Anticoagulant use in patients with chronic renal impairment.
Patients with renal failure have an increased risk of both thrombotic and bleeding complications. A number of antithrombotic drugs undergo renal clearance. Therefore, estimation of renal function is necessary when prescribing these drugs to patients with renal dysfunction. Pharmacokinetic and clinical data in patients with chronic renal impairment are limited for several anticoagulants, and adequate administration information is often absent. Dose adjustment of anticoagulants may be indicated when the creatinine clearance falls below 30 mL/min. Unfractionated heparin, argatroban, and vitamin K antagonists generally do not require dose adjustment with renal dysfunction. However, smaller doses of warfarin may be required to achieve a particular target international normalized ratio. Close monitoring of anticoagulation is recommended when argatroban or high doses of unfractionated heparin are administered in patients with severe chronic renal impairment. Low-molecular weight heparins, danaparoid sodium, hirudins, and bivalirudin all undergo renal clearance. Lower doses and closer anticoagulation monitoring may be advisable when these agents are used in patients with chronic renal failure. We recommend that fondaparinux sodium and ximelagatran (not yet licensed) be avoided in the presence of severe renal impairment and be used with caution in patients with moderate renal dysfunction. While acknowledging the lack of pharmacokinetic data, this review provides specific recommendations for the use of anticoagulants in patients with chronic renal impairment.


Entrainment of the respiratory rhythm by periodic lung inflation during vagal cooling.
The aim of this study was to determine whether pulmonary receptors other than slowly adapting stretch receptors are capable of entraining the respiratory rhythm when periodically stimulated during artificial ventilation. Experiments were performed on anaesthetised (urethane, 1.5 g/kg) and paralysed (pancuronium bromide, 0.1 mg/kg) rabbits. Vagi were cooled in order to block conduction in the myelinated fibres innervating slowly adapting receptors. The effectiveness of this cooling was assimilated to the absence of the Hering-Breuer inflation reflex and the presence of the deflation reflex. Our results indicate that under such conditions: (1) harmonic entrainment (one phrenic burst for one pump period) can be observed, (2) the range of harmonic entrainment is more limited when the vagi are cooled, and (3) during harmonic entrainment the inspiratory duration and phrenic activity are similar to what is observed at the same period with intact vagi, whereas vagal cooling modifies the phase difference between the phrenic burst and the pump. We have concluded that periodic input from rapidly adapting receptors and/or vagal C-fibres can entrain the respiratory rhythm as does input from slowly adapting receptors but with different patterns as evidenced by phase relationship.


Defective Fe3 O4- x Few-Atom Clusters Anchored on Nitrogen-Doped Carbon as Efficient Oxygen Reduction Electrocatalysts for High-Performance Zinc-Air Batteries.
It remains a challenge to develop cost-effective, high-performance oxygen electrocatalysts for rechargeable metal-air batteries. Herein, zinc-mediated zeolitic imidazolate frameworks are exploited as the template and nitrogen and carbon sources, onto which is deposited a Fe3 O4 layer by plasma-enhanced atomic layer deposition. Controlled pyrolysis at 1000 °C leads to the formation of high density of Fe3 O4- x few-atom clusters with abundant oxygen vacancies deposited on an N-doped graphitic carbon framework. The resulting nanocomposite (Fe3 O4- x /NC-1000) exhibits a markedly enhanced electrocatalytic performance toward oxygen reduction reaction in alkaline media, with a remarkable half-wave potential of +0.930 V versus reversible hydrogen electrode, long-term stability, and strong tolerance against methanol poisoning, in comparison to samples prepared at other temperatures and even commercial Pt/C. Notably, with Fe3 O4- x /NC-1000 as the cathode catalyst, a zinc-air battery delivers a high power density of 158 mW cm-2 and excellent durability at 5 mA cm-2 with stable 2000 charge-discharge cycles over 600 h. This is ascribed to the ready accessibility of the Fe3 O4- x catalytic active sites, and enhanced electrical conductivity, oxygen adsorption, and electron-transfer kinetics by surface oxygen vacancies. Further contributions may arise from the highly conductive and stable N-doped graphitic carbon frameworks.


My Experience as a Foot and Ankle Trauma Surgeon in Montreal, Canada: What's Not in the Books.
Foot and ankle fractures are sometimes seen as routine and easy to treat. However, many fractures vary from typical patterns and require more complex management. Obtaining good outcomes in these situations can be challenging. Often, the difference between average and good results has to do with preoperative planning and good surgical technique. This article outlines numerous techniques and tricks that are not always mentioned in classic textbooks. It focuses on ankle, talus, calcaneus, and midfoot fractures, and discusses numerous techniques and aids to avoid potential problems that may be encountered intraoperatively.


Changes in reward-related signals in the rat nucleus accumbens measured by in vivo oxygen amperometry are consistent with fMRI BOLD responses in man.
Real-time in vivo oxygen amperometry, a technique that allows measurement of regional brain tissue oxygen (O(2)) has been previously shown to bear relationship to the BOLD signal measured with functional magnetic resonance imaging (fMRI) protocols. In the present study, O(2) amperometry was applied to the study of reward processing in the rat nucleus accumbens to validate the technique with a behavioural process known to cause robust signals in human neuroimaging studies. After acquisition of a cued-lever pressing task a robust increase in O(2) tissue levels was observed in the nucleus accumbens specifically following a correct lever press to the rewarded cue. This O(2) signal was modulated by cue reversal but not lever reversal, by differences in reward magnitudes and by the motivational state of the animal consistent with previous reports of the role of the nucleus accumbens in both the anticipation and representation of reward value. Moreover, this modulation by reward value was related more to the expected incentive value rather than the hedonic value of reward, also consistent with previous reports of accumbens coding of "wanting" of reward. Altogether, these results show striking similarities to those obtained in human fMRI studies suggesting the use of oxygen amperometry as a valid surrogate for fMRI in animals performing cognitive tasks, and a powerful approach to bridge between different techniques of measurement of brain function.


Identification and in-vitro analysis of potential proteasome inhibitors targeting PSMβ5 for multiple myeloma.
The proteasome subunit β5 (PSMβ5) is a chief target of proteasome inhibitors (PIs) for treatment of multiple myeloma (MM). The relevance of PSMβ5 mutations and their functional impact on the development of resistance to PIs have been demonstrated recently. Therefore, this present study deals with an in-depth E-pharmacophore based screening and repurposing of FDA-approved drugs that could target PSMβ5 for MM. Our molecular docking-based investigation revealed risedronate and zoledronate as potential alternative therapeutic molecules for targeting the PSMβ5 gene. Risedronate and zoledronate displayed high binding affinity (-9.51 and -8.56 kcal/mol respectively) to PSMβ5. Moreover, 100 ns molecular dynamics simulation analysis of docking complexes revealed risedronate and zoledronate with a superior binding free energies and stable interactions with PSMβ5. The RMSD plot shows that the risedronate-PSMβ5 (mean: 0.24 nm) and zoledronate-PSMβ5 (mean: 0.25 nm) complexes are identical and stays stable until 100 ns. We further validated the activity of zoledronate in MM cell lines RPMI8226 and U266 where zoledronate showed significant anti-proliferative and apoptotic activity. Importantly, zoledronate showed an enhanced anti-proliferative activity when combined with bortezomib in MM cell lines. Thus, this study demonstrates that combining bortezomib with zoledronate could have a significant impact on reducing MM cell growth and can be an alternative strategy for treating MM.


Suppression of synaptic input of defense behavior command neurons by stimulation of neurons of the mesocerebrum in a preparation of the isolated CNS of the common snail.
The intestinal nerve was stimulated in combination and uncombined with extracellular stimulation of the mesocerebral region of the brain, as well as with stimulation of serotoninergic neurons, in experiments on a preparation of the isolated CNS of the common snail, with preservation of the nerve connections with the sexual system. Responses were recorded in command neurons of defense behavior. The data were obtained indicating that, in the case of combinations with extracellular stimulation of the mesocerebrum, an analog of a conditioned reaction of diminution of EPSP in the command neurons of defense behavior was developed. When stimulation of the same nerve was reinforced by stimulation of the serotoninergic neurons, sensitization appears, both in the case of combined and uncombined presentation of the stimuli.


Relationship between working stress and anxiety of medical workers in the COVID-19 situation: A moderated mediation model.
The COVID-19 pandemic has brought a lot of working stress to medical workers and has a certain impact on their mental health. Working stress is closely related to the increase in anxiety, but few studies have explored whether their relationship will be affected by positive psychological factors in the special situation. 798 medical workers were investigated online after the outbreak of the COVID-19 (10 February to 1 March 2020) in China. The relevant questionnaires were used to evaluate working stress, anxiety, sense of control, and psychological capital. The moderated mediation model test was performed using the SPSS software and PROCESS macro program. Working stress could directly affect anxiety, and indirectly affect anxiety through sense of control. In addition, psychological capital moderated the direct effect of working stress on anxiety, which is more effective at high level of psychological capital. Psychological capital also moderated the second half of the indirect effect of working stress on anxiety, at low level of psychological capital, sense of control was more effective in predicting anxiety. All the data in this study was collected through online questionnaire. The anxiety response measured in this study cannot be specific to the viral epidemic. Under the COVID-19 epidemic situation, for medical workers, low sense of control and low level of psychological capital may be important risk factors of anxiety caused by working stress. Thus, strengthening the sense of control and psychological capital of medical workers would be helpful to reduce their anxiety and maintain their mental health.


Regulation of the inducible chloramphenicol acetyltransferase gene of the Staphylococcus aureus plasmid pUB112.
Analyses of deletion mutants of the gene for chloramphenicol (Cm) acetyltransferase (CAT) carried by the staphylococcal plasmid pUB112 revealed a regulatory region, which is indispensable for Cm-inducible cat gene expression, located 70 bp in front of the CAT-coding sequence. This region consists of a possible ribosome binding site followed by an open reading frame coding for a peptide of nine amino acids and overlaps partially with an inverted repeat capable of forming a stem-loop structure. Deletion of the ribosome binding site and of parts of the open reading frame abolishes inducibility and results in a low-level cat gene expression, if the inverted repeat remains intact. Deletion of the 5' part of the possible stem leads to high-level constitutive CAT synthesis. The inverted repeat, therefore, exhibits negative control on cat gene expression whereas the preceding ribosome binding site is needed to enhance CAT synthesis in the presence of an inducer. These results suggest that translation of a leader peptide is a prerequisite for Cm-induced cat gene expression and that ribosome stalling on cat leader mRNA caused by Cm opens the stem-loop structure thereby releasing its negative effect on CAT synthesis.


