Expression of microRNA (miR126*, miR155, miR21, miR29a) in breast milk cell fraction in women with hypertension: a comparative analysis with women without hypertension.
The ideal option of food for a newborn's nourishment has traditionally been human breast milk (HBM). Previous studies have demonstrated a connection between the length of exclusively breastfeeding and its preventive effects on several conditions in neonates. Considering the significance of HBM, the study aimed at detecting the expression of microRNA (miR126*, miR155, miR21, and miR29a) in the breast milk cell fraction of women with hypertension. This was a cohort study of 35 postpartum women. Five ml of milk was collected into a sterile container from patients in the morning on the second and third days after the labor. The collected milk has been centrifuged, total cellular RNA has been isolated from cell fraction from the collected milk, isolated RNA has been subject to qualitative and quantitative analysis, next reverse transcription has been conducted, followed by that, evaluation of the expression of the selected microRNA has been conducted using the synthesized cDNA. Finally, the tested microRNA's relative expression level has been calculated. Among patients with hypertension, the analysis of cell fraction of breast milk reported lower mean expression of miR126*, miR155, miR21, and miR29a as compared to patients without hypertension. Strong and very strong positive correlation between the expression of miR126* and miR155, miR126* and miR21, miR155 and miR21, miR 155 and miR29a, and miR 21 and miR29a have been noted. Comparing patients with and without hypertension, it has been noted that patients with hypertension had lower mean expression of miR126*, miR155, miR21, and miR29a.


Phenotypical and morphological changes in the thymic microenvironment from ageing mice.
The thymus is crucial for T-cell output and the age-associated involution of this organ, is thought to have a major impact in the decline in immunity that is seen in later life. The mechanism that underlines thymic involution is not known, however, we have evidence to suggest that this is may be due to changes in the thymic microenvironment. To further test this hypothesis, we quantified the in situ changes to markers that identify cortical and medullary thymic epithelial cells. This analysis revealed an age-dependent decline in cortical and medullary markers together with an increase in Notch and Delta expression, in older mice, as judged by immunohistochemistry. This was accompanied by alterations of the archetypal staining patterns and three dimensional analysis revealed changes in the morphology of the thymic microenvironment. These studies suggest that there are age-associated alterations in the thymic microenvironment, which may therefore play a role in thymic involution.


"A mixture of positive and negative feelings": a qualitative study of primary care midwives' experiences with non-western clients living in the Netherlands.
Non-western women living in the Netherlands are diverse in origin, which implies diversity in their needs and expectations for midwifery care. Furthermore, it has also been shown that non-western women make suboptimal use of prenatal care. Midwives may therefore face difficulties when caring for these clients. The main objective of our study was to explore Dutch primary care midwives' experiences with non-western clients. A qualitative design was used. Thirteen midwives were interviewed individually and 8 participated in a focus group. All interviews were transcribed and analysed by two researchers who compared and discussed their results. Analytical codes were organised into subthemes and main themes. Midwives perceived ethnic diversity as both difficult and interesting. Caring for these women was perceived as demanding, but also rewarding. They experienced a variety of difficulties when caring for these women: communication problems, suboptimal health literacy, socioeconomic problems, lack of knowledge of the maternity care system, pressure from the family and a strong preference for physicians. In spite of these difficulties, midwives aim for optimal care by being alert and proactive, taking these women by the hand and making use of alternative resources. Provision of care to non-western clients can be difficult and may require additional measures. These problems and measures should be included in midwifery education programmes as well as training programmes for midwives.


Spontaneous peritonitis and systemic lupus erythematosus. Importance of accurate diagnosis of gram-positive bacterial infections.
Primary Gram-positive bacterial peritonitis developed in three patients with systemic lupus erythematosus (SLE). These cases suggest a possible association between these two entities. Furthermore, they emphasize the importance of accurate diagnosis when evaluating abdominal symptoms in patients with SLE.


Environmental correlates of the intrinsic rate of natural increase in primates.
The intrinsic rate of natural increase (r m) is calculated for 72 primate species, using Cole's (1954) equation. The value of r m relative to body mass is then calculated by use of allometric analysis. Both r mand relative r m are used to test the prediction that animals in unpredictable and/or harsh habitats will have a higher r mthan will those in more predictable and/or less harsh habitats. No significant link between habitat type and r mis found. However, correlations between ecology and relative r msuggest that relative r mis high in primate species living in more open habitats and low in species found in primary rainforest. Although there are few correlations between relative r m and climate parameters, those that are found suggest that variable climates, dry climates and hot climates will select for a high relative r m.


Examination of purification methods and development of intravitreal injection of triamcinolone acetonide.
Intravitreal injection of triamcinolone acetonide (TA) is used in ophthalmic treatment, but the reliability of commercially available TA preparations has still not been established. We evaluated two previously reported purification methods, and developed a more reliable TA injection which can be prepared in a hospital pharmacy. We tested the two methods previously reported for purifying commercial TA preparations, the sedimentation and the filtration and backflushing methods. We developed a new TA injection made of pure TA suspended in 0.5% sodium hyaluronate. We measured the TA content in each preparation by high-performance liquid chromatography to evaluate the three methods. In the sedimentation purification method, the TA content of a nominal 4-mg preparation varied from 1.43 to 7.37 mg, and the average recovery rate was 91.6%. In the filtration and backflushing method, TA content was 0.10-10.33 mg and recovery was 59.5%. In the TA injection we developed, the mean TA content was 102.5% (SD, 0.24; CV, 2.9%). The stability of this preparation was 99% after sterilization, and 97% after 3 months of storage. The results of our investigation showed that the purification methods used for commercial preparations are simple and easy but not precise enough for an intravitreal injection. In contrast, the TA injection prepared by our method is reliable, stable, and safe enough for clinical use.


Widespread Neuronal Transduction of the Rodent CNS via Neonatal Viral Injection.
The rapid pace of neuroscience research demands equally efficient and flexible methods for genetically manipulating and visualizing selected neurons within the rodent brain. The use of viral vectors for gene delivery saves the time and cost of traditional germline transgenesis and offers the versatility of readily available reagents that can be easily customized to meet individual experimental needs. Here, we present a protocol for widespread neuronal transduction based on intraventricular viral injection of the neonatal mouse brain. Injections can be done either free-hand or assisted by a stereotaxic device to produce lifelong expression of virally delivered transgenes.


ANK1 Methylation regulates expression of MicroRNA-486-5p and discriminates lung tumors by histology and smoking status.
The intragenic tumor-suppressor microRNA miR-486-5p is often down-regulated in non-small cell lung cancer (NSCLC) but the mechanism is unclear. This study investigated epigenetic co-regulation of miR-486-5p and its host gene ANK1. MiR-486-5p expression in lung tumors and cell lines was significantly reduced compared to normal lung (p < 0.001) and is strongly correlated with ANK1 expression. In vitro, siRNA-mediated ANK1 knockdown in NSCLC cells also reduced miR-486-5p while the DNA methylation inhibitor 5-aza-2'-deoxycytidine induced expression of both. ANK1 promoter CpG island was unmethylated in normal lung but methylated in 45% (118/262) lung tumors and 55% (17/31) NSCLC cell lines. After adjustment for tumor histology and smoking, methylation was significantly more prevalent in adenocarcinoma (101/200, 51%) compared to squamous cell carcinoma (17/62, 27%), p < 0.001; HR = 3.513 (CI: 1.818-6.788); and in smokers (73/128, 57%) than never-smokers (28/72, 39%), p = 0.014; HR = 2.086 (CI: 1.157-3.759). These results were independently validated using quantitative methylation data for 809 NSCLC cases from The Cancer Genome Atlas project. Together, our data indicate that aberrant ANK1 methylation is highly prevalent in lung cancer, discriminate tumors by histology and patients' smoking history, and contributes to miR-486-5p repression.


Bioreactor hydrodynamic effect on Escherichia coli physiology: experimental results and stochastic simulations.
A microorganism circulating in a bioreactor can be submitted to hydrodynamic conditions inducing a significant effect on its physiology. The mixing time exhibited by the stirred bioreactor and the circulation of microorganisms are both involved in this reacting system. The mixing component determines the intensity of the concentration gradient and the circulation component determines the way in which the microorganism is exposed to this gradient. These two components linked to the experimental evaluation of microbial physiology can be analysed by a structured stochastic model in the case of a partitioned or "scale-down" reactor (SDR). A stochastic model indeed enables to simulate the mixing process as well as the circulation of microorganisms in SDRs. The superimposition of mixing and circulation processes determines the concentration profile experienced by a microorganism in the reactor. In the present case, the glucose concentration experienced by Escherichia coli has been modelled during a fed-batch culture. In this context, the use of a stochastic hydrodynamic model has permitted to point out an interesting feed pulse retardant effect in the SDRs. Nevertheless, the metabolic response of E. coli is not easy to interpret because of the possible simultaneous developments of overflow metabolism and mixed acid fermentation induced by the strong glucose concentration in the reactor.


Thiol modified mycolic acids.
Patient serum antibodies to mycolic acids have the potential to be surrogate markers of active tuberculosis (TB) when they can be distinguished from the ubiquitously present cross-reactive antibodies to cholesterol. Mycolic acids are known to interact more strongly with antibodies present in the serum of patients with active TB than in patients with latent TB or no TB. Examples of single stereoisomers of mycolic acids with chain lengths corresponding to major homologues of those present in Mycobacterium tuberculosis have now been synthesised with a sulfur substituent on the terminal position of the α-chain; initial studies have established that one of these binds to a gold electrode surface, offering the potential to develop second generation sensors for diagnostic patient antibody detection.


The oculomotor internuclear pathway: a double retrograde labeling study.
To determine whether oculomotor internuclear neurons (INOs) establish unilateral or bilateral connections with the abducens nucleus (nVI), horseradish peroxidase (HRP) and either DAPI or Nuclear Yellow (NY) were injected into nVI and the oculomotor complex (nIII) examined for retrogradely labeled cells. Such injections resulted in retrograde labeling of a large number of INOs within and just dorsal to nIII in the ventral periaqueductal gray; approximately 10% of HRP-positive cells were also labeled with a fluorescent marker. Within the conditions of the experiment, this frequency of double-labeling was largely independent of the amount of HRP or fluorescent label injected or the degree of spread of label at the injections sites. It was also independent of which fluorochrome was used as a second label. Individual double-labeled cells were scattered within and immediately dorsal to nIII within the distribution of single-labeled INOs. These findings provide strong evidence for a subset of nIII INOs that have bilateral projections to nVI; the low frequency of double-labeling, however, suggests that the population of INOs projecting to both nVI may be small.


