The effect of local hyperthermia on allergen-induced nasal congestion and mediator release.
Local hyperthermia reduces mast cell degranulation, the severity of acute lung injury, and exercise-induced asthma and decreases symptoms of rhinitis. We have investigated the effect of local hyperthermia on mast cell degranulation and symptom generation in allergic rhinitis to assess its effect and mechanism of action within the nose. In a randomized, double-blind, placebo-controlled, crossover study, 10 subjects with rhinitis were treated for 30 minutes with local hyperthermia or placebo, which was followed 30 minutes later by nasal allergen challenge. During the first two visits nasal lavages were performed to assess vascular leakage and mediator release. During the last two visits nasal airway resistance, the number of sneezes, and mucus secretion were monitored. Local hyperthermia significantly reduced both nasal airway resistance (p < 0.05) and vascular leakage (p < 0.02) but had no significant effect on the number of sneezes, on mucus secretion, or on tryptase release. Local hyperthermia reduces allergen-provoked nasal blockage and vascular leakage but has no effect on sneezing, rhinorrhea, or tryptase release. Nasal blockage occurs predominantly via newly formed lipid mediators and kinins, whereas sneezing and rhinorrhea occur predominantly via preformed mediators. We propose that local hyperthermia inhibits newly formed mediator production or release or reduces the sensitivity of the vasculature to inflammatory mediators in general. Further investigation into the mechanisms and potential uses of local hyperthermia is warranted.


Can Gartland II and III supracondylar humerus fractures be treated using Blount's method in the emergency room?
Studies have established that Blount's method is reliable for treating extension supracondylar fractures (SCFs) in paediatric patients. Reduction in the emergency room (ER) under procedural sedation followed by orthopaedic treatment is increasingly used for many fracture types. The primary objective of this study was to determine whether SCF reduction in the ER was feasible, by determining the failure rate. The secondary objective was to identify causes of failure with the goal of improving patient selection to reduction in the ER. Gartland II and III SCFs (Lagrange-Rigault grades 2-4) can be treated in the emergency room under fluoroscopic guidance and with procedural sedation. A retrospective study was conducted in 128 paediatric patients who underwent ER reduction of an SCF in 2014-2015. Mean age was 5.6 years. Reduction was performed either by an orthopaedic surgery resident or by a specially trained emergency physician. Of the 128 SCFs, 101 (79%) were Gartland II and 27 Gartland III. In the Lagrange-Rigault classification, 55 (43%) fractures were grade 2, 59 (46%) were grade 3, and 14 (11%) were grade 4. The arm was immobilised using the cuff-and-collar method described by Blount for 4 weeks. All 128 fractures healed without delay. Blount's method alone was effective in 112 (87.5%) patients. Of the 16 other patients, 15 (Lagrange-Rigault 3, n=14; and 4, n=1) had an unstable fracture after ER reduction and were managed by reduction and internal fixation in the operating room. The remaining patient (0.5%) experienced secondary displacement requiring revision surgery in the operating room. SCFs grades 2 to 4 in the Lagrange-Rigault classification (Gartland II and III) can be treated in the ER by specially trained physicians. Lagrange-Rigault grade 3/Gartland III SCFs are more likely to require subsequent internal fixation but do not contraindicate reduction in the ER. IV, retrospective study.


Sinus tachycardia in term infants preceding sudden infant death.
The quantities of sinus tachycardia in 24-h recordings of the electrocardiogram from 16 full-term infants (greater than or equal to 37 weeks gestation) who were subsequently victims of the sudden infant death syndrome (SIDS), from 230 randomly selected age-matched full-term survivors and from 64 full-term survivors matched for age and birth weight were measured by computer and manual analysis techniques. Of 16 infants dying of SIDS, 7 had elevated levels of sinus tachycardia (greater than 95th centile in controls) (P less than 0.01). Although high levels of sinus tachycardia might be of value in identifying infants at high risk of SIDS, these encouraging findings must first be validated by further prospective studies.


How Well Do Seven Self-Report Measures Represent Underlying Back Pain Impact?
The extent to which different measures of back pain impact represent an underlying common factor has implications for decisions about which one to use in studies of pain management and estimating one score from others. To determine if different self-report back pain impact measures represent an underlying pain latent variable and estimate associations with it. Seven pain impact measures completed by Amazon Mechanical Turk adults are used to estimate internal consistency reliability and associations: Oswestry Disability Index (ODI), Roland-Morris Disability Questionnaire (RMDQ), short form of the Örebro Musculoskeletal Pain Questionnaire (OMPQ), Subgroups for Targeted Treatment (STarT) Back Tool, the Graded Chronic Pain Scale (GCPS) disability score, PEG (Pain intensity, interference with Enjoyment of life, interference with General activity), and Impact Stratification Score (ISS). The sample of 1,874 adults with back pain had an average age of 41 and 52% were female. Sixteen percent were Hispanic, 7% non-Hispanic Black, 5% non-Hispanic Asian, and 71% non-Hispanic White. Internal consistency reliability estimates ranged from 0.710 (OMPQ) to 0.923 (GCPS). Correlations among the measures ranged from 0.609 (RMDQ with OMPQ) to 0.812 (PEG with GCPS). Standardized factor loadings on the pain latent variable ranged from 0.782 (RMDQ) to 0.870 (ISS). Scores of each measure can be estimated from the others for use in research.


The miR-5694/AF9/Snail Axis Provides Metastatic Advantages and a Therapeutic Target in Basal-like Breast Cancer.
Epigenetic deregulation, especially mutagenesis or the abnormal expression of epigenetic regulatory factors (ERFs), plays an important role in malignant tumorigenesis. To screen natural inhibitors of breast cancer metastasis, we adopted small interfering RNAs (siRNAs) to transiently knock down 591 ERF-coding genes in luminal breast cancer MCF-7 cells and found that depletion of AF9 significantly promoted MCF-7 cell invasion and migration. A mouse model of metastasis further confirmed the suppressive role of AF9 in breast cancer metastasis. RNA profiling revealed enrichment of AF9 targets genes in the epithelial-mesenchymal transition (EMT). Mechanistically, tandem mass spectrometry showed that AF9 interacts with Snail, which hampers Snail transcriptional activity in basal-like breast cancer (BLBC) cells. AF9 reconstitutes an activated state on the promoter of Snail, which is a master regulator of EMT, and derepresses genes by recruiting CBP or GCN5. Additionally, microRNA-5694 (miR-5694) targeted and degraded AF9 messenger RNA (mRNA) in BLBC cells, further enhancing cell invasion and migration. Notably, AF9 and miR-5694 expression in BLBC clinical samples correlated inversely. Hence, miR-5694 mediates downregulation of AF9 and provides metastatic advantages in BLBC. Restoring expression of the metastasis suppressor AF9 is a possible therapeutic strategy against metastatic breast cancer.


Surgical management of thirty-nine children with lymphedema.
Thirty-nine children underwent staged excisional surgery for lymphedema. The procedures are described in detail. All the children operated on have improved and have a more normal appearance. The decrease in attacks of cellulitis and lymphangitis is striking. The morbidity of this simple procedure is negligible. The operation is tedious, fatiguing, anatomically unexciting, and has a vague end-point. At this time, staged subcutaneous excision appears to be the procedure of choice in moderate to severe lymphedema in children regardless of etiology or classification. The procedure is not a cure.