Reactive Maillard intermediates leading to coloured products-5-hydroxymethyl- and 5-(1,2-dihydroxyethyl)-3(2H)-furanone.
In the course of the Maillard reaction, labile sugar degradation products are formed that are susceptible to secondary reactions and therefore have a decisive influence on the product spectrum. Such reactive intermediates may be transformed into stable derivatives with trapping reagents, and thus be protected from further reactions. Secondary processes may also be forestalled if the primary products are removed from the reaction mixture by high-vacuum distillation. By this procedure, 5-hydroxymethyl- and 5-(1,2-dihydroxyethyl)-3(2H)-furanone have been identified directly from Maillard reaction mixtures for the first time. The activated methylene group of these 3(2H)-furanones can easily enter into condensation reactions. The coloured condensation products in turn react with primary amines to pyrrolinone derivatives, which may also contribute to the colouring observed in non-enzymatic browning.


Analysis of the characteristics of major pollutants discharged from wastewater in China's provinces.
In recent years, the discharge of major pollutants in China's wastewater has been decreasing but remains at a high level. Controlling the discharge of pollutants in sewage is of great importance for protecting water quality and maintaining ecological balance. Based on data collected from 31 provinces in China from 2011 to 2020 (except 2018), this study analyzes the spatiotemporal variation emissions of the wastewater pollutants: chemical oxygen demand (COD), ammonia nitrogen (NH3-N), total nitrogen (TN), and total phosphorus (TP). The entropy method was used to evaluate the effectiveness of water pollution control in different provinces. Our results revealed that the total emission per gross domestic product (GDP) for COD, NH3-N, TN and TP in China decreased by 50.7%, 81.9%, 65.4% and 70.8%, respectively. In terms of regional annual emission differences, the Northwest region was the lowest compared with other regions, accounting for 4.87%-6.59% of the national pollutant emissions, and the Central China region was the highest, accounting for 22.4%-26.05% of the national pollutant emissions. The average value of pollutant emissions per unit of GDP decreased year-to-year overall, but Guangxi and Tibet showed a trend of first decreasing and then increasing. The correlation results indicated a significant correlation (0.977) between TN and TP emissions in wastewater in China during 2011-2020. Through clustering and Multidimensional Scaling model (MDS) analysis, Beijing and Shanghai have been performing well in controlling water pollution discharge, while the provinces of Tibet and Guangxi must still increase their efforts in water pollution control. Furthermore, these results demonstrate the experience and achievements of the Chinese government in the treatment of wastewater pollution and provide a useful reference for treatment of wastewater pollution in the world.


Transitional cell carcinoma of fossa navicularis. Fourth reported case.
The fourth reported case of transitional cell carcinoma arising in the fossa navicularis is described. Failure of carbon dioxide laser treatment to eradicate an apparent condyloma of the urethra is an indication for biopsy.


One-year outcomes of percutaneous coronary intervention with the 38-mm Resolute zotarolimus-eluting stent.
This study was designed to prospectively evaluate the safety and efficacy of the 38-mm Resolute zotarolimus-eluting stent (R-ZES). Drug-eluting stents with long lengths are needed to ensure coverage of long lesions in some patients. Patients recruited from the RESOLUTE US and RESOLUTE Asia studies were implanted with at least one 38-mm R-ZES. Up to 2 lesions (in separate vessels) could be implanted with length ≤35 mm and a reference vessel diameter of 3.0 to 4.2 mm. The primary end point was 1-year target lesion failure, defined as cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. The 1-year target lesion failure rate using 1 vessel per patient was compared with a performance goal (19%) derived from historical data. There were 223 patients enrolled (n = 269 lesions). The mean age was 60.9 ± 10.9 years, 79% were men, and 38% had diabetes. Target lesion failure rate using a single-vessel analysis was 4.5%, and the upper limit of the 1-sided 95% confidence interval (7.5%) was less than the performance goal of 19%. A secondary analysis using all lesions resulted in a target lesion failure rate of 5.4% (upper limit of 1-sided 95% confidence interval, 8.6%). Baseline characteristics and clinical outcomes were similar between patients with and without diabetes. The rate of probable or definite stent thrombosis was 0.9%. In conclusion, the 38-mm length of the R-ZES was found to be safe and effective with a low rate of target lesion failure and stent thrombosis and no differences in outcomes between patients with and without diabetes.


Using data to motivate action: the need for high quality, an effective presentation, and an action context for decision-making.
Three common barriers to the effective use of data to inform decisions and motivate action for the planning of cancer control are (1) failure to recognize the availability of high-quality data, (2) not presenting the data in a compelling format, and (3) failing to place the data in a historical and action context. Overcoming these barriers will go a long way toward demonstrating that high-quality data can be used to accomplish the desired outcomes in a Comprehensive Cancer Control (CCC) program. The article identifies existing sources of high-quality data, provides examples of effective presentation, and discusses successes in using data for program planning and implementation. The paper is not meant to provide a comprehensive discussion of using data for decision making, instead providing options to help key CCC stakeholders improve the effectiveness of their decisions as CCC plans are developed and implemented.


[Periodontal-orthodontic treatment possibilities for migrated front teeth. Possibilities and limits of orthodontic therapy].
An interdisciplinary approach for the rehabilitation of patients with pathologic tooth movement caused by advanced periodontal disease is presented. The special demands to the orthodontic therapy are illustrated by a case report. The necessity for precise treatment planning and for the use of controlled treatment is demonstrated.


Poor right ventricular function is associated with impaired exercise capacity and ventilatory efficiency in transthyretin cardiac amyloid patients.
CardioPulmonary Exercise Test (CPET) is the gold standard to evaluate functional capacity in patients at high risk of heart failure (HF). Few studies with a limited number of subjects and conflicting results, analyzed the role of CPET in patients with systemic amyloidosis. Aims of our study were the assessment of the response to exercise in patients with Transthyretin amyloid (ATTR) cardiomyopathy (CA), and the correlation of clinical, biohumoral and echocardiographic parameters with CPET parameters, such as VO2 peak and VE/VCO2 slope. From February 2018 to March 2019, 72 cardiac ATTR patients were prospectively enrolled and underwent a complete clinical, biohumoral, echocardiographic and CPET assessment. All patients completed the exercise stress test protocol, without any adverse event. At CPET, they achieved a mean VO2 peak of 14 mL/Kg/min and a mean VE/VCO2 slope of 31. The blood pressure response to exercise was inadequate in 26 (36%) patients (flat in 25 and hypotensive in 1), while 49/72 patients (69%) showed an inadequate heart rate recovery. In multivariate analysis, s' tricuspidalic was the only independent predictor of VO2 peak, while in the two test models performed to avoid collinearity, both TAPSE and s' tricuspidalic were the strongest independent predictors of VE/VCO2 slope. Our data demonstrate the role of right ventricular function as an independent predictor of exercise capacity and ventilatory efficiency in ATTR. In CPET evaluation, a significant proportion of patients presented an abnormal arterial pressure response and heart rate variation to exercise.


Pathogenesis of Hemophagocytic Lymphohistiocytosis.
Hemophagocytic Lymphohistiocytosis (HLH), an inherited life-threatening inflammatory disorder, has gained growing recognition not only in children but also increasingly in adults over the past 2 decades. HLH involves inborn defects in lymphocytes, which normally mediate control of infectious and inflammatory conditions within the immune system and in other tissues. In the context of inherited defects in cytotoxic cells and other immune cells, the disorder is classified as familial or primary HLH. Secondary HLH occurs in the settings of infections or underlying rheumatologic disorders. Secondary HLH also accompanies some lymphoid malignancies.


Intra-partum fever and cerebral palsy in Khartoum, Sudan.
Cerebral palsy (CP) is a major cause of childhood disability. There are various maternal and neonatal predictors associated with the development of CP, and they are variable across different populations. This case-control study was designed to investigate maternal and neonatal predictors of CP at Khartoum pediatric neurology clinics. Data (maternal sociodemographic characteristics and neonatal expected predictors) were collected from mothers of children with CP and healthy controls using questionnaires. One hundred and eleven cases of CP and 222 controls were included. Spastic CP was the most common type (69.4%). In logistic regression, maternal age, parity, birth weight, and sex were not associated with CP. However, maternal fever (OR = 8.4, CI = 2.3-30.5; P = 0.001), previous neonatal death (OR = 5.4, CI = 1.8-16.2; P = 0.003), and poor sucking (OR = 30.5, CI = 10.0-93.1; P < 0.001) were predictors of CP. Fever during labor is a significant risk factor for developing CP in children. Further efforts are required for labor management to prevent CP in this setting.


The role of radiation therapy in stages A2 and B adenocarcinoma of the prostate.
Between 1965 and 1982 definitive external beam radiation therapy was given to 114 patients with clinically Staged A2 (32 patients) and B (82 patients) adenocarcinoma of the prostate. These patients were not considered to be surgical candidates because of age, comorbidity or disease extent, or because they had refused surgery. Total prostatic doses ranged from 60 to 70 Gy. For 90 surviving patients, follow-up duration ranged from 32 to 188 months with a median of 5 years. The 5- and 10-year uncorrected survival rates for all patients, which were 89% and 68% respectively, were no different from the survival expectation of age-matched men in the general population. Disease-free survival rates at the same time periods were 89% and 86%. There were no significant differences in disease-free survival between Stage A2 and Stage B. Four patients (3.5%) developed local recurrence. Bone metastases, which occurred in 9 of 11 treatment failures were the predominant cause of failure. An analysis of 11 potential prognostic factors was fruitless. Pelvic node irradiation did not improve the outcome. The incidence of complications was acceptable. Anorectal problems developed in 20% of patients and urinary manifestations occurred in 20%, and only 2 patients (1.8%) developed serious problems. We concluded that localized external beam high-energy radiation therapy provides excellent local control for disease limited to the prostate, with survival rates that rival those of radical surgery.


Mechanical hyperalgesia in complex regional pain syndrome: a role for TNF-alpha?
Plasma concentrations of soluble tumor necrosis factor alpha (TNF-alpha) receptor type I (sTNF-RI) were assessed in two complex regional pain syndrome (CRPS) patient groups (n = 30 and n = 16) and healthy controls (n = 25). Patients with CRPS and mechanical hyperalgesia had higher levels of sTNF-RI (1,661.8 +/- 146.8 pg/mL) compared with those with CRPS with identical clinical appearance but without hyperalgesia (1,155.9 +/- 56.3 pg/mL) and controls (1,239.5 +/- 42.9 pg/mL). This study suggests involvement of TNF-alpha in mechanical hyperalgesia of CRPS.


