, such as cell division, spore formation, nutrient starvation, pathogenesis, antibiotic resistance, and stress sense. To better understand the role of this family in physiology and pathology in the important pathogen-Mycobacterium tuberculosis, WhiB and WhiB-like proteins function and structures of were bioinformatically dissected. Seven WhiB proteins can be found in M. tuberculosis genome, most are highly conserved. Based on the data mining of published microarray profiling of wild type and mutants transcriptome response to diverse treatments, a regulatory network of whiB is established. Some findings from this network are obvious. WhiB2 and WhiB7 might be key nodes in drug resistance, WhiB3 might involve in the maintenance of redox homeostasis. These works provide new Mycobacterium persistence and virulence hypothesis for future experimental validation.


Iron(III)-nitrilotriacetate: an agent for reducing the time interval of tumor imaging with gallium citrate.
Increasing interest in the short-lived radionuclide 68Ga (t1/2: 68.2 min) has revived basic studies of gallium radiopharmaceuticals. Ga-citrate (Ga-cit), described as a polynuclear complex, possesses great affinity for tumor cells but is also bound by blood transferrin (Tf). Exploitation of reaction-rate differences in metal ion transference from Ga-cit to Tf (slow) and Fe-nitrilotriacetate (Fe-NTA) to Tf (fast) is put to use to attain a proper tumor/tissue ratio within practical time limits. Studies on administration mode, time and dose offered promising results for future 68Ga-cit tomographic studies.


Termination of early pregnancy with RU 486 (mifepristone) in combination with a prostaglandin analogue (sulprostone).
The antiprogestin RU 486 (mifepristone) has been shown to induce abortion when administered in early pregnancy, but the rate of incomplete abortion is high, around 40%. As blockage of the progesterone receptor increases the myometrial sensitivity to prostaglandins, a combination of RU 486 and a prostaglandin E2-analogue was tested for termination of pregnancy. One hundred and sixteen women, with a gestational length of less than 49 days from the first day of the last menstrual period, were treated with a daily dose of 50 or 100 mg RU 486 for 3 to 6 days, complemented with an intramuscular dose of 0.25 mg sulprostone (16-phenoxy-PGE2-sulfonylamide) on the last day of RU 486 treatment. The results confirmed that a reduction of treatment duration to 3 days is just as effective for inducing abortion (91% complete abortion) as a 4-6-day treatment regimen (95% complete abortion). Six patients had an incomplete abortion and in one the pregnancy continued unaffected. Side effects included intense uterine pain after the prostaglandin administration (16%), vomiting associated with the antiprogestin intake (9%) and after the prostaglandin administration (9%). One woman needed emergency curettage due to heavy bleeding. Six percent of the treated patients had a decrease in hemoglobin exceeding 20 g/l during the first week but no patient needed blood transfusion. No serious side effects were recorded.


Effect of synthetic prostaglandin E2 analog enprostil on omeprazole-induced hypergastrinemia and hyperpepsinogenemia.
This study was undertaken to determine whether the synthetic prostaglandin E2 analog enprostil is able to inhibit basal and postprandial hypergastrinemia induced by omeprazole. We also studied the effect of omeprazole, enprostil, and the combination of both drugs on serum pepsinogen A and C levels. Eight normal subjects received in random order five-day courses of 40 mg omeprazole once a day, 35 micrograms enprostil three times a day, the combination of both drugs, and placebo. Omeprazole induced significant increases in basal and postprandial serum gastrin and in pepsinogen A and C levels. These increments persisted on the day after stopping treatment. Coadministration of enprostil inhibited omeprazole-induced basal hypergastrinemia and postprandial integrated serum gastrin, but not basal serum pepsinogen A and C, while the inhibition on the day after the treatment courses only reached statistical significance for the postprandial integrated serum gastrin concentration. It is concluded that enprostil inhibits omeprazole-induced basal and postprandial hypergastrinemia, with a tendency to protracted inhibition after stopping the drugs, and that enprostil does not significantly influence omeprazole-induced increases in pepsinogen A and C level. Coadministration of enprostil may be helpful in preventing pronounced hypergastrinemia in the few patients who show large serum gastrin increases during treatment with omeprazole.


Developing a gender sensitive women's mental health service in Qatar: A rewarding challenge.
Investigations into gender differences in the epidemiology of common mental disorders have highlighted the fundamental role of socio-economic factors as the key determinants in experiencing mental ill health and access to treatment. Women are almost always at a socio-economic disadvantage across cultures throughout the world and as a result experience mental health inequality. This disparity in control over their socio-economic determinants is even more stark in the Middle Eastern and North African region. This region has additionally also cultural and legal conditions that make women empowerment and access to health difficult. Qatar launched an ambitious National Health Strategic program and identified women's mental health as a priority. This paper describes the development of a gender aware mental health service in Qatar, first of its kind in the region. It describes the challenges that exist in the region when attempting to develop such a service and some challenges that are unique to Qatar. This paper sets out a template of important principles that will be valuable for countries in the MENA region and beyond to develop evidence-based gender aware service that focuses on female empowerment and better mental health outcomes.