Probing the gel to liquid-crystalline phase transition and relevant conformation changes in liposomes by (13)C magic-angle spinning NMR spectroscopy.
A straightforward way to visualize gel to liquid-crystalline phase transition in phospholipid membranes is presented by using ¹³C magic-angle spinning NMR. The changes in the 13C isotropic chemical shifts with increasing temperature are shown to be a sensitive probe of the main thermotropic phase transition related to lipid hydrocarbon chain dynamics and relevant conformational changes. The average value of the energy difference between trans and gauche states in the central C4–11 fragment of the DMPC acyl chain was estimated to be 4.02 ± 0.2 kJ mol⁻¹ in the liquid crystalline phase. The reported spectral features will be useful in 13C solid state NMR studies for direct monitoring of the effective lipid chain melting allowing rapid uniaxial rotation of membrane proteins in the biologically relevant liquid-crystalline phase.


Differences in breast cancer incidence in Australia and England by age, extent of disease and deprivation status: women diagnosed 1980-2002.
To compare breast cancer incidence in England and Australia by age, extent of disease and deprivation. We analysed data for women aged 15-99 years diagnosed with breast cancer in England or Australia during the period 1990 to 1994, and in West Midlands or New South Wales during the period 1980 to 2002. We calculated three-year rolling average incidence rates and incidence rate ratios (IRR) between West Midlands and New South Wales by age, extent of disease and category of deprivation. Breast cancer incidence was higher in England than in Australia, and in West Midlands than in New South Wales but became more similar over time. Socio-economic differences in incidence were greater in New South Wales than in West Midlands. The most deprived women in West Midlands were diagnosed at a later stage of disease than the most deprived women in New South Wales. Incidence among elderly women was higher in West Midlands than in New South Wales. There were also high proportions of tumours with unknown stage among elderly women in West Midlands. Although the overall incidence of breast cancer is similar, differences by age, extent of disease and deprivation exist. The underlying reasons for these patterns require further examination.


Social capital and farmer's willingness-to-join a newly established community-based health insurance in rural China.
In 2002, China announced a new funding strategy that would reestablish community-based health insurance (CHI) in rural areas, whereby the Chinese government will entice farmers' participation by providing each participant an annual subsidy of 10-20 Yuan (US 1.25-2.50 dollars). However, there is no evidence demonstrating how many farmers would be willing-to-join (WTJ) such newly developed government subsidized voluntary-based CHI scheme and what factors influence farmers' willingness-to-join. In this study, we examine the probability of farmers' willingness-to-join such CHI under the different scenarios of government subsidy and individual contribution, and also explore factors that influence farmers' willingness-to-join with the emphasis on social capital. The study is based on data collected from a 2002 household survey conducted in Fengsan Township, located in China's Guizhou Province. Logistic regression is used in the analysis. The findings from this study show that even with the government subsidy to the premium, the probability of WTJ the new voluntary-based CHI only reach 50%. The results also indicate that community level social capital, as measured by reciprocity index, and individual level social capital, as measured by trust index, are significantly and positively associated with the probability of farmers' WTJ newly developed government subsidized CHI. Policy recommendations have been made based on those findings.


Using plain language to communicate with clinical trials participants: Comparison of readability calculators.
It is important that patient-facing clinical trial information is easily understood by potential trial participants, active trial participants, family members, friends and carers. The readability of a document refers to its typographic and linguistic characteristics that allow the text to be read and comprehended and it is recommended that healthcare providers aim that all information disseminated to the lay public be at a suitable readability level. Whilst there are established readability calculators for literature, there is no standard for health information. Several readability calculators are available that aid in the analysis of a text, URL or website's readability, however, to date there has been no head-to-head comparison of these. Five readability calculators were compared, including four online realtime calculators, (i) Readable (www.readable.com), (ii) www.webfx.com, (iii) www.datayze.com and (iv) www.online-utility.org, as well as the PC-based analyzer Microsoft Word (Microsoft Corp., USA). Three categories of text information were analysed, including (i) childrens' fairy tales (n = 20) (ii) scientific reports (n = 20) from BBC News websites and (iii) scientific abstracts (n = 20). This study demonstrated that varying scores were obtained by using different readability calculators. Based on these data in combination with issues including availability and ease-of-use, we advocate the use of Readable or Microsoft Word software to aid in the preparation of patient-facing clinical trial information. Clinical trial networks should now consider the need for standardisation of readability calculators and provide guidance to stakeholders so that readability of materials may be improved in a standardised and uniform manner.


SARS-CoV-2 recurrent RNA positivity after recovering from coronavirus disease 2019 (COVID-19): a meta-analysis.
Isolation of subjects with active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a pivotal preventive measure in the ongoing coronavirus disease 2019 (COVID-19) pandemic. A growing number of studies reported cases of recurrent SARS-CoV-2 RNA positivity following disease recovery, which were identified with a critical literature search and then meta-analyzed in this article. A digital search was performed in Medline and Web of Science, using the keywords "coronavirus disease 2019" OR "COVID-19" OR "severe acute respiratory disease 2" OR "SARS-CoV-2" AND "recurrence" OR "repositivization" OR "retesting", without date or language restrictions. Recovery was defined as resolution of symptoms, with at least two consecutive negative molecular tests. A total number of 17 studies, with 5,182 COVID-19 patients, were included. SARS-CoV-2 recurrent RNA positivity in recovered COVID-19 patients ranged between 7-23% across the studies, with follow-up testing between 1-60 days. The estimated cumulative rate of SARS-CoV-2 recurrent RNA positivity was 12% (95% confidence interval, 12-13%; I2, 74%). Repeated molecular testing on respiratory tracts specimens at 1 and 2 months after recovery from COVID-19 is strongly advisable for early identification, isolation and clinical management of subjects with SARS-CoV-2 recurrent RNA positivity.


Investigating the effects of myofascial induction therapy techniques on pain, function and quality of life in patients with chronic low back pain.
Low back pain (LBP) is well documented as a common health problem; it is the leading cause of activity limitation and work absence throughout much of the world, and it causes an enormous economic burden on individuals, families, communities, industry, and governments. The aim of this study was to comparatively investigate the effects of myofascial induction therapy (MIT) against pain neuroscience education (PNE) on pain and function in patients with chronic low back pain (CLBP). Forty patients with CLBP were included and randomly divided into two groups according to the treatment program (40 min/session, 2 sessions/week during 8-week), as follows: the MIT and the PNE groups. The outcome measures were the fear-avoidance beliefs questionnaire (FABQ), Roland Morris disability questionnaire, McGill pain questionnaire, finger floor test, SF-36 quality-of-life questionnaire, and thoracolumbar fascia ultrasound imaging results. Patients were evaluated before and after treatment. Within both groups, all outcome scores showed a significant improvement (p < 0.05). After 8-week, SF-36 physical function, physical role and mental health scores significantly improved in MIT group compared with PNE group, finger floor test score significantly decreased in MIT group compared with PNE group, and FABQ score significantly decreased in PNE group compared with MIT group (p < 0.05). Although both MIT and PNE were found to be effective on pain and function in patients with CLBP, MIT techniques were substantially better in improving the mobility of trunk flexion and quality of life in these patients.