Focused Ultrasound Thalamotomy for Tremor in Parkinson's Disease: Outcomes in a Large, Prospective Cohort.
Magnetic resonance guided focused ultrasound (MRgFUS) is United States Food and Drug Administration approved for the treatment of tremor-dominant Parkinson's disease (TdPD), but only limited studies have been described in practice. To report the largest prospective experience of unilateral MRgFUS thalamotomy for the treatment of medically refractory TdPD. Clinical outcomes of 48 patients with medically refractory TdPD who underwent MRgFUS thalamotomy were evaluated. Tremor outcomes were assessed using the Fahn-Tolosa-Marin scale and adverse effects were categorized using a structured questionnaire and clinical exam at 1 month (n = 44), 3 months (n = 34), 1 year (n = 22), 2 years (n = 5), and 3 years (n = 2). Patients underwent magnetic resonance imaging <24 hours post-procedure. Significant tremor control persisted at all follow-ups (P < 0.001). All side effects were mild. At 3 months, these included gait imbalance (38.24%), sensory deficits (26.47%), motor weakness (17.65%), dysgeusia (5.88%), and dysarthria (5.88%), with some persisting at 1 year. MRgFUS thalamotomy is an effective treatment for sustained tremor control in patients with TdPD. © 2023 International Parkinson and Movement Disorder Society.


Step-down vs. step-up noxious stimulation: differential effects on pain perception and patterns of brain activation.
We hypothesize that pain and brain responses are affected by changes in the presentation sequence of noxious stimuli that are, overall, identical in intensity and duration. During functional magnetic resonance imaging (fMRI) scanning, 21 participants experienced three patterns of noxious stimulation: Up-type (step-up noxious stimulation, 15 s), Down-type (step-down noxious stimulation, 15 s), and Down-up-type (decreasing and increasing pattern of noxious stimulation, 15 s). The total intensity and duration of the three noxious stimulation patterns were identical, but the stimulation sequences were different. Pain and unpleasantness ratings in the Down- and Down-up-type noxious stimulations were lower than in the Up-type noxious stimulation. The left prefrontal cortex [(PFC, BA (Brodmann area) 10, (-45, 50, 1)] was more highly activated in the Down- and Down-up-type noxious stimulations than in the Up-type noxious stimulation. The S1, S2, insula, bilateral PFC (BA 46), and midcingulate cortex were more highly activated in the Up-type noxious stimulation than in the Down-type noxious stimulation. PFC BA 10 was located at an inferior level compared to the bilateral PFC BA 46 (Z axis = 1 for BA 10, compared to 22 and 25 for the right and left BA 46, respectively). When cortisol level was increased, the left hippocampal cortex, along with the left parahippocampal cortex, was greatly activated for the Up-type noxious stimulation. When pain cannot be avoided in clinical practice, noxious stimuli should be applied to patients in a step-down pattern that delivers the most intense pain first and the least intense pain last.


[Sessile tubulo-villous polyps in the rectum: problems of diagnosis and treatment. Personal experience].
A retrospective analysis was performed on 22 patients (mean age 65) in whom preoperative rectosigmoidoscopy had diagnosed tubulovillous rectal polyp. In 12 cases the polyps were removed transanally and the remaining 10 were subjected to laparotomy. The incidence of error in the preoperative histological diagnosis was 18.2% (9% for the nature and 10% for degree of dysplasia of the polyp). There were 25% recurrences after transanal exeresis, 10% after laparotomy. Total survival at 42 months was 86.3%. The study confirms the validity of transanal exeresis of tubulovillous polyps of the rectum assuming careful preoperative patient selection.


Separation and identification of the DL-forms of short-chain peptides using a new chiral resolution labeling reagent.
There are several reports of D-amino acids being the causative molecules of serious diseases, resulting in the formation of, for example, prion protein and amyloid β. D-Amino acids in peptides and proteins are typically identified by sequencing each residue by Edman degradation or by hydrolysis with hydrochloric acid for amino acid analysis. However, these approaches can result in racemization of the L-form to the D-form by hydrolysis and long pre-treatment for hydrolysis. To address these problems, we aimed to identify the DL-forms of amino acids in peptides without hydrolysis. Here, we showed that the DL-forms in peptides which are difficult to separate on a chiral column can be precisely separated by labeling with 1-fluoro-2,4-dinitrophenyl-5-D-leucine-N,N-dimethylethylenediamine-amide (D-FDLDA). Additionally, the peptides could be quantitatively analyzed using the same labeling method as for amino acids. Furthermore, the detection sensitivity of a sample labeled with D-FDLDA was higher than that of the conventional reagents Nα-(5-fluoro-2,4-dinitrophenyl)-L-alaninamide (L-FDAA) and Nα-(5-fluoro-2,4-dinitrophenyl)-L-leucinamide (L-FDLA) used in Marfey's method. The proposed method for identifying DL-forms of amino acids in peptides is a powerful tool for use in organic chemistry, biochemistry, and medical science.


Spatiotemporal trends in PM2.5 levels from 2013 to 2017 and regional demarcations for joint prevention and control of atmospheric pollution in China.
The promulgation and implementation of the Air Pollution Prevention and Control Action Plan (APPCAP) have greatly accelerated air quality improvements in China. In this study, these improvements were assessed and analyzed using arithmetic mean and percentile methods. Air quality status and trends were illustrated meticulously. Air pollution risks remaining since the implementation of the APPCAP were also identified. In addition, a complex network correlation model was created and used to demarcate highly inter-correlated regions within China, which were identified using long-term PM2.5 concentration data. The results indicate that the annual mean PM2.5 concentration decreased by more than 30% throughout the country since the implementation of the APPCAP. However, more than 1 billion people were still exposed to polluted air containing PM2.5 concentrations exceeding the WHO Interim Target-1 (WHO IT-1). Cities with populations of more than 10 million were generally among the most polluted regions in China, while PM2.5 concentrations in locations with populations of less than 1 million met WHO IT-1 standards. Moreover, PM2.5 network correlation analysis defined 7 key Joint Prevention and Control of Atmospheric Pollution (JPCAP) regions with strong synchronicity in PM2.5 mass concentrations; these results suggest that JPCAP could be implemented separately with in each of these demarcated regions. The atmospheric pollution control concepts and methods proposed herein are also broadly applicable for the implementation of JPCAP policies in other regions worldwide.


Effect of carbon nanotubes on properties of soft materials based on carbon nanotubes-ionic liquid combinations.
Soft materials resulting from the combination of carbon nanotubes with ionic liquids have aroused analytical interest; thank to their peculiar characteristics. This paper compares the sorption capacity of eight different soft materials obtained from the combination of 1-hexyl 3-methylimidazolium hexafluorophosphate (ionic liquid) with different types of carbon nanotubes. The main characteristics of carbon nanotubes were established by Raman spectroscopy. The results obtained pointed out the critical role of the carbon nanotube types on the stability as well as the sorption capacity of the soft material. By using the adequate carbon nanotube it is possible to improve the LOD 4 times when they are used as sorbent materials for SPE. Working in the recommended conditions the LOD for the analysis of 5 mL of water sample was 5 μg/L of fluoranthene and the precision 5.9%.


Toward a Molecular Definition of Leucine-Dependent mTORC1 Activation.
The mechanistic target of rapamycin complex 1 (mTORC1) coordinates nutrient availability with cell growth. Recent reports by Sabatini and coworkers (Saxton et al., 2016; Wolfson et al., 2016) characterize a cytoplasmic amino acid receptor that couples the binding of leucine to the activation of mTORC1.


Incidentally detected cystic lesions of the pancreas on CT: review of literature and management suggestions.
To facilitate a better understanding of incidentally noted cystic pancreatic lesions, since these lesions often pose a challenge regarding appropriate management. This article reviews pathophysiology, prevalence, significance, and recommendations for management of the various pancreatic cystic lesions. Illustrative cases are demonstrated. Diagnostic benign lesions can be left alone. Cross-sectional imaging can be used to follow-up benign appearing lesions and to stage more aggressive ones. Endoscopic ultrasound with fine needle aspiration and cyst fluid analysis can be performed on certain indeterminate lesions. Lesions with high malignant potential should undergo resection. A better understanding of the variety of incidentally detected pancreatic cystic lesions can help direct appropriate management.


Molecular structure and biological and pharmacological properties of 3-hydroxy-2-methyl-1-(beta-D-ribofuranosyl or pyranosyl)-4-pyridinone: potential iron overload drugs for oral administration.
Replacing alkyl groups by sugar moieties at N-1 position of 3-hydroxy-2-methyl-4-pyridinone did not affect the geometry of the iron chelating sites but increased the hydrophilic nature. The formation of a polymer cluster through the intermolecular hydrogen bonds was also revealed by X-ray crystal structure analysis for the first time in all known 3-hydroxy-4-pyridinone crystal structures. Iron removal from ferritin by the title compounds was more efficient than with DFO.


Selective reduction of the posterior superior vermis in men with chronic schizophrenia.
Cerebellar structures were measured in 30 chronic schizophrenic men and 18 healthy men using high resolution MRI. The volume of the posterior superior vermis was found to be significantly smaller in the schizophrenic men, but there was no difference in other cerebellar regions or the intracranial volume. The findings support the view that within the cerebellum the posterior superior vermis may be selectively reduced in men with chronic schizophrenia.


Measurement and Analysis of Thermal Conductivity of Ti₃C₂Tx MXene Films.
A new class of 2D materials named "MXene" has recently received significant research interest as they have demonstrated great potential for the applications in batteries, supercapacitors, and electronic devices. However, the research on their thermal properties is still very limited. In this work, Ti₃C₂Tx films were prepared by the vacuum-assisted filtration of delaminated nano-flake Ti₃C₂Tx MXenes. The thermal and electrical conductivity of the Ti₃C₂Tx films were measured by the state-of-the-art T-type method. The results showed that the effective thermal conductivity of the films increased from 1.26 W·m-1·K-1 at 80 K to 2.84 W·m-1·K-1 at 290 K, while the electrical conductivity remained at 12,800 Ω-1·m-1 for the same temperature range. Thermal resistance model was applied to evaluate the inherent thermal conductivity of the Ti₃C₂Tx flakes, which was estimated to be in the range of tens to hundreds W·m-1·K-1.