An integrative review: application of self-efficacy instruments for walking in populations with peripheral arterial disease.
The study objective was to identify which self-efficacy measurement instruments are being used for walking in patients with peripheral arterial disease (PAD), the psychometrics of these instruments, and recommendations for use in research on patients with PAD. PAD is a common problem for individuals with similar risk factors as cardiovascular disease (CVD). Experts recommend a supervised walking program with incremental increases in speed and distance as an initial treatment for patients with intermittent claudication. Because patients may experience pain while walking, there is a tendency to be nonadherent with exercise therapy, and many limit or avoid walking all together, resulting in a sedentary lifestyle. Self-efficacy plays a role in determining a person's confidence in his or her ability to participate in an exercise program. Data sources for this study were PubMed, Cumulative Index of Nursing and Allied Health Literature, PsycINFO, and the Cochrane database. The integrative review method described by Wittemore and Knafl was used for this review (Wittemore R, Knafl K. The integrative review: updated methodology. J Adv Nurs 2005;52:546-53.). Publications were retrieved electronically and reviewed for inclusion on the basis of studies that measured self-efficacy for walking in populations with PAD, peripheral vascular disease, and CVD. The analysis consisted of 9 publications. Only 2 studies were specific to the population with PAD. The remaining studies addressed self-efficacy issues in CVD or congestive heart failure. The analysis identified 4 instruments based on Bandura's Social Cognitive Theory that were used to assess self-efficacy: (1) the Self-Efficacy Expectation Scale, (2) the Self-Efficacy for Managing Chronic Disease Scale, (3) the Performance-Based Efficacy Scale, and (4) the Barriers Self-Efficacy Scale. The Self-Efficacy Expectation Scale was most frequently used in these studies. The use of the Self-Efficacy Expectation Scale instruments for walking in patients with PAD is limited because reliability and validity have been demonstrated in an older, mostly white population with CVD and congestive heart failure. Instruments that encompass the key constructs of self-efficacy, including physical, personal, and environmental aspects, would allow full evaluation with identification of potential explanations for success or failure for the chosen outcome. This should be taken into consideration in future studies when using instruments of self-efficacy.


Association of angiotensin-converting enzyme insertion/deletion (ACE I/D) gene polymorphism with susceptibility to prostate cancer: an updated meta-analysis.
This meta-analysis aims to explore the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and susceptibility to prostate cancer (PCa). We searched studies related to ACE I/D polymorphism and susceptibility to PCa through PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases from inception to June 1, 2022. Five gene models, including allelic, dominant, recessive, homozygote, and heterozygote models, were analyzed. The pooled odds ratio (OR) was calculated using Stata 15.0 software. Publication bias was judged by the funnel plot and Egger's test, with the robustness of the findings verified by sensitivity analysis. Eight published articles (including ten studies) were identified. The pooled results showed that ACE I/D locus polymorphism was significantly correlated with the risk of PCa under all gene models except for the heterozygous model (D vs. I: OR= 1.58, 95% CI: 1.14-2.21; DD vs. DI+II: OR=1.68, 95% CI: 1.11-2.54; DD+DI vs. II: OR=1.76, 95% CI: 1.11-2.80; DI vs. II: OR= 1.44, 95% CI: 0.99-2.10; DD vs. II: OR= 2.12, 95% CI: 1.15-3.93). Subgroup analysis based on genotype frequencies in the control group meeting Hardy-Weinberg equilibrium showed statistically significant differences in all gene models. The funnel plot and Egger's test indicated no publication bias. The sensitivity analysis verified the robustness of the conclusions obtained in this meta-analysis. ACE I/D locus polymorphism correlates to PCa risk. Allele D, genotype DD+DI, and DD at the ACE I/D locus increase susceptibility to PCa and can therefore serve as a potential diagnostic and screening molecular marker for PCa patients.


A community-based cross-sectional survey of orthostatic hypotension among elderly from south India.
Orthostatic hypotension (OH) increases the risk of falls and associated morbidity and mortality in elderly. Hence, determining the prevalence of OH and its associated factors is important, especially in understudied LMIC settings. A community-based cross-sectional study was conducted among randomly selected 240 community-dwelling elderly from Thiruvananthapuram, Kerala. The OH symptoms were assessed by standard clinical measurements and frailty was assessed by modified Fried frailty phenotype. Logistic regression analysis was conducted to assess the factors associated with OH. The prevalence of OH and frailty among participants was 9.6 and 29.2 percent respectively. In the first minute, OH was associated with increased odds of falls (OR = 1.97 [95%CI = 1.05, 3.72]). Increase in number of co-morbidities (ORadj = 1.82 [95%CI = 1.36, 2.48]), number of medicines used (ORadj = 1.73 [95%CI = 1.28, 2.34]), and orthostatic intolerance (ORadj = 3.67 [95%CI = 1.13, 11.94]) increased the odds of having OH. Elderly with diabetes (ORadj = 4.81 [95%CI = 1.57, 14.77]), hypertension (ORadj = 4.97 [95%CI = 1.01, 24.46]) and cognitive impairment (ORadj = 5.01 [95%CI = 1.40, 18.51]) were at a higher odds of having OH. OH and frailty are prevalent in community dwelling elderly in Thiruvananthapuram district. Frailty may be a risk factor for OH in the first minute. The number of co-morbidities may be an independent risk factor for OH. Hence, elderly people with comorbidities and cognitive impairment may be actively assessed for OH to prevent falls and associated injuries.


Induction of MLR-Bf and protection of fetal loss: a current double blind randomized trial of paternal lymphocyte immunization for women with recurrent spontaneous abortion.
The present study was conducted to evaluate the efficacy of paternal lymphocyte (PL) immunotherapy and its relation with the development of mixed lymphocyte reaction blocking antibodies (MLR-Bf) and the success of pregnancy outcome in women with recurrent spontaneous abortion (RSA). A total of 124 women with unknown causes of abortions was registered for immunotherapy under double blind randomized trial by using the list of computer-generated numbers. Each 5 x 10(6) autologous lymphocyte (AL), third party lymphocyte (TPL) and PL was dissolved separately in 1 ml of sterile normal saline (NS). Each 1 ml of cell suspension and neat NS was injected in women with RSA through intramuscular (250 microl), intradermal (250 microl), subcutaneous (250 microl) and intravenous (250 microl) routes. All women participants with RSA received six identical immunizations at the regular interval of 4 weeks, and were then screened for the development of MLR-Bf after the completion of immunization course, and also at the first, second and third trimesters (12th, 24th and 36th weeks) of pregnancy. However, nonimmunized MLR-Bf positive women with RSA did not receive any kind of therapy (NT) and were used as one of the control group in the present study. We have observed that PL-immunized women with RSA showed a significantly increased level of MLR-Bf (>30) and pregnancy success (84%) as compared to those women with RSA who received either AL (33%), TPL (31%), NS (25%) or those who did not receive any kind of treatment (NT, 44%; P<0.001). Our results indicated the importance of immunotherapy with PL in women with RSA and also showed that MLR-Bf can be considered as one of the important factors for pregnancy improvement.


The APSA Board of Governors enthusiastically endorses the position paper ``Diversity, Equity, and Inclusion: A Strategic Priority for the American Pediatric Surgical Association''.
This Commentary by the APSA Board of Governors enthusiastically endorses the position paper "Diversity, Equity, and Inclusion: A Strategic Priority for the American Pediatric Surgical Association".


Prevalence of chronic kidney disease in China: a cross-sectional survey.
The prevalence of chronic kidney disease is high in developing countries. However, no national survey of chronic kidney disease has been done incorporating both estimated glomerular filtration rate (eGFR) and albuminuria in a developing country with the economic diversity of China. We aimed to measure the prevalence of chronic kidney disease in China with such a survey. We did a cross-sectional survey of a nationally representative sample of Chinese adults. Chronic kidney disease was defined as eGFR less than 60 mL/min per 1·73 m(2) or the presence of albuminuria. Participants completed a lifestyle and medical history questionnaire and had their blood pressure measured, and blood and urine samples taken. Serum creatinine was measured and used to estimate glomerular filtration rate. Urinary albumin and creatinine were tested to assess albuminuria. The crude and adjusted prevalence of indicators of kidney damage were calculated and factors associated with the presence of chronic kidney disease analysed by logistic regression. 50,550 people were invited to participate, of whom 47,204 agreed. The adjusted prevalence of eGFR less than 60 mL/min per 1·73 m(2) was 1·7% (95% CI 1·5-1·9) and of albuminuria was 9·4% (8·9-10·0). The overall prevalence of chronic kidney disease was 10·8% (10·2-11·3); therefore the number of patients with chronic kidney disease in China is estimated to be about 119·5 million (112·9-125·0 million). In rural areas, economic development was independently associated with the presence of albuminuria. The prevalence of chronic kidney disease was high in north (16·9% [15·1-18·7]) and southwest (18·3% [16·4-20·4]) regions compared with other regions. Other factors independently associated with kidney damage were age, sex, hypertension, diabetes, history of cardiovascular disease, hyperuricaemia, area of residence, and economic status. Chronic kidney disease has become an important public health problem in China. Special attention should be paid to residents in economically improving rural areas and specific geographical regions in China. The Ministry of Science and Technology (China); the Science and Technology Commission of Shanghai; the National Natural Science Foundation of China; the Department of Health, Jiangsu Province; the Sichuan Science and Technology Department; the Ministry of Education (China); the International Society of Nephrology Research Committee; and the China Health and Medical Development Foundation.


Targeting excitotoxic/free radical signaling pathways for therapeutic intervention in glaucoma.
Glaucoma is a visual disorder characterized by progressive loss of retinal ganglion cells (RGCs), which is often associated with high intraocular pressure. However, mechanisms of RGC death in glaucoma still remain a mystery. Two theories have been proposed as pathogeneses of glaucoma: mechanical and vascular. We demonstrate that glutamate excitotoxicity triggered by overactivation of the N-methyl-D-aspartate (NMDA)-type glutamate receptors may contribute according to both theories to RGC death in glaucoma and other retinal diseases such as ischemia. From a therapeutic standpoint, NMDA receptors and downstream signaling pathways, triggered by p38 mitogen-activated protein kinase (MAPK) and caspases, are potential targets of intervention to prevent RGC death. Glutamate, however, mediates synaptic transmission essential for normal function of the nervous system. Hence, complete blockade of NMDA receptor activity causes unacceptable side effects. Studies in our laboratory have shown that an open-channel blocker of the NMDA receptors, memantine, blocks only excessive NMDA receptor activity while leaving normal function relatively intact. This characteristic endows memantine with clinical tolerability, as demonstrated by its approval for treatment of Alzheimer's disease and vascular dementia, and clinical trials for glaucoma. In this review, we discuss improved memantine derivatives, p38 MAPK, and caspase inhibitors as plausible therapeutics to prevent RGC death.


