A novel investigations on medical and non-medical mask performance with influence of marine waste microplastics (polypropylene).
The entire human race is struggling with the spread of COVID-19. Worldwide, the wearing of face masks is indispensable to prevent such spread. Despite numerous studies reporting on the fabrication of face masks and surgical masks to reduce spread and thus human deaths, this novel work is considered the marine waste of microplastics, namely Polypropylene (PP) polymer, used to fabricate non-woven fabric masks through the melt-blown process. This experimental work aims to maximize the mask's quality and minimize its fabrication cost by optimizing the melt-blown process parameters and using microplastics. The melt-blown process was used to make masks. Parameters such as extruder temperature, hot air temperature, melt flow rate, and die-to-collector distance (DCD) were investigated as independent variables. The quality of the mask was investigated in terms of bacterial filtration efficiency (BFE), particle filtration efficiency (PFE), and differential pressure. The Taguchi L16 orthogonal array and Taguchi analysis were employed for experimental design and statistical optimization, respectively. The results reveal that the higher BFE and PFE are recorded at 96.7 % and 98.6 %, respectively. The surface morphological investigation on different layers ensured the fine and uniform porosity of the layers and exhibited minimum breath resistance (a low differential pressure of 0.00152 kPa/cm2). Hence the chemically treated marine waste microplastics improved the masks' performance.


Chromatographic separation for domoic acid using a fragment imprinted polymer.
We prepared molecularly imprinted polymers for an amnesic shellfish poison, domoic acid. To prepare the polymer, we tested several commercial aromatic dicarboxylic compounds such as isomers of phthalic acid for templates of molecularly imprinted polymers. The highest selective recognition ability of the polymer for domoic acid in the tested compounds was found when o-phthalic acid was used as the template. The ability was due to the acidity of the carboxylic acids in the domoic acid and the similarity of the shape around the carboxylic acids of domoic acid and the templates. The effective chromatographic separation of domoic acid in the extract from blue mussels was achieved with a LC column packed with the fragment imprinted polymer using o-phthalic acid as the template. This polymer can be utilized for a clean up procedure of domoic acid in toxic shellfish.


Gas chromatographic-mass spectrometric analysis of N-acetylated amino acids: the first case of aminoacylase I deficiency.
During the metabolic work-up of a patient presenting with neonatal convulsions, we consistently observed the presence of unusual peaks in the gas chromatographic-mass spectrometric analysis of urinary organic acids. The gas chromatographic-mass spectrometric characteristics of the unusual peaks suggested that they corresponded to derivatives of N-acetylated amino acids. The tentative identification was confirmed by the identity of retention times and mass spectra of the trimethylsilyl derivatives of the authentic compounds. We describe our observations that led to the identification of the various N-acetylated amino acids in this first patient with a confirmed deficiency of aminoacylase I, an enzyme involved in the cytosolic degradation of N-terminally modified proteins. The potential and limitations of urinary organic acid analysis for the detection of N-acetylated amino acids was further studied using pure compounds. In addition, we provide mass spectral data for 37 trimethylsilyl derivatives from 17 N-acetylated amino acids, most of which have not been reported previously. Our data provide valuable information that will help the clinical laboratorians who are responsible for organic acid analysis to recognize this new condition and could aid its detection in other patients.


Young adult-form of dementia with neurofibrillary changes and Lewy bodies.
Alzheimer's neurofibrillary tangles, Lewy bodies and chromatolytic neurons were found in the brain at autopsy of a 28-year-old male with pyramidal and extrapyramidal signs, and severe dementia of 7-year duration prior to his death. Review of histological material showed generalized changes involving both cortical and subcortical structures. These changes were characterized by the presence of neurofibrillary myelin in long tracts and in subcortical regions. The neurofibrillary tangles were mostly composed of Alzheimer's paired helical filaments (PHF), PHF were immunostained with both polyclonal and monoclonal antibodies to PHF and the microtubule-associated protein tau. Some Lewy bodies were immunolabelled with monoclonal antibodies to PHF. To the best of our knowledge it is the first reported case of a young adult-form of dementia with extensive formation of neurofibrillary changes and Lewy bodies.


Characterization of assortative mating in medaka: Mate discrimination cues and factors that bias sexual preference.
Somatolactin alpha (SLα) is a peptide hormone that regulates skin color, and SLα-deficient and SLα-excess strains have been established in medaka (Oryzias latipes). Their skin colors differ conspicuously and males prefer to mate with females from the same strain. Pre-mating sexual isolation in this model vertebrate provides an ideal platform for investigating the molecular mechanisms of mate choice. Thus, we studied the sensory cues utilized by these fish to discriminate the same and different strains. When males were given a choice under monochromatic light, where the skin colors differed only in terms of brightness but not in hue, mating occurred but it was not assortative. This suggests that: (1) a visual cue is essential for mate discrimination rather than odor or acoustic cues; (2) the visual cue is color and not shape, size, or motion; and (3) the color cue needs to be perceived as the relative balance of brightness at multiple wavelengths rather than the brightness at a specific wavelength. In addition, we introduced another skin-color mutation into the SLα-excess strain and found that this new strain and the original SLα-excess strain, which also overexpressed SLα but exhibited distinct skin colors, preferred different colors. This demonstrates that SLα is not a primary determinant of sexual preference. The symmetrically biased sexual preferences of the SLα-deficient and SLα-excess strains may be acquired postnatally depending on their individual skin color or that of tank mates.


Role of L-carnosine in the control of blood glucose, blood pressure, thermogenesis, and lipolysis by autonomic nerves in rats: involvement of the circadian clock and histamine.
L-carnosine (β-alanyl-L-histidine; CAR) is synthesized in mammalian skeletal muscle. Although the physiological roles of CAR have not yet been clarified, there is evidence that the release of CAR from skeletal muscle during physical exercise affects autonomic neurotransmission and physiological functions. In particular, CAR affects the activity of sympathetic and parasympathetic nerves innervating the adrenal glands, liver, kidney, pancreas, stomach, and white and brown adipose tissues, thereby causing changes in blood pressure, blood glucose, appetite, lipolysis, and thermogenesis. CAR-mediated changes in neurotransmission and physiological functions were eliminated by histamine H1 or H3 receptor antagonists (diphenhydramine or thioperamide) and bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN), a master circadian clock. Moreover, a carnosine-degrading enzyme (carnosinase 2) was shown to be localized to histamine neurons in the hypothalamic tuberomammillary nucleus (TMN). Thus, CAR released from skeletal muscle during exercise may be transported into TMN-histamine neurons and hydrolyzed. The resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of CAR on neurotransmission and physiological function. Thus, CAR appears to influence hypoglycemic, hypotensive, and lipolytic activity through regulation of autonomic nerves and with the involvement of the SCN and histamine. These findings are reviewed and discussed in the context of other recent reports, including those on carnosine synthetases, carnosinases, and carnosine transport.


Publisher Correction: Guest Edited Collection: Gravitational biology and space medicine.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


ACR appropriateness criteria(®)acute respiratory illness in immunocompromised patients.
The respiratory system is often affected by complications of immunodeficiency, typically manifesting clinically as acute respiratory illness. Ongoing literature reviews regarding the appropriateness of imaging in these patients are critical, as advanced medical therapies such as stem cell transplantation, chemotherapy, and immunosuppressive therapies for autoimmune disease continue to keep high the population of immunosuppressed patients in our health care system today. This ACR Appropriateness Criteria(®) topic describes clinical scenarios of acute respiratory illness in immunocompromised patients with cough, dyspnea, chest pain, and fever; in those with negative, equivocal, or nonspecific findings on chest radiography; in those with diffuse or confluent opacities on chest radiography; and in those in whom noninfectious disease is suspected. The use of chest radiography, chest CT, transthoracic needle biopsy, and nuclear medicine imaging are all discussed in the contexts of these clinical scenarios. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.


Breast Textiloma: An unending medico-legal issue about a case report.
Textiloma is a mass composed of retained surgical textile foreign body. It is a rare iatrogenic complication that can engage the doctor's responsibility. The aim of this manuscript is to report an unusual case of breast Textiloma mimicking a recurrent tumor and to highlight its medico-legal implications. A 47-year-old lady, without past medical history, was diagnosed with a breast infiltring intraductal carcinoma. She was treated with mastectomy. Four years later, the patient consulted her surgeon for a subcutaneous mass in the operative site. Both medical and radiological investigations concluded to recurrent tumor. Histological examination confirmed the diagnosis of Textiloma. Retained foreign bodies in the operative site are infrequent but serious iatrogenic complications. Clinical manifestations of Textiloma are variable and non-specific. It should be suspected in any postoperative case with unresolved or unusual problems. It can mimic other conditions such as tumor. Textiloma is a frequently injurious situation that can lead to medico-legal implications. It is considered to be a sample of medical negligence that involves the surgeon responsibility. Textiloma is a preventable condition and it can be avoidable by maintaining standard recommendations.


Construction of Zn-heptapeptide bionanozymes with intrinsic hydrolase-like activity for degradation of di(2-ethylhexyl) phthalate.
Nanozyme with intrinsic enzyme-like activity has emerged as favorite artificial catalyst during recent years. However, current nanozymes are mainly limited to inorganic-derived nanomaterials, while biomolecule-sourced nanozyme (bionanozyme) are rarely reported. Herein, inspired by the basic structure of natural hydrolase family, we constructed 3 oligopeptide-based bionanozymes with intrinsic hydrolase-like activity by implementing zinc induced self-assembly of histidine-rich heptapeptides. Under mild condition, divalent zinc (Zn2+) impelled the spontaneous assembly of short peptides (i.e. Ac-IHIHIQI-CONH2, Ac-IHIHIYI-CONH2, and Ac-IHVHLQI-CONH2), forming hydrolase-mimicking bionanozymes with β-sheet secondary conformation and nanofibrous architecture. As expected, the resultant bionanozymes were able to hydrolyze a serious of p-nitrophenyl esters, including not only the simple substrate with short side-chain (p-NPA), but also more complicated ones (p-NPB, p-NPH, p-NPO, and p-NPS). Moreover, the self-assembled Zn-heptapeptide bionanozymes were also proven to be capable of degrading di(2-ethylhexyl) phthalate (DEHP), a typical plasticizer, showing great potential for environmental remediation. Based on this study, we aim to provide theoretical references and exemplify a specific case for directing the construction and application of bionanozyme.