Expression of a pemphigoid gestationis-related antigen by human placenta.
We studied the antigen binding of sera from 25 patients with pemphigoid gestationis (PG) using skin and amnion as substrates in an indirect immunofluorescence technique. In addition, skin was studied after prior incubation with I M NaCl which allows BMZ cleavage through the lamina lucida. Linear BMZ staining was obtained with sera from patients with PG using human amnion as substrate. This was seen with both full-term and second trimester placentae, but not with first trimester placentae. In NaCl incubated skin all sera bound to the epidermal aspect of the separated tissue. The pattern of staining in skin, chemically split skin and amnion was identical to that previously seen with the sera of patients with bullous pemphigoid suggesting that the antigen against which circulating anti-BMZ antigens are directed may be the same in the two conditions.


Hinged and Wide: A New P^P Ligand for Emissive [Cu(P^P)(N^N)][PF6] Complexes.
Heteroleptic [Cu(BIPHEP)(N^N)][PF6] complexes (BIPHEP = 1,1'-biphenyl-2,2'-diylbis(diphenylphosphane)), in which N^N is 2,2'-bipyridine (bpy), 6-methyl-2,2'-bipyridine (6-Mebpy), 6-ethyl-2,2'-bipyridine (6-Etbpy), or 5,5'-dimethyl-2,2'-bipyridine (5,5'-Me2bpy), have been synthesized and characterized using multinuclear NMR spectroscopies and electrospray ionization mass spectrometry. The single crystal structures of [Cu(BIPHEP)(bpy)][PF6]∙CH2Cl2, [Cu(BIPHEP)(5,5'-Me2bpy)][PF6]∙CH2Cl2, [Cu(BIPHEP)(6-Mebpy)][PF6]∙Et2O∙0.5H2O and [Cu(BIPHEP)(6-Etbpy)][PF6] confirm distorted tetrahedral {Cu(P^P)(N^N)} coordination environments. Each compound shows a quasi-reversible Cu+/Cu2+ process. In deaerated solution, the compounds are weak emitters. Powdered samples are yellow emitters (λemmax in the range 558-583 nm) and [Cu(BIPHEP)(5,5'-Me2bpy)][PF6] exhibits the highest photoluminescence quantum yield (PLQY = 14%). On cooling to 77 K (frozen 2-methyloxolane), the emission maxima are red-shifted and the excited state lifetimes increase from τ1/2 < 8 μs, to τ1/2 values of up to 53 μs, consistent with the compounds with N^N = 6-Mebpy, 6-Etbpy and 5,5'-Me2bpy exhibiting thermally activated delayed fluorescence (TADF).


Impaired vascular nitric oxide bioactivity in women with previous gestational diabetes.
Dysfunction of the vascular endothelium, preceding vascular morbidity and type 2 diabetes, is present in women with previous gestational diabetes (GDM). However, it is unknown whether excess weight, insulin resistance, and asymmetric dimethylarginine (ADMA)--an endogenous nitric oxide (NO) synthase inhibitor--also contribute to the vascular changes observed in these patients. The aim of this study was therefore to identify factors other than GDM that impair vascular function. Seven overweight and five non-overweight women with previous GDM were included in this study. Vascular function was assessed from forearm blood-flow responses to the endothelium-dependent vasodilator acetylcholine (ACh), the endothelium-independent vasodilator glyceryltrinitrate, the vasoconstrictor norepinephrine and the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). ADMA was measured in venous blood, and insulin resistance was estimated from a modified intravenous glucose tolerance test. Twenty healthy male volunteers served as a historical control group. Vasodilation of forearm resistance vessels in response to ACh was impaired in overweight women when compared with non-overweight women (P < 0.05); similarly, vasoconstrictor reactivity tended to be smaller in the overweight group. In addition, there was a significant relationship between vascular responsiveness to ACh and L-NMMA, body-mass index, serum ADMA concentrations and stimulated glucose levels (all P < 0.05). ACh responses and ADMA levels in non-overweight women were similar to those of healthy controls. Factors such as obesity, increased ADMA levels and insulin resistance appear to be strong contributors to endothelial dysfunction observed in women with GDM.


Percutaneous radiofrequency ablation for treatment of giant cell tumor of bone guided by real-time US fused with CT.
Radiofrequency ablation (RFA) is a well-established technique for the treatment of soft tissue tumors of the liver and kidney that has increasingly been used for both benign and malignant bone tumors, such as giant cell tumor of bone (GCT). Reports in the literature pertaining to RFA for GCT have involved computed tomography (CT)-guided RFA, which presents several drawbacks such as radiation, lack of real-time monitoring, and the fact that it may be time-consuming. We report a case of GCT treated with percutaneous RFA using ultrasound guidance with CT fusion, which offers a simple, real-time guidance solution without radiation.


Isolation and partial purification of ceruloplasmin messenger RNA from rat liver.
Partially purified ceruloplasmin mRNA was isolated using indirect immunoprecipitation of rat liver polysomes and poly(U)-Sepharose chromatography of polysomal RNA. This RNA programmed the synthesis of ceruloplasmin polypeptides in a cell-free system from mitochondria. Immunochemical analysis of the translation products revealed a 40-fold enrichment of the ceruloplasmin mRNA activity. The purified ceruloplasmin mRNA migrated as a major homogeneous component with an apparent molecular weight about 1 X 10(6) daltons in polyacrylamide gels containing sodium dodecyl sulfate. The immunoprecipitated products of the cell-free translation had molecular weights in the range 4.5--5.4 X 10(4) daltons as estimated by gel-electrophoresis under denaturating conditions. These values approach the weight of the half-molecule of native ceruloplasmin.


The modification of meteorological factors on the relationship between air pollution and periodontal diseases: an exploration based on different interaction strategies.
We aimed to characterize the association between air pollutants exposure and periodontal diseases outpatient visits and to explore the interactions between ambient air pollutants and meteorological factors. The outpatient visits data of several large stomatological and general hospitals in Hefei during 2015-2020 were collected to explore the relationship between daily air pollutants exposure and periodontal diseases by combining Poisson's generalized linear model (GLMs) and distributed lag nonlinear model (DLNMs). Subgroup analysis was performed to identify the vulnerability of different populations to air pollutants exposure. The interaction between air pollutants and meteorological factors was verified in both multiplicative and additive interaction models. An interquartile range (IQR) increased in nitrogen dioxide (NO2) concentration was associated with the greatest lag-specific relative risk (RR) of gingivitis at lag 3 days (RR = 1.087, 95% CI 1.008-1.173). Fine particulate matter (PM2.5) exposure also increased the risk of periodontitis at the day of exposure (RR = 1.049, 95% CI 1.004-1.096). Elderly patients with gingivitis and periodontitis were both vulnerable to PM2.5 exposure. The interaction analyses showed that exposure to high levels of NO2 at low temperatures was related to an increased risk of gingivitis, while exposure to high levels of NO2 and PM2.5 may also increase the risk of gingivitis and periodontitis in the high-humidity environment, respectively. This study supported that NO2 and PM2.5 exposure increased the risk of gingivitis and periodontitis outpatient visits, respectively. Besides, the adverse effects of air pollutants exposure on periodontal diseases may vary depending on ambient temperature and humidity.


B cell targeted therapies in autoimmune disease.
FDA-approved B cell-targeted therapy has expanded to a multitude of autoimmune diseases ranging from organ specific diseases, like pemphigus and multiple sclerosis, to systemic diseases such as ANCA-associated vasculitis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In this review, we discuss the variability in response to B cell-targeted therapies with a focus on the diversity of human B cells and plasma cells, and will discuss several of the promising new B cell-targeted therapies. The pathogenic roles for B cells include autoantibody-dependent and autoantibody-independent functions whose importance may vary across diseases or even in subsets of patients with the same disease. Recent data have further demonstrated the diversity of human B cell subsets that contribute to disease as well as novel pathways of B cell activation in autoimmune disease. The importance of eliminating autoreactive B cells and plasma cells will be discussed, as well as new approaches to do so. The past several years has witnessed significant advances in our knowledge of human B cell subsets and function. This has created a nuanced picture of the diverse ways B cells contribute to autoimmunity and an ever-expanding armamentarium of B cell-targeted therapies.


Patient safety considerations in the rehabilitation of the individual with cognitive impairment.
Deficits in cognitive functioning are associated with many safety concerns, including difficulties performing activities of daily living, medication errors, motor vehicle accidents, impaired awareness of deficits, decision-making capacity, falls, and travel away from home. Preventing adverse safety outcomes is particularly relevant in rehabilitation patients. Integration of information and recommendations stemming from allied disciplines, such as rehabilitation medicine, physical therapy, occupational therapy, speech therapy, and neuropsychology, is the most effective way to limit poor outcomes. Education and prevention counseling by health care professionals is an important approach in limiting adverse safety outcomes in patients with cognitive impairment.


Sponge-based microfluidic sampling for potentiometric ion sensing.
This work demonstrates an application of the new materials, sponges, for the use in microfluidic solution sampling integrated with ion-selective electrodes. The microfluidic sponge-based sampling was developed and studied as novel sampling and sample handling method to serve as alternative for microfluidic paper- and textile-based sampling for ion analysis in various environmental (Cd2+, Pb2+ and pH) and clinically (K+, Na+, Cl-) relevant samples. Three types of polyurethane, cellulose and natural sponges were used as substrates for microfluidic solution sampling. Polyurethane based sponge was found to have low heavy metal sorption capacity thus it was recognized as suitable for microfluidic sampling coupled with solid-state as well as solid-contact ion-selective electrodes. The application of sponge-based microfluidic sampling, contrary to previous findings of paper- and textile-based microfluidic sampling, allowed measurements of heavy metals without prior modification of the sampling substrate. Finally, the determination of potassium, sodium and chloride in wastewater sludge and sweat samples done with sponge-based microfluidic sampling integrated with ISEs was found similar to analysis done by ICP-OES and IC.