The Role of Regulatory T Cells in Heart Repair After Myocardial Infarction.
Myocardial infarction (MI) remains one of the leading causes of death worldwide. Inflammation and immune responses after MI are of significance to the adverse cardiac remodeling. Regulatory T cells (Tregs) play an important role in suppressing the immune response and thus benefit the post-MI remodeling. After MI, damaged cardiomyocytes may be replaced by scar tissue, leading to systolic and diastolic dysfunction and subsequently adverse remodeling. In this review, we provide an overview of the function and possible mechanisms of Tregs in post-MI heart repair. Specifically, after the occurrence of MI, Tregs infiltrated to peri-infarcted myocardium through CCR5 pathway, CXCR4-CXCL12 axis, and Hippo pathway. Normal functional Tregs can reduce the size of the MI area, improve heart function, and ameliorate myocardial remodeling by inhibiting proinflammatory cells accumulation, changing the proportion of macrophages phenotypes, improving myocardial fibrosis, protecting myocardial cells, and promoting angiogenesis. Eventually, Functional Tregs recruited into the heart can improve MI outcomes. Therefore, targeted therapies with Tregs might provide a promising approach to the treatment of MI remodeling.


Importance of the replication origin sequestration in cell division of Escherichia coli.
The DNA adenine methyltransferase of Escherichia coli methylates adenines at GATC sequences. The mutant deficient in this methylase has no apparent deficiency in the cell division process in spite of the absence of both synchrony in initiations of chromosomal DNA replication and sequestration of replication origin (oriC) at hemimethylated state. However, the dam mutant cannot resume cell division after hyperosmotic shock differing from the wild-type strain. This inhibition is not provoked by induction of the cell division inhibitor, SfiA protein. Although the FtsZ protein is present in the dam mutant in a reduced amount compared to wild-type, the quantitative difference of this protein is not the main reason of division arrest provoked by hyperosmotic shock. This observation supports the idea of oriC-membrane interaction playing a role both in chromosome partitioning and cell division as predicted by replicon theory.


Synthesis of Acetone-Derived C6 , C9 , and C12 Carbon Scaffolds for Chemical and Fuel Applications.
A simple, inexpensive catalyst system (Amberlyst 15 and Ni/SiO2 -Al2 O3 ) is described for the upgrading of acetone to a range of chemicals and potential fuels. Stepwise hydrodeoxygenation of the produced ketones can yield branched alcohols, alkenes, and alkanes. An analysis of these products is provided, which demonstrates that this approach can provide a product profile of valuable bioproducts and potential biofuels.


Coronary artery air embolism following pulmonary valvotomy for pulmonary atresia: a note of caution.
A case of coronary artery air embolism following open pulmonary valvotomy for pulmonary atresia with intact ventricular septum is reported. The presumptive source of this complication is a fistulous communication between the coronary artery and right ventricle, and may be preventable by certain modifications in technique.


Clinicoradiological Outcomes and Complication Profiles of Bilateral Dual Sacral-Alar-Iliac Screws versus Bilateral Single Sacral-Alar-Iliac Screws in Patients with Spinal Deformity Who Underwent Grade 3 or 4 Spinal Osteotomies: A Retrospective Comparative Study.
To compare short-term clinical and radiological outcomes and complication profiles between bilateral dual sacral-2-alar-iliac (S2AI) screw and bilateral single S2AI screw fixation techniques in patients who underwent grade 3 or 4 spinal osteotomies. A retrospective review of 83 patients treated with bilateral dual S2AI screws and 32 patients treated with bilateral single S2AI screws was conducted between 2018 and 2020 with a minimum 1-year follow-up. Clinical and radiological outcomes of patients and incidence of perioperative complications, including rod breakage, screw dislodgment, proximal junctional kyphosis, proximal junctional failure, need for reoperation, and systemic adverse effects, were collected and statistically compared between the groups. With a mean follow-up of 18.2 months, rod fracture (6.0% vs. 18.7%, P = 0.03), screw dislodgment (0 vs. 12.5%, P < 0.01), and S2AI screw loosening (1.2% vs. 18.7%, P < 0.01) were significantly lower in the dual S2AI screws group than in the single S2AI screws group. However, the reoperation rate was similar between the 2 groups (24.1% vs. 34.3%, P = 0.26). No significant differences in clinical and radiological outcomes as well as proximal junctional kyphosis (10.8% vs. 18.7%, P = 0.25) and proximal junctional failure (9.6% vs. 18.7%, P = 0.18) were identified between the 2 groups. The dual S2AI screw fixation technique showed more advantages over the single S2AI screw fixation technique with reduced incidence of screw dislodgment, rod fractures, and sacral-alar-iliac screw loosening.


Mycobacterium tuberculosis virulence is mediated by PtpA dephosphorylation of human vacuolar protein sorting 33B.
Entry into host macrophages and evasion of intracellular destruction mechanisms, including phagosome-lysosome fusion, are critical elements of Mycobacterium tuberculosis (Mtb) pathogenesis. To achieve this, the Mtb genome encodes several proteins that modify host signaling pathways. PtpA, a low-molecular weight tyrosine phosphatase, is a secreted Mtb protein of unknown function. The lack of tyrosine kinases in the Mtb genome suggests that PtpA may modulate host tyrosine phosphorylated protein(s). We report that a genetic deletion of ptpA attenuates Mtb growth in human macrophages, and expression of PtpA-neutralizing antibodies simulated this effect. We identify VPS33B, a regulator of membrane fusion, as a PtpA substrate. VPS33B and PtpA colocalize in Mtb-infected human macrophages. PtpA secretion combined with active-phosphorylated VPS33B inhibited phagosome-lysosome fusion, a process arrested in Mtb infections. These results demonstrate that PtpA is essential for Mtb intracellular persistence and identify a key host regulatory pathway that is inactivated by Mtb.


Fast drosophila enterocyte regrowth after infection involves a reverse metabolic flux driven by an amino acid transporter.
Upon exposure to a bacterial pore-forming toxin, enterocytes rapidly purge their apical cytoplasm into the gut lumen, resulting in a thin intestinal epithelium. The enterocytes regain their original shape and thickness within 16 h after the ingestion of the bacteria. Here, we show that the regrowth of Drosophila enterocytes entails an inversion of metabolic fluxes from the organism back toward the intestine. We identify a proton-assisted transporter, Arcus, that is required for the reverse absorption of amino acids and the timely recovery of the intestinal epithelium. Arcus is required for a peak of amino acids appearing in the hemolymph shortly after infection. The regrowth of enterocytes involves the insulin signaling pathway and Myc. The purge decreases Myc mRNA levels, which subsequently remain at low levels in the arcus mutant. Interestingly, the action of arcus and Myc in the intestinal epithelium is not cell-autonomous, suggesting amino acid fluxes within the intestinal epithelium.


The role of radiation therapy in the treatment of spine metastases from hepatocellular carcinoma: a systematic review and meta-analysis.
Spine hepatocellular carcinoma (HCC) metastases severely worsen quality of life and prognosis, with the role of radiotherapy being controversial. The authors systematically reviewed the literature on radiotherapy for spine metastatic HCCs. The PubMed, Scopus, Web of Science, and Cochrane databases were searched according to the PRISMA guidelines to include studies of radiotherapy for spine metastatic HCCs. Outcomes, complications, and local control were analyzed with indirect random-effect meta-analyses. The authors included 12 studies comprising 713 patients. The median time interval from diagnosis of HCC to spine metastases was 12 months (range 0-105 months). Most lesions were thoracic (35.9%) or lumbar (24.7%). Radiotherapy was delivered with conventional external-beam (67.3%) or stereotactic (31.7%) techniques. The median dose was 30.3 Gy (range 12.5-52 Gy) in a median of 5 fractions (range 1-20 fractions). The median biologically effective dose was 44.8 Gy10 (range 14.4-112.5 Gy10). Actuarial rates of postradiotherapy pain relief and radiological response were 87% (95% CI 84%-90%) and 70% (95% CI 65%-75%), respectively. Radiation-related adverse events and vertebral fractures had actuarial rates of 8% (95% CI 5%-11%) and 16% (95% CI 10%-23%), respectively, with fracture rates significantly higher after stereotactic radiotherapy (p = 0.033). Fifty-eight patients (27.6%) had local recurrences after a median of 6.8 months (range 0.1-59 months), with pooled local control rates of 61.6% at 6 months and 40.8% at 12 months, and there were no significant differences based on radiotherapy type (p = 0.068). The median survival was 6 months (range 0.1-62 months), with pooled rates of 52.5% at 6 months and 23.4% at 12 months. Radiotherapy in spine metastatic HCCs shows favorable rates of pain relief, radiological responses, and local control. Rates of postradiotherapy vertebral fractures are higher after high-dose stereotactic radiotherapy.


Evaluating stored platelet shape change using imaging flow cytometry.
Platelets are routinely stored at room temperature for 5-7 days before transfusion. Stored platelet quality is traditionally assessed by Kunicki's morphology score. This method requires extensive training, experience, and is highly subjective. Moreover, the number of laboratories familiar with this technique is decreasing. Cold storage of platelets has recently regained interest because of potential advantages such as reduced bacterial growth and preserved function. However, platelets exposed to cold temperatures change uniformly from a discoid to a spherical shape, reducing the morphology score outcomes to spheroid versus discoid during cooling. We developed a simpler, unbiased screening tool to measure temperature-induced platelet shape change using imaging flow cytometry. When reduced to two dimensions, spheres appear circular, while discs are detected on a spectrum from fusiform to circular. We defined circular events as having a transverse axis of >0.8 of the longitudinal axis and fusiform events ≤0.8 of the longitudinal axis. Using this assay, mouse and human platelets show a temperature and time-dependent, two-dimensional shape change from fusiform to circular, consistent with their three-dimensional change from discs to spheres. The method we describe here is a valuable tool for detecting shape change differences in response to agonists or temperature and will help screening for therapeutic measures to mitigate the cold-induced storage lesion.


Morphometric evaluation of the spermatogonial stem cell distribution and niche in vertebrates.
Morphometry is a classical quantitative method often used in biology to provide a data basis for functional interpretations/interactions of a particular organ or system. Herein we took advantage of this valuable approach to evaluate the spermatogonial stem cell niche using the horse testis and immunocytochemical localization of GFRA1 [glial cell line-derived neurotrophic factor receptor produced by Sertoli cells)] as an example. Using the NIH ImageJ free software, we describe in detail all the necessary steps to investigate this specific and crucial microenvironment. Based on several recently published papers from our research group, this approach has proved to be fast, simple, and adaptable to a wide range of species and has the potential to be easily reproducible in different laboratories.