7T versus 3T MRI in the presurgical evaluation of patients with drug-resistant epilepsy.
MRI has a crucial role in presurgical evaluation of drug-resistant focal epilepsy patients. Whether and how much 7T MRI further improves presurgical diagnosis compared to standard of care 3T MRI remains to be established. We investigate the added value 7T MRI offers in surgical candidates with remaining clinical uncertainty after 3T MRI. 7T brain MRI was obtained on sequential patients with drug-resistant focal epilepsy undergoing presurgical evaluation at a comprehensive epilepsy center, including patients with and without suspected lesions on standard 3T MRI. Clinical information and 3T images informed the interpretation of 7T images. Detection of a new lesion on 7T or better characterization of a suspected lesion was considered to add value to the presurgical workup. Interpretable 7T MRI was acquired in 19 patients. 7T MRI identified a lesion relevant to the seizures in three of eight patients (38%) without a lesion on 3T MRI; no lesion in 7/11 patients (64%) with at least one suspected lesion on 3T MRI, contributing to the final classification of all seven as nonlesional; and confirmed and better characterized the lesion suspected at 3T MR in the remaining 4/11 patients. 7T MRI detected new lesions in over a third of 3T MRI nonlesional patients, confirmed and better characterized a 3T suspected lesion in one third of patients, and helped exclude a 3T suspected lesion in the remainder. Our initial experience suggests that 7T MRI adds value to surgical planning by improving detection and characterization of suspected brain lesions in drug-resistant focal epilepsy patients.


The outcomes of Ilizarov treatment in aseptic nonunions of the tibia stratified by treatment strategies and surgical techniques.
Nonunions of the tibia, particularly those located in the distal third of the bone, are relatively common in clinical practice. There is no gold standard for the treatment of nonunions of the tibia. The purpose of our study was to assess the results of treatment with the Ilizarov method in patients with aseptic nonunions of the tibia, depending on the employed treatment strategies and surgical techniques. A total of 75 patients with Ilizarov treatment of aseptic nonunions of the tibia were evaluated in the study. The patients's mean age at the beginning of treatment was 46 years. The mean follow-up period was 10 years and 11 months. The evaluated patients underwent either closed technique or open technique. The operators used one of two treatment strategies: neutral fixation without compression or continued compression. The following were assessed: rates of union, ASAMI bone scores, ASAMI functional scores, treatment time, complications, duration of hospital stay. Bone union was achieved in all of the 75 evaluated patients. The results of most analyses showed no significant differences in the assessed variables, except for the ASAMI functional scores, which were higher in the group of patients who underwent closed surgery (Me = 6.00 vs. Me = 4.00). We observed better ASAMI functional score outcomes in the patients who underwent closed fixation than in the open fixation group. The different surgical techniques and treatment strategies had no effect on the number of complications, rates of bone union, length of hospital stay, duration of Ilizarov treatment, or ASAMI bone scores. For managing nonunions of the tibia we recommend the technique of closed fixation without continued compression. The Ilizarov method in the treatment of nonunions of the tibia gives good outcomes.


The metabolic role of the gut microbiota in health and rheumatic disease: mechanisms and interventions.
The role of the gut microbiome in animal models of inflammatory and autoimmune disease is now well established. The human gut microbiome is currently being studied as a potential modulator of the immune response in rheumatic disorders. However, the vastness and complexity of this host-microorganism interaction is likely to go well beyond taxonomic, correlative observations. In fact, most advances in the field relate to the functional and metabolic capabilities of these microorganisms and their influence on mucosal immunity and systemic inflammation. An intricate relationship between the microbiome and the diet of the host is now fully recognized, with the microbiota having an important role in the degradation of polysaccharides into active metabolites. This Review summarizes the current knowledge on the metabolic role of the microbiota in health and rheumatic disease, including the advances in pharmacomicrobiomics and its potential use in diagnostics, therapeutics and personalized medicine.


On The Nature of FeIV =Oaq in Aqueous Media: A DFT analysis.
FeIV =Oaq is a key intermediate in many advanced oxidation processes and probably in biological systems. It is usually referred to as FeIV =O2+ . The pKa's of FeIV =Oaq as derived by DFT are: pKa1=2.37 M06 L/6-311++G(d,p) (SDD for Fe) and pKa2=7.79 M06 L/6-311++G(d,p) (SDD for Fe). This means that in neutral solutions, FeIV =Oaq is a mixture of (H2 O)4 (OH)FeIV =O+ and (H2 O)2 (OH)2 FeIV =O. The oxidation potential of FeIV =Oaq in an acidic solution, E0 {(H2 O)5 FeIV =O2+ /FeIII (H2 O)6 3+ , pH 0.0} is calculated with and without a second solvation sphere and the recommended value is between 2.86 V (B3LYP/Def2-TZVP, with a second solvation sphere) and 2.23 V (M06 L/Def2-TZVP without a second solvation sphere). This means that FeIV =Oaq is the strongest oxidizing agent formed in systems involving FeVI O4 2- even in neutral media.


The adhesive disc in the mobilid ciliate Trichodina pediculus: evidence for centrin-related, calcium-sensitive filaments.
The adhesive disc is a highly complex apparatus that allows mobilid ciliates to attach to the tissues of a variety of aquatic invertebrates and vertebrates. The disc comprises concentric rings of rigid skeletal pieces interconnected by filamentous material. This study explored the biochemical properties of the filamentous disc material in the trichodinid Trichodina pediculus. Calcium sensitivity of this material was suggested in vitro by the appearance of transverse cross-striation along bundles of filaments following calcium shock, and complete solubilization of the filamentous material in the presence of EGTA. A 23-kDa immunoanalog of centrins was immunoprecipitated from the EGTA extract. The protein binds calcium as indicated by (45) Ca(2+) blot overlay and Ca(2+) -induced shifts in electrophoretic mobility. Using Ca(2+) /EGTA buffers, we demonstrated a direct relationship between extraction of the filaments and solubilization of the protein. Immunofluorescence and immunoelectron microscopy confirmed that the protein localized to the filamentous disc material and revealed cross-reactivity with the spasmoneme, which is the prototype of ion-sensitive, centrin-like contractile systems in ciliates. The possibility that the filamentous disc material may be a novel example of Ca(2+) -sensitive, centrin-based systems found in ciliates is discussed.