Brain oxidative metabolism of the newborn dog: correlation between 31P NMR spectroscopy and pyridine nucleotide redox state.
The effects of both anoxia and short- and long-term hypoxia on brain oxidative metabolism were studied in newborn dogs. Oxidative metabolism was evaluated by two independent measures: in vivo continuous monitoring of mitochondrial NADH redox state and energy stores as calculated from the phosphocreatine (PCr)/Pi levels measured by 31P nuclear magnetic resonance (NMR) spectroscopy. The hemodynamic response to low oxygen supply was further evaluated by measuring the changes in the reflected light intensity at 366 nm (the excitation wavelength for NADH). The animal underwent surgery and was prepared for monitoring of the two signals (NADH and PCr/Pi). It was then placed inside a Phosphoenergetics 260-80 NMR spectrometer magnet with a 31-cm bore. Each animal (1-21 days old) was exposed to short-term anoxia or hypoxia as well as to long-term hypoxia (1-2 h). The results can be summarized as follow: (a) In the normoxic brain, the ratio between PCr and Pi was greater than 1 (1.2-1.4), while under hypoxia or asphyxia a significant decrease that was correlated to the FiO2 levels was recorded. (b) A clear correlation was found between the decrease in PCr/Pi values and the increased NADH redox state developed under decreased O2 supply to the brain. (c) Exposing the animal to moderately long-term hypoxia led to a stabilized low-energy state of the brain with a good recovery after rebreathing normal air. (d) Under long-term and severe hypoxia, the microcirculatory autoregulatory mechanism was damaged and massive vasoconstriction was optically recorded simultaneously with a significant decrease in PCr/Pi values.(ABSTRACT TRUNCATED AT 250 WORDS)


Development and validation of a contouring guideline for the taste bud bearing tongue mucosa.
To introduce a contouring guideline for the taste bud bearing tongue mucosa for head and neck cancer patients receiving radiotherapy. CT simulation images of oropharyngeal cancer patients were used to delineate both the whole tongue (extrinsic/intrinsic tongue muscles, floor of mouth) and the taste bud bearing tongue mucosa (method A: adaptation of the whole tongue structure; method B: axial adaptation of a mid-sagittal contour). Volumetric and dosimetric parameters of the whole tongue and the two methods of mucosal delineation, spatial overlap between methods A and B, and inter-observer variability for method B were calculated. The study cohort was comprised of 70 patients with T1-4 N0-1 tonsillar (83%) and base of tongue (17%) cancers. Most of the comparative parameters between the whole tongue and mucosa (method A) significantly differed (mean, minimum, and maximum dose, V5-V70, D40-D90). The mean dose calculated for the whole tongue deviated on average 3.77 Gy compared to method A. No significant differences were found between methods A and B of the taste bud bearing tongue mucosa structure, and none of the dosimetric parameters differed more than 1.03 Gy on average. The mean Dice similarity coefficient for both mucosal structures was 0.79 ± 0.05, and 0.63 ± 0.12 for the inter-observer analysis of method B. We defined two methods for delineating the taste bud bearing mucosa and both are equally satisfactory procedures. Either method is preferable over delineation of the whole tongue as organ at risk for taste impairment.


Contemporary Perioperative Management of Direct Oral Anticoagulants.
Direct oral anticoagulants (DOACs) have rapidly emerged as popular alternatives to warfarin in the setting of nonvalvular atrial fibrillation, prevention and treatment of venous thromboembolism, and secondary prevention of arterial thrombosis. It is now estimated that more patients in the United States take DOACs than warfarin for approved indications. Studies to date have shown that these drugs are similarly efficacious with perhaps a lower bleeding risk than warfarin. The purpose of this review is to provide insight into the currently available DOACs and discuss the management and reversal strategies for patients in the perioperative period.


Isospora elmahalensis n. sp. (Apicomplexa, Eimeriidae), a parasite of the white-cheeked bulbul (Pycnonotus leucogenys) in Saudi Arabia.
Isospora elmahalensis n. sp. is described from the Saudi Arabian bird, Pycnonotus leucogenys, from the Elmahala valley. Sporulated oocysts of I. elmahalensis were spherical or nearly subspherical, 19.5-22.5 X 18.5-20 (21.34 +/- 0.4 X 19.06 +/- 0.5) microns. Oocysts lacked a micropyle, residuum, and polar granule. Sporocysts were ovoid, 14-17.5 X 7-12 (16.08 +/- 1.05 X 9.9 +/- 1.55) microns, and had a Stieda body and sporocyst residuum, but lacked a substiedal body. Sporozoites were elongated with a clear globule at one end. The host bird belongs to the order Passeriformes.


General Olefin Synthesis by the Palladium-Catalyzed Heck Reaction of Amides: Sterically Controlled Chemoselective N-C Activation.
Metal-catalyzed reactions of amides proceeding via metal insertion into the N-CO bond are severely underdeveloped due to resonance stabilization of the amide bond. Herein we report the first Heck reaction of amides proceeding via highly chemoselective N-CO cleavage catalyzed by Pd(0) utilizing amide bond ground-state destabilization. Conceptually, this transformation provides access to a myriad of metal-catalyzed transformations of amides via metal insertion/decarbonylation.


Effects on blood pressure of a decrease in sodium use in institutional food preparation: the Exeter-Andover Project.
To judge the effect on blood pressure, sodium intake of students at two boarding high schools was reduced by 15-20% through changes in food purchasing and in preparation practices in the schools' kitchens. Students were not asked to change their usual eating habits. Each school served alternately as the control or intervention school for one school year. Blood pressure was monitored among 341 subjects during control years and 309 subjects during intervention years. Analysis of blood pressure differences between early in the school year and near the end of the school year, with adjustment for sex and initial blood pressure, showed the effect of the dietary intervention to be -1.7 mmHg for systolic (95% CI = -0.6, -2.9, p = 0.003) and -1.5 mmHg for diastolic pressure (95% CI = -0.6, -2.5, p = 0.002). Such modest and easily attainable changes in sodium intake, if maintained, could have a significant effect on the future risk of essential hypertension among young people.


'Thou shalt not throw away a living thing': A single-centre 10-year experience using the spare parts principle for complex sarcoma reconstruction.
For aggressive limb sarcomas beyond reconstructive reach, an amputation may be the only alternative to achieve a complete tumour resection. However, very proximal amputations result in greater loss of function and quality-of-life impact. The spare parts principle advocates utilising tissues distal to the amputation site, for reconstructing complex defects and preserving the function. We aim to present our 10-year experience utilising this principle in complex sarcoma surgery. A retrospective review of our prospective sarcoma database was conducted for sarcoma patients treated with an amputation between 2012 and 2022. Cases in which distal segments were used for the reconstruction were identified. Demographic data, tumour characteristics, and surgical and non-surgical treatment, along with oncological outcomes and complications, were recorded and analysed. Fourteen patients were eligible for inclusion. The median age was 54 years at presentation (8-80 years) with 43% being females. Nine had a primary sarcoma resection, two were treated for recurrent tumours, two presented intractable osteomyelitis following sarcoma treatment and one had an amputation as a palliative procedure. The latter was the only oncological case in which tumour clearance was not achieved. Three patients developed metastasis and subsequently died during follow-up. Careful balancing of oncological goals and preservation of function is required for proximal limb-threatening sarcomas. When an amputation is required, tissues distal to the cancer site provide a safe reconstructive alternative, optimising patient recovery and preserving function. Our experience is limited by the small number of cases presenting with these rare and aggressive tumours.


Microwave assisted extraction and characterization of polysaccharide from waste jamun fruit seeds.
The intention of current work is to recover/extract polysaccharide from jamun fruit seeds (waste) by microwave assisted solid-liquid extraction (MAE) technique using four-factor (microwave power (MWP), pH, time (MWT) and solid to liquid (SL) ratio) five-level central composite rotatable experimental design (CCRED). The observed data was evaluated by statistically and a mathematical model (polynomial) was developed to predict the polysaccharide yield. Numerical optimization technique is used to attain the ideal optimal condition (microwave power of 515 w, pH of 3.2, MWT of 3.1 min and SL ratio of 1:15 g/ml) to retrieve maximal yield of polysaccharide and attained optimal condition was experimentally validated. The experimental yield of polysaccharide (4.71 ± 0.02%) was matched with predicted value (4.72%). Physico-chemical properties of the polysaccharide extracted at optimal condition was investigated. Fourier Transform Infrared Spectroscopy (FTIR) evaluation were carried out in this study to characterize the polysaccharide. Scanning Electron Microscopy (SEM) was also utilized to reveal the morphology of raw and extracted plant sample.


Reconstruction of hepatic or portal veins by use of newly customized great saphenous vein grafts.
Segmental resection of major hepatic veins or the portal vein is sometimes required if one is to secure adequate surgical margins from hepatic or pancreatic malignancies. An external iliac vein is widely sacrificed as a vein graft to replace the defect, but this is associated with postoperative edema of the lower leg. We developed a new method for constructing the great saphenous vein to interpose the hepatic or portal veins. The great saphenous vein was divided transversely into three sections, which were aligned side-to-side. The three pieces were anastomosed to make a sheet 3 x 2 cm, which was rolled up into a cylindrical form of approximately 1 cm in diameter and 2 cm in length. We applied the finished vein grafts to interpose the major hepatic veins in three patients with metastatic liver tumors and the portal vein in two patients with pancreatic malignancies in cylindrical form and to reconstruct the portal vein in one patient with a pancreas cancer, using a three-row sheet as a patch graft. No patient developed venous thrombosis of the graft or edema of the lower leg. The newly customized vein graft was safe and useful for the reconstruction of the major hepatic or portal veins.


A Novel COL4A2 Mutation Associated with Recurrent Strokes.
Mutations in type four collagens, specifically COL4A1 and COL4A2, have been associated with cerebral small vessel disease (SVD), defined as lacunar infarcts, deep intracerebral hemorrhages (ICH), and leukoaraiosis. We present a case of a man with recurrent cerebral infarcts, related to a novel COL4A2 mutation, the p.A1534S variant. Magnetic resonance imaging demonstrated multiple lacunar infarcts, numerous deep and lobar microhemorrhages and advanced leukoaraiosis. Evaluation for COL4A2 mutations should be considered when suspecting a genetic cerebral small vessel disease.


Posterior auricular artery helix root free flap-part II: clinical application.
The surgical repair of full-thickness defects involving the alae nasi is complex. Pedicle flaps such as frontal and nasolabial flaps can be used, but require several interventions with different techniques. In contrast, free flaps from the foot of the ear helix allow the three layers of the nasal wings to be reconstructed in a single operation. Nevertheless, in the classical approach, the vascular pedicle is short. Although some authors have proposed raising the flap in a retrograde manner, this still yields a relatively short pedicle with narrow vessels. In the companion paper, we demonstrated that a posterior auricular artery helix root free flap (PAAHF) can be harvested from the posterior auricular vessels, thus increasing the useful pedicle length. The case of a patient with basal cell carcinoma of the left ala is presented here. A right helix root free flap was anastomosed with the facial vessels at the left mandibular notch. This new flap overcomes the main limitation of the classical helix root flap, namely the length of the pedicle. It has all of the morphological qualities of the classical flap, but with simpler vascular assembly, since autologous venous grafts and complex anastomoses are not required.