Twenty-year survivorship cohort study of total knee arthroplasty in Asian patient using a single posterior-stabilized implant performed by a single surgeon.
As life expectancy has improved, the potential number of revision candidates is also expected to increase among patients who have undergone a total knee arthroplasty (TKA). The longevity of modern posterior stabilized knee prostheses after 20 years of use has not been well documented, especially in Asian populations that require a deeper flexion range due to a floor-based lifestyle. Firstly, the implant longevity regarding mechanical failures such as aseptic loosening and polyethylene (PE) wear would vary over a longer follow-up depending on the age groups; and secondly there would be unique risk factors for revision surgery in an Asian TKA cohort. We conducted this age-stratified survival analysis in a consecutive series of 368 NexGen Legacy Posterior Stabilized (LPS) TKAs performed by a single surgeon. These cases were divided into four age groups (< 60 years, early 60s, late 60s, and ≥ 70 years). The implant longevity against aseptic mechanical failures was calculated using the Kaplan-Meier method. The revision surgery risk was evaluated using postoperative factors including a deep flexion capability (> 135̊), and postoperative mechanical alignments. Overall survivorship was significantly lower in the youngest groups than other groups (Log-rank test, p=0.001). The cumulative 20-year implant longevity was more than 95% in the two oldest groups, but less than 60% in the youngest group. It was notable that the post-TKA implant longevity was not apparent up to 10 years between the age groups (p=0.073∼0.458). Aseptic loosening was observed with an earlier onset (3.1 to 18.9 years) trend than PE wear (9.8∼17.9 years), with most cases arising in the youngest groups. Flexion limitation and varus alignment were significant risks to aseptic loosening and PE wear (Cox proportional hazard regression: p=0.001 and 0.045, respectively). A younger age (< 60 years), inability of postoperative deep flexion, and varus alignment were significant risk factors for aseptic loosening and PE wear after modern PS design in this Asian cohort. The difference in postoperative longevity affected by these factors was not obvious during the first 10 years but emerged over a second decade. III; retrospective cohort study.


A role for mossy fiber activation in the loss of CA3 and hilar neurons induced by transduction of the GluR6 kainate receptor subunit.
Transduction of a viral vector expressing the GluR6 receptor subunit (HSVGluR6) to cultured hippocampal slices resulted in loss of CA3 and hilar neurons. Synaptic activity was required for this neuronal loss. This study investigates which synaptic connections were needed. Slice cultures responded heterogenously to HSVGluR6; cultures originating from the septal hippocampus showed greater neuronal loss than temporal cultures. Septal cultures also exhibited mossy fiber sprouting suggesting that activation of mossy fiber synapses contributed to neuronal loss. This was tested by transection of fiber tracts between the dentate gyrus and CA3 stratum pyramidale. Neuronal loss was blocked in transected cultures even though HSVGluR6-induced epileptiform activity was unaltered. These data suggest a role for mossy fiber activation in selective neuronal loss.


From the Journals.
RISK FACTORS IN THE HEALING OF VENOUS ULCERS THE ACTIVATION AND EFFECTS OF NEUTROPHILS AND MONOCYTES COMPRESSION STOCKINGS AND LEG ULCER RECURRENCE PRESSURE SORE PREVENTION AND TREATMENT.


An assay for measuring functional activated thrombin-activatable fibrinolysis inhibitor in plasma.
Thrombin-activatable fibrinolysis inhibitor (TAFI), also called procarboxypeptidase U (proCPU), is a plasma zymogen that can be activated by thrombin, the thrombin-thrombomodulin complex, or plasmin. The activated form of TAFI (TAFIa, CPU) removes C-terminal lysine residues of plasmin-modified fibrin (FN') that mediates a positive feedback mechanism in plasminogen (Pg) activation, thereby attenuating fibrinolysis. The plasma concentration of TAFI is approximately 75 nM. Because the half-maximal effect of TAFIa occurs at 1 nM, only approximately 1.3% of TAFI needs to be activated to exert an effect on clot lysis. The assay is performed by mixing soluble FN' covalently attached to a quencher and fluorescein-labeled Pg. The sample containing TAFIa is then added, and the rate of fluorescence increase due to removal of C-terminal lysine from FN' and loss of Pg binding is measured with a fluorescence plate reader. The assay was shown to be sensitive for TAFIa at a concentration as low as 12 pM. The intraassay variability and interassay variability of the assay were 6.3 and 8.3%, respectively. This assay was not confounded by the naturally occurring TAFI Thr325Leu polymorphism that affects the thermal stability of TAFIa or endogenous plasminogen in plasma.


Effect of in utero exposure to the atypical anti-psychotic risperidone on histopathological features of the rat placenta.
For clinical management of different forms of psychosis, both classical and atypical anti-psychotic drugs (APDs) are available. These drugs are widely prescribed, even during pregnancy considering their minimal extra-pyramidal side effects and teratogenic potential compared to classical APDs. Among AAPDs, risperidone (RIS) is a first-line drug of choice by physicians. The molecular weight of RIS is 410.49 g/mol; hence, it can easily cross the placental barrier and enter the foetal bloodstream. It is not known whether or not AAPDs like RIS may affect the developing placenta and foetus adversely. Reports on this issue are limited and sketchy. Therefore, this study has evaluated the effects of maternal exposure to equivalent therapeutic doses of RIS on placental growth, histopathological and cytoarchitectural changes, and to establish a relationship between placental dysfunction and foetal outcomes. Pregnant rats (n = 24) were exposed to selected doses (0.8, 1.0 and 2.0 mg/kg) of RIS from gestation days 6-21. These dams were sacrificed; their placentas and foetuses were collected, morphometrically examined and further processed for histopathological examination. This study revealed that in utero exposure to equivalent therapeutic doses of RIS during organogenesis-induced placental dystrophy (size and weight), disturbed cytoarchitectural organization (thickness of different placental layers), histopathological lesions (necrosis in trophoblast with disruption of trophoblastic septa and rupturing of maternal-foetal interface) and intrauterine growth restriction of the foetuses. It may be concluded that multifactorial mechanisms might be involved in the dysregulation of structure and function of the placenta and of poor foetal growth and development.


Reasons for unsafe sex among a community sample of people with HIV/AIDS.
In a sample of 117 HIV positive men and women, 34 (29%) were identified as engaging in risky sexual behavior in the past six months and were asked for reasons they did so. Analysis using broad categories revealed that partner-related reasons and hedonistic reasons were the most frequent reasons overall (71%). More male (87%) than female (60%) responses were captured by those two categories. Differences by partner status, viral load and age were not as pronounced. Specific interventions and intervention frameworks are suggested.


A possible reason for the phalloidin tolerance of hepatoma cells.
In contrast to normal liver cells, AS-30D hepatoma cells are insensitive to phalloidin. The lack of the typical phalloidin response in the latter cells is not due to a deficiency of contractile proteins. Actin prepared from hepatoma cells is able to form filamentous structures and is stabilized in a manner similar to muscle actin. Isolated liver cells were exposed to a medium containing phalloidin and removed after 20 min by centrifugation. The supernatant was incubated again with fresh cells. The procedure was repeated four times. The phalloidin response decreased to about 19% of the control because of the uptake of phalloidin during each incubation. When the same procedure was carried out with AS-30D hepatoma cells, and aliquots of the supernatants were tested with hepatocytes no marked decrease of the phalloidin response was seen. This indicates that hepatoma cells do not consume the toxin as do normal liver cells.


Hypernatremia with choroid plexus hematomas and elevated CSF protein level.
A 3-month-old infant had hypernatremia, neurologic dysfunction, and an unusually high level of cerebrospinal fluid protein. The autopsy findings included cerebral edema, intravascular coagulation, and bilateral choroid plexus hematomas. Extensive destruction of the choroid plexus, in combination with diffuse intravascular coagulation may explain the much greater elevation of CSF protein than previously described with hypernatremia.


Loofa sponge immobilized fungal biosorbent: a robust system for cadmium and other dissolved metal removal from aqueous solution.
The potential of loofa sponge discs to immobilize fungal biomass of Phanerochaete chrysosporium (a known biosorbent) was investigated as a low cost biosorbent for the removal of Cd(II) ions from aqueous solution. A comparison of the biosorption of Cd(II) by immobilized and free fungal biomass from 10 to 500 mg l(-1) aqueous solutions showed an increase in uptake of over 19% when the biomass is immobilized (maximum biosorption capacity of 89 and 74 mg Cd(II) g(-1) biomass for immobilized and free biomass respectively at a solution pH of 6). Equilibrium was established within 1h and biosorption was well defined by the Langmuir isotherm model. The immobilized biomass could be regenerated using 50 mM HCl, with up to 99% metal recovery and reused in ten biosorption-desorption cycles without significant loss of capacity. This study suggests that such an immobilized biosorbent system has the potential to be used in the industrial removal/recovery of cadmium and other pollutant metal ions from aqueous solution.


Kainic acid lesions of the nucleus accumbens selectively attenuate morphine self-administration.
The influence of kainic acid lesions of intrinsic and efferent neurons of the central medial nucleus accumbens on responding simultaneously maintained by food, water and morphine self-administration was assessed. Rats were trained on a multioperant baseline to respond on three different levers that resulted in either a food pellet, the presentation of a water dipper or an infusion of morphine. While responding on the morphine lever was related to dose (0.83-13.2 mg/infusion), increasing concentrations of the drug had little or no effect on responding maintained by food and water before the lesion. Bilateral infusions of the neurotoxin into the nucleus accumbens decreased morphine self-administration but did not appreciably alter food or water intake. Food extinction probes before the lesion produced significant increases in drug intake and decreases in responding on the water lever, but the neurotoxin lesion attenuated the food extinction induced decrease in water intake. These data suggested that kainic acid lesions of the nucleus accumbens decrease the reinforcing efficacy of morphine but do not alter the reinforcing properties of food and water. The neuronal systems potentially involved in mediating the reinforcing effects of environmental events are discussed.


USP19 exacerbates lipogenesis and colorectal carcinogenesis by stabilizing ME1.
Lipogenesis plays a critical role in colorectal carcinogenesis, but precisely how remains unclear. Here, we show that ERK2 phosphorylates ME1 at T103, thereby inhibiting its polyubiquitination and proteasomal degradation and enhancing its interaction with USP19. USP19 antagonizes RNF1-mediated ME1 degradation by deubiquitination, which in turn promotes lipid metabolism and NADPH production and suppresses ROS. Meanwhile, ROS dramatically increases PD-L1 mRNA levels through accelerating expression of the transcription factor NRF2. Increased lipid metabolism is correlated with ERK2 activity and colorectal carcinogenesis in human patients. Therefore, the combination of ERK2 inhibitor and anti-PD-L1 antibody significantly inhibits spontaneous and chemically induced colorectal carcinogenesis. Collectively, the USP19-ME1 axis plays a vital role in colorectal carcinogenesis and may also provide a potential therapeutic target.