Towards a mechanistic understanding of soil nitrogen availability responses to summer vs. winter drought in a semiarid grassland.
More frequent and intense drought events resulting from climate change are anticipated to become important drivers of change for terrestrial ecosystem function by affecting water and nutrient cycles. In semiarid grasslands, the responses of soil nitrogen availability to severe drought and the underlying mechanisms are largely unknown. Moreover, the responses and mechanisms may vary between summer and winter drought. We examined soil nitrogen availability responses to extreme reductions in precipitation over summer and winter using a field experiment in a semiarid grassland located in northeast China, and we explored the mechanisms by examining associated changes in abiotic factors (soil property responses) and biotic factors (plant and soil microbial responses). The results demonstrated that both the summer and winter severe drought treatments significantly reduced plant and microbial biomass, whereas summer drought also changed soil microbial community structure. Summer drought, winter drought and combined summer and winter drought decreased the resistance of soil nitrogen availability by 38.7 ± 11.1%, 43.3 ± 11.4% and 43.8 ± 6.0%, respectively. While both changes in abiotic factors (reduced soil water content and total nitrogen content) and biotic factors (reduced plant and microbial biomass) explained the resistance of soil nitrogen availability to drought over summer, only changes in biotic factors (reduced plant and microbial biomass) explained the legacy effect of winter drought. Our results highlight that severe drought can have important consequences for nitrogen cycling in semiarid grasslands, and that both the effects of summer and winter drought must be accounted for in predicting these responses.


Imaging Early Postoperative Complications of Cardiothoracic Surgery.
Imaging plays a central role in the evaluation of patients following cardiothoracic surgery, both for monitoring in the early postoperative period and for assessing for suspected complications. Patients with postsurgical complications can develop a range of signs and symptoms, from hypotension and tachycardia, as the result of severe bleeding, to fever and leukocytosis because of infection. The radiologist is an important member of the care team in the postoperative period, helping identify and manage complications of cardiothoracic surgery. This article reviews the common complications of cardiothoracic surgery focusing on the role of imaging and clues to diagnosis.


Platelets and neoplasia.
Numerous platelet abnormalities have been recognized in animals with malignancy. Because platelets play a key role in hemostasis, it is vital that clinicians recognize those neoplastic conditions that are associated with platelet disorders. A review of these platelet abnormalities, their underlying pathophysiology, and treatment is presented in this article.


Comparative mitochondrial genomic analysis provides new insights into the evolution of the subfamily Lamiinae (Coleoptera: Cerambycidae).
The genus Monochamus within the subfamily Lamiinae is the main vector of Bursaphelenchus xylophilus, which causes pine wilt disease and induces substantial economic and ecological losses. Only three complete mitochondrial genomes of the genus Monochamus have been sequenced to date, and no comparative mitochondrial genomic studies of Lamiinae have been conducted. Here, the mitochondrial genomes of two Monochamus species, M. saltuarius and M. urussovi, were newly sequenced and annotated. The composition and order of genes in the mitochondrial genomes of Monochamus species are conserved. All transfer RNAs exhibit the typical clover-leaf secondary structure, with the exception of trnS1. Similar to other longhorn beetles, Lamiinae mitochondrial genomes have an A + T bias. All 13 protein-coding genes have experienced purifying selection, and tandem repeat sequences are abundant in the A + T-rich region. Phylogenetic analyses revealed congruent topologies among trees inferred from the five datasets, with the monophyly of Acanthocinini, Agapanthiini, Batocerini, Dorcaschematini, Pteropliini, and Saperdini receiving high support. The findings of this study enhance our understanding of mitochondrial genome evolution and will provide a basis for future studies of population genetics and phylogenetic investigations in this group.


Zearalenone toxicosis on reproduction as estrogen receptor selective modulator and alleviation of zearalenone biodegradative agent in pregnant sows.
Zearalenone (ZEA) is a resorcylic acid lactone derivative derived from various Fusarium species that are widely found in food and feeds. The molecular structure of ZEA resembles that of the mammalian hormone 17β-oestradiol, thus zearalenone and its metabolites are known to compete with endogenous hormones for estrogen receptors binding sites and to activate transcription of oestrogen-responsive genes. However, the effect of long-term low-dose ZEA exposure on the reproductive response to Bacillus subtilis ANSB01G culture for first-parity gilts has not yet been investigated. This study was conducted to investigate the toxic effects of ZEA as an estrogen receptor selective modulator and the alleviating effects of Bacillus subtilis ANSB01G cultures as ZEA biodegraders in pregnant sows during their first parity. A total of 80 first-parity gilts (Yorkshire × Landrace) were randomly assigned to four dietary treatments during gestation: CO (positive control); MO (negative control, 246 μg ZEA/kg diet); COA (CO + B. subtilis ANSB01G culture with 2 × 109 CFU/kg diet); MOA (MO + B. subtilis ANSB01G culture with 2 × 109 CFU/kg diet). There were 20 replications per treatment with one gilt per replicate. Feeding low-dose ZEA naturally contaminated diets disordered most of reproductive hormones secretion and affected estrogen receptor-α and estrogen receptor-β concentrations in serum and specific organs and led to moderate histopathological changes of gilts, but did not cause significant detrimental effects on reproductive performance. The addition of Bacillus subtilis ANSB01G culture to the diet can effectively relieve the competence of ZEA to estrogen receptor and the disturbance of reproductive hormones secretion, and then ameliorate toxicosis of ZEA in gilts. Collectively, our study investigated the effects of feeding low-dose ZEA on reproduction in pregnant sows during their first parity. Feeding low-dose ZEA could modulate estrogen receptor-α and -β concentrations in specific organs, cause disturbance of reproductive hormones and vulva swelling, and damage organ histopathology and up-regulate apoptosis in sow models. Diet with Bacillus subtilis ANSB01G alleviated negative effects of the ZEA on gilts to some extent.


Asssessment of practice in intensive care: students' perceptions of a clinical competence assessment tool.
Part I of this paper (literature review) identified some of the challenges around the development of suitable assessment tools to measure clinical competence. The lack of research on competence assessment, especially within an intensive care environment was also high lighted. In this, part 2, findings from a qualitative study aimed at exploring student nurses' perceptions of a new clinical competence assessment tool, recently introduced into a postgraduate intensive care nursing course are presented. Semi- structured interviews and a focus group interview were used to collect the data. Eleven students were involved in the study. The findings are presented in narrative form and in the context of literature on assessment and competence. Although the clinical competence assessment tool was in its infancy at the time of this study, the findings suggest that students not only had difficulty interpreting the language of the tool, but considered that because of its generic nature, it failed to capture the specialist skills required for intensive care nursing.


Effect of co-culturing bacteria and microalgae and influence of inoculum ratio during the biological treatment of tannery wastewater.
This present investigation is carried out to study the effect of algal and bacterial inoculum concentrations on the removal of organic pollutants and nutrients from the tannery effluent by the combined symbiotic treatment process. The bacterial and microalgal consortia was developed in laboratory setup and mixed together to perform this study. The Influence of algae and bacteria inoculum concentrations on the removal of pollutants such as Chemical Oxygen Demand (COD) and Total Kjeldahl Nitrogen (TKN) were studied using statistical optimization through Response surface methodology. For the design of experimental set up and optimization, full factorial Central composite design was used. The profiles of pH, Dissolved Oxygen (DO) and nitrate were also monitored and studied. The inoculum concentrations of microalgae and bacteria showed significant effect on Co-culturing on COD, TKN and nitrate removals as major response. The linear effect of bacterial inoculum has positive dominant influence on COD and TKN removal efficiencies. Nitrate utilization by microalgae increases with the increase in microalgal inoculum concentration. The maximum removal efficiencies of COD and TKN with 89.9% and 80.9% were obtained at optimum bacterial and algal inoculum concentrations of 6.7 g/L and 8.0 g/L respectively. These outcomes of this study are immensely favorable for maximizing the COD and nitrogen (nutrients) removal capabilities of microalgae-bacterial consortia in tannery effluent.


Percutaneous surgery: a safe procedure for trigger finger?
Trigger finger is relatively common problem among hand disorders. There are open and percutaneous surgical methods for the treatment. This study was designed to examine the mid-term results of the percutaneous surgical technique on patients with chronic trigger finger. We included 48 trigger fingers of 48 patients (36 females and 12 males). They were between the ages of 42-68 years (mean age, 52 years). We performed release of the trigger finger by using a 14-gauge needle via the percutaneous technique. We performed open surgery on the trigger fingers of 20 patients in order to evaluate the results obtained from percutaneous surgery. The patients were followed for 30 months on average (18-46 months) following the procedure. Following the procedure, pain and locking of the fingers were resolved completely. On the fingers that had open surgery, we observed that the release of the pulley was successful. Only 2 patients had minor abrasions, without any tendon injury. During the follow-up period, no complications were reported in either of the patient groups. Percutaneous surgical technique in the treatment of trigger finger is an effective, convenient and cost-effective method with a low complication rate, and is therefore a preferable alternative to open surgery.


Emissions from commercial-grade charbroiling meat operations induce oxidative stress and inflammatory responses in human bronchial epithelial cells.
Commercial charbroiling emissions are a significant source of ambient particulate matter (PM) in urban settings. The objective of this study was to determine whether organic extract of PM emissions from commercial charbroiling meat operations could induce an inflammatory response in human bronchial epithelial cells and whether this effect was mediated by oxidative stress. PM samples were collected during cooking hamburgers on a commercial-grade under-fired charbroiler and sequentially extracted with water and methanol to obtain the aqueous PM suspension (AqPM) and organic extract (OE). The pro-oxidative and pro-inflammatory effects of OE were assessed using human bronchial epithelial cell line BEAS-2B. While AqPM did not have any effect, OE effectively induced the expression of heme oxygennase-1 and cyclooxygenase-2 in BEAS-2B cells. OE also up-regulated the levels of IL-6, IL-8, and prostaglandin E2. OE-induced cellular inflammatory response could be effectively suppressed by the antioxidant N-acetyl cysteine, nuclear factor (erythroid-derived 2)-like 2 activator sulforaphane and p38 MAPK inhibitor SB203580. In conclusion, organic chemicals emitted from commercial charbroiling meat operations could induce an inflammatory response in human bronchial epithelial cells, which was mediated by oxidative stress and p38 MAPK.


The distal portion of the short arm of wheat (Triticum aestivum L.) chromosome 5D controls endosperm vitreosity and grain hardness.
Kernel vitreosity is an important trait of wheat grain, but its developmental control is not completely known. We developed back-cross seven (BC(7)) near-isogenic lines in the soft white spring wheat cultivar Alpowa that lack the distal portion of chromosome 5D short arm. From the final back-cross, 46 BC(7)F(2) plants were isolated. These plants exhibited a complete and perfect association between kernel vitreosity (i.e. vitreous, non-vitreous or mixed) and Single Kernel Characterization System (SKCS) hardness. Observed segregation of 10:28:7 fit a 1:2:1 Chi-square. BC(7)F(2) plants classified as heterozygous for both SKCS hardness and kernel vitreosity (n = 29) were selected and a single vitreous and non-vitreous kernel were selected, and grown to maturity and subjected to SKCS analysis. The resultant phenotypic ratios were, from non-vitreous kernels, 23:6:0, and from vitreous kernels, 0:1:28, soft:heterozygous:hard, respectively. Three of these BC(7)F(2) heterozygous plants were selected and 40 kernels each drawn at random, grown to maturity and subjected to SKCS analysis. Phenotypic segregation ratios were 7:27:6, 11:20:9, and 3:28:9, soft:heterozygous:hard. Chi-square analysis supported a 1:2:1 segregation for one plant but not the other two, in which cases the two homozygous classes were under-represented. Twenty-two paired BC(7)F(2):F(3) full sibs were compared for kernel hardness, weight, size, density and protein content. SKCS hardness index differed markedly, 29.4 for the lines with a complete 5DS, and 88.6 for the lines possessing the deletion. The soft non-vitreous kernels were on average significantly heavier, by nearly 20%, and were slightly larger. Density and protein contents were similar, however. The results provide strong genetic evidence that gene(s) on distal 5DS control not only kernel hardness but also the manner in which the endosperm develops, viz. whether it is vitreous or non-vitreous.


Biology and management of clear cell sarcoma: state of the art and future perspectives.
Clear cell sarcoma (CCS) is an aggressive tumor, typically developing in tendons or aponeuroses. The outcome of this orphan disease is poor, with 5-year and 10-year survival rates of localized CCS around 60-70% and 40-50%. Once the disease has metastasized, it is usually fatal due to its chemotherapy-resistant nature. Systemic treatment options are poorly standardized and the use of chemotherapy is based on weak scientific evidence. In this review, we systematically discuss the current scientific evidence for the systemic treatment of CCS, including tyrosine kinase inhibitors, immunotherapy and MET inhibitors. Expert commentary: Recent insights in the biology of CCS have identified new potential therapeutic targets, which should be tested in prospective clinical trials. Whenever possible, patients with metastatic CCS should be included in clinical trials with good biological rationale. Innovative trial methodology and new regulatory mechanisms are required to provide patients with uncommon cancers with active drugs.


Breast feeding policies in practice--'no wonder they get confused'.
This paper presents the findings on breast feeding from the Policy and Practice of Midwifery Study which is a study of midwifery care in English Health Districts. Policies and practice that concern breast feeding were studied in both a national survey of maternity units and in local in-depth studies. The paper demonstrates the variations between and anomalies within maternity hospital policies and practice on breast feeding. Findings indicate that many current practices are not consistent with the available research evidence and may actively hinder the establishment of successful breast feeding.


FoxO3 transcription factor and Sirt6 deacetylase regulate low density lipoprotein (LDL)-cholesterol homeostasis via control of the proprotein convertase subtilisin/kexin type 9 (Pcsk9) gene expression.
Elevated LDL-cholesterol is a risk factor for the development of cardiovascular disease. Thus, proper control of LDL-cholesterol homeostasis is critical for organismal health. Genetic analysis has identified PCSK9 (proprotein convertase subtilisin/kexin type 9) as a crucial gene in the regulation of LDL-cholesterol via control of LDL receptor degradation. Although biochemical characteristics and clinical implications of PCSK9 have been extensively investigated, epigenetic regulation of this gene is largely unknown. In this work we have discovered that Sirt6, an NAD(+)-dependent histone deacetylase, plays a critical role in the regulation of the Pcsk9 gene expression in mice. Hepatic Sirt6 deficiency leads to elevated Pcsk9 gene expression and LDL-cholesterol as well. Mechanistically, we have demonstrated that Sirt6 can be recruited by forkhead transcription factor FoxO3 to the proximal promoter region of the Pcsk9 gene and deacetylates histone H3 at lysines 9 and 56, thereby suppressing the gene expression. Also remarkably, overexpression of Sirt6 in high fat diet-fed mice lowers LDL-cholesterol. Overall, our data suggest that FoxO3 and Sirt6, two longevity genes, can reduce LDL-cholesterol levels through regulation of the Pcsk9 gene.


Comparison of in vivo effects of nitroglycerin and insulin on the aortic pressure waveform.
Individuals whose platelets are resistant to the antiaggregatory effects of insulin in vitro are also resistant to the antiaggregatory effects of nitroglycerin (GTN). We have previously shown that insulin acutely diminishes central wave reflection in large arteries and that this action of insulin is blunted in insulin-resistant subjects. However, as yet, no studies have compared the haemodynamic effects of insulin and GTN on large arterial function in the same group of subjects. The aim of this study was to determine whether resistance to the haemodynamic effects of insulin is a defect specific to insulin or whether individuals resistant to the vascular actions of insulin are also resistant to GTN. Dose-response characteristics of insulin and GTN on the aortic waveform were determined using applanation tonometry and pulse wave analysis (PWA) in seven healthy men (age 26 +/- 1 year, BMI 25 +/- 2 kg m(-2)). Three doses of sublingual GTN (500 microg for 1, 3 or 5 min) and insulin (0.5, 1 or 2 mU kg(-1) min(-1) for 120 min) were administered on three separate occasions. Both agents dose-dependently decreased central pulse pressure and the augmentation index (AIx) without changing brachial artery blood pressure. We next compared responses to insulin (2 mU kg(-1) min(-1) for 120 min) and sublingual GTN (500 microg for 5 min) in 20 nondiabetic subjects (age 50 +/- 2 year, BMI 21.0-36.3 kg m(-2)). Again, both agents significantly decreased AIx. Although the vascular effects of insulin and GTN vascular were positively correlated [Spearman's r=0.92 (95% confidence interval 0.81-0.97), P<0.0001], the time-course for the action GTN was faster than that of insulin. Brachial systolic blood pressure remained unchanged during the insulin infusion (122 +/- 3 vs. 121 +/- 3 mmHg, 0 vs. 120 min) but aortic systolic blood pressure decreased significantly by 30 min (111 +/- 3 vs. 107 +/- 3 mmHg, 0 vs. 30 min, P<0.01). Similarly, GTN decreased aortic systolic blood pressure from 119 +/- 4 to maximally 112 +/- 3 mmHg (P<0.001) without significantly decreasing systolic blood pressure in the brachial artery. The effects of insulin and GTN on large arterial haemodynamics are dose-dependent and significantly correlated. The exact mechanisms and sites of action of insulin and GTN in subjects with insulin resistance remain to be established.


Preparation of cupric palmitate membrane, its characterization and evaluation of thermodynamically effective fixed charge density.
Membrane potentials have been measured across parchment-supported cupric palmitate membrane separating various 1:1 electrolytes at concentrations C1 and C2 such that C2 = 10 C1. Membrane potential data have been used to calculate transference number of ions, permselectivity and also to derive the thermodynamically effective fixed charge density which is an important characteristic governing the membrane phenomena by utilizing the generally accepted and most widely used theory of Teorell-Meyer and Sievers as well as the recent theories for membrane potential of Kobatake et al. and Nagasawa et al. based on the principles of nonequilibrium thermodynamics. The values of charge densities derived from different theories were almost the same, confirming thereby the validity of the recently developed theories of membrane potential.


Relationship between serum HDL-C levels and common genetic variants of the endothelial lipase gene in Japanese school-aged children.
Endothelial lipase (EL) is a new member of the triglyceride lipase family, the genes of which play a central role in dietary fat absorption, energy homeostasis, and plasma lipoprotein metabolism. One physiologic role of EL is thought to be hydrolysis of high-density lipoprotein (HDL) phospholipid, although the precise function of endothelial lipase has yet to be fully clarified. Furthermore, genetic variation in EL has been suggested to influence serum HDL-C levels. In the present study, we detected two common single nucleotide polymorphisms in the EL gene associated with serum HDL cholesterol levels in healthy school-aged children. Our data support the hypothesis that variations in the EL gene are one of the genetic determinants of serum HDL-C levels.


Microsurgical robotic system enables the performance of microvascular anastomoses: a randomized in vivo preclinical trial.
Technical advances in microsurgery have enabled complex oncological reconstructions by performing free tissue transfers, nerve and lymphatic reconstructions. However, the manual abilities required to perform microsurgery can be affected by human fatigue and physiological tremor resulting in tissue damage and compromised outcomes. Robotic assistance has the potential to overcome issues of manual microsurgery by improving clinical value and anastomoses' outcomes. The Symani Surgical System, a robotic platform designed for microsurgery, was used in this in-vivo preclinical study using a rat animal model. The tests included anastomoses on veins and arteries performed by microsurgeons manually and robotically, with the latter approach using Symani. The anastomoses were assessed for patency, histopathology, and execution time. Patency results confirmed that the robotic and manual techniques for venous and arterial anastomoses were equivalent after anastomosis, however, the time to perform the anastomosis was longer with the use of the robot (p < 0.0001). Histological analysis showed less total average host reaction score at the anastomotic site in robotic anastomosis for both veins and arteries. This study demonstrates the equivalence of vessel patency after microsurgical anastomoses with the robotic system and with manual technique. Furthermore, robotic anastomosis has proven to be slightly superior to manual anastomosis in terms of decreased tissue damage, as shown by histological analysis.


Experiments to increase return in a medical screening drive: two futile attempts to apply theory to practice.
Two experiments are reported which attempted to apply techniques derived from an extensive set of psychological theories and research to enhance return compliance in a tuberculosis detection drive. Experiment 1 manipulated four methods of providing return reminders (postcard, telephone call, direct person-to-person or take-home card) in combination with two types of authority sources (expert vs nonexpert). Experiment 2 manipulated types of patient commitment (verbal, verbal plus written or no commitment) and importance-or-returning message (enhanced vs standard) in combination with two types of return reminders (take-home card vs no reminder card). These theoretically-derived procedures failed to significantly enhance return compliance. The experiments are examined for procedural failures and the findings are discussed in terms of the limited applicability of some theoretical notions in health settings and particular populations. It is asserted that through such failures useful knowledge is gained for understanding the complex phenomenon of compliance.


[Acute heart failure in patients over 70 years of age: Precipitating factors of decompensation].
Heart failure decompensation is the most common reason for hospitalization in persons over 65 years old. There is limited information on the prevalence of precipitating factors of heart failure decompensation in this population. In this study we prospectively examined the factors associated with decompensation of heart failure in patients over 70 years of age. During the 36 months from January 2006 to December 2008, we included 386 patients over 70 years of age that were admitted through emergencies with these three criteria: Dyspnea (class III or IV of the New Yourk Heart Association), pulmonary edema and echocardiographic data of left ventricular systolic or diastolic dysfunction. The mean age of the patients was 82 years and 58.5% were female. Left ventricular systolic dysfunction was diagnosed in 41.2% of them. We identified one or more precipitating factors of heart failure decompensation in 89.6% of the patients. The most common were atrial tachyarrhythmia (22.3%), respiratory infection (21.2%), severe anemia (17.1%), acute renal failure (12.7%), severe hypoalbuminemia (11.4%) and acute coronary syndrome (9.1%). Fifty-two patients (13.5%) died. The variables independently associated with hospital mortality were acute renal failure, severe hypoalbuminemia, systolic blood pressure <110mmHg, white blood cell count >10.000 per mm³ and valvular heart disease. In most patients over 70 years of age hospitalized with acute heart failure it is possible to identify one or more precipitating factors of decompensation, some of which are independently associated with hospital mortality.


The light-addressable potentiometric sensor for multi-ion sensing and imaging.
The light-addressable potentiometric sensor (LAPS) is a semiconductor-based chemical sensor with an electrolyte-insulator-semiconductor structure. The LAPS can have many measuring points integrated on the sensing surface, which are individually accessed by a light beam. By modifying the measuring points with different materials, a single sensor plate can be used as a multi-analyte sensor. In this paper, instrumentation and application of LAPS to multi-ion sensing and imaging are described. As a new application of LAPS, potentiometric imaging of a microfluidic channel is proposed.


Behavioral profiles in Rett syndrome: Data from the natural history study.
Rett syndrome (RTT) is a complex neurodevelopmental disorder with known behavioral abnormalities, both internalizing (e.g., anxiety, social withdrawal) and externalizing (e.g., aggression, self-abuse). However, a broad evaluation of behavioral abnormalities in a large cohort is lacking. In this report, we describe profiles of internalizing and externalizing behaviors in individuals evaluated in the multi-center U.S. Rett Natural History Study. Cross-sectional and longitudinal data were collected from 861 females with RTT and from 48 females who have MECP2 mutations without meeting criteria for RTT. Standard statistical methods including linear regression evaluated internalizing behavioral components from the Child Health Questionnaire (CHQ-PF50) and externalizing components from the Motor Behavioral Assessment (MBA). We found mildly to moderately severe internalizing behaviors in nearly all individuals with RTT, while externalizing behaviors were mild and uncommon. Internalizing behavior in RTT was comparable to groups with psychiatric disorders. Participants with mixed (internalizing and externalizing) behaviors were younger and less affected overall, but showed prominent self-injury and worsening internalizing behaviors over time. This study revealed that internalizing behaviors are common at a clinically significant level in RTT. Understanding clinical features associated with behavioral profiles could guide treatment strategies.


Prognostic and immune infiltrative biomarkers of CENPO in pan-cancer and its relationship with lung adenocarcinoma cell proliferation and metastasis.
The centromere protein O (CENPO) is an important member of the centromere protein family. However, the role of CENPO in pan-cancer and immune infiltration has not been reported. Here, we investigated the role of CENPO in pan-cancer and further validated its role in lung adenocarcinoma (LUAD) by in vitro experiments. The UCSC Xena database and The Cancer Genome Atlas (TCGA)-LUAD data were used to assess the expression levels of CENPO. The potential value of CENPO as a diagnostic and prognostic biomarker for pan-cancer was evaluated using TCGA data and the GEPIA database. The -expression profiles of LUAD patients and the corresponding clinical data were downloaded for correlation analysis. The role of CENPO in immune infiltration was investigated using the UCSC Xena database. Subsequently, qRT-PCR was performed to detect the expression of CENPO. Cell proliferation, migration, and invasion were determined using CCK-8, wound-healing assay, and transwell assay, respectively. CENPO is highly expressed in most cancers, and the upregulation of CENPO is associated with poor prognosis in many cancers. CENPO expression correlates with age, TNM stage, N stage, T stage, and receipt of radiotherapy in LUAD patients, and LUAD patients with high CENPO expression have poorer overall survival (OS) and disease-free survival (DFS). In addition, CENPO expression is associated with immune cell infiltration and immune checkpoint inhibitors. Moreover, the expression of CENPO was closely related to the expression of tumor mutational load and microsatellite instability. In vitro experiments showed that CENPO expression was increased in LUAD cell lines and that knockdown of CENPO significantly inhibited the proliferation, cell invasion, and migration ability of LUAD cells. CENPO may be a potential pan-cancer biomarker and oncogene, especially in LUAD. In addition, CENPO is associated with immune cell infiltration and may serve as a new molecular therapeutic target and effective prognostic marker for LUAD.


Biological properties of mouse interferon bound to a high molecular weight carrier: Blue Dextran 2000.
Mouse C-243 cell interferon (IF) binds to Blue Dextran 2000 (BD). The BD-IF complex could be precipitated by polyethylene glycol. When 0.05 to 0.2 per cent solutions of BD were used for binding IF, the recovery of IF activity in the sediment was complete. The BD-IF complex was shown to have high antiviral activity, it was stable for months at 4 degrees C but it was inactivated by heating at 37 degrees, 56 degrees and 65 degrees C as native IF. The rate of clearance of IF bound to BD from the mouse peritoneal cavity was found to be significantly slower than that of native IF. The BD-IF complex was highly immunogenic for rabbits and sheep. Furthermore, the BD-IF complex was neutralized to a greater extent by specific antibodies than native IF.


Full monosomy 21: a clinically recognizable syndrome?
A female newborn with multiple malformations and with full monosomy 21 is described. Clinical resemblance to the three cases described in the literature is striking.


Actuarial survival, freedom from reoperation, and other events after repair of atrioventricular septal defects.
Repair of an atrioventricular septal defect was performed in 134 patients from 1973 to 1985. Interventricular communication was present in 54 (40%) and none was present in 80 (60%). There were 12 hospital deaths (9%; 70% confidence limits 6%-12%). Earlier date of operation (p = 0.03) and younger age at repair (p = 0.005) were incremental risk factors for hospital death after repair of partial atrioventricular septal defect. Smaller size (p = 0.003) and longer cross-clamp time (p = 0.002) were risk factors for hospital death in those patients with complete atrioventricular septal defect. Higher preoperative pulmonary vascular resistance was a risk factor for death in both groups (p = 0.007). The 10 year actuarial survival rate was 82% overall. Increasing preoperative severity of left atrioventricular valve incompetence was not a risk factor for early (p = 0.001) or late (p = 0.002) death. The 10 year actuarial freedom from reoperation after repair of partial atrioventricular defects was 85%, and it was 68% for complete atrioventricular defects (p = 0.06). We conclude that the intermediate term results after repair of atrioventricular septal defects are good. Incompetence of the left atrioventricular valve has apparently been neutralized as a risk factor for hospital death in this series. However, the durability of the repair has been disappointing. A policy of earlier repair has been adopted and should improve hospital mortality and permit better preservation of the atrioventricular valve structures with resultant improved late term functional status.


The Partnership of Medical Genetics and Oral and Maxillofacial Surgery When Evaluating Craniofacial Anomalies.
A medical geneticist who has an interest in craniofacial anomalies forms a natural partnership with an oral and maxillofacial surgeon, which facilitates patient care. Using complementary diagnostic and therapeutic skills, the search for a recognizable pattern can lead to a syndrome diagnosis. After the initial examination, there is usually genetic testing to confirm the clinical diagnosis. Once established, care coordination and genetic counseling can be provided for the parents and the patient. Enrolling the patient into a research study could be helpful to understand the diagnosis but, in some circumstances, might not have immediate clinical relevance. A multidisciplinary craniofacial team is generally necessary for long-term management. This article discusses illustrative patients evaluated from 2007 through 2011 with the senior oral and maxillofacial surgeon at the Massachusetts General Hospital (Leonard B. Kaban, DMD, MD). These include single patients with the Nablus mask-like facies syndrome and auriculo-condylar syndrome and a series of 20 patients with Gorlin syndrome followed by a multispecialty team. A successful collaboration between a medical geneticist and an oral and maxillofacial surgeon optimizes the treatment of patients with craniofacial anomalies.


Human regeneration: An achievable goal or a dream?
The main objective of regenerative medicine is to replenish cells or tissues or even to restore different body parts that are lost or damaged due to disease, injury and aging. Several avenues have been explored over many decades to address the fascinating problem of regeneration at the cell, tissue and organ levels. Here we discuss some of the primary approaches adopted by researchers in the context of enhancing the regenerating ability of mammals. Natural regeneration can occur in different animal species, and the underlying mechanism is highly relevant to regenerative medicine-based intervention. Significant progress has been achieved in understanding the endogenous regeneration in urodeles and fishes with the hope that they could help to reach our goal of designing future strategies for human regeneration.


Evidence, detailed characterization and clinical context of complement activation in acute multisystem inflammatory syndrome in children.
Multisystem inflammatory syndrome in children (MIS-C) is a rare, life-threatening complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. MIS-C develops with high fever, marked inflammation and shock-like picture several weeks after exposure to, or mild infection with SARS-CoV-2. Deep immune profiling identified activated macrophages, neutrophils, B-plasmablasts and CD8 + T cells as key determinants of pathogenesis together with multiple inflammatory markers. The disease rapidly responds to intravenous immunoglobulin (IVIG) treatment with clear changes of immune features. Here we present the results of a comprehensive analysis of the complement system in the context of MIS-C activity and describe characteristic changes during IVIG treatment. We show that activation markers of the classical, alternative and terminal pathways are highly elevated, that the activation is largely independent of anti-SARS-CoV-2 humoral immune response, but is strongly associated with markers of macrophage activation. Decrease of complement activation is closely associated with rapid improvement of MIS-C after IVIG treatment.


ATP synthesis at physiological nucleotide concentrations.
Synthesis of ATP by the F1F0 ATP synthase in mitochondria and most bacteria is energized by the proton motive force (pmf) established and maintained by respiratory chain enzymes. Conversely, in the presence of ATP and in the absence of a pmf, the enzyme works as an ATP-driven proton pump. Here, we investigate how high concentrations of ATP affect the enzymatic activity of the F1F0 ATP synthase under high pmf conditions, which is the typical situation in mitochondria or growing bacteria. Using the ATP analogue adenosine 5'-O-(1-thiotriphosphate) (ATPαS), we have developed a modified luminescence-based assay to measure ATP synthesis in the presence of millimolar ATP concentrations, replacing an assay using radioactive nucleotides. In inverted membrane vesicles of E. coli, we found that under saturating pmf conditions, ATP synthesis was reduced to ~10% at 5 mM ATPαS. This reduction was reversed by ADP, but not Pi, indicating that the ATP/ADP ratio controls the ATP synthesis rate. Our data suggests that the ATP/ADP ratio ~30 in growing E. coli limits the ATP synthesis rate to ~20% of the maximal rate possible at the applied pmf and that the rate reduction occurs via product inhibition rather than an increased ATP hydrolysis rate.


Mind Map: a new way to teach patients and staff.
As home care agencies look for new ways to achieve patient outcomes and staff competencies in a cost-effective manner, Mind Map is a method that can be used to quickly organize patient and staff education while evaluating the learner's comprehension of critical information.


Musculoskeletal load of municipal employees aged 44 to 58 years in different occupational groups.
This study is part of a comprehensive multidisciplinary project aimed at determining criteria for retirement ages in municipal occupations in Finland. Musculoskeletal load at work was studied in eight different occupational groups to see what differences between occupational groups exist. A job analysis of the work of 116 subjects was made with the ergonomic job description analysis method (AET). The work of 116 men and women, mean age 52 years, was studied in the work place. The study revealed three levels of overall musculoskeletal load. The groups with high musculoskeletal load worked in installation, auxiliary, home care and transport groups, with an assessed load of on average about one third of the maximal on the AET scale. Both quantitative and qualitative loading problems were concentrated in these groups. In contrast, teaching and administration groups had low musculoskeletal load averaging about 10% of the maximal. The nursing and office groups were between these two levels with a load of approximately 20% of the maximal. However, with the same overall quantity, the quality of the musculoskeletal load varied. In the transport group, monotonous static work with both arms (about 60% of workshift) and legs (30%) was most common, while the musculoskeletal load of the auxiliary and home care groups consisted of heavy dynamic muscular work with arms (60% of workshift) and legs (70%). On the other hand, the administration group alone had a static load of the arms (about 15% of workshift) and legs (2%) and also a low dynamic load with arms (0%) and legs (33%), which could have hypokinetic effects. In conclusion, there are significant differences between the profile groups in both the quantitative and qualitative load of the musculoskeletal system. The differences are even more pronounced when aging employees are studied. These facts support different retirement ages for the profile groups, at least when the musculoskeletal system is concerned.


Ultrasound in Early Pregnancy: Viability, Unknown Locations, and Ectopic Pregnancies.
Ultrasound is essential in the evaluation and management of pregnancies of unknown location. Differential diagnoses include early pregnancy loss, pregnancy of unknown location, and ectopic pregnancies. Both transabdominal and transvaginal routes should be available, in addition to physical examination, for complete evaluation. Diagnostic criteria for early pregnancy loss have expanded in recent years to ensure false positive results do not lead to inappropriate evacuation of desired pregnancies.


Studying Neutrophil Migration In Vivo Using Adoptive Cell Transfer.
Adoptive cell transfer experiments can be used to study the roles of cell trafficking molecules on the migratory behavior of specific immune cell populations in vivo. Chemoattractants and their G protein-coupled seven-transmembrane-spanning receptors regulate migration of cells in vivo, and dysregulated expression of chemoattractants and their receptors is implicated in autoimmune and inflammatory diseases. Inflammatory arthritides, such as rheumatoid arthritis (RA), are characterized by the recruitment of inflammatory cells into joints. The K/BxN serum transfer mouse model of inflammatory arthritis shares many similar features with RA. In this autoantibody-induced model of arthritis, neutrophils are the critical immune cells necessary for the development of joint inflammation and damage. We have used adoptive neutrophil transfer to define the contributions of chemoattractant receptors, cytokines, and activation receptors expressed on neutrophils that critically regulate their entry into the inflamed joint. In this review, we describe the procedure of neutrophil adoptive transfer to study the influence of neutrophil-specific receptors or mediators upon the their recruitment into the joint using the K/BxN model of inflammatory arthritis as a model of how adoptive cell transfer studies can be used to study immune cell migration in vivo.


Is localized acquired resistance the mechanism for effector-triggered disease resistance in plants?
Plant nucleotide-binding leucine-rich repeat receptors (NLRs) are intracellular immune receptors that are activated by their direct or indirect interactions with virulence effectors. NLR activation triggers a strong immune response and consequent disease resistance. However, the NLR-driven immune response can be targeted by virulence effectors. It is thus unclear how immune activation can occur concomitantly with virulence effector suppression of immunity. Recent observations suggest that the activation of effector-triggered immunity does not sustain defence gene expression in tissues in contact with the hemi-biotrophic pathogen Pseudomonas syringae pv. tomato. Instead, strong defence was observed on the border of the infection area. This response is reminiscent of localized acquired resistance (LAR). LAR is a strong defence response occurring in a ~2 mm area around cells in contact with the pathogen and probably serves to prevent the spread of pathogens. Here we propose that effector-triggered immunity is essentially a quarantining mechanism to prevent systemic pathogen spread and disease, and that the induction of LAR is a key component of this mechanism.


1,1'-Ethylidenebis(tryptophan) (Peak E) induces functional activation of human eosinophils and interleukin 5 production from T lymphocytes: association of eosinophilia-myalgia syndrome with a L-tryptophan contaminant.
This study was designed to clarify the important association between eosinophilia-myalgia syndrome (EMS) and the L-tryptophan contaminant, "Peak E." To determine the functional activation of eosinophils induced by Peak E, eosinophil cationic protein (ECP) release was examined. Peak E augumented the release of ECP from peripheral blood normodense eosinophils by degranulation. Proliferative analysis using the human eosinophilic leukemia cell line EoL-3 showed prominent cellular replication in the presence of Peak E. Moreover, Peak E upregulated interleukin 5 (IL-5) receptor levels on normodense eosinophils. Of particular interest, Peak E-stimulated human splenic T cells produced bioactive and immunoreactive IL-5. Marked induction of IL-5 mRNA in Peak E-stimulated T cells was also shown by reverse-transcriptase polymerase chain reaction (RT-PCR). In contrast, L-tryptophan without the contaminant showed none of these effects. Thus, these data suggest that Peak E might be involved in the pathogenesis of EMS through bimodal mechanism including IL-5 generation by T cells and potentiation of eosinophil functional activation.


Therapeutic limited bronchoalveolar lavage with fiberoptic bronchoscopy as a bridging procedure prior to total lung lavage in a patient with pulmonary alveolar proteinosis: a case report.
Therapeutic total lung lavage under general anesthesia is the current mainstay of treatment for pulmonary alveolar proteinosis, which is a rare lung disease characterized by alveolar accumulation of surfactant. Therapeutic limited bronchoalveolar lavage is considered an alternative treatment to conventional total lung lavage. A 61-year-old, previously healthy, Sri Lankan Moor woman presented to our facility with progressively worsening difficulty in breathing and persistent dry cough for one year. Her respiratory examination revealed bibasal fine end-inspiratory crepitations. A chest radiograph showed bilateral mid and lower zone alveolar interstitial shadows and a high-resolution computed tomography scan of her chest revealed septal thickening with ground-glass shadows more on mid and lower zones bilaterally. A diagnostic bronchoalveolar lavage fluid analysis revealed diastase-resistant protein clumps in periodic acid Schiff stain. The diagnosis was made as pulmonary alveolar proteinosis. An arterial blood gas analysis performed prior to intervention revealed a significant hypoxia (partial pressure of oxygen - 64 mmHg) with alveolar-arterial gradient was 35.4 mmHg. Therapeutic limited bronchoalveolar lavage was arranged and her right and her left lung were lavaged separately in two sessions done two weeks apart under local anesthesia. Our patient had significant clinical improvement and resolution of the bilateral septal thickening with minimal resolution of the ground-glass opacities in a repeat high-resolution computed tomography scan done two weeks later. Subsequently, a total lung lavage under general anesthesia was also done, which improved her dyspnea and arterial hypoxemia. Therapeutic limited bronchoalveolar lavage can be successfully performed as an interval bridging procedure, as a 'prewash', prior to conventional total lung lavage for pulmonary alveolar proteinosis.


Electrostatic modeling of ion pores. II. Effects attributable to the membrane dipole potential.
This paper presents calculations of the shielded dipole potential in the interior of a pore piercing a lipid membrane that is at a potential V0 with respect to the aqueous solution. Except in the case of long narrow pores, there is substantial shielding of the membrane dipole potential. The associated dipole field never extends a significant distance into the aqueous region. The fact that the single-channel conductance of gramicidin B is only twice as large in glyceryl monooleate membranes as in phosphatidyl choline (PC) membranes, even though PC is approximately 120 mV more positive with respect to water, is interpreted in terms of the potential energy profile calculated for a gramicidin-like channel. It is demonstrated that the membrane dipole potential can significantly affect channel conductance only if the pore is narrow and if the peak in the potential energy profile occurs in the pore interior.


Quality of life of very young spina bifida patients after initial surgical treatment.
The objectives of this study were to assess the quality of life (QOL) of operated patients with spina bifida (SB) in their initial years and to elucidate the factors affecting the QOL and the timing of proposed interventions. We studied 18 patients operated on for SB, aging 3 years or more at the time of assessment. The quality of life score was calculated for all the patients by the parental-administered questionnaire method. The impact of all these factors on the social and school lives of these patients was studied. Eleven patients were having neurogenic bladder. Thirteen patients were having stool problems which ranged from mild to severe constipation and soiling. Five patients were having lower limb deformities interfering with normal ambulation. Ten patients were able to walk on their own without any help, four patients were using either crutches or help of the caregiver for ambulation while the remaining four patients were non-ambulatory. Twelve patients were attending school. The calculated QOL scores ranged from 2 to 15. The Barthel Index (BI) ranged from 15 to 100. The QOL questionnaire score and BI were showing significant positive correlation. The patients operated on for SB commonly have the neurological sequelae. The QOL score identifies the important problems in the initial years after surgery which can help in initiating and maintaining rehabilitative services in these patients. The treatment of urinary and fecal incontinence very early in life will allow these children to have a normal social and school life.


Symptomatic intracranial pneumatocele from mastoid sinus of spontaneous origin. Case report.
A case of a large intracranial pneumatocele arising from mastoid air cells is reported. The patient became symptomatic after multiple coughing spells and required craniotomy for repair of the dural hiatus. The possible etiology of such a large spontaneous pneumatocele is discussed in the context of a review of the pertinent literature.


Malignancies presenting at a performing arts medicine clinic.
Four performing artists with musculoskeletal complaints were found to have an underlying malignancy.


[Superior cervical ganglion: an anatomical variant. Are variations of the cranial carotid artery a risk factor for accidental intravascular injection?].
A variation of the cranial carotid artery is demonstrated in an anatomical specimen revealing possible complications of ganglionic local opioid analgesia at the superior cervical ganglion. Located in the area of the puncture site, a loop of the aberrant carotid artery adheres closely to the pharyngeal wall in the medial position, shortening the distance between the arterial lumen and the oral cavity to 5 mm. With an incidence of 25%, an aberrant carotid artery could possibly facilitate an accidental intravascular injection during ganglionic local opioid application at the superior cervical ganglion.


Electrolyte redistribution in cystic fibrosis fibroblasts studied by electron probe X-ray microanalysis.
The elemental composition of fibroblasts from cystic fibrosis (CF) patients and from healthy controls was compared by means of electron probe X-ray micro-analysis. Significantly lower sodium levels (p < .01) and higher calcium levels (p < .02) were found in CF fibroblasts, indicating a disturbance of ion regulation in these cells. Treatment with Staphylococcus aureus protein A and gammaglobulin (proteins that may influence the ciliotoxic CF factor) did not change the elemental composition of the fibroblasts.


Biophysical characterization of OprB, a glucose-inducible porin of Pseudomonas aeruginosa.
OprB, a glucose-inducible porin of P. aeruginosa, was characterized by black lipid bilayer analysis and circular dichroism spectroscopy. Black lipid bilayer analysis of OprB revealed a single-channel conductance of 25 pS, the presence of a glucose binding site with a Ks for glucose of 380 +/- 40 mM, and the formation of channels with a strong selection for anions. Analysis of P. aeruginosa OprB circular dichroism spectra revealed a high beta sheet content (40%) which is within the range of that determined for other porins. Values obtained from black lipid bilayer analysis were compared to those previously obtained for OprB of P. putida [Saravolac et al. (1991). J. Bacteriol. 173, 4970-4976] and indicated extensive similarities in the single-channel conductance and glucose-binding properties of these two porins. Immunological and amino terminal sequence analysis revealed a high degree of homology. Of the first 14 amino terminal residues, 12 were identical. A major difference between the two porins was found in their ion selectivity. Whereas P. aeruginosa OprB is anion selective, P. putida OprB and other carbohydrate selective porins are known to be cation selective.


Esthetics and psyche-part 1: assessment of the influence of patients' perceptions of body image and body experience on selection of existing natural tooth color.
The aim of this research was to test the hypothesis that patients' attitudes toward their body affect their capacity to accurately select their existing natural tooth color. Standard validated psychologic assessments were used to determine a person's perception of body image and experience. Oral images were compared with the patients' perceptions of their natural tooth color, which were then compared with the actual tooth color judged by a dental professional. For the vital body dynamic and disliking body experience subscales, women exhibited a significantly more negative attitude toward their bodies than men (P = .000). Patients with a negative attitude toward their body tended to choose a lighter tooth color. The correlation between patients' and the testing physician's choices of color was r = 0.540 for women and r = 0.746 for men. Unhappiness with body image and experience results in poor perception of a patient's own oral image, which in turn results in a patient perceiving that his or her natural tooth color is lighter than that judged by a dental professional. This has clinical implications when trying to achieve patient satisfaction with dental prostheses.


Challenges in the pre- and post-natal diagnosis of posterior fossa cysts: A case report and review of historical evolution of descriptive terminologies.
Radiological diagnoses of posterior fossa cystic abnormalities during antenatal and postnatal periods pose significant challenges as they may have similar early imaging features. Some of the frequently described entities are arachnoid cysts and Dandy-Walker malformations. Blake's pouch cyst is relatively underdiagnosed. The main aim of the study was to explore these diagnostic challenges in the context of various descriptive terminologies and their prognostic implications. We illustrate this through our case, where fetal magnetic resonance imaging (MRI) at 36 weeks gestation showed small right cerebellum without hydrocephalus or hemorrhage. Possible differential diagnoses included Dandy-Walker malformation or posterior fossa malformations, facial hemangiomas, arterial anomalies, cardiac and eye anomalies, sternal clefting, and supraumbilical raphe. Postnatal sonography noted posterior fossa cyst without hydrocephalus in a normal term infant, who went on to develop symptomatic hydrocephalus by 15 weeks. Computed tomography brain scan confirmed large subtentorial posterior fossa cyst and extensive internal hydrocephalus. Despite emergent ventriculoperitoneal shunt insertion, head circumference continued to rise. MRI scan showed persistent cyst. Subsequently, infant underwent endoscopic fenestration of the cyst with balloon septostomy and now has an age appropriate developmental profile. There is considerable discordance between antenatal and postnatal neuroimaging findings as highlighted in our case. Diagnostic conundrum here was whether this was an arachnoid or Blake's pouch cyst. Differentiating between posterior fossa fluid collections is crucial for management, prognosis, and parental counseling. Close postnatal follow-up is essential to avert complications due to acute hydrocephalus.


Which medical and social decision topics are important after early diagnosis of Alzheimer's Disease from the perspectives of people with Alzheimer's Disease, spouses and professionals?
The relevance of early decision making will rise with increasing availability of early detection of Alzheimer's disease (AD) using brain imaging or biomarkers. Five people with mild AD, six relatives and 13 healthcare professionals with experience in the management of AD were interviewed in a qualitative study regarding medical and social decision topics that emerge after early diagnosis of Alzheimer's disease. Medical treatment, assistance in everyday life and legal issues emerged as the main decision topics after an early diagnosis of AD. People with AD mostly got in contact with the health and social care system through the initiative of their spouses. They were usually aware of their illness and most received antidementia drugs and/or behavioural interventions. Following diagnosis people with AD received support by their spouses. Healthcare professionals were aware of the risk of excessive demand on relatives due to supporting their family member with AD. In the opinion of healthcare professionals legal issues should be arranged in time before patients lose their decisional capacity. In addition, people with AD and spouses reported various coping strategies, in particular "carry on as normal" after diagnosis but mostly are reluctant to actively plan for future stages of the disease. Due to the common desire to "carry on as usual" after a diagnosis of AD, many people with AD and spouses may miss the opportunity to discuss and decide on important medical and social topics. A structured approach e.g. a decision aid might support people with AD and spouses in their decision making process and thereby preserve persons' with AD autonomy before they lose the capacity in decision-making.


Molecular detection and typing of duck hepatitis A virus directly from clinical specimens.
To develop a new approach for the detection and typing of duck hepatitis A virus (DHAV), a pair of non-degenerate primers was designed to amplify a approximately 250-bp genomic region in the 5'UTR. 3 reference strains and 6 duck embryo-derived isolates from various regions in China, involving 2 serotypes, were successfully amplified with the primer set. By determining the nucleotide sequence of the amplicon, a molecular typing method was developed. If isolate sequences were compared to DHAV 5'UTR sequences available in public databases, nucleotide identity was > or =94% with homologous serotype and < or =73% with heterologous serotypes. Phylogenetic analysis revealed monophyletic clustering of 5'UTR sequences of a homologous serotype, confirming the new classification of DHAV (serotype 1 and the two new serotypes recently described in Taiwan and South Korea, respectively) into three genotypes (A, B and C) defined by the capsid coding region. Analysis of the results showed that the primer pair should aid in the detection of DHAV, and that the amplicon sequence contains type-specific information and can be used for effective and rapid molecular typing. The molecular methods proved their utility through the detection and typing of DHAV directly from 28 liver specimens collected from dead ducklings during duck viral hepatitis outbreaks in different regions of China between 2001 and 2007. The results confirmed the presence of DHAV in all of the 28 samples and demonstrated that genotypes A (13/28) and C (15/28) of DHAV are co-circulating in China.


Piecemeal degranulation (PMD) morphology in feline circulating eosinophils.
Buffy coat preparation from six cats with 600-4560 circulating eosinophils/microL was collected by either blood centrifugation or sedimentation, fixed in 2.5% glutaraldehyde, post-fixed in either 1% osmium or in 1.5% potassium ferrocyanide-reduced osmium, ultra-sectioned and examined by transmission electron microscopy. Ultrastructural changes of piecemeal degranulation (PMD), which is a mechanism of eosinophil granule contents release indicative of eosinophil activation, were observed in specific granules from all the samples examined. The spectrum of PMD included coarsening of the granule matrix, budding vesicles, fragmented granule cores and lucent granules. The number of presumably activated eosinophils with ultrastructural evidence of PMD did not correlate with the level of eosinophilia. The lack of correlation suggested that, analogously with humans, blood eosinophil count might not represent the best criterion to evaluate the contribution of eosinophils to tissue damage in certain feline eosinophil-associated diseases.


Expression of a monocyte-specific esterase isoenzyme in cases of acute myeloid leukemias.
The carboxylic esterase (E.C. 184.108.40.206) isoenzymes from cases of acute myeloid leukemias were separated by analytical isoelectric focusing on horizontal thin-layer gels. One isoenzyme consisting of one or two components (bands) could be completely and selectively inhibited by addition of 40 mM sodium fluoride (NaF) to the staining bath. The 105 cases were classified into the groups M1-M6 according to the FAB proposals. The NaF-sensitive isoenzyme was not detected in cases of FAB groups M1/2 (acute myeloblastic leukemia without or with maturation), group M3 (acute promyelocytic leukemia) or group M6 (erythroleukemia). Thirty-one out of 33 cases in the FAB group M4 (acute myelomonocytic leukemia) and 9/9 cases in FAB group M5 (acute monocytic leukemia) expressed the NaF-sensitive isoenzyme. The NaF-sensitive isoenzyme was found at different staining intensities; all M5 cases showed the isoenzyme at strong or very strong intensity, whereas most of the M4 cases displayed the isoenzyme at weak, medium or strong staining intensity. The data presented are further evidence that the presence of the NaF-sensitive esterase isoenzyme indicates monocytic involvement or differentiation in cases of myeloid leukemias. The easy and fast to perform method of isoelectric focusing can be used to distinguish the monocytic variants among the acute myeloid leukemias and can supplement the morphological analysis of these cases.


Characterizing imidacloprid and metabolites in songbird blood with applications for diagnosing field exposures.
Neonicotinoids are the most widely used insecticides globally, but their rapid metabolism in vertebrates makes diagnosing wildlife exposure challenging. More detailed information on the pattern of imidacloprid metabolites over time could be used to better approximate the timing and level of exposure. Here, we applied recently developed sensitive analytical methods to measure imidacloprid (IMI) parent compound along with an expanded suite of metabolites (5-OH-IMI, IMI-olefin, desnitro-IMI, IMI-urea, 6-chloronicotinic acid, 5-AMCP, 6-OH nicotinic acid) and six other neonicotinoids in adult red-winged blackbirds (Agelaius phoeniceus) that were experimentally exposed to one of two field-realistic concentrations of imidacloprid (0.8 or 6.9 mg/kg bw). We measured concentrations in small (25 μL) plasma samples collected pre-exposure and at 1-, 6-, 24- and 48-h post-exposure. Imidacloprid was rapidly absorbed and metabolized within 48 h at both doses, with the largest decrease within 6 h post-exposure. The average proportion of parent IMI decreased from 68% of total detectable residues at 1-h to 34% at 6-h post-exposure. Two primary metabolites in blood were 5-OH-IMI and IMI-olefin, and 5-OH-IMI was the most persistent marker of exposure at 48-h. Desnitro-IMI was consistently detected following very recent (≤ 1-h) IMI exposure, and a higher ratio of parent IMI to metabolites also indicated recent exposure. Other metabolites were only detected in the higher dose group, and could be used as indicators of exposure to higher IMI concentrations. This sensitive analytical method and the observed metabolite patterns could be used to inform a growing body of field studies linking neonicotinoid exposure and effects in free-living birds.


Concentration responses of toxicity sensor with Shewanella oneidensis MR-1 growing in bioelectrochemical systems.
Bioelectrochemical systems (BESs) provide an opportunity to detect biological toxicity of water samples. However, the concentration responses of toxins had not been investigated in detail. Using formaldehyde as a toxic substance, the current responses were analyzed over a concentration range from 0.01% to 0.10% in a single chambered BES with 0mV (versus saturated calomel electrode) applied on the anode. The decay percentages of currents increased in proportion with the concentration of formaldehyde after 10000s (∼2.8h), with the peak R(2) of 0.9361 observed at 35,000s (∼9.7h). Fitting results of exponential decay equation showed that the magnification factor (a) closely related with baseline currents and the toxicity factor (b) was in direct proportion to formaldehyde concentration (from 0% to 0.08%) except over the high concentration of 0.10%. These results provide preliminary information about toxin concentration responses in BESs.


Determining severe respiratory distress in older out-of-hospital patients.
This preliminary investigation represents the first step in developing a clinical decision rule (CDR) to assist out-of-hospital providers in caring for older patients in respiratory distress. The specific aims of the study were: 1) to identify up to ten candidate clinical indicators of severe respiratory distress in older out-of-hospital patients and 2) to determine the feasibility of obtaining data on these indicators from out-of-hospital treatment records, and of obtaining a measure of severe respiratory distress from the emergency department (ED) medical record. This mixed-methods study included a qualitative component to list possible clinical indicators of severe respiratory distress, and a Delphi survey N = six experts) to reduce the comprehensive list that resulted (aim 1). The feasibility of gathering clinical indicators and a measure of severe distress was evaluated using a retrospective chart review (N = 640) of out-of-hospital and ED medical records (aim 2). Nine clinical indicators were identified: level of consciousness/mentation, inability to speak in full sentences, position of the patient on arrival, decreased oxygen saturation, accessory muscle use, dyspnea, increased respiratory effort, altered respiratory rate, and retractions. There were sufficient data available on all indicators except dyspnea and retractions; a measure of severe distress was readily obtained from the ED medical record. Medical record data were available on seven out-of-hospital clinical indicators and an ED measure of severe distress. Further work needs to be done to refine the operational definitions of the indicators and to standardize the way they are documented in the out-of-hospital medical record.


Satisfactory functional results and complication rates after anterior glenoid bone block reconstruction in recurrent shoulder dislocation: a mean 4-year follow-up comparative study.
Anterior recurrent instability of the glenohumeral joint is a common clinical problem among the young population. Glenoid reconstruction with bone graft has become the treatment of choice, particularly in significant deficiency (˃20%). This study aims to assess the functional results of glenoid reconstruction using Latarjet and iliac bone graft in the management of glenoid insufficiency associated with recurrent anterior dislocation of the glenohumeral joint. Patients suffering from anterior shoulder instability with glenoid defect >20% were included in this study between 2016 and 2021. The university of California at Los Angeles (UCLA) shoulder scale and Constant score were used to assess the functional improvement. Preoperative and final postoperative continuous outcomes were compared with a one-tailed paired t-test and the outcomes across groups were compared using a two-tailed independent t-test. A P-value of <0.05 was considered statistically significant for both tests. This trial included 50 patients; twenty-five underwent mini-open Latarjet, and 25 underwent arthroscopic tricortical iliac crest bone grafting (ICBG). The mean follow-up durations were 50.1 ± 5.9 months for Laterjet and 51.6 ± 6.8 months for ICBG. Both techniques showed statistically significant improvement in the final UCLA (31.1 ± 2.1 in Laterjet and 30.2 ± 2.2 in ICBG) and Constant (90.2 ± 4.6 in Laterjet and 89 ± 5.01 in ICBG) scores. There was no statistically significant difference regarding mean age, sex, side of injury, mechanism of injury, follow-up period and clinical outcome between both surgical treatments. At the end of the study, both groups demonstrated statistically significant improvement in the range of motion (p ˂ 0.00001). Only one, non-adherent patient in Laterjet group had post-operative dislocation. In ICBG group, two patients had partial bone graft resorption, 3 graft site morbidities and 1 hardware prominence. Both Laterjet and iliac bone graft procedures had satisfactory functional results in reconstruction of glenoid defect >20% in unstable shoulders with a mean 4-year follow-up. No statistically significant difference was reported in the last postoperative Constant and UCLA scores between both techniques, but Latarjet procedure had fewer complications (4%) than ICBG (24%). Prospective non-randomized comparative study; level II.


Adolescent morphine induces emotional signs of withdrawal paired with neurotoxicity selectively in male rats: Female resilience.
This study evaluated the immediate and persistent behavioral and molecular consequences (i.e., emotional signs emerging during withdrawal and signs of neurotoxicity) following adolescent morphine exposure with a sex perspective. Basally, and prior to drug treatment, adolescent female rats showed smaller body weight and lower pain threshold than their male counterparts. Adolescent morphine treatment induced some sex-specific differences, while morphine impaired normal weight gain in male rats, no effects were observed for female rats. Plus, morphine produced an attenuated antinociceptive response in female rats. Moreover, following adolescent morphine treatment some emotional signs of withdrawal emerged exclusively in male rats in conjunction with signs of neurotoxicity, while female rats were not affected. In particular, an anxiolytic-like effect in adolescence during early withdrawal was followed by the development of a depressive-like phenotype (i.e., behavioral despair, anxiety-like behavior and anhedonia) in adulthood during prolonged withdrawal and paired with decreased contents of neurofilaments proteins in the prefrontal cortex. In conclusion, morphine administration during adolescence induced persistent changes in negative affect and brain toxicity selectively in male rats, suggesting female rats were resilient to these harmful effects. Given the widespread availability and use of opiate-based painkillers, the interplay between addiction, analgesia and emotional behaviors, and since adolescents and young adult humans are the age group with the highest abuse potential, these results add to the current literature by reporting distinct sex-specific opioid actions when administered in adolescence.


miR-506 Inhibits Epithelial-to-Mesenchymal Transition and Angiogenesis in Gastric Cancer.
Gastric cancer is one of the most common malignancies in developing countries. We examined the possible role of miR-506 in gastric cancer, investigated its associations with the clinical outcomes of gastric cancer patients, and explored its potential role in angiogenesis and the metastasis of gastric cancer cells. We found that miR-506 expression was a useful marker for stratifying patients from early to advanced clinical stages and for overall survival prediction. miR-506 overexpression inhibited the epithelial-to-mesenchymal transition of gastric cancer cells; however, depletion of miR-506 promoted it. In addition, miR-506 suppressed gastric cancer angiogenesis and was associated with decreased matrix metalloproteinase-9 expression. We also found that ETS1 was a miR-506 target, and it was expressed in 71.10% of gastric cancer tissue samples. Moreover, ETS1 expression was associated with matrix metalloproteinase-9 expression (P < 0.001). In conclusion, miR-506 was identified as an ETS1 targeting suppressor of metastatic invasion and angiogenesis in gastric cancer.


Decabromodiphenyl ether (deca-BDE) commercial mixture components, and other PBDEs, in airborne particles at a UK site.
The occurrence of the major components of the decabromodiphenyl ether (deca-BDE) flame retardant and other PBDEs was investigated in daily air particulate samples from 17th April to 20th May 2004 at a semi-rural site in north-west England. BDE-209 was found at between <0.49 and 100 pg m(-3) (median 13 pg m(-3)), and other higher-brominated PBDE congeners were also found, particularly the nona-BDEs (e.g. BDE-207: <0.042-79 pg m(-3), median 2.5 pg m(-3)). Deca- and nona-BDEs dominated the median particulate sample congener profile: 60% BDE-209, 16% BDE-207, 6% BDE-208 and 4% BDE-206. Nona-BDEs were greatly enriched, relative to BDE-209, compared to the deca-BDE commercial mixture, which may suggest degradation of BDE-209 between source and sampling site, or release from older deca-BDE commercial mixtures, which may have contained higher proportions of nona-BDEs. The highest PBDE concentrations occurred when air-masses passed over urban and industrial areas to the SSW-SW, though small local influences may also be seen. PBDE concentrations appear to have been influenced mainly by particle levels: 1-3 microm diameter particles for BDE-153, and 3-10 microm particles for BDEs with 7-10 Br atoms. BDE-153 may either be released from combustion sources, or re-condense onto small particles after emission, whereas BDE-209 and nona-BDEs appear to be associated with larger dust particles from industrial or domestic sources.


Peritoneal fluid modifies the response of human spermatozoa to follicular fluid.
The aim of this study was to elucidate the mechanism involved in the acrosome reaction (AR) induced by follicular fluid (FF) in spermatozoa previously exposed to peritoneal fluid (PF). The influence of progesterone was also investigated. Semen samples were from 18 normozoospermic donors. PF samples were from 13 women with unexplained infertility and from a woman treated with synthetic progestagen. FF samples were collected from six women undergoing IVF/embryo transfer and pooled. Motile spermatozoa were capacitated overnight and a kinetic and inhibition study on the FF-induced AR was performed. Spermatozoa pretreated with PF were challenged with either FF or progesterone. The ability of progesterone- and progestagen-supplemented PF to induce AR was analysed. Enzyme-digested PF was also tested. Pre-incubation with PF for 60 min completely prevented the FF-induced AR; spermatozoa treated with PF were unable to respond to FF or progesterone and this effect was not reversible. Progesterone- and progestagen-supplemented PF stimulated the AR relative to controls. Enzyme-digested PF did not have an inhibitory capacity. These data strongly suggest that there are one or more inhibitory proteins in PF that interact with spermatozoa so as to prevent access of progesterone to its receptor and thus inhibit the occurrence of the AR. The oviduct, or Fallopian tube, provides a place for spermatozoa and egg transport and storage, fertilization and early embryo development. If ovulation has not occurred, spermatozoa may reside in the oviduct for several hours or even a few days, awaiting oocyte arrival. It is assumed that fluids present in the female genital tract may have a role in synchronizing the timing required to guarantee the success of fertilization. We previously observed that the peritoneal fluid that bathes the peritoneal cavity is a suitable medium for sperm survival and we also reported that this fluid could stabilize spermatozoa. In this study we show further evidence that the exposure to peritoneal fluid modifies the response of spermatozoa to oocyte signals.


Vector control in China, from malaria endemic to elimination and challenges ahead.
Vector control is an important approach to preventing and controlling malaria. From the malaria epidemic to malaria elimination in China, vector control has played an essential and irreplaceable role in the historical process. This review systematically summarizes the evolution, adjustment, and optimization of vector control strategy towards elimination and discusses the challenges ahead. This review first summarizes the evolution of vector control strategies during different stages of malaria epidemic, control, elimination, and post-elimination in China. We then distill the vector control experience and lessons in different stages. We discuss the current and future challenges and propose future research directions and developments for novel malaria vector control strategies. Vector control has played an invaluable role in achieving malaria elimination. China adopted different prevention and control measures in response to the different malaria-endemic situations and vector distributions. Firstly, baseline surveys were initiated to establish the entomological data and helped clarify the prevention priorities and targets. Secondly, targeted and adjusted vector control strategies were conducted in various regions according to the local epidemic characteristics and different vector species. Thirdly, scientific research facilitated efficient vector-control strategies. In addition, the overall economic and social development have promoted environmental improvement, personal protection, and health care. Prediction of the vector distribution was integrated into risk assessment strategies, allowing for sustaining achievements in risk areas. The tailored and adapted vector control strategies have played a critical role in China's malaria prevention, control, and elimination. Achievements and lessons learned on vector control from this progress would provide a practical reference in coping with the challenges and potential barriers other countries face in the global effort to eliminate malaria.


Concomitant changes in adenylate cyclase and cytolytic activities of lymphoid cells during graft versus host reaction.
Spleen cells from adult F1 hybrid mice undergoing the graft versus host reaction due to the inoculation of lymphoid cells of parental origin showed increased adenylate cyclase activity and cytolytic activity. A time-course study revealed that both the adenylate cyclase and cytolytic activities started increasing at Day 4 and reached maximum at Day 8 of initiation of the graft versus host reaction. Furthermore, the magnitude of both adenylate cyclase activation and cytolytic activity were dependent upon the number of parental cells injected into the F1 hybrid recipients. Elevated adenylate cyclase activity was also observed in spleen cells from irradiated animals undergoing the graft versus host reaction in which the nonspecific, but not the specific cytolytic activity was markedly depressed.


Significant changes in autumn and winter aerosol composition and sources in Beijing from 2012 to 2018: Effects of clean air actions.
A seven-year long-term comprehensive measurement of non-refractory submicron particles (NR-PM1) in autumn and winter in Beijing from 2012 to 2018 was conducted to evaluate the effectiveness of the clean air actions implemented by the Chinese government in September 2013 on aerosols from different sources and chemical processes. Results showed that the NR-PM1 concentrations decreased by 44.1% in autumn and 73.2% in winter from 2012 to 2018. Sulfate showed a much larger reduction than nitrate and ammonium in both autumn (55%) and winter (86%) and that nitrate even slightly increased by 15.8% in autumn. As a result, aerosol pollution in winter gradually changed from sulfate-rich to nitrate-rich with a sudden change after 2016 and the dominant role of nitrate in autumn was also strengthened after 2016. Among primary organic aerosol (OA) types, biomass burning OA and coal combustion OA exhibited the largest decline in autumn and winter, with reductions of 87.5% and 77.3%, respectively, while hydrocarbon-like OA (HOA) exhibited the smallest decline in both autumn (24.4%) and winter (37.1%). These significant changes in aerosol compositions were highly consistent with the much faster reduction of SO2 (75-85%) than NOx (36-59%) and were mainly due to the clean air actions rather than the impact of meteorological conditions. What's more, the enhanced atmospheric oxidizing capacity, which was indicated by increased O3, altered the chemical processes of oxygenated OA (OOA), especially in autumn. Both of less-oxidized OOA (LO-OOA) and more-oxidized OOA showed elevated contributions in OA by 4% in autumn. The increased oxygen-to-carbon ratios of LO-OOA in autumn (from 0.42 to 0.58) and winter (from 0.44 to 0.52) indicated the enhanced atmospheric oxidizing capacity strengthened photochemical reactions and resulted in the increased oxidation degree of LO-OOA. This study demonstrates the effectiveness of the clean air actions for air quality improvement in Beijing.


Docetaxel Treatment for Metastatic Hormone-sensitive Prostate Cancer in Daily Practice.
Currently, metastatic hormone-sensitive prostate cancer (mHSPC) patients are often treated with docetaxel chemotherapy at the initiation of hormonal therapy. This treatment is based on the results of two pivotal trials. However, trial populations are not a representative of real-world patient populations. We aimed to analyze whether survival rates in our daily practice cohort is comparable with those in clinical trials and to characterize the tolerability of docetaxel chemotherapy in daily practice. In this retrospective cohort analysis, we studied 159 mHSPC patients treated with early docetaxel from April 2014 up to June 2020 in a top clinical hospital in The Netherlands. Patients were selected using hospital pharmacy records. We compared the results of our cohort with the results of the cohorts of the two pivotal trials. We aimed to analyze the survival rates in our cohort and characterize the tolerability of docetaxel chemotherapy in daily practice. Despite the relatively high number of comorbidities in our daily practice cohort, overall survival of our cohort showed great similarity with that of the two pivotal trials: 60.2 mo compared with 57.6 and 59.1 mo. Furthermore, early docetaxel was well tolerated in daily practice. Nearly 90% of the patients completed the full six cycles, and polyneuropathy led to relatively few dose reductions (6.9%). Early docetaxel is well tolerated in daily practice. Our daily practice cohort showed great similarity in overall survival to the clinical trials. Our results might be of interest in the developing landscape of mHSPC treatment. We studied docetaxel chemotherapy for metastatic prostate cancer in daily practice. These patients have the same survival as selected patients participating in clinical trials. Docetaxel was well tolerated in daily practice.


[An outbreak of legionnaires' disease in the Danish community in Rome: clinical-therapeutic-epidemiologic aspects].
The authors report five Danish patients affected by Legionnaire's disease observed during the 1987 spring. They focus on the epidemiological, clinical, and therapeutic aspect of the outbreak.


Quantitative RT-PCR luminometric hybridization assay with an RNA internal standard for cytokeratin-19 mRNA in peripheral blood of patients with breast cancer.
To develop a highly sensitive quantitative RT-PCR hybridization assay for the determination of CK-19 mRNA in peripheral blood of patients with breast cancer. Quantification of CK-19 mRNA was based on the coamplification of CK-19 mRNA with a recombinant CK-19 RNA internal standard (CK-19 RNA-IS) through RT-PCR. The biotinylated amplification products were immobilized on steptavidin coated wells, hybridized with digoxigenin labeled probes and determined through an antidigoxigenin antibody conjugated to alkaline phosphatase by luminometric detection. The developed luminometric hybridization assay was validated with samples containing total RNA of known amounts from CK-19 expressing cells (MCF-7) in the presence of 1 microg total RNA isolated from peripheral blood mononuclear cells (PBMC) of healthy controls and a constant amount of CK-19 RNA-IS. The method was applied for the quantitative determination of CK-19 mRNA in the peripheral blood of 26 healthy volunteers, 14 patients with stage IV breast cancer and 37 patients with stage I/II breast cancer before chemotherapy. Luminescence ratios for CK-19 mRNA and CK-19 RNA-IS were linearly related to the number of MCF-7 cells within the range of 1 to 2000 cells. The overall reproducibility of the assay (between-run) varied between 8.9% and 13.4%. The method can clearly detect CK-19 mRNA from 1 MCF-7 cell in the presence of 10(6) normal PBMC and is highly specific as none of the 26 healthy controls tested had detectable CK-19 mRNA levels, while 10 out of 14 (71.4%) and 9 out of 37 (24.3%) patients with stage IV and stage I/II breast cancer, respectively, were tested positive. The developed quantitative RT-PCR hybridization assay for CK-19 is reproducible, highly sensitive and specific, and can be used for a large-scale prospective evaluation of clinical samples.