Collagen and chondroitin sulfate functionalized bioinspired fibers for tendon tissue engineering application.
Functional tendon tissue engineering depends on harnessing the biochemical and biophysical cues of the native tendon extracellular matrix. In this study, we fabricated highly-aligned poly(L-lactic acid) (PLLA) fibers with surfaces decorated by two of the crucial tendon ECM components, type 1 collagen (COL1) and chondroitin sulfate (CS), through a coaxial stable jet electrospinning approach. Effects of the biomimetic COL1-CS (shell)/PLLA (core) fibers on the tenogenic differentiation of human mesenchymal stem cells (hMSCs) in vitro were investigated. Higher rates of cell spreading and proliferation are observed on the aligned COL1-CS/PLLA fibers compared to that on the plain PLLA fibers. Expression of the tendon-associated genes scleraxis (SCX) and COL1 as well as protein tenomodulin (TNMD) are significantly increased. Introduction of mechanical stimulation gives rise to synergistic effect on tenogenic differentiation of hMSCs. Higher expression of TGF-β2, TGFβR-II, and Smad3 by the cells on the COL1-CS/PLLA fiber substrates are observed, which indicates that COL1-CS/PLLA ultrafine fibers dictate the hMSC tenogenic differentiation through activating the TGF-β signaling pathway. Animal study in rat Achilles tendon repair model corroborated the promoting role of COL1-CS/PLLA in regenerating a tendon-like tissue. Thus, our highly aligned biomimicking fibers may serve as an efficient scaffolding system for functional tendon regeneration.


An ultrastructural comparison of mesotheliomas and adenocarcinomas of the ovary and endometrium.
The ultrastructural features of 16 malignant mesotheliomas were compared qualitatively and quantitatively with nine ovarian adenocarcinomas and 11 endometrial adenocarcinomas. The mesotheliomas could be distinguished ultrastructurally by their significantly greater content of tonofilaments (p less than 0.001) and their lack of structures found in both ovarian and endometrial adenocarcinomas, specifically abundant mucin, numerous cilia, and dense core granules of the neurosecretory type.


Schwannoma of the breast showing massive exophytic growth: a case report.
Schwannoma is a slow-growing tumor that frequently occurs in the extremities, the trunk and the head region. Its occurrence in the breast is rare with only a few cases being reported. We present here the case of breast schwannoma in a 41-year-old woman who presented with a palpable mass in her right breast. This is the first report of breast schwannoma that showed massive exophytic growth with invasion of the skin, and it was initially presumed to be a breast cancer on preoperative mammography, ultrasonography and breast MRI examinations. Complete excision of the mass was done and pathology revealed a plexiform schwannoma.


[A special instrument: the halo fixator].
Installation of an external fixator in combination with a body cast for temporary or definitive immobilization and retention of unstable fractures of the craniocervical junction and upper part of the cervical spine. Further established applications include presurgical extension treatment of paralytic scoliosis and temporary retention within complex spine deformity operations after ventral release or mobilized osteotomies. Closed reposition and temporary retention of unstable injuries of the cervical spine up to operation. Extension treatment for careful reposition of fresh or dated malpositions of the cervical spine. Conservative treatment of injuries of the craniocervical junction and the upper part of the cervical spine. Presurgical extension of paralytic scoliosis. Temporary extension after ventral release. Cranial fractures and intracranial injuries. Soft-tissue infections of the skull. Children < 3 years. Adiposity, chest injuries and paraplegia as relative contraindications using the halo body cast. Halo traction is applied in two stages; first, the head ring is attached to the skull, then, the body cast and suspension assembly are added. Local anesthesia, depending on circumstances. Sizing of the components; the optimal size of the ring is about 1.5" larger than the circumference of the patient's head. Patient in sitting or supine position. The halo ring is held in proper position by stabilizer plates; the lower margin of the ring should be just above the ears and about 0.4" above the eyebrows. The anterior pins are placed in shallow groove on the forehead between supraorbital ridges and frontal protuberances. Threaded skull pins are screwed with defined torque (4-8"/pounds) in the lamina externa of the cranial calotte without perforating the lamina interna. To avoid side-to-side drifting, the diagonally opposite pins should be tightened simultaneously. Finally, connection of the halo ring with a body cast or putting on an extension device. Secure external stabilization of unstable injuries of upper cervical spine. Improvement of correction results of patients with neuromuscular scoliosis who underwent surgical treatment. Disadvantages are procedure-specific complications (infection and loosening of head pins) with different published frequencies and decreased patient's acceptance at longer therapy duration.


Clinical trials in pregnancy and the "shadows of thalidomide": Revisiting the legacy of Frances Kelsey.
Despite great need for improved understanding of the use of drugs and biological products in pregnancy, clinical trials in pregnancy are rare, therapeutics in pregnancy are woefully understudied, and pregnant individuals are routinely excluded as trial participants. Recently, however, the U.S. Food and Drug Administration (FDA) has signaled strong support for advancing scientific research with pregnant populations, marking a significant shift from the past. Over the last sixty years, precaution and fear have largely characterized clinical research in pregnancy, deriving in large part from a protectionist ethic that materialized after the thalidomide drug disaster. FDA reviewer Frances Kelsey courageously prevented thalidomide from being marketed in the United States, and her work guided and solidified the FDA's image as protector of the general population from unsafe and ineffective drugs. Yet, when it comes to protection, pregnant persons have been left behind, and experts refer to the "shadows of thalidomide" that hamper clinical trials in pregnancy. Drawing on analysis of Frances Kelsey's archived papers in addition to focused media coverage of Kelsey and thalidomide, we discuss the durable cultural narrative surrounding Kelsey's important work. We argue that revisiting Kelsey's legacy with attention to themes that have characterized her achievement-staying vigilant, prioritizing safety, and mitigating pharmaceutical-based harm-in fact facilitates progress toward the ethical obligation to protect pregnant people through research, toward the generation of pregnancy-specific data for evidence-based care, and toward realizing Kelsey's legacy of safeguarding pregnant people and their offspring from the harms of untested drugs.


The critical review of methodologies and approaches to assess the inherent skin sensitization potential (skin allergies) of chemicals. Part III.
For those chemicals identified in point 2 above, to collect and critically analyse clinical and statistical evidence on the incidence and morbidity (clinical picture) of skin contact allergy (contact dermatitis) cases in the EU before (at least 3 years) and after the limits were set, so as to allow an assessment of the possible effect of the limits in the reduction/prevention of the incidence and morbidity of contact dermatitis.


Polyaconitic acid/functional amine/azo dye composite as a novel hyper-branched polymer for cotton fabric functionalization.
A new hyperbranched polymer based on aconitic acid and two different amine (triethnaol amine and diethylenetriamine) with different functional groups; hydroxyl and amine groups respectively was successfully synthesised by A2B3 polymerization technique and characterised using Fourier Transform Infrared (FT-IR), Nuclear Magnetic Resonance (NMR), rheological properties, antimicrobial and cytotoxicity activity. In addition, a new heterocyclic azo dye was synthesised and characterised using FT-IR, NMR, mass spectra and antimicrobial activity. Characterisation provides that both composites and azo dye have been well prepared. A mixture from both hyberbranched polymer and synthesised azo dye have been applied to cotton fabrics. Evaluation of treated fabrics shows that, the surface of treated fabrics has a thin film from applied composite which coated the whole fibre surface. Treated fabrics have good antimicrobial activity against gram positive, gram negative bacteria and fungi. Fastness properties, physical and mechanical properties for treated fabrics were also evaluated.


Organization and integration sites in the human genome of endogenous retroviral sequences belonging to HERV-E family.
The present paper reports the characterization of HERV-E endogenous retroviral sequences in the human genome by using three complementary approaches. Firstly, we identified genomic clones containing HERV-E by BLAST screening of human DNA databases by using the entire sequence of a characterized HERV-E clone (M10976) as a query. The genomic structure and integration sites of the HERV-E elements were characterized. Secondly, new integration sites of HERV-E elements were revealed by a retroviral LTR-arbitrary primer-PCR (RELAP-PCR) technique. BLAST analysis of the PCR products identified a subgroup that shows low identity (75%) to the original clone M10976 and slightly higher identity (80%) to a closely related HERV-E (Ac. n. K02166). Finally, we performed FISH mapping, which revealed sites of integration of HERV-E not previously identified at the cytogenetic level. A preliminary analysis of genes mapping in the same bands as HERV-E integration sites was performed: several loci relevant to physiological and/or pathological processes were detected. Our findings may provide clues to identify HERV-E integration sites adjacent to genes with important biological roles.


Novel MicroRNA Binding Site SNPs and the Risk of Clear Cell Renal Cell Carcinoma (ccRCC): A Case-Control Study.
Renal cell carcinoma represents 3% of all adult malignancies. MicroRNAs exhibit specific functions in various biological processes through their interaction with cellular mRNA involved in apoptosis and cell cycle control. Recent studies have reported the potential association of single-nucleotide polymorphisms (SNPs) in miRNA-binding sites of VHL-HIF1α pathway genes with renal cancer development and progression. The objective of this study is to investigate SNPs invoking an alteration in the nature of interaction with miRNA binding sites of VHL-HIF1α pathway genes. Total 450 cases of histologically and clinically verified ccRCC and 490 controls were included in our study. Genotyping was performed using a TaqMan PCR allelic discrimination method. Kaplan-Meier method of statistical analysis was implemented to analyze the overall patient survival rate. Polymorphism rs10491534 in TSC1 gene was significantly associated with risk of developing advanced ccRCC. Allele G of rs1642742 in VHL gene was significantly prevalent in ccRCC compared with control group aged 55 and older (OR = 1.5566; CI [1.1532-2.1019]). Results from the dominant model combining individuals with AG or AA genotype showed that the A allele bearers of CDCP1 rs6773576 exhibited higher risk of death compared to GG carriers (HR 3.93, 95% CI 1.76-17.21, log-rank P = 0.0033). The present study delineated the association of miRNA binding site variants in VHL-HIF1α pathway genes with the ccRCC risk, which may affect clinical outcome.


[Islam and caring].
There are more and more followers of the Muslim religion in France. All caregivers need to understand the fundamental principles that their Muslim patients hold sacred in the area of health and care. For Muslims, it is of utmost importance to observe the fundamentals of Islam and the values of brotherhood, tolerance, fairness and truth are essential.