Infantile autism and developmental receptive dysphasia: a comparative follow-up into middle childhood.
An interim follow-up study of a group of "higher functioning" boys with infantile autism and control group of boys with severe (receptive) developmental language disorder (or dysphasia) is reported. The boys were compared both initially and at follow-up for overall functioning in the areas of language, peer relationships, stereotyped behaviors, and disruptive public behaviors, as well as for the presence of a number of specific symptoms. In some respects, the behaviors that differentiated the groups initially did so also at follow-up, although there were important differences. Very few of the autistic boys had good language skills at follow-up, whereas nearly half of the dysphasic group were communicating well, a difference that is striking in view of the initial general similarity between the groups in terms of poor language functioning. However, some of the dysphasic children had developed greater difficulties in peer relationships. The implications for concepts of the nature of the deficit in severe receptive developmental language disorders are considered.


The persistence of regulatory cells developing after rat spontaneous liver acceptance.
We have previously reported that the spontaneous acceptance of Lewis (LEW, RT1(l)) to Dark Agouti (DA, RT1(a)) rat orthotopic liver transplant (OLT) is eliminated by donor gamma-irradiation. The acceptance of the irradiated LEW liver is also reestablished in a naïve rat after the adoptive transfer of T regulatory (T-reg) cells from a LEW to a DA liver-tolerant long-term (>60 days) survivor (LTS) into a naïve DA rat. However, little is known about the growth conditions required to maintain T-reg function. In this study, we examined the need for continued donor-specific alloantigen stimulation for the maintenance and function of T-reg cells. Splenocytes (SCs; 1.5 x 10(8) cells) from a LEW liver allograft-tolerant LTS DA recipient were adoptively transferred fresh or after in vitro stimulation into another naive DA rat on day 1, 4, or 7 before an irradiated (1000R) LEW liver transplant. For in vitro alloantigen stimulation, SCs from LEW to DA LTS were co-cultured with mitomycin-C (MMC)-treated naïve LEW (donor alloantigen-specific) or Brown Norway (BN) (RT1(n); third party) SCs for 72 hours. Graft rejection, as defined by death of the recipient, was confirmed histologically. All LEW liver grafts were accepted spontaneously by DA recipients for more than 60 days (n=32), while all irradiated LEW livers were acutely rejected (n=9; mean survival time [MST]=12.8 +/- 4.0 days). When LTS DA SCs were adoptively transferred into a naive DA rat 1 day before OLT, all irradiated LEW grafts were accepted greater than 60 days (n=9). However, when fresh LTS DA SCs were transferred to a new naïve DA rat on 4 or 7 days before OLT, all irradiated LEW liver grafts were acutely rejected (MST=10.2 +/- 0.5 days [n=4] and MST=13.5 +/- 5.0 days [n=4], respectively). When LTS DA SCs were stimulated in vitro before adoptive transfer, irradiated LEW liver grafts after 4 days (n=5) were then accepted. In vitro culture of LTS DA SCs with MMC-treated BN SCs (third-party) for 72 hours before adoptive transfer resulted in 3 of 5 irradiated LEW livers at day 4 being accepted (n=5). The maintenance of T-reg function requires continuous LEW donor-specific alloantigen stimulation.


The marker channel: a telemetric diagnostic aid.
Interpretation of ECG records from patients who have sophisticated pacemakers is often difficult. To address this problem, radiofrequency telemetry of diagnostic data is now being provided in varying forms from such pacemakers. A particularly useful aid to ECG analysis is offered by transmission of a Marker Channel which provides detailed information regarding occurrence and timing of pacing and sensing events. Use of the Marker Channel in combination with an appropriate programmer makes it possible to obtain ECGs with fully diagrammed pacemaker operation in minutes, with sufficient detail to free the user from the need to memorize unique pacemaker characteristics. This system is described and sample records are discussed.


Density dependent effects between three competitive bird species.
Density and breeding success of the great tit Parus major, blue tit Parus caeruleus and collared flycatcher Ficedula albicollis were studied in nest box colony in oak forest over a period of 19 years.Intraspecific density dependent clutch size reduction was found with blue tit and great tit. In interspecific relation the high density of blue tits reduced the clutch size of great tits.In the hatching period neither intraspecific nor interspecific density dependence were showed between the tits when the third competitive species, collared flycatcher was present. The collared flycatcher significantly reduced the hatching success of both tit species and the number of fledglings of great tit.The effects of the great tits and combined density of the great and blue tits on the hatching failure and number of fledglings of collared flycatcher were found when the density of the tits was high. There were not significant relationships to the single density of blue tits.The temporal variability of the competition of the three bird species is discussed.


Role of adherence vs. spreading in the induction of membrane-associated interleukin-1 on mouse peritoneal macrophages.
Adherence of peritoneal exudate cells (PEC) to plastic has been shown to activate several PEC functions, such as tumor cell lysis and membrane-associated interleukin-1 (mIL-1) expression. Several studies have demonstrated that leukocyte adherence is dependent on divalent cations. In this study, ethylenediaminetetraacetic acid (EDTA), a known chelator of divalent cations, was used to evaluate the role of cell attachment vs. spreading in adherence-induced mIL-1 activity on resident C57BL/6 mouse PEC. Significant inhibition of PEC spreading on plastic and mIL-1 expression was noted when PEC were cultured in the presence of 10 mM EDTA. However, PEC remained adherent in the presence of EDTA and were able to express mIL-1 activity in response to a soluble stimulus lipopolysaccharide (LPS) 1 microgram/ml. These results suggest that the divalent cation-dependent spreading of PEC on plastic initiates or enhances the expression of mIL-1 activity. Additionally, adhesion and LPS stimulate mIL-1 expression by independent mechanisms.


Impact of estimation versus direct measurement of predonation glomerular filtration rate on the eligibility of potential living kidney donors.
While direct measurements of glomerular filtration rate (GFR) provide the most accurate evaluation of pre-donation kidney function, guidelines do not systematically require the use of a reference method. We evaluated whether and to what extent relying upon creatinine-based estimating equations (eGFR) rather than direct measurement of GFR (mGFR) alters the selection of potential living donors. We compared the impact of 4 equations (the MDRD study equation, the CKD-EPI equation, the revised Lund-Malmö equation, and the full age spectrum [FAS] equation) on the evaluation of 2733 potential donors with GFR measured by reference methods. We also considered the impact of using either absolute or age-adapted GFR thresholds. The CKD-EPI and FAS equations had the best performances (P10 of 50.6% and 47.8%; P30 of 94.4% and 93.1%, respectively) and led to the lowest proportion of improperly evaluated candidates. Misclassification was more frequent when GFR adequacy was defined as an absolute threshold of 90 ml/min/1.73m2 as compared to an age-adapted definition (26% and 5%, respectively). Interpretation of eGFR according to an absolute threshold of 90 ml/min/1.73m2 identified 1804 candidates eligible to donate, compared to 2648 when mGFR was interpreted with age-adapted thresholds. We conclude that creatinine-based estimates cannot substitute for direct GFR measurement to evaluate candidates for kidney donation. When reference methods for direct GFR measurement are not available, our data suggest that a strategy based on age-adapted eGFR values estimated with either the CKD-EPI or FAS equation should be preferred.


Counting on comparative maps.
Comparative maps record the history of chromosome rearrangements that have occurred during the evolution of plants and animals. Effective use of these maps in genetic and evolutionary studies relies on quantitative analyses of the patterns of segment conservation. We review the analytical methods that have been developed for characterizing these maps and evaluate their application to existing comparative maps mainly for plants and animals.


FBR murine osteosarcoma virus. I. Molecular analysis and characterization of a 75,000-Da gag-fos fusion product.
The FBR murine osteosarcoma virus complex induces bone tumors with a similar latency and pathology to those induced by the FBJ virus complex. FBR murine sarcoma virus ( FBR -MSV) has been isolated from its helper virus(es) by the establishment of transformed nonproducer cells. These cells were found to express a 75,000-Da protein (P75) which was antigenically related to the p55 oncogene product of the FBJ murine osteosarcoma virus ( FBJ -MSV). P75 also contained antigenic determinants of murine leukemia virus (MLV) gag gene p15, p12, and p30 proteins, and is therefore a gag- fos fusion protein ( P75gag - fos ). P75gag - fos is a phosphoprotein and is found primarily in the nucleus. Only a single species of RNA, of 3.3 kb, was identified in FBR -MSV-transformed nonproducer cells using both fos and MLV probes, which suggested that P75gag - fos was expressed from genome-sized RNA. Chromosomal DNA from one nonproducer cell line was found to contain a single EcoRI restriction fragment of 12 kb pairs (kbp) which encompassed the FBR -MSV provirus. This DNA fragment was molecularly cloned into bacteriophage Charon 30 (lambda FBR -1), and a 7.5-kbp HindIII restriction fragment containing the entire provirus was subsequently subcloned into pBR322 ( pFBR -1). DNA from pFBR -1 was capable of inducing morphological transformation of mouse and rat fibroblasts in tissue culture. In addition, transfected cells expressed the FBR -MSV P75gag - fos protein.


Isolation of a Plasmodium falciparum rhoptry protein.
A monoclonal antibody raised against the malaria parasite Plasmodium falciparum recognised a protein of 140000 molecular weight which was synthesized during schizogony. The protein has been purified by monoclonal antibody affinity chromatography from extracts of parasitized red cells. Antibodies against the protein have been used to determine its subcellular location. The protein is not expressed on the merozoite surface and has been located in the rhoptries, the apical organelles of the merozoite.


Copper binding by peat fulvic and humic acids extracted from two horizons of an ombrotrophic peat bog.
We studied the binding of Cu(II) to humic acids and fulvic acids extracted from two horizons of an ombrotrophic peat bog by metal titration experiments at pH 4.5, 5.0, 5.5, and 6.0 and 0.1 M KNO3 ionic strength. Free metal ion concentrations in solution were measured using an ion selective electrode. The amounts of base required to maintain constant pH conditions were recorded and used to calculate H+/Cu2+ exchange ratios. The amount of Cu(II) bound to the humic fractions was greater than the amount bound to the fulvic fractions and only at the highest concentrations of metal ion the amount of Cu(II) sorbed by both fractions became equal. The proton to metal ion exchange ratios are similar for all humic substances, with values ranging from 1.0 to 2.0, and decreasing with increased pH. The amount of Cu(II) bound is practically independent of the horizon from which the sample was extracted. The results indicate that the humic substances show similar cation binding behaviour, despite the differences in chemical composition. The copper binding data are quantitatively described with the NICA-Donnan model, which allows to characterize only the carboxylic type binding sites. The values of the binding constants are higher for the humic acids than for the fulvic acids.