Adenoma malignum of the uterine cervix: Clinicopathologic analysis of 18 cases.
The aim of this study was to evaluate the clinical and pathologic features of a rare tumor (adenoma malignum, AM). We retrospectively analyzed the medical records of 18 patients diagnosed with AM at a single institute between March 1992 and November 2009. The median age of the patients was 45.8 years (range 29-76 years) and the mean follow-up period was 49.2 months (range 4-168 months). A preoperative cytologic diagnosis (Papanicolaou smear) of AM was made in 22.2% (4/18) of the cases. Ten (55.6%) of the 18 patients were misdiagnosed with other benign diseases and underwent hysterectomies, which confirmed AM. Sixteen patients with AM were in the early stage (IB1, 11/18; IB2, 5/18) and the other two patients were in the advanced stage. Fourteen of 18 patients (77.8%) had pure AM alone. Adjuvant therapy was administered to eight of the patients (44.4%) with AM. The recurrence rate was zero, but the disease progressed in two of the patients (11.1%), who died of the disease. The 5-year survival rate was 88.8%. A cytological diagnosis of AM based on a Papanicolaou smear is rarely made; a deep biopsy (cone biopsy or endocervical curettage) is necessary to diagnose this rare tumor preoperatively when there is any clinical suspicion of AM.


Direct and indirect effects of amphidromous shrimps on nutrient mineralization in streams in Japan.
Animals affect element cycling in ecosystems by consumption and excretion. Amphidromous shrimps frequently dominate low-mid altitude streams, where downstream connectivity to oceans is sustained. Although shrimps' direct influence on benthic communities has been studied, little is known about their influences on nutrient cycling. Here, we hypothesized that the dominance of shrimps alters nutrient mineralization by benthic macroinvertebrates in streams due to the difference in the quality and quantity of excretion between shrimps and aquatic insects. We tested this hypothesis through a field manipulative experiment, excretion measurements of animals, and field surveys. In the field manipulative experiment, the presence of shrimps slightly decreased the biomass of aquatic insects but tripled total benthic macroinvertebrate biomass directly through their own biomass. The mass-specific NH4+ excretion rate by shrimps was similar to aquatic insects, and the areal NH4+ excretion by benthic macroinvertebrates was increased by 2.5 times in the presence of shrimps. In contrast, shrimps excreted significantly less soluble reactive phosphorus (SRP) than aquatic insects, and the presence of shrimps did not affect areal SRP excretion by benthic macroinvertebrates. The field survey showed a positive correlation of NO3- concentration with the shrimp density, inferring the excess NH4+ was nitrified. Although the nutrient concentration of stream water is frequently attributed to watershed conditions, the results of this study indicate that downstream connectivity to oceans may also influence nutrient dynamics of the stream through the density of amphidromous shrimps.


Enhanced myocardial washout and retrograde blood delivery with synchronized retroperfusion during acute myocardial ischemia.
The effects of synchronized coronary venous retroperfusion of arterial blood on myocardial washout were studied with digital subtraction angiography in 10 closed chest dogs during balloon occlusion of the proximal left anterior descending coronary artery. The center lumen of the intracoronary balloon catheter was used for sequential injections of 1 ml (meglumine diatrizoate) Renografin-76, and contrast washout rate was determined by videodensitometry in myocardial regions subserved by the left anterior descending coronary artery. Before coronary artery occlusion, washout rate was 22.4 +/- 2.7 min-1 (mean +/- SEM). Five minutes after occlusion, and immediately before synchronized retroperfusion, washout rate dropped sharply to 2.0 +/- 0.7 min-1. Twenty-five minutes after occlusion, with 50 ml/min synchronized retroperfusion treatment applied for 5 minutes, washout rate was 5.0 +/- 1.5 min-1. Thus, synchronized retroperfusion significantly (p less than 0.05) accelerated contrast disappearance over that during presynchronized retroperfusion ischemia. To determine the effects of synchronized retroperfusion on retrograde delivery to the ischemic myocardium, monastral blue dye was retroinfused through the system into the great cardiac vein before the dog was killed. Transverse heart slices were then studied by light microscopy, and regional intravascular dye content was scored from 0 to 3 (0 = no dye, 3 = maximal dye). After great cardiac vein synchronized retroperfusion, blue dye content in capillaries of ischemic anterior and nonischemic posterior aspects of the left ventricle was 2.3 +/- 0.5 versus 0.7 +/- 0.3, respectively (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Mechanized procedures for the serology of Salmonella.
A mechanized microtechnique originally designed for the serotyping of E. coli was adapted to the specificity control of diagnostic Salmonella agglutinating antisera as well as for the serotyping of Salmonella. Salmonella strains sent for serotyping were inoculated into a tube with broth which was used as H antigen and, after heating also as O antigen. The agglutination reactions were carried out in clear plastic trays with U formed wells. The antigens were strained with gentian violet in order to obtain a better contrast. With only 6 monofactor O sera, 97% of 100,000 cultures received for serotyping in 1979-1982 could be O antigen typed. Eight H antisera were sufficient for the complete serotyping of 27% of these strains whereas 64% was partly typed. The technique has a high degree of versatility.


A soluble ectodomain of LRIG1 inhibits cancer cell growth by attenuating basal and ligand-dependent EGFR activity.
Leucine-rich repeats and immunoglobulin-like domains-1 (LRIG1) is a transmembrane protein with an ectodomain containing 15 leucine-rich repeats (LRRs) homologous to mammalian decorin and the Drosophila kekkon1 gene. In this study, we demonstrate that a soluble ectodomain of LRIG1, containing only the LRRs, inhibits ligand-independent epidermal growth factor receptor (EGFR) activation and causes growth inhibition of A431, HeLa and MDA-468 carcinoma cells. In contrast, cells that do not express detectable levels of EGFR fail to respond to soluble LRIG1. However, when a functional EGFR gene is introduced in these cells, they become growth-inhibited by soluble LRIG1 protein. Furthermore, we demonstrate the existence of high-affinity (K(d)=10 nM) binding sites on the A431 cells that can be competitively displaced (up to 75%) by molar excess of EGF. Even more powerful effects are obtained with a chimeric proteoglycan harboring the N-terminus of decorin, substituted with a single glycosaminoglycan chain, fused to the LRIG1 ectodomain. Both proteins also inhibit ligand-dependent activation of the EGFR and extracellular signal-regulated protein kinase 1/2 signaling in a rapid and dose-dependent manner. These results suggest a novel mechanism of action evoked by a soluble ectodomain of LRIG1 protein that could modulate EGFR signaling and its growth-promoting activity. Attenuation of EGFR activity without physical downregulation of the receptor could represent a novel therapeutic approach toward malignancies in which EGFR plays a primary role in tumor growth and survival.


Atherosclerotic Process in Seroreverter Children and Adolescents Exposed to Fetal Antiretroviral Therapy.
Human immunodeficiency virus infection is a recognized risk factor for premature atherosclerosis in children and adolescents. However, the atherosclerotic process in uninfected children exposed in utero to the virus and antiretroviral therapy is less clear. To determine the potential cardiovascular risk associated to this in utero milieu exposition. A total of 115 individuals were studied (77 in the sample group and 38 in the controls). Eighteen analytical mediators involved in the atherogenic pathways (metabolic dysregulation, inflammation, and prothrombotic state) were analyzed. The carotid intima-media thickness, which is a subclinical marker of atherosclerosis, was also measured. No significant statistical differences were identified between the sample and control groups, either in the biochemical or the echographic markers. In utero exposure to the HIV virus and antiretroviral therapy in uninfected children and adolescents is not correlated to accelerated atherosclerosis.