Renal transplantation in Mapuche people.
Previous studies have demonstrated higher concentrations of some histocompatibility antigens in Mapuche people compared with non-Mapuche Chileans in the renal transplantation program. With the aim of evaluating whether those antigenic differences might induce differences in the outcomes of renal transplantation among patients belonging to that ethnic group, we reviewed HLA studies and at least 6 months follow-up of all patients with a first kidney transplant between 1980 and 2006. The 248 patients had a mean age of 37.6 years, 40% were females, and 48% had living related donors. The mean kidney follow-up was 90 months and patient follow-up was 106 months. Thirty-nine patients (16%) were classified as Mapuche, according to their surnames, including 16 women with overall mean age of 34.5 years, and 14 had been transplanted from a living related donor. Mapuche patients received organs with better HLA matching expressed as number of identities (3.4 +/- 0.1 versus 2.8 +/- 0.1 among non-Mapuche; P < .05), and the proportion receiving organs with > or = 3 compatibilities was significantly higher (Mapuche 38% versus non-Mapuche 22%; P < .05). Kaplan-Meier survival curves showed nonsignificant differences in kidney survival: 86% at 5 years and 68% at 10 years in Mapuche; and 83% and 65%, respectively, for non-Mapuche. Patient survival rates were 97% at 5 years and 86% at 10 years in the Mapuche group versus 91% and 79%, respectively, in the non-Mapuche group; both results were not significantly different. Our results showed similar outcomes of kidney and patient survivals among Mapuche people even when they received organs with better HLA matches.


Ultrasonography in Pelvic Floor Dysfunction.
Obstetric anal sphincter injury (OASI) and levator ani muscle (LAM) trauma are common disorders in parous women. Four sonographic signs have been published in cases of OASI: external or internal anal sphincter discontinuity; thickening of external anal sphincter at the area of repair; thinning of internal anal sphincter in the area of rupture in conjunction with thickening opposite the rupture site ("half-moon" sign); and abnormality of mucous folds ("mucosal star sign"). Levator trauma can be asymptomatic, with abnormality arising years later. Discontinuity of the LAM is the main sonographic sign but may appear as increased hiatal area in severe cases.


Probing Aspergillus niger glucose oxidase with pentacyanoferrate(III) aza- and thia-complexes.
Complexes of pentacyanoferrate(III) and biologically relevant ligands, such as pyridine, pyrazole, imidazole, histidine, and other aza- and thia-heterocycles, were synthesized. Their spectral, electrochemical properties, electron exchange constants, electronic structure parameters, and reactivity with glucose oxidase from Aspergillus niger were determined. The formation of the complexes following ammonia replacement by the ligands was associated with the appearance of a new band of absorbance in the visible spectrum. The constants of the complexes formation calculated at a ligand-pentacyanoferrate(III) concentrations ratio of 10:1, were 7.5 x 10(-5), 7.7 x 10(-5), and 1.8 x 10(-3) s(-1) for benzotriazole, benzimidazole, and aminothiazole ligands, respectively. The complexes showed quasi-reversible redox conversion at a glassy carbon electrode. The redox potential of the complexes spanned the potential range from 70 to 240 mV vs. saturated calomel electrode (SCE) at pH7.2. For most of the complexes self-exchange constants (k(11)) were similar to or larger than that of hexacyanoferrate(III) (ferricyanide). The complexes containing pyridine derivatives and thia-heterocyclic ligands held a lower value of k(11) than that of ferricyanide. All complexes reacted with reduced glucose oxidase at pH7.2. The reactivity of the complex containing pyrazole was the largest in comparison to the rest of the complexes. Correlations between the complexes' reactivity and both the free energy of reaction and k(11) shows that the reactivity of pentacyanoferrates obeys the principles of Marcus's electron transfer theory. The obtained data suggest that large negative charges of the complexes decrease their reactivity.


Dopaminergic modulation of striatal neurons, circuits, and assemblies.
In recent years, there has been a great deal of progress toward understanding the role of the striatum and dopamine in action selection. The advent of new animal models and the development of optical techniques for imaging and stimulating select neuronal populations have provided the means by which identified synapses, cells, and circuits can be reliably studied. This review attempts to summarize some of the key advances in this broad area, focusing on dopaminergic modulation of intrinsic excitability and synaptic plasticity in canonical microcircuits in the striatum as well as recent work suggesting that there are neuronal assemblies within the striatum devoted to particular types of computation and possibly action selection.


Variation and transmission of the human gut microbiota across multiple familial generations.
Although the composition and functional potential of the human gut microbiota evolve over the lifespan, kinship has been identified as a key covariate of microbial community diversification. However, to date, sharing of microbiota features within families has mostly been assessed between parents and their direct offspring. Here we investigate the potential transmission and persistence of familial microbiome patterns and microbial genotypes in a family cohort (n = 102) spanning 3 to 5 generations over the same female bloodline. We observe microbiome community composition associated with kinship, with seven low abundant genera displaying familial distribution patterns. While kinship and current cohabitation emerge as closely entangled variables, our explorative analyses of microbial genotype distribution and transmission estimates point at the latter as a key covariate of strain dissemination. Highest potential transmission rates are estimated between sisters and mother-daughter pairs, decreasing with increasing daughter's age and being higher among cohabiting pairs than those living apart. Although rare, we detect potential transmission events spanning three and four generations, primarily involving species of the genera Alistipes and Bacteroides. Overall, while our analyses confirm the existence of family-bound microbiome community profiles, transmission or co-acquisition of bacterial strains appears to be strongly linked to cohabitation.


Suppression of experimental allergic encephalomyelitis by intraventricular administration of interferon-gamma in Lewis rats.
Experimental allergic encephalomyelitis (EAE) is an autoimmune inflammatory disease of the central nervous system (CNS) which causes paralysis. Several studies have reported the involvement of Ia antigen-expressing cells in the pathogenesis of EAE. Interferon-gamma (IFN-gamma) can induce Ia antigen expression on a wide range of cells. We examined the effect of IFN-gamma on EAE in Lewis rats. Systemically administered IFN-gamma did not change the disease course of EAE, whereas IFN-gamma applied locally into the ventricular system of the CNS resulted in complete suppression of clinical signs. Furthermore, we found that systemic administration of anti-IFN-gamma just prior to the onset of clinical symptoms resulted in a more severe disease course. We conclude that IFN-gamma is capable of exerting a suppressive action in EAE, possibly through induction of Ia antigen expression or through the induction of suppressive mechanisms locally in the CNS.


The early chest radiographic changes of Pneumocystis pneumonia.
In a retrospective 3-year survey, 14 immunosuppressed patients from a renal unit were diagnosed as having Pneumocystis pneumonia. All 14 patients had a chest radiograph taken within 48 h of the onset of the acute illness. In only three out of the 14 cases did the radiograph show 'classical' bilateral perihilar infiltration: In six the film was normal and in five there were minimal non-specific changes only. We conclude that normal radiographic appearances are common in the early stages of Pneumocystis pneumonia and 'classical' radiological features are rarely seen.


The temporal dynamics of tics in Gilles de la Tourette syndrome.
Statistical characterization of tic behavior in Gilles de la Tourette syndrome (GTS) may provide insight into the dynamic functioning of the human central nervous system, as well as improve the quantitative assessment of tic symptom severity. Twenty-two medication-free GTS subjects underwent videotaping of their tics. The intervals between temporally adjacent tics were measured, and the statistical properties of these intervals were assessed through graphical representation of frequency distributions, autoregressive integrated moving average (ARIMA) modeling, spectral analysis, and construction of first return maps. The frequency distribution of tic interval durations followed an inverse power law of temporal scaling. Spectral analyses similarly demonstrated that the spectral power density of tic interval duration scales inversely with frequency. ARIMA modeling suggested that the time series for tics are nonstationary as well as moving average processes. The first return maps demonstrated "burstlike" behavior and short-term periodicity in tics, and proved that successive tic intervals are not statistically independent. Graphic display of the time series confirmed shortterm periodicity, and in addition suggested the presence of period doubling. These findings are suggestive though not conclusive evidence for the presence of a fractal, deterministic, and possibly chaotic process in the tic time series. These analytic methods provide insight into the temporal features of tics that commonly are described clinically (such as short-term bouts or bursting, and longer term waxing and waning), and they reveal certain important temporal features of tics that have not been clinically described. The methods may also prove useful in the improved characterization of tic symptom severity.


WNT1 mutations in families affected by moderately severe and progressive recessive osteogenesis imperfecta.
Osteogenesis imperfecta (OI) is a heritable disorder that ranges in severity from death in the perinatal period to an increased lifetime risk of fracture. Mutations in COL1A1 and COL1A2, which encode the chains of type I procollagen, result in dominant forms of OI, and mutations in several other genes result in recessive forms of OI. Here, we describe four recessive-OI-affected families in which we identified causative mutations in wingless-type MMTV integration site family 1 (WNT1). In family 1, we identified a homozygous missense mutation by exome sequencing. In family 2, we identified a homozygous nonsense mutation predicted to produce truncated WNT1. In family 3, we found a nonsense mutation and a single-nucleotide duplication on different alleles, and in family 4, we found a homozygous 14 bp deletion. The mutations in families 3 and 4 are predicted to result in nonsense-mediated mRNA decay and the absence of WNT1. WNT1 is a secreted signaling protein that binds the frizzled receptor (FZD) and the coreceptor low-density lipoprotein-receptor-related protein 5 (LRP5). Biallelic loss-of-function mutations in LRP5 result in recessive osteoporosis-pseudoglioma syndrome with low bone mass, whereas heterozygous gain-of-function mutations result in van Buchem disease with elevated bone density. Biallelic loss-of-function mutations in WNT1 result in a recessive clinical picture that includes bone fragility with a moderately severe and progressive presentation that is not easily distinguished from dominant OI type III.


Suppression of milk-derived miR-148a caused by stress plays a role in the decrease in intestinal ZO-1 expression in infants.
Milk-derived miR-148a-3p (miR-148a), which is abundant in breast milk, has been shown to be associated with the development of infants' intestines. Although it is well known that stress during lactation changes milk constituents in terms of lipid and protein, no studies have examined the influence of stress on miR-148a expression in breast milk. The objective of this study is to investigate the relationship between stress and miR-148a expression in milk, and to evaluate whether the changes in milk-derived miR-148a expression-caused by the mother's exposure to stress-influence intestinal ZO-1 expression in infants. The participants of this study were healthy Japanese women who were nursing. Psychological stress evaluation of the subjects was conducted using a short form of the Profile of Mood State Second Edition-Adult (POMS-2). Additionally, miR-148a expressions in restraint stressed nursing mice were investigated using quantitative real-time PCR. The levels of a tight junction protein zonula occludens-1 (ZO-1) and DNA methyltransferase 1 (DNMT1), which is a direct target of miR-148a, in ileum in neonatal mice breastfed by stressed nursing mice were investigated using Western blot. Furthermore, to investigate the influence of miR-148a on ZO-1 expression within the intestine, the levels of ZO-1 and DNMT1 in human intestinal epithelial Caco-2 cells with lentivirus-mediated miR-148a overexpression were evaluated. A significantly negative correlation was observed between relative miR-148a expression in breast milk and the total mood disturbance T-score. Each T-score on negative mood subscales of anger-hostility, confusion-bewilderment, depression-dejection, fatigue-inertia, and tension-anxiety was significantly negatively correlated with relative miR-148a expression in breast milk: a positive mood subscale vigor-activity T-score was significantly positively correlated with relative miR-148a expression in breast milk. A positive mood friendliness T-score, estimated separately from other scores, was significantly positively correlated with relative miR-148a expression in breast milk. Additionally, the relative expression of miR-148a in the milk obtained from stressed mice was significantly lower than that of control mice. The relative level of ZO-1 in ileum of neonatal mice nursed by stressed mice was significantly lower than that of neonatal mice nursed by control mice. Additionally, the relative level of DNMT1 in ileum of neonatal mice nursed by stressed mice was significantly higher than that of neonatal mice nursed by control mice. Furthermore, the relative level of ZO-1 in miR-148a-overexpressed Caco-2 cells was significantly higher than that in control cells. The relative level of DNMT1 in miR-148a-overexpressed Caco-2 cells was significantly lower than that in control cells. Mothers' exposure to stress during lactation may cause miR-148a expression in breast milk. Additionally, stressed-induced suppression of miR-148a expression in breast milk may cause a decrease in intestinal ZO-1 level via the increase in DNMT1 in infants' intestines. These observations are beneficial information for breastfeeding mothers and their families and perinatal medical professionals. Our findings encourage monitoring maternal psychological stress during lactation to promote breastfeeding and adequate infant nutrition.


Retention, adherence, and compliance: special needs of HIV-infected adolescent girls and young women.
To demonstrate that whereas all HIV-infected youth evidence complex factors that challenge retention in care and adherence to treatment, HIV-infected females have additional issues that are gender-specific. Preliminary data from a subset of 21 adolescent/young women under age 25 from the Whole Life mental health-perinatal HIV care project were analyzed to illustrate the needs of these patients. Of the 21 young women assessed, all but one was of minority background, and a sizeable majority had limited education (<high school diploma) and were quite poor (incomes <$500/mo.). Nearly 67% first learned of their HIV status between ages 16 and 19 years. More than three-fourths were pregnant and, of these, more than one-third entered prenatal care in the last trimester. More than half had responsibility for one to two other children. Two-thirds reported having unprotected sex in the prior 6 months. Nearly 43% had CD4 counts of 500 or below. About one-third screened positive for a mental health problem, and the majority reported a striking frequency of exposure to abusive events and traumatic losses across their short lifetimes. Adolescent girls and young women have unique needs for developmentally appropriate medical and psychosocial approaches to promote retention and adherence.


Combined advanced parental age has an additive negative effect on live birth rates-data from 4057 first IVF/ICSI cycles.
The purpose of this study is to determine if there is an additive effect of combined advanced maternal and paternal age on pregnancy and live birth rates. Retrospective data analysis of 4057 first cycles at a fertility centre between 2009 and 2013 was compiled. Donor, preimplantation genetic screening and double embryo transfer cycles were excluded. Main outcomes measured were clinical pregnancy, viable pregnancy, live birth and term birth. Logistic regression indicated strong negative associations for maternal ages exceeding 27 years with clinical pregnancies (p < 0.001), viable pregnancies (p < 0.001), live births (p < 0.001) and term births (p < 0.001). There was evidence of negative associations between paternal age and both viable pregnancies (p = 0.06) and live births (p = 0.04), such that the probability of pregnancy was 10% further reduced for women who were 35 years with a partner over 40 years vs. women aged 35 years with a partner under 30 years. There was evidence of an interaction between maternal age and the paternal age on term births (p = 0.02) such that advanced paternal age's effect on the probability of a term birth was only evident in couples where the maternal age ranged between ~27 and 35 years. There is an additive effect to pregnancy and live birth rates when both partners are of an advanced age, thus highlighting the need for pre-conception public health messaging and a combined approach to ART counselling assessing both parental ages in combination.


From source to sink: Review and prospects of microplastics in wetland ecosystems.
The source, distribution, migration, and fate of microplastics (MPs) in aquatic and terrestrial ecosystems have received much attention. However, the relevant reports in wetland ecosystems, the boundary area between water and land, are still rare. Where are the sources and sinks of MPs in the wetland? The latest researches have shown that the sources of MPs in wetlands include sewage discharge, surface runoff, and plastic wastes from aquaculture. Fibers and fragments are the most common shapes, and PE, PP, PS can be detected in water or sediment matrices, and biota of wetlands. The distribution is affected by hydrodynamic conditions, sediment properties, and vegetation coverage. Factors affecting the vertical migration of MPs include their own physical and chemical properties, the combination of substances that accelerate deposition (mineral adsorption and biological flocculation), and resuspension. Minerals tend to adsorb negatively charged MPs while algae aggregates have a preference for positively charged MPs. The wetlands vegetation can trap MPs and affect their migration. In water matrices, MPs are ingested by organisms and integrated into sediments, which makes them seem undetectable in the wetland ecosystem. Photodegradation and microbial degradation can further reduce the MPs in size. Although recent research has increased, we are still searching for a methodological harmonization of the detection practices and exploring the migration rules and fate patterns of MPs. Our work is the first comprehensive review of the source, distribution, migration, and fate of MPs in wetland ecosystems. It reveals the uniqueness of wetland habitat in the research of MPs and indicates the potential of wetlands acting as sources or sinks for MPs.


Interhemispheric transfer of voluntary motor commands in man.
The lack of callosal fibres between homotopic areas of the hand in the sensorimotor cortex in man and its possible functional correlates were investigated in normal adult subjects by comparing simple reaction times (RTs) of voluntary movements triggered by a somaesthetic stimulus to the same or opposite side of the body. An air jet was delivered to the skin of distal (index finger) or proximal (shoulder) ipsi- or contralateral zones, and triggered voluntary extension of the index finger or flexion of the forearm. The RT was measured from the arrival of the stimulus to the skin to the onset of the surface EMG of the muscle extensor indicis proprius or biceps brachii. The RTs of the contralateral finger movements triggered by either proximal or distal skin stimuli were significantly longer than the RTs of the corresponding ipsilateral movements (mean difference 11.72 and 15.10 msec respectively). When the task was flexion of the forearm, the differences in RTs between contra- and ipsilateral movements were instead compatible with a transcallosal transfer (mean difference about 2 msec in both cases). It is concluded that transcallosal connections between hand sensorimotor areas are conceivably absent also in man. Furthermore, the delay in contralateral distal performance appears to be due to a lack of transfer of the command through the motor areas, rather than to a lack of transfer of the triggering cutaneous afferent information to the performing hemisphere.


Mucosal immunoglobulin response in Epinephelus coioides after Cryptocaryon irritans infection.
The teleost mucosal immune system consists mainly of the skin, gills and gut, which play crucial roles in local immune responses against invading organisms. Immunoglobulins are essential molecules in adaptive immunity that perform crucial biological functions. In our study, a mucosal immunity model was constructed in Epinephelus coioides groupers after Cryptocaryon irritans infection, according to previous experience. Total IgM and IgT in the groupers increased in the serum and mucus in the immune group, whereas only pathogen-specific IgM were detected existence. More critically, pathogen-specific IgM was detected in the head kidney, gill and skin supernatants, thus suggesting that the systematic immune and mucosal immune system secreted immunoglobulins. Furthermore, an early response in the skin was observed, on the basis of the detection of pathogen-specific IgM in the skin supernatant. In conclusion, this research characterized the grouper IgM and IgT in mucosal immune responses to pathogens in the gills and skin, thus providing a theoretical basis for future studies on vaccines against C. irritans.


A follow-up study of age-associated memory impairment: neuropsychological predictors of dementia.
To examine the clinical course of age-associated memory impairment (AAMI) and to evaluate the value of neuropsychological tests in predicting cognitive decline in AAMI subjects in a follow-up period of more than 3 years. Prospective cohort study. The outpatient Memory Research Unit of the Department of Neurology at the University of Kuopio in Eastern Finland. A sample of 229 subjects (mean age 71.7 years) identified in two screening studies as having AAMI. A battery of neuropsychological tests and a structured inquiry for health status and subjective memory complaints were performed at baseline and follow-up to diagnose AAMI according to the criteria proposed by a National Institute of Mental Health work group. Of the 229 subjects, 176 (76.9%) participated in the follow-up for, on average, 3.6 years after the baseline. Of the participants, 104 (59.1%) still met the AAMI criteria. Other subjects were classified into five subgroups: (1) subjects showing decline in cognition meeting dementia diagnosis (16, 9.1% (13 of them AD)); (2) subjects with mild cognitive decline meeting neither dementia nor AAMI criteria (13, 7.4%); (3) subjects with memory performance now superior to AAMI criteria (17, 9.7%); (4) subjects having a disease classified as exclusion in the criteria (15, 8.5%); (5) subjects not now reporting subjective memory loss in everyday life (9, 5.1%). Two subjects (1.1%) were not classified because of incomplete data. Neuropsychological tests predicted which subjects would develop dementia during the follow-up period. The best discriminators between these subjects and those who remained AAMI were memory and verbal fluency tests. The study suggests that, in general, AAMI is nonprogressive, but the AAMI population also includes subjects with early dementia and subjects without genuine memory loss. However, these subjects can be differentiated with a more detailed neuropsychological evaluation.


Risk factors for discharge to an acute care hospital from inpatient rehabilitation among stroke patients.
To identify medical and functional health risk factors for being discharged directly to an acute-care hospital from an inpatient rehabilitation facility among patients who have had a stroke. Retrospective cohort study. Academic medical center. A total of 783 patients with a primary diagnosis of stroke seen from 2008 to 2012; 60 were discharged directly to an acute-care hospital and 723 were discharged to other settings, including community and other institutional settings. Logistic regression analysis. Direct discharge to an acute care hospital compared with other discharge settings from the inpatient rehabilitation unit. No significant differences in demographic characteristics were found between the 2 groups. The adjusted logistic regression model revealed 2 significant risk factors for being discharged to an acute care hospital: admission motor Functional Independence Measure total score (odds ratio 0.97, 95% confidence interval 0.95-0.99) and enteral feeding at admission (odds ratio 2.87, 95% confidence interval 1.34-6.13). The presence of a Centers for Medicare and Medicaid-tiered comorbidity trended toward significance. Based on this research, we identified specific medical and functional health risk factors in the stroke population that affect the rate of discharge to an acute-care hospital. With active medical and functional management, early identification of these critical components may lead to the prevention of stroke patients from being discharged to an acute-care hospital from the inpatient rehabilitation setting.