The clinical link between depression and obesity: Role of Ca2+/cAMP signalling.
A link between depression and obesity has been established by several reports. Consistent data support a bidirectional link between depression and obesity, e.g. obese people have demonstrated an increased risk of developing depression in their lifetime, whereas depressed people have shown an increased risk of becoming obese. An intensive debate in the field is that a Ca2+ signalling dysregulation may be an upstream issue which could link obesity and depression. In fact, Ca2+ and cAMP signalling pathways (Ca2+/cAMP signalling) control the release of both neurotransmitters and hormones, in addition to neuronal death and lipogenesis. Then, I herein discussed the putative contribution of Ca2+/cAMP signalling in this link between depression and obesity.


Effect of coacervation conditions on the viscoelastic properties of N,O-carboxymethyl chitosan - gum Arabic coacervates.
The effects of coacervation acidity, phase separation temperature, ionic strength, and biopolymer ratio on the viscoelasticity of the N,O-carboxymethyl chitosan (NOCC) - gum Arabic (GA) coacervate were investigated by using coacervate yield as the indicator of electrostatic interaction strength. The strongest interaction between NOCC and GA occurred at pH 3.0, whereas the highest modulus values were found in the coacervate separated at pH 6.0. The coacervate yield did not vary with phase separation temperature in the range 4-55°C, but the coacervate viscoelasticity declined as the temperature increased from 25°C to 45°C and then peaked at 55°C. The presence of NaCl weakened the electrostatic interaction between the two polyelectrolytes, but no dose-dependent reduction in viscoelasticity was observed for their coacervates. Besides, the highest electrostatic interaction strength and coacervate viscoelasticity were recorded at different GA to NOCC ratios. It is proposed that the strength of electrostatic interaction is not the only parameter that determines the viscoelasticity of the NOCC - GA coacervate.


Ancient surgeons: A characterization of Mesopotamian surgical practices.
The Ancient Mesopotamian civilization, the earliest known, emerged in the fourth millennium BCE.1 While the advent of medicine is established, there is little understanding of surgery's origins. We sought to describe the characteristics and medical acumen of the surgeons of the first civilization. Source documents and commentary on Mesopotamian medicine were systematically analyzed for evidence of surgery and physician descriptions. Early tablets reveal evidence of the incisional drainage of a scalp abscess and empyema, advanced wound care, fracture alignment, and possible caesarians without evidence of wound suturing, emergency procedures, trephination, or circumcision.2 While the asû and āšipu understood disease processes, strong evidence of an inextricable connection between spiritual and diagnostic/curative roles exists. Mesopotamian physicians were diagnosticians and healers, approaching surgery as part of their holistic practice rather than a separate entity. Surgery was utilized as an endpoint to a careful process aided by objective evaluation and spiritual incantation.


Surgical management of esophageal strictures.
The cases of 50 consecutive patients requiring operative treatment for esophageal strictures were reviewed to evaluate results and develop principles of management. Forty-eight had gastroesophageal reflux disease and 2 had chronic lye strictures. Of the patients with gastroesophageal reflux disease, 21 had a Barrett's esophagus. Esophageal dilations had been performed in 29 patients, 12 of whom also had undergone previous surgical procedures. Preoperative dilations by our group were used to determine further intervention. Patients with dilatable strictures were randomized to either a Nissen or a Belsey operation. In this group, there were no operative deaths, and excellent or good clinical results were obtained in 28 of 34 (82%) patients, with no significant differences noted in the outcomes between the two operations. Patients with undilatable strictures, Barrett's ulcer, or mucosal dysplasia underwent resection plus colon interposition (N = 12) or resection plus gastric interposition (N = 4). Two of the patients in the Nissen operation group later required resection and colon interposition, bringing that total to 14. Resection plus colon interposition resulted in excellent or good results in 71% of patients, with a 7% operative mortality. These results suggest that a standard transthoracic antireflux procedure can be performed with a low risk when strictures are dilatable. Excellent or good results were obtained in 82% of patients, which is equivalent to results for more complex operations. There was no significant difference in the outcome for the transthoracic Nissen procedure compared with the Belsey procedure. In addition, when required, resection plus colon interposition provided excellent or good results in 71% of the patients.


Cancer cells stemness: A doorstep to targeted therapy.
Recent advances in research on cancer have led to understand the pathogenesis of cancer and development of new anticancer drugs. Despite of these advancements, many tumors have been found to recur, undergo metastasis and develop resistance to therapy. Accumulated evidences suggest that small population of cancer cells known as cancer stem cells (CSC) are responsible for reconstitution and propagation of the disease. CSCs possess the ability to self-renew, differentiate and proliferate like normal stem cells. CSCs also appear to have resistance to anti-cancer therapies and subsequent relapse. The underlying stemness properties of the CSCs are reliant on multiple molecular targets such as signaling pathways, cell surface molecules, tumor microenvironment, apoptotic pathways, microRNA, stem cell differentiation, and drug resistance markers. Thus an effective therapeutic strategy relies on targeting CSCs to overcome the possible tumor relapse and chemoresistance. The targeted inhibition of these stem cell biomarkers is one of the promising approaches to eliminate cancer stemness. This review article summarizes possible targets of cancer cell stemness for the complete treatment of cancer.


Heteronuclear decoupling under fast MAS by a rotor-synchronized Hahn-echo pulse train.
A new heteronuclear decoupling mechanism under fast magic-angle spinning MAS is introduced. It is based on refocusing the coherences responsible for the dephase of low-gamma nuclei ((13)C, (15)N) transverse spin-polarization in the presence of strongly dipolar-coupled protons, and has the advantage that can be implemented by pulsed techniques, with all the benefits resulting from a reduced duty cycle compared with conventional decoupling by continuous rf irradiation. The decoupling efficiency of a simple rotor-synchronized Hahn-echo pulse train is analyzed both theoretically and experimentally. It was found that a substantial improvement in sensitivity and resolution can be achieved in compounds with small (1)H chemical shielding parameters even at moderate sample spinning, and some interesting applications are shown. It is also shown that much faster spinning frequencies, or alternative refocusing sequences, are needed for applications on rigid organic solids, i.e., in systems with larger (1)H chemical shifts.


The Impact of Comorbidity and Age on Timing of Androgen Deprivation Therapy in Men with Biochemical Recurrence after Radical Prostatectomy.
Older men with major comorbidities have higher risks of morbidity and mortality from androgen deprivation therapy, and the benefits of immediate androgen deprivation therapy after biochemical recurrence in these men are unclear. We assessed variation in timing of androgen deprivation therapy by age and comorbidity in a cohort of men with biochemical recurrence after radical prostatectomy. We analyzed 2,097 men with biochemical recurrence after radical prostatectomy from 2000 to 2017 in the VA SEARCH database. We ascertained age and Deyo-Charlson comorbidity index scores at biochemical recurrence. Kaplan-Meier analysis and multivariable logistic regression were used to determine association of age and Deyo-Charlson comorbidity index with prostate specific antigen at the initiation of androgen deprivation therapy. In Kaplan-Meier analysis with prostate specific antigen at androgen deprivation therapy as the outcome, median prostate specific antigen at androgen deprivation therapy initiation was 6.2 ng/ml (95% CI 5.1-7.1) across all patients but differed among those who received adjuvant/salvage radiation (3.6 ng/ml, 95% CI 2.8-4.3) and those who did not (12.1 ng/ml, 95% CI 9.6-15.2, p <0.001). In multivariable Cox regression, advanced age (p=0.03) but not worse comorbidity (p=0.25) was associated higher prostate specific antigen at initiation of androgen deprivation therapy. Across all patients, prostate specific antigen at androgen deprivation therapy was lower among those <60 years old (3.7 ng/ml, 95% CI 2.6-5.8) compared to those 60-64 (5.0 ng/ml, 95% CI 3.9-6.6), 65-69 (6.6 ng/ml, 95% CI 4.9-8.8), 70-74 (8.8 ng/ml, 95% CI 6.1-12.3) and ≥75 years old (14.1 ng/ml, 95% CI 5.5-37.8). In contrast, prostate specific antigen at androgen deprivation therapy was similar among comorbidity subgroups (Deyo-Charlson comorbidity index 0: 6.3 ng/ml, 95% CI 5.0-7.9 vs Deyo-Charlson comorbidity index 3 or higher: 5.6 ng/ml, 95% CI 4.1-7.4). In general, these relationships were consistent among subgroups receiving adjuvant/salvage radiation. Men with comorbid disease at increased risk of morbidity and mortality with androgen deprivation therapy often receive androgen deprivation therapy at low prostate specific antigen values.


Proximal convoluted tubules of the rats kidney--a stereological analysis.
The aim of this work was to order quantitative parameters of the proximal convoluted tubules (PCT) in the normal rat kidney cortex. Volume density (VV), both surface and specific surface density toward interstitium (SVi and SVi/VV) and toward lumen (SVl and SVl/VV) and thickness (T) of tubules epithelium have been stereologically ordered. Stereologically were analysed 170 test fields by lattice L36 on the paraffin sections of the three adult male Wistar rats kidney dyeing by PAS-method. The mean values of the variables analysed were: VV=76.4 % +/-0.012; SVi=0.056 microm-1 +/-0.004; SVl=0.028 microm-1 +/-0.003; SVi/VV=0.073 microm-1 +/-0.003; SVl/VV=0.037 microm-1 +/-0.005; T=18,26 microm +/-0.897. Stereological methods are making a very valuable contribution to science over recent years. We have used unbiased stereological counting methods to obtain objective quantitative parameters of the PCT epithelium in the normal rats' kidney cortex.


Interleukin-1 receptor antagonist attenuates the heat stroke-induced neuronal damage by reducing the cerebral ischemia in rats.
The effects of interleukin-1 receptor antagonist (IL-Ira) on both local cerebral blood flow and neuronal damage of the hypothalamus, corpus striatum, cortex or thalamus were assessed in rats with heat stroke. Heat stroke was induced by exposing the urethane-anesthetized rats to a high ambient temperature (42 degrees C). Damage to the hypothalamus, corpus striatum, cortex or thalamus was scored on a scale of zero to three modified from the grading system of Pulsinelli and colleagues in which: 0 = normal, 1 = few neurons damaged, 2 = many neurons damaged, and 3 = all neurons damaged. During the onset of heat stroke, as compared to those of normothermia controls, the heat stroke rats displayed a higher value of colonic temperature or neuronal damage score, as well as a lower value of local cerebral blood flow or mean arterial blood pressure. In addition, compared to those of normothermic, control rats, the heat stroke rats had increased interleukin-1 and tumor necroting factor production in the diencephalon, brain stem and cortex. The heat stroke-induced neuronal damage and diminished local cerebral blood flow in different brain structures, as well as the systemic hypotension, were attenuated in animals pretreated with IL-1ra (200 micrograms/kg, iv) 30 min before the onset of heat stroke. The results indicate that IL-1ra attenuates the heat stroke-induced cerebral neuronal damage by reducing cerebral ischemia in rats.