Association between use of ERAS protocols and complications after radical cystectomy.
Implementation of enhanced recovery protocols in cystectomy patients has significantly changed the perioperative course of this major operation. This paper summarizes evidence based interventions to enhance the postoperative course of radical cystectomy. A comprehensive search of PubMed and Embase databases was performed and also the results of our institutional enhanced recovery protocol were discussed. One of the major advantages of such changes is the reduced rate of postoperative gastrointestinal (GI) complications especially postoperative ileus which could be contributed to several components of these protocols. However, Alvimopan is the only component which its use is supported by level I evidence. Although there are some evidence suggesting the decreased rate of urinary tract infection with the use of prophylactic antibiotics and wound complications by the use of negative wound pressure devices, their clear benefit is yet to be shown. Although robotic approach has proven advantages in intraoperative blood loss and postoperative blood transfusion rate, surgical team's experience and dedicated infrastructure seem to be more influential in optimized outcome than just the surgical approach. current evidence suggests that such protocols have not only reached the goal of maintaining complication rate while decreasing length of hospital stay, but it might have caused a decrease in the rate of low-grade complications, especially GI complications.


COVID-19 and patients with cancer: Investigating treatment impact, information sources, and COVID-19-related knowledge, attitudes, and practices.
The coronavirus disease 2019 (COVID-19) pandemic has caused enormous strain on public health. Patients with cancer are particularly susceptible to the disease, and their treatment plans have been threatened by public health restrictions designed to contain the spread. This study examined the effects of the pandemic on cancer patients' psychology, knowledge, attitudes, and practices concerning COVID-19 as well as their perceptions of the impact of COVID-19 on their cancer health care services. A survey was sent to 5800 patients at a cancer center in Toronto, Canada. Descriptive results were summarized. Qualitative feedback was coded and summarized. To examine for potential associations, regression models were tested for the outcomes of patient psychological well-being, knowledge, attitudes, and practices, and they accounted for several demographic, health literacy, and disease variables. A total of 1631 surveys were completed. Most patients saw their appointments shifted to virtual visits, and for a substantial minority, there was no change. A majority of the patients (62%) expressed fears about contracting the virus. There were no independent predictors of COVID-19-related knowledge. Fears were more pronounced among patients who did not speak English and those who used social media more often. Female participants, those who scored higher on knowledge questions, and those who used cancer center materials were more likely to take preventative measures against infection. This study provides a snapshot of the state of cancer patient treatment and the knowledge, attitudes, and practices of patients between the first 2 waves of the pandemic. The study's results can inform our understanding of adaptation to conditions during and after the outbreak.


Hyaluronan in follicular fluid and embryo implantation following in vitro fertilization and embryo transfer.
To determine whether the concentration of hyaluronan (HA) in follicular fluid predicts implantation success following embryo transfer. Follicular fluids from 170 IVF patients were tested by ELISA for HA concentration. The mean (standard error) HA concentration in follicular fluids was 158.0 (21.9) ng/ml from women whose embryos did not implant, 220.0 (21.3) ng/ml from women in which one embryo implanted and 239.3 (40.1) ng/ml from women with 2-3 implantations (implantation vs. no implantation p = .019). The HA level was unrelated to maternal age, number of oocytes harvested or fertilized or number of embryos transferred. Follicular fluids from women with an endocrine problem had a lower mean HA level (142.0 ng/ml) as compared to women undergoing IVF due to male factor infertility (257.3 ng/ml) (P = .05). HA in follicular fluid is decreased in women with unsuccessful implantation or with an endocrine disorder. A woman's level of HA production may influence the potential for implantation of her embryos.


Syringomyelia due to Lumbar Spinal Fluid Drainage in the Acute Phase of Subarachnoid Hemorrhage: A Case Report.
Lumbar spinal fluid drainage is a common procedure for treating hydrocephalus and alleviating vasospasm by egesting blood in the subarachnoid cavity after subarachnoid hemorrhage. Despite being an effective and safe procedure, cerebrospinal fluid overdrainage might result in serious complications. Here we report the case of a 49-year-old man who suffered from tonsillar herniation with subsequent cervicothoracic syringomyelia in the acute phase of subarachnoid hemorrhage due to vertebral artery dissection. About 2 weeks after lumbar drainage was switched from external ventricular drainage initiated on the day of subarachnoid hemorrhage, the recovery from the disturbance of consciousness revealed tetraplegia, and magnetic resonance imaging demonstrated tonsillar herniation and syringomyelia. Removal of the spinal drain and resumption of external ventricular drainage resulted in the restoration of the herniated tonsils to the normal position and the complete disappearance of syringomyelia 11 days later. We should consider that spinal syringomyelia could develop as a complication of lumbar spinal fluid drainage in the acute phase of thick subarachnoid hemorrhage, particularly in the posterior cranial fossa.


Simultaneous in vitro fertilization and gamete intrafallopian transfer (GIFT).
During a 6-month period, a combination of gamete intrafallopian transfer (GIFT) and in vitro fertilization (IVF) was offered to all couples beginning an IVF treatment cycle in whom the wife had anatomically normal fallopian tubes. It was recommended to these couples that sufficient oocytes be reserved for insemination in vitro to determine whether the husband's spermatozoa could fertilize the wife's oocytes. During this interval, 16 couples underwent the combined IVF-GIFT procedure. All of the IVF-GIFT couples had at least two oocytes inseminated in vitro and at least two oocytes for GIFT. Of the 16 IVF-GIFT couples, only 1 (6.25%) achieved a clinical pregnancy. More important, 50% (8/16) of the IVF-GIFT couples had no oocytes fertilized in vitro. With the information concerning lack of fertilization in vitro, appropriate recommendations concerning future fertility management can be made. If the same couples had undergone the GIFT procedure alone, without additional oocytes fertilized in vitro, this information would not have been obtained.


Prevention of prostate cancer.
Prostate cancer is an ideal candidate for chemoprevention because of its high prevalence, long latency time, hormone dependency, precursor lesions, and its unique serum marker, PSA. Chemoprevention is the administration of drugs or other agents which aim to prevent the induction or inhibit/delay cancer progression. Large-scale studies favor environmental rather than genetic factors as key determinants of prostate cancer development. Among these environmental factors, nutrition certainly has a leading role. Numerous basic science studies but also clinical studies indicate that dietary compounds or diet modifications may ultimately play a major role in prostate cancer promotion and inhibition. Definitive proofs are often difficult because of methodological problems and complex triggering cascades. New pharmaceutical drugs with minimal toxicity are also currently evaluated.


Effects of vaccination prior to transit and administration of florfenicol at time of arrival in a feedlot on the health of transported calves and detection of Mannheimia haemolytica in nasal secretions.
To determine effects of vaccination prior to transit and prophylactic administration of florfenicol at time of arrival at a feedyard on health of cattle and colonization of the nasopharynx by Mannheimia haemolytica (MH). 121 steers from Tennessee and 84 steers from New Mexico. Half of the steers were vaccinated before transport to a feedyard. Steers from Tennessee were vaccinated with MH bacterin-toxoid, and steers from New Mexico were vaccinated intranasally with modified-live leukotoxin-deficient MH. Half of the vaccinates and nonvaccinates were randomly selected to receive florfenicol on arrival at the feedyard. Steers were observed daily for respiratory tract disease (RTD). Administration of florfenicol at time of arrival reduced the incidence of RTD, delayed the interval before onset of RTD, and reduced the incidence of MH colonization of the nasopharynx for at least 4 days, but vaccination did not have any effect. Vaccination elicited an increase in serum antibody titers to MH. Administration of florfenicol at time of arrival reduced the development of serum antibody titers in intranasally vaccinated steers and both groups of nonvaccinated steers, but intranasal vaccination did not affect colonization by wild-type MH. Administration of florfenicol at time of arrival decreased the incidence of MH organisms in the nasopharynx and delayed the onset of RTD. Prophylactic use of suitable antibiotics is likely to reduce the incidence of acute RTD in calves for several days after arrival at feedyards, which is the period when they are most susceptible to infectious organisms.


Translational coupling in a penP-lacZ gene fusion in Bacillus subtilis and Escherichia coli: use of AUA as a restart codon.
An out-of-frame fusion between the penicillinase gene (penP) of Bacillus licheniformis and the beta-galactosidase gene (lacZ) of Escherichia coli was shown to direct the synthesis of an active beta-galactosidase with the same electrophoretic mobility as the wild-type protein, both in B. subtilis and E. coli. This synthesis was dependent on translation of the truncated penP gene and appeared to result from translational coupling. The fusion point between penP and lacZ contained the sequence AUAG, in which the UAG and AUA codons were in-frame with the penP and lacZ reading units, respectively. N-terminal amino acid sequence analysis of the beta-galactosidase protein suggested that, both in B. subtilis and E. coli, reinitiation of translation occurred at the AUA codon present at the gene fusion point.


Unmet substance use disorder treatment need among reproductive age women.
Substance use disorder (SUD) is a chronic medical condition in need of long-term treatment. The objective of the study is to describe the current unmet SUD treatment need among reproductive age women living in the United States with a focus on pregnancy and parenting status. Data were drawn from the 2007-2014 National Survey of Drug Use and Health for women 18-44 years old. The primary outcomes were past year SUD treatment need and receipt. Women with a SUD treatment need included those with a SUD and/or expressing a need for SUD treatment. Women were classified as pregnant, parenting (living with their children) or not pregnant nor parenting. Multivariable logistic regression determined if pregnancy/parenting status was associated with treatment need and receipt controlling for demographic factors. Among reproductive age women with a past year SUD treatment need, only 9.3 % (95 % CI 8.4-10.2 %) received treatment. Pregnant and parenting women were not more likely to receive treatment (pregnant AOR 0.9; 95 % CI 0.5-1.8 & parenting AOR 0.7; 95 % CI 0.5-0.9) compared to not pregnant nor parenting women. Black (AOR 0.3; 95 % CI 0.2-0.5) and Hispanic women (AOR 0.6; 95 % CI 0.4-0.9) were less likely to receive treatment. Few reproductive age women who need SUD treatment receive it in the US. Although pregnant women are considered a priority population, they are not receiving priority services. Racial disparities in unmet SUD treatment need exist. Barriers to SUD treatment, such as expanding gender informed services, must be addressed.


Application of hot medicated fomentation for pain alleviation in non-specific low back pain - A randomized controlled clinical trial.
Non-specific low back pain is a leading contributor to disease burden and works absenteeism worldwide with a lifetime prevalence of 60-70% in industrialized countries. This clinical study aimed to assess the efficacy of hot fomentation with half-baked medicated bread (khubz) compared to hot water bag fomentation to alleviate pain and disability in non-specific low back pain. In this randomized-controlled study, fifty-four patients with low back pain were randomly assigned into two groups to receive either hot fomentation (Takmīd-e-haar) with half-baked medicated bread in the test group or hot water bag fomentation in the control group, on the lumbosacral region daily for 30 min for 15 consecutive days. Patients were assessed statistically using the visual analogue scale (VAS) and Oswestry disability index (ODI) at baseline, 7th and after treatment (15th day). After the intervention, statistically significant improvements (p < 0.001) were observed in VAS and ODI scores in both the groups on the intragroup comparison. The test treatment showed better efficacy in comparison to the control treatment with a mean difference of 1.75 in VAS (p < 0.0001) and 8.20 in ODI (p = 0.001). The tested intervention showed significantly better efficacy in comparison to the hot water bag fomentation probably due to the analgesic (musakkin-i-alam), anti-inflammatory (muḥallil-i-awrām), and demulcent (mulaṭṭif) properties of the ingredients of tested Unani formulation in addition to the effects of heat. It may therefore be concluded that medicated fomentation is an effective, safer, feasible, and less expensive regimen for patients with non-specific low back pain. The Clinical Trials Registry-India (CTRI/2020/03/024107).


Breast cancer and hormone receptors: a preliminary report.
An assay is available to determine the presence or absence of oestrogen receptors in breast cancer cells. The presence of oestrogen receptors predicts a 60% response rate to empirical hormonal therapy, and the absence a 10% response rate. Early evidence suggests that the additional presence of other hormone receptors in breast cancer cells will improve this response rate.


Zinc and cadmium concentration in prostatic carcinoma of different histological grading in comparison to normal prostate tissue and adenofibromyomatosis (BPH).
Zn and Cd concentrations in tissue of normal prostate gland, BPH and prostatic carcinoma of different histological grades have been determined by atomic absorption spectrometry before therapy. We found a distinct biological antagonistic effect between Zn and Cd in the human prostate gland. We have seen an increasing amount of Zn in BPH, but a decrease in prostatic cancer. In contrast, we found a continuous increase of cadmium concentration from the normal prostate via BPH through carcinoma.


Biochemical changes in dementia disorders of Alzheimer type (AD/SDAT).
In postmortem investigations of patients with dementia of Alzheimer type (AD/SDAT) (n = 14) the brain weight was significantly reduced when compared to controls (n = 16). In four AD/SDAT-brain parts investigated the concentrations of 5-hydroxy-tryptamine and noradrenaline were significantly reduced while 3-methoxy-4-hydroxyphenylglycol was significantly increased. In the caudate nucleus of the AD/SDAT-brains the concentrations of dopamine and homovanillic acid were significantly reduced. The activity of monoamine oxidase B was increased suggesting a proliferation of extra neuronal tissue in the AD/SDAT-brains. The activity of choline acetyl transferase was reduced in the four brain parts investigated, showing a general reduction in the acetylcholine system in the AD/SDAT-brains. The ganglioside concentration was significantly reduced suggesting a reduced density of nerve endings in the demented brains. The AD/SDAT-group was according to rating scales severely demented. Patients with an early onset of the dementia disease were more severely intellectually reduced and had more pronounced biochemical disturbances than those with a late onset of the dementia.


p53-dependent X-ray-induced modulation of cytokine mRNA levels in vivo.
In vitro studies have shown that ionizing radiation can cause increases in some cytokine mRNA levels and activation of the nuclear NF-kappa B and/or AP1 transcription factors which have been implicated in the transcriptional regulation of many cytokine genes. Thus, radiation-induced upregulation of cytokine mRNAs appeared to be in part a direct consequence of transcription factor activation. To test this in vitro model in vivo, the effects of whole-body X-irradiation (0-10 Gy) on cytokine and other gene mRNA levels have been examined in mice. Increases and decreases in cytokine mRNA levels were detected in tissues which underwent an early wave of apoptosis (bone marrow and/or spleen), but not in more radioresistant tissues (kidney, liver, brain, and heart). Some mouse strain-specific differences were observed, but none of the changes in mRNA level was detected in p53-/- mice. As activation of the NF-kappa B and AP1 transcription factors was not detected in early-(spleen) or late-(liver) responding tissues in 10 Gy X-irradiated p53+/+ mice in vivo, it is concluded that the modulation of cytokine gene expression in vivo is p53-dependent and indirectly associated with apoptosis.


Encapsulation of Graphene in the Hydrophobic Core of a Lipid Bilayer.
Theoretical simulations have predicted that a lipid bilayer forms a stable superstructure when a sheet of graphene is inserted in its hydrophobic core. We experimentally produced for the first time a lipid-graphene-lipid assembly by combining the Langmuir-Blodgett and the Langmuir-Schaefer methods. Graphene is sandwiched and remains flat within the hydrophobic core of the lipid bilayer. Using infrared spectroscopy, ellipsometry, and neutron reflectometry, we characterized the superstructure at every fabrication step. The hybrid superstructure is mechanically stable and graphene does not disturb the natural lipid bilayer structure.


Prevalence and clinical implications of bone marrow involvement in pediatric anaplastic large cell lymphoma.
Anaplastic large cell lymphoma (ALCL) harbors the reciprocal chromosomal translocation t(2;5)(p23;q35) in approximately 80% of the cases. The genes involved are nucleophosmin (NPM) and anaplastic lymphoma kinase (ALK) and the resulting chimeric NPM-ALK protein is thought to play a key role in the pathogenesis of t(2;5) positive ALCL. Few data on bone marrow (BM) involvement in ALCL have been published and they mostly rely on morphological examination of BM smears. We studied 52 ALCL for NPM-ALK expression by RT-PCR: 47/52 biopsies were positive. In 41 of the 47 cases we obtained the BM at diagnosis and investigated the prevalence of minimal BM infiltration by RT-PCR and real-time PCR. Minimal disseminated disease was positive in 25/41 patients (61%), of whom six had morphologically infiltrated BM. Survival analysis demonstrated a 5-year progression-free survival of 41 +/- 11% for patients with molecularly positive BM vs 100% for patients with negative BM (P = 0.001). These results suggest that minimal BM involvement at diagnosis is a common event in pediatric ALCL and that minimal BM disease monitoring could identify patients at risk of relapse.


Odor control in lagoons.
Lagoons are widely used in rural area for wastewater treatment; however, the odor problem has hampered its application. The root of odor emission from lagoons varies from one to another. The key of controlling the odor is to find out the cause and accordingly provide strategies. Various physical, chemical, and biological methods have been reported and applied for odor control. Physical technologies such as masking, capturing and sorption are often employed to mitigate the pressure from compliant while not to cut off the problem. Chemical technologies which act rapidly and efficiently in odor control, utilize chemicals to damage the odorant production root or convert odorant to odorless substances. Biological methods such as aeration, biocover and biofiltration control the odor by enhancing aerobic condition or developing methanogens in lagoon, and biologically decomposing the odorants. Comparing to physical and chemical methods, biological methods are more feasible.


The Aging Surgeon: Implications for the Workforce, the Surgeon, and the Patient.
Surgeons suffer from the same physiologic impairments common to all people with advancing age. These impairments not only affect the surgeon but also the patients under their care. This article delineates the epidemiologic context of the graying population of surgeons and the cognitive and physiologic changes that occur as the result of aging, the consequence of which is that greater experience does not necessarily equate with better clinical outcomes. This work also addresses potential methods for the ongoing evaluation of the aging surgeon and how elder surgeons may be best used as they reach the conclusion of their career.


Changes in insulin sensitivity induced by short-term growth hormone (GH) and insulin-like growth factor I (IGF-I) treatment in GH-deficient adults are not associated with changes in adiponectin levels.
To test potential effects of altered insulin sensitivity on circulating adiponectin levels, we studied patients with GH deficiency (GHD) undergoing high dose GH and IGF-I treatment in a well-defined short-term setting. This design allowed to exclude confounding effects of GH and IGF-I treatment on body composition. Six patients (three women and three men) with acquired GHD were treated in a randomised cross-over trial with GH (subcutaneous injections of GH 0.03 IU/kg/daily) or IGF-I (continuous subcutaneous infusion of 5 microg/kg/h recombinant IGF-I) for 5 days. Median age of patients was 60 (range 25-72) years, BMI 24.7 (20.7-30.7) kg/m(2), and baseline IGF-I concentration 60 (30-83) microg/L. HOMA scores (to assess insulin sensitivity) at baseline were 0.8 (0.3-11.7) and adiponectin concentrations were 7.0 (2.5-14.8) mg/L. HOMA scores increased rapidly and significantly up to a maximum of 2.7-fold (from baseline) at day 5 of GH treatment and returned promptly to baseline when GH was stopped, while adiponectin serum levels remained within the baseline range throughout the study period. HOMA scores dropped to a nadir of 0.66 from baseline at day 2 of IGF-I treatment whereas adiponectin levels remained within the baseline range. These data suggest that changes in insulin sensitivity (induced by high dose and short-term GH and IGF-I treatment) in patients with GHD are not associated with changes in adiponectin levels.


Malignant transformation of NIH-3T3 cells after subcutaneous co-injection with a reconstituted basement membrane (matrigel).
NIH-3T3 cells are non-tumorigenic when injected into athymic mice. If these cells are mixed with an extract of basement-membrane proteins (matrigel) and injected s.c., they form locally invasive and highly vascularized tumors. Cells cultured from the NIH-3T3-matrigel-induced tumors showed a transformed phenotype and lacked contact inhibition. When cultured in a gel of matrigel, they proliferated and formed branched and invasive colonies. In contrast, the parental NIH-3T3 cells cultured on matrigel remained as cell aggregates and were not invasive. I.V. injections of the tumor-derived NIH-3T3 cells produced many colonies on the surface of the lungs, whereas the parental NIH-3T3 cells were not metastatic. Zymographic analysis of the conditioned media obtained from both the tumor-derived and parental NIH-3T3 cells demonstrated higher amounts of the 72-kDa gelatinase (type-IV collagenase) enzyme in the tumor-derived cells. Also, tumor-derived NIH-3T3 cells, but not parental NIH-3T3 cells, secreted the 92-kDa type-IV collagenase. These studies suggest that the interaction of pre-malignant NIH-3T3 cells with extracellular matrix components may contribute to the process of tumor progression.


Randomized controlled trial of omeprazole or endoscopy in patients with persistent dyspepsia: a cost-effectiveness analysis.
Cost-effectiveness analysis, Helicobacter pylori research and the development of proton pump inhibitors are having an increasing impact on the management of dyspepsia. However, clinical trials have not always included both H. pylori diagnosis and proton pump inhibitors in their protocols. Patients who were referred for upper gastrointestinal endoscopy by their general practitioner were randomized to either prompt endoscopy followed by directed medical treatment (conventional group, n=38), or to empirical treatment with omeprazole and, in the case of symptom relapse, serological screening for H. pylori infection followed by eradication therapy in seropositive patients (empirical group, n=42). The study lasted for up to 1 year. In the empirical group, only 13 patients (31%) underwent endoscopy. The average number of days for which the patients kept records of their dyspeptic symptoms was 266 (95% CI: 226-307) in the empirical group, of which 166 (95% CI: 128-204) were symptom-free. In the conventional group, 159 (95% CI: 119-198) out of 255 days (95% CI: 209-302) were recorded as symptom-free. The average medical cost in the empirical group was $284 (95% CI: 218-350) and in the conventional group $491 (95% CI: 383-600). In the empirical group, two malignancies were found, whereas in the conventional group one malignancy was found. The empirical drug treatment strategy in patients with persistent dyspeptic symptoms resulted in 69% fewer diagnostic endoscopies with lower medical costs and equal effectiveness in the first year, compared to prompt endoscopy followed by directed medical treatment.


Impact of allograft ischemic time on long-term survival in lung transplantation: a Swedish monocentric study.
Purpose: The influence of allograft ischemic time (IT) on short- and long-term mortality remains under debate in lung transplantation (LTx). Due to a scarcity in donors, better understanding of IT might improve the outcome after LTx. Methods: Between January 1990 and June 2016; 307 patients underwent LTx at Lund university hospital, Sweden. The end-point used was death/Re-LTx assessed by Cox regression and Kaplan-Meier survival. Results: Kaplan-Meier survival for mean IT (min) between subgroups ≤120, 121-240, 241-360 and 361+ showed significant difference for pairwise-comparisons with superior outcome for IT between ≤120 and 240 min. Cox regression analyses for each hour of IT in patients with a limited survival up to 1- and 5-year had a hazard ratio (HR) of 1.119 and 1.063 respectively (p < .05). Conclusions: In LTx, every 2-hour increase of IT is equivalent to an increased mortality of up to 24% within 5 years. LTx with an IT of ≤120 min had a superior survival in both 1- and 5 years in comparison to an IT of up to 360 min. Better application of IT provides a key role in improving LTx outcome.


Rapid assessment of islet viability with acridine orange and propidium iodide.
A simple, rapid method for estimating the viability of isolated islets of Langerhans with fluorescent dyes is described. Low concentrations of acridine orange and propidium iodide (AO/PI) were used to visualize living and dead islet cells simultaneously. AO/PI-stained islets can be divided into three distinct groups. Group A islets fluoresce green, contain insulin, and have normal ultrastructure; group C islets fluoresce primarily red, contain little or no insulin, and have cells with disrupted cellular membranes. Group B islets fluoresce red, green, and yellow. The yellow color is due to the addition of two primary colors from the superimposed red and green fluorescing cells. In this assay, the interpretation that red islet cells are dead and green islet cells are alive was confirmed by sequentially staining single islet cells with AO/PI and trypan blue. The observation that red islets are dead was confirmed by heat-killing, enzymatically damaging, treating with ethanol, or depriving islets of nutrients and observing the red fluorescence. This assay should be useful in studies where the assessment of islet viability is essential.


Labisia pumila standardized extract (SKF7®) reduces percentage of waist circumference and waist-to-height ratio in individuals with obesity.
Evidence from the literature points towards a viable choice of utilizing Labisia pumila to improve the metabolic profile in animal studies. To that end, this prospective study was designed to assess the health impact of the consumption of L. pumila standardized extract (SKF7®) on key parameters of obesity in humans such as body weight (BW), body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR). A dose-ranging analysis using SKF7® was conducted through a randomized, double-blind, multicentre, placebo-controlled, phase 2 clinical trial involving individuals with obesity (N = 133) between January 2020 and April 2021. The potential percentage of change was assessed in relation to BW, BMI, WC and WHtR. Average treatment effect estimates (treatment group vs. placebo) show a statistically significant reduction in the percentage of change for BW (mean = -2.915; CI: -4.546, -1.285), BMI (-2.921; CI: -4.551, -1.291), WC (mean = -2.187; CI: -3.784, -0.589) and WHtR (mean = -2.294, CI: -3.908, -0.681) in the group with a total of 750 mg of SKF7® (p < .01). An incremental reduction in WC and WHtR was consistent with the gradual increase in the total daily concentration of SKF7® from 375 to 750 mg. WC and WHtR had higher effect size (f 2 = 0.11 and f 2 = 0.13 respectively) in comparison with BW and BMI. SKF7® is potentially a novel therapeutic treatment for obesity, reflected by reductions in BW, BMI, WC and WHtR. The use of SKF7® suggests a dose-dependent reduction in abdominal obesity, exemplified by a decline in WC and WHtR.


Postprandial triglyceride levels in familial combined hyperlipidemia. The role of apolipoprotein E and lipoprotein lipase polymorphisms.
The effect of apolipoprotein E genotype and polymorphisms of lipoprotein lipase gene on plasma postprandial triglyceride levels in familial combined hyperlipidemic subjects and their relatives have not been sufficiently studied. This study included sixteen familial combined hyperlipidemic parents (G1): age: 52 +/- 9 years with total-cholesterol: 7.2 +/- 1.7 mmol/L, fasting triglycerides: 2.8 +/- 1.4 mmol/L and sixteen children (G2) (twelve were normolipidemic): of age: 22 +/- 5 years with total-cholesterol: 5.2 +/- 1.1 mmol/L, fasting triglycerides: 2.06 +/- 1.8 mmol/L and twelve normolipidemic, healthy controls. Blood samples were taken fasting and 2, 4, 6, 8, 10 hr postprandially after the standard fat rich test meal. We determined lipid parameters, apolipoprotein E and lipoprotein lipase HindIII and PvuII polymorphisms as well. The 6-hr critical postprandial triglyceride values were abnormal in both G1: 5.88 +/- 2.7 mmol/L and G2: 3.53 +/- 2.7 mmol/L (p <0.001), respectively, and differed significantly (p <0.001) from each other. The subjects of familial combined hyperlipidemic families with E4 allele in both generations exhibited significantly (p <0.001) higher and extended postprandial lipemia. We did not find significant effects of lipoprotein lipase HindIII or PvuII polymorphisms on the fasting lipid values alone, however in normolipidemic subjects from the same families the homozygosity of HindIII variation was associated with higher triglyceride postprandial peak (p <0.01). The main findings of our study are that i.) normolipidemic G2 subjects in familial combined hyperlipidemic families have already abnormal postprandial status, and ii.) the 6 h postprandial triglyceride values were correlated with fasting triglyceride levels, which showed association with the apolipoprotein E4 allele.


Síndrome de Poland. Presentacíon de un caso. [Poland's syndrome. A case report].
A case of Poland's syndrome in a 19-year-old male is briefly described. This syndrome is characterized by congenital absence of the pectoralis major and minor muscles as well as homolateral brachysyndactyly. The etiology is unknown. Surgical repair is aimed at constructing a functional hand. Chest deformities usually does not require surgery except in cases of lung herniation or breast hypoplasia.


Role of supramolecular cellulose structures in enzymatic hydrolysis of plant cell walls.
The study of biomass deconstruction by enzymatic hydrolysis has hitherto not focussed on the importance of supramolecular structures of cellulose. In lignocellulose fibres, regions with a different organisation of the microfibrils are present. These regions are called dislocations or slip planes and they are known to be more susceptible to various forms of degradation such as acid hydrolysis. Traditionally the cellulose within these regions has been assumed to be amorphous, but in this study it is shown by use of polarized light microscopy that dislocations are birefringent. This indicates that they have a crystalline organisation. Dislocations may be entry points for endoglucanases. Using a fluorescent labelled endoglucanase combined with confocal fluorescence microscopy, it is shown that the enzyme selectively binds to dislocations during the initial phase of the hydrolysis. Using a commercial cellulase mixture on hydrothermally treated wheat straw, it was found that the fibres were cut into segments corresponding to the sections between the dislocations initially present, as has previously been observed for acid hydrolysis of softwood pulps. The results indicate that dislocations are important during the initial part of enzymatic hydrolysis of cellulose. The implications of this phenomenon have not yet been recognized or explored within cellulosic biofuels.


Wittig reaction of unprotected D-aldopentoses with stabilized ylides: metal-ion effects.
Each of the four D-aldopentoses (1-4) reacts in the unprotected form with Ph3PCHCO2Me (5) in THF to give stereoselectively the corresponding trans-alpha,beta-unsaturated C7 Wittig adducts, isolated as the corresponding 4,5,6,7-tetraacetates (7-10) or 4,5:6,7-di-O-isopropylidene derivatives (11-14). Concurrently formed are also bicyclic, 1,4-lactone derivatives, isolated as their 5,7-diacetates (15-18) or 5,7-O-isopropylidene derivatives (19), arising through intramolecular Michael addition from the initial acyclic adducts. Formation of the cyclized products is suppressed by incorporation of Cu(OAc)2 in the reaction mixture, permitting preparative isolation of the hept-3-enonate derivatives 7-10, useful as dienophiles in Diels-Alder carbocyclizations with chirality transfer. Optimized yields were 25% (D-ribo), 50% (D-arabino), 49% (D-xylo), and 61% (D-lyxo). Under Cu(OAc)2-catalyzed conditions, the formation of small proportions of 3,7-anhydroheptonic acid esters (21 and 23) was observed in the D-arabino and D-xylo series, but not with the other two pentoses.


Identifying three-dimensional structures of autophosphorylation complexes in crystals of protein kinases.
Protein kinase autophosphorylation is a common regulatory mechanism in cell signaling pathways. Crystal structures of several homomeric protein kinase complexes have a serine, threonine, or tyrosine autophosphorylation site of one kinase monomer located in the active site of another monomer, a structural complex that we call an "autophosphorylation complex." We developed and applied a structural bioinformatics method to identify all such autophosphorylation complexes in x-ray crystallographic structures in the Protein Data Bank (PDB). We identified 15 autophosphorylation complexes in the PDB, of which five complexes had not previously been described in the publications describing the crystal structures. These five complexes consist of tyrosine residues in the N-terminal juxtamembrane regions of colony-stimulating factor 1 receptor (CSF1R, Tyr(561)) and ephrin receptor A2 (EPHA2, Tyr(594)), tyrosine residues in the activation loops of the SRC kinase family member LCK (Tyr(394)) and insulin-like growth factor 1 receptor (IGF1R, Tyr(1166)), and a serine in a nuclear localization signal region of CDC-like kinase 2 (CLK2, Ser(142)). Mutations in the complex interface may alter autophosphorylation activity and contribute to disease; therefore, we mutated residues in the autophosphorylation complex interface of LCK and found that two mutations impaired autophosphorylation (T445V and N446A) and mutation of Pro(447) to Ala, Gly, or Leu increased autophosphorylation. The identified autophosphorylation sites are conserved in many kinases, suggesting that, by homology, these complexes may provide insight into autophosphorylation complex interfaces of kinases that are relevant drug targets.


Single-Molecule Imaging of Enzymatic Reactions on DNA Origami.
The interaction between enzymes is very important for understanding of enzyme functions and shed light on enzymatic reaction mechanisms. With the development of DNA nanotechnology, DNA origami has become a powerful tool for analyzing the dynamic behavior of enzyme molecules. In this protocol, a method for imaging and analysis of single-molecule cascade enzyme reactions on DNA origami raft by total internal reflection fluorescence microscopy (TIRFM) is described. Through trajectory analysis and calculation, the diffusion of downstream enzymes in enzymatic reaction and chemotaxis of enzymatic reactions were elucidated at the single molecular level.


[Deep venous incompetence of legs: experimental studies].
To seek best wrapping materials of valvular wrapping operation of deep veins in the lower limbs and to understand the value of diagnostic value of duplex scanning for incompetence of the deep veins and the function of the popliteal valve. Strips of the autogenous saphenous vein, autogenous fascia lata and PEFE graft were used respectively as the material for valve constriction. The results were compared of duplex scanning and trans-popliteal venography. In the saphenous vein and fascia lata groups, diffuse fibrosis and marked narrowing of the femoral vein were found, whereas in the vascular graft group the graft was intact without prominent fibrosis and narrowing of the vein. The accurate rates of duplex scanning and trans-popliteal venography were 91.86%. at the same time the thigh and popliteal valve was closed when held breath. Vascular graft is the best constriction material. Duplex scanning is a important method. Popliteal valve is an important barrier for protecting the function of the deep vein.


[Compounds from Caesalpinia sappan L].
Two compounds were isolated from the stem of Caesalpinia sappan. Their structures were elucidated on the basis of physical and spectral analysis. They were named as tetraacetylbrazilin and protosappanin A respectively.


The spectrum of activity of the small RNA DsrA: not so narrow after all.
For a long time, the small regulatory RNA DsrA has been considered as a regulator with a narrow spectrum of action due to its restricted targetome. Since the first reports on DsrA characterization, only two targets of DsrA have been described: rpoS and hns mRNAs, encoding the sigma factor σS and the nucleoid-associated protein H-NS, respectively. Recently, the scope of DsrA targetome has been expanded by the characterization of two negatively regulated mRNAs, mreB and rbsD, involved in cell wall biosynthesis and ribose metabolism, respectively. In this review, we summarize new insights in DsrA-mediated regulation and emphasize the versatility of DsrA modes of action.


Nationwide data on home care and care home residence: presentation of the Swedish Social Service Register, its content and coverage.
All Swedish municipalities are legally obliged to provide publicly funded elder care to individuals in need. The Swedish Social Service Register collects data on such care. It is the only nationwide source of information on care home residency and use of home care but has rarely been used for research. This study aims to present the content and coverage of the Social Service Register and to provide guidance for researchers planning to use these data. For each month between 2013 and 2020, we examined which of Sweden's 290 municipalities reported data to the Social Service Register. We calculated proportions of the population (restricted to ages 80-89 years to enable comparison) that were reported to the Social Service Register in each municipality and presented the types and amount of care recorded in the register. The proportion of municipalities reporting to the Social Service Register increased from 82% to 98% during the study period but several municipalities reported fragmentarily and inconsistently, particularly during earlier years. Among municipalities reporting to the Social Service Register, 9% of the population aged 80-89 years resided in care homes and 19% received home care, but the registered amount and types of care varied substantially between municipalities and over time. The Swedish Social Service Register provides valuable data for research on aging and elder care utilisation, but data should be selected and vetted carefully, especially for earlier years. The amount and types of care may not always be comparable between geographical regions and different time periods. In recent years, however, the coverage of the Social Service Register is good.


Oral mucositis in childhood cancer patients receiving high-dose methotrexate: Prevalence, relationship with other toxicities and methotrexate elimination.
Oral mucositis (OM) is one of the main adverse effects of the chemotherapeutic agent methotrexate (MTX). To evaluate the