The effect of monensin on thyroglobulin secretion. Studies with isolated follicles from pig thyroids.
The effect of monensin on the secretion of thyroglobulin was studied in open follicles isolated from pig thyroid tissue; in this system, thyroglobulin is secreted into the incubation medium. When monensin was present during a 4-h chase incubation after pulse-labelling with 3H-leucine, the secretion of labelled thyroglobulin was reduced by about 85%; in electron-microscopic autoradiographs of rat thyroid lobes labelled and chase-incubated under similar conditions the relative number of grains over follicle lumina was strongly reduced when monensin was present during the chase. These observations are in agreement with the consensus that monensin arrests transport of secretory proteins in the Golgi complex. In other experiments, pulse-labelled follicles were chase-incubated for 1.5 h whereby labelled thyroglobulin was transported from the RER to exocytic vesicles. Monensin present during a subsequent chase of 0.5 h caused only a moderate decrease of labelled thyroglobulin secretion. TSH present during the second chase-stimulated secretion in both control and monensin-exposed follicles. TSH also caused a drastic reduction of exocytic vesicles in rat thyroid lobes, and the number of vesicles remaining in the cells was the same in controls and lobes exposed to the ionophore. The observations are interpreted to show that monensin does not inhibit the basal or TSH-stimulated transport of thyroglobulin from the site of monensin-induced arrest in the Golgi complex to the apical cell surface or the exocytosis of thyroglobulin.


NaCl reflection coefficients in proximal tubule apical and basolateral membrane vesicles. Measurement by induced osmosis and solvent drag.
Two independent methods, induced osmosis and solvent drag, were used to determine the reflection coefficients for NaCl (sigma NaCl) in brush border and basolateral membrane vesicles isolated from rabbit proximal tubule. In the induced osmosis method, vesicles loaded with sucrose were subjected to varying inward NaCl gradients in a stopped-flow apparatus. sigma NaCl was determined from the osmolality of the NaCl solution required to cause no initial osmotic water flux as measured by light scattering (null point). By this method sigma NaCl was greater than 0.92 for both apical and basolateral membranes with best estimates of 1.0. sigma NaCl was determined by the solvent drag method using the Cl-sensitive fluorescent indicator, 6-methoxy-N-[3-sulfopropyl]quinolinium (SPQ), to detect the drag of Cl into vesicles by inward osmotic water movement caused by an outward osmotic gradient. sigma NaCl was determined by comparing experimental data with theoretical curves generated using the coupled flux equations of Kedem and Katchalsky. By this method we found that sigma NaCl was greater than 0.96 for apical and greater than 0.98 for basolateral membrane vesicles, with best estimates of 1.0 for both membranes. These results demonstrate that sigma NaCl for proximal tubule apical and basolateral membranes are near unity. Taken together with previous results, these data suggest that proximal tubule water channels are long narrow pores that exclude NaCl.


High-resolution alignment of action potential waveforms using cubic spline interpolation.
A cubic spline interpolation technique is applied to the problem of aligning action potential waveforms. Interpolation is an attractive alternative to sampling at many times the Nyquist rate in order to reduce errors caused by asynchronous sampling of rapidly changing waveforms. Alignment is achieved by locating the peak of the interpolated waveform, which can be found by solving a quadratic equation. The waveform is then reconstructed for comparison with existing templates. The technique was tested using simulated noisy, randomly arriving waveforms, the interpolated signal and alignment time errors being computed as functions of the signal/noise ratio. The spline technique is superior in accuracy to sampling at eight-times the Nyquist rate and is comparable to a Fourier-transform-based interpolation algorithm. It is computationally efficient, requiring approximately five multiplications per sample point. The interpolation concept is extended to the principal component technique for separation of action potential waveforms. The energy function is interpolated and used to align the waveforms, after which the interpolated coefficients can be used for high speed classification. The technique shows an improvement in both alignment error and effective signal/noise ratio in comparison with sampling or interpolation to a voltage peak.


Lung metastasectomy after colorectal cancer: prognostic impact of resection margin on long term survival, a retrospective cohort study.
Pulmonary metastasectomy is considered a potentially curative treatment for selected patients with metastatic colorectal cancer (CRC). Several prognostic factors have been analysed, but to date, it is still not well defined which is the optimal resection margin during lung metastasectomy (LM). This study analyses the long-term results and prognostic factors after LM in CRC patients with particular attention to the resection margins. Primary endpoint of this study is to assess the correlation between resection margins and long-term outcomes. Observational cohort study on all proven cases of CRC lung metastases (2000-2016) resected with curative intent in a single centre. The series included 210 consecutive patients (M/F 133/77) with a mean age of 65.4 (± 9.96) years, 75% (159/210) of them with a solitary metastasis. Mean size of metastasis was 2.57 cm (± 1.45). One hundred sixty-eight patients underwent wedge resections (80%) and lymphadenectomy was carried out in 90 cases (42.9%). With a mean follow-up of 56 months (range 5-192), we observed a 1-, 3- and 5-year overall survival (OS) of 95%, 74% and 54%, respectively. The patients were divided into three groups according to the resection margin distance from the tumour: (a) ≥ 2 cm (145 cases); (b) < 2, ≥ 1 cm (37 cases); and (c) < 1 cm (12 cases). The OS was significantly different between the three groups (p = 0,020); univariate and multivariate analyses showed that a narrow resection margin was an independent prognostic factor of worse survival (p = 0.006 and HR 3.4 p = 0.009). Long-term survival of patients after LM is strongly associated with a greater distance between the lesion and the resection margin.


Noradrenaline inhibition of acetylcholine release from guinea-pig brain.
The effect of noradrenaline (NA) on acetylcholine (ACh) release from guinea-pig brain was investigated in superfused cerebral cortex slices and in unrestrained unanaesthetized animals provided with epidural cups. The amine reduced the ACh release from electrically stimulated tissue and its effect was antagonized by phentolamine and phenoxybenzamine, but not by propranolol and spiroperidol. The injection of NA (150 microgram) into the cerebral ventricles caused sedation, E.Co.G. synchronization and reduced ACh outflow from the parietal cortex. This inhibition was counteracted by alpha-blocking agents. A lower dose of NA (50 microgram) did not change the behaviour, but produced a late increase in ACh outflow, prevented by spiroperidol. These results fit well with the hypothesis that NA restrains, via alpha-receptors, the ACh secretion from the nerve endings and indirectly support the view that the amine reduces the firing rate of the corticopetal cholinergic neurones. The late increase in ACh outflow, observed in vivo, may be referred to secondary activation of the dopaminergic neurones, known to enhance the cortical ACh release in this animal species.


The effects of glutathione on malondialdehyde expression and seminiferous tubule damage in experimental testicular torsion-detorsion in Wistar rats.
Testicular damage caused by ischemia reperfusion injury can be determined by malondialdehyde (MDA) expression and grading of the histopathological damage to seminiferous tubules. The aim of this study was to investigate the effect of Tationil Glutathione administration on testicular damage following experimental torsion and detorsion. Eighteen Wistar albino rats, 5.5-6 months old and weighing 250-300 g, were divided into three equal groups. In the first group (T), torsion was created by rotating the left testis 720° in a clockwise direction and maintained for 4 h. In the T/D group, after 4 h of torsion, detorsion was performed and maintained for 3 h. In the T/D-GLUT group, we injected 25 mg iv gluthatione before performing detorsion (onset time of agent is ±5 min). The lowest malondialdehyde (MDA) expression was observed in the T/D-GLUT rats (P < 0.05). Grading of the histopathological damage to seminiferous tubules showed the damage to be worst in T/D and least in T/D-GLUT rats (P < 0.05). Tationil Glutathione inhibits formation of reactive oxygen species in testicular tissue during ischemia and reperfusion injury caused by experimental torsion and detorsion in Wistar rats.


Association of Vitamin D and Parathyroid Hormone with Insulin Sensitivity, Beta Cell Function and Gestational Diabetes in Pregnancy: A Cross-Sectional, Observational Study.
Vitamin D (25OHD) and parathyroid hormone (PTH) are associated with dysglycemia, and we investigated them in gestational diabetes mellitus (GDM). In this cross-sectional, observational study, we included 75 pregnant women between 24 and 28 weeks of gestation. A fasting venous sample was collected for plasma glucose (FPG), insulin, PTH and 25OHD. Glucose and insulin samples were collected hourly after 75 g glucose load for 2 h. Insulin sensitivity was estimated by the Matsuda index (MI) and beta cell function by the insulin secretion sensitivity index (ISSI-2). The subjects were stratified into three groups and tertiles according to the 25OHD and PTH, respectively. Appropriate statistical tests were used to compare the MI, ISSI-2 and GDM among the groups. GDM was seen in 14/75, and of these patients, 2 were 25OHD deficient, 7 insufficient and 5 had sufficient 25OHD. MI and ISSI-2, though not correlated with the 25OHD, decreased from the lower to higher PTH tertile (P < 0.001). FPG, AUCgluc (area under the curve glucose) and prevalence of GDM increased from the lower to higher PTH tertile (P < 0.001). Increased PTH was associated with decreased insulin sensitivity, beta cell function and GDM in pregnancy, irrespective of the underlying 25OHD level.


Revolution as a care plan: ethnography, nursing and somatic solidarity in Honduras.
While diagnosis is not within the biomedical scope of a nurse's work, assessment-an inherently ethnographic exercise-is. In Honduras, as in the United States, nurses' proximity with patients, in terms of both time spent at the bedside and shared class identification (embodied as habitus), mean that nurses are often more effective than physicians in assessment and healing. Following the 2009 coup that brought a violently repressive regime to power in Honduras, subjectivation as citizen healers brought many nurses to assess patient health as a function of neoliberal and political violence. This assessment framed radical struggle that required nurses to block political violence with their own bodies as being a necessary part of patient care. Similarly, as ethnographer, I came to share with nurses and other Hondurans certain violent processes of subjectivation (albeit from a privileged subject position) that strengthened my solidarity with them as well as my deeply embodied investment in their care plan of organizing for radical social change. This paper examines the politicizing impact of the 2009 coup on Honduran auxiliary and professional nurses and the ways in which nurse assessment and ethnographic analysis can overlap and combine in somatic and political solidarity with patients and others resisting state and political violence through their bodies.


Type II Na-Pi cotransport is regulated transcriptionally by ambient bicarbonate/carbon dioxide tension in OK cells.
The purpose of the present study was to determine whether isohydric changes in HCO3 concentration and PCO2 directly affect apical Na-dependent Pi (Na-Pi) cotransport in OK cells (opossum kidney cell line). Cells were kept at either 44 mM NaHCO3/10% CO2, pH 7.4 (high-HCO3/CO2 condition), or 22 mM NaHCO3/5% CO2, pH 7.4 (low-HCO3/CO2 condition) (for 14-24 h). Incubation in lower HCO3/CO2 concentrations increased Na-Pi cotransport 1.5-fold. The increased Na-Pi cotransport was paralleled by a two- to threefold increased expression of the NaPi-4 transporter protein and a two- to threefold increase in NaPi-4 mRNA abundance. The increase in NaPi-4 mRNA could be completely prevented by incubation in the presence of a transcriptional inhibitor, suggesting that the increase in NaPi-4 mRNA results from an increased NaPi-4 mRNA transcription. In agreement, the NaPi-4 promoter activity was stimulated by 50% at lower HCO3/CO2 concentrations. In conclusion, our data demonstrate that isohydric changes in HCO3 concentration and PCO2 exert a significant, direct cellular effect on Na-Pi cotransport and NaPi-4 protein expression in OK cells by affecting NaPi-4 mRNA transcription.


Long-term outcomes of radiofrequency ablation for unifocal low-risk papillary thyroid microcarcinoma: a large cohort study of 414 patients.
The purpose of this study was to evaluate the long-term efficacy and safety of radiofrequency ablation (RFA) for low-risk papillary thyroid microcarcinoma (PTMC) in a large population. From June 2014 to December 2017, 414 patients (323 females, 91 males, mean age 43.56 ± 9.79 years, range 18-73 years) with unifocal low-risk PTMC confirmed by core-needle biopsy (CNB) were treated by RFA. Patients were followed up at 1, 3, 6, and 12 months and every 6-12 months thereafter by ultrasound and contrast-enhanced ultrasound (CEUS). The volume and the volume reduction ratio (VRR) were calculated. Recurrence and lymph node or distant metastasis were evaluated. The mean initial volume was 92.74 ± 83.43 mm3 (range 4.19-490.07 mm3), which decreased significantly to 1.37 ± 7.94 mm3 (range 0-67.97 mm3) at a mean follow-up time of 42.15 ± 11.88 months (range 24-69 months) with a mean VRR of 98.81 ± 6.41% (range 50-100%). No life-threatening or delayed complications occurred. After RFA, 366 tumors (88.41%) completely disappeared. The overall incidence of local tumor progression rate was 3.62%. Among them, one patient (0.24%) was diagnosed to have residual cancer by CNB and underwent additional RFA. Four patients (0.97%) developed metastatic lymph node, and 10 patients (2.42%) had recurrent PTMC. A total of 13 patients underwent additional RFA, and 11 lesions completely disappeared during the follow-up. RFA is an effective and safety treatment for low-risk PTMC after a long-term follow-up period for a large cohort with careful patient enrollment evaluation. • Radiofrequency ablation is an effective and safe alternative for low-risk PTMC. • The overall incidence of local tumor progression rate was low. • No life-threatening or delayed complications occurred.


Successful conservative treatment of an isolated inflammatory superior mesenteric artery aneurysm.
Inflammatory superior mesenteric artery aneurysm is an extremely rare but life-threatening condition that can result in fatal rupture. Early surgery has been emphasized to prevent aneurysm rupture. We present a case that was successfully managed with conservative treatment. The patient was treated with intravenous methylprednisolone pulse therapy followed by oral prednisolone. Steroid therapy should be considered for unruptured inflammatory superior mesenteric artery aneurysms before surgery.


Crystallization and preliminary X-ray data for the exocellular beta-lactamase of Bacillus licheniformis 749/C.
The exocellular beta-lactamase from Bacillus licheniformis 749/C has been crystallized from polyethylene glycol solution at pH 5.5. An X-ray examination of the monoclinic crystals shows the space group is P21, with unit cell dimensions a = 66.77 A, b = 93.77 A, c = 43.57 A and beta = 104.5 degrees. The asymmetric unit consists of two molecules of 28,500 Mr each. The crystals are suitable for structure analysis to at least 2 A resolution.


Neutrophil apoptosis, proinflammatory mediators and cell counts in bronchiectasis.
Lower airway secretions from patients with bronchiectasis show inflammatory cell infiltration and increased proinflammatory mediators. The aim of this study was to investigate the effects of antibiotic treatment for exacerbations on neutrophil apoptosis and necrosis. Sputum was induced from 15 subjects with idiopathic bronchiectasis at the beginning of an acute exacerbation and after intravenous antibiotic treatment. Neutrophil apoptosis and necrosis were assessed using flow cytometry and morphology and the supernatant was analysed for concentrations of inflammatory mediators. Neutrophil numbers (x10(6) cells/g sputum) in sputum were significantly greater on day 0 than on day 14 (median difference (95% confidence interval (CI)) 5.14 (1.27 to 8.46), p = 0.02). Controls had a significantly higher percentage of sputum macrophages than patients with bronchiectasis (day 0, 1.35 (95% CI 0.48 to 2.89), p = 0.004; day 14, 1.09 (95% CI 0.26 to 2.86), p = 0.02). The concentrations of tumour necrosis factor alpha (pg/ml), interleukin 8 (ng/ml), and neutrophil elastase (ng/ml) in sputum supernatant were significantly reduced on day 14 compared with day 0 (median difference -94 (95% CI -158 to -27), p = 0.005; -106 (95% CI -189 to -50), p = 0.0006; and -73 451 (95% CI -135 495 to -12 303), p = 0.02 respectively). Patients with bronchiectasis had a significantly lower percentage of cells which were neither apoptotic nor necrotic than healthy controls (both days, -38.8 (95% CI -49.6 to -8.5), p = 0.002; -45.0 (95% CI -58.0 to -34.1), p = 0.0003, respectively), and on day 14 they had a significantly higher percentage of secondary necrotic cells than healthy controls (40 (95% CI 11.6 to 57.5), p = 0.004). This study shows that antibiotic treatment affects concentrations of proinflammatory mediators and cell death and clearance may be altered in bronchiectasis.


Facilitation of cardiac sympathetic function by angiotensin II: role of presynaptic angiotensin receptors.
Intravenous infusion of two separate doses of angiotensin II in pentobarbital-anesthetized, desipramine-treated animals produced dose-related increases in arterial blood pressure and caused significant potentiation of the cardioacceleration observed during the stimulation of the right postganglionic cardiac sympathetic nerve fibers. Positive chronotropic effects of intravenous norepinephrine were not altered during angiotensin II infusion. Prior administration of Saralasin, an angiotensin receptor antagonist, caused significant attenuation of the pressor action of angiotensin II, and also significantly antagonized the facilitatory effect of angiotensin II on sympathetic transmission to the myocardium. These results suggest that angiotensin II can cause facilitation of sympathetic nerve function to the myocardium via an action on angiotensin receptors which may be located on sympathetic nerve terminals.


Non-periodicity in chemostat equations: a multi-dimensional negative Bendixson-Dulac criterion.
We establish conditions which exclude periodic solutions in a simple chemostat with a single nutrient and N competing species. Growth rates are not required to be proportional to food uptake. Instead of a Lyapunov function approach, we develop and apply a multi-dimensional Bendixson-Dulac type exclusion principle based on differential forms.


Microbial degradation of fipronil by Bacillus thuringiensis.
Fipronil, a phenyl pyrazole insecticide has been found to be effective for the control of various insect pests. Due to its higher persistence in soil bioremediation is a promising approach to degrade the pesticide from soil. Isolation and identification of soil microbes was conducted for bioremediation of fipronil contaminated soils. Soil samples collected from different sugarcane growing fields in Gurdaspur district with extensive use of pesticide history served as a source of pesticide degrading microbes. The microbe cultures were grown in Luria broth and maintained at 28°C. After that Dorn's broth enrichment culture supplemented with fipronil was used and Bacillus thuringiensis were isolated. Clay loam soil samples were fortified with fipronil @ 0.50, 0.75, 1.00, 1.25 and 1.50mgkg(-1) along with 45×10(7) microbe cells. Each treatment was replicated thrice and from each fortified (insecticide+microbes) sample, 50g soil sample was taken at 7, 14, 28, 35, 42, 49 and 56 days after initiation of this experiment. Residues were not detected after 28, 35, 35, 35 and 42 days in soil samples after fortification with fipronil @ 0.50, 0.75, 1.00, 1.25 and 1.50mgkg(-1). Among metabolites, sulfide was found to be the main metabolite followed by sulfone and amide. Desulfinyl metabolite was not produced in any of the sample. Total fipronil residues were not found to follow the first order kinetics.


Interactions of miR-34b/c and TP-53 polymorphisms on the risk of nasopharyngeal carcinoma.
Growing evidence indicates that tumor suppressor gene TP-53 and non-coding RNA miR-34b/c independently and/or jointly play crucial roles in carcinogenesis. We hypothesized that the polymorphisms of rs4938723 in the promoter region of pri-miR-34b/c and TP-53 Arg72-Pro may be related to the risk of nasopharyngeal carcinoma (NPC). We performed a case-control study between 217 patients with NPC and 360 healthy controls in a Chinese population using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. A significantly increased risk of NPC was observed in the miR-34b/c rs4938723 CT/CC genotypes compared with the TT genotype (adjusted OR=1.44, 95 % CI 1.02-2.03, p=0.04), and also the C allele (adjusted OR=1.33, 95 % CI 1.04-1.70, p=0.03). The gene-gene interaction of miR-34b/c rs4938723 and TP-53 Arg72-Pro showed that the combined genotypes of rs4938723CT/CC and TP-53CG/CC increased the risk of NPC (rs4938723CT/CC + TP-53CG/CC vs. rs4938723 TT+TP-53 CG/CC: OR=1.58, 95 % CI 1.04-2.42, p=0.03). These findings suggest that miR-34b/c rs4938723 and TP-53 Arg72Pro polymorphisms may singly or collaboratively contribute to the risk of NPC.


[Field 5. Safety practices procedures for mechanical ventilation. French-speaking Society of Intensive Care. French Society of Anesthesia and Resuscitation].
Invasive or endotracheal mechanical ventilation can lead to numerous complications likely to burden morbidity and mortality of patients in the intensive care unit. Various safety practices for mechanical ventilation may involve intubation, the mechanical ventilation period, weaning and extubation, the use of tracheostomy as well as non-invasive ventilation. The main objective of safety practices described in this chapter is to prevent or avoid the main risks due to invasive mechanical ventilation.


Effect of potassium citrate salts on the vapor-liquid equilibrium properties of aqueous solutions of alanine at different temperatures.
Water activity measurements by isopiestic method have been carried out on the aqueous solutions of alanine+potassium di-hydrogen citrate (KH(2)Cit) and alanine+tri-potassium citrate (K(3)Cit) over a range of temperatures at atmospheric pressure. From these measurements, values of the vapor pressure of solutions were determined. The effect of temperature and charge on the anion of salts on the vapor-liquid equilibrium of the investigated systems has been studied. The experimental water activities have been correlated successfully with the segment-based local composition Wilson and NRTL models. The agreement between the correlations and the experimental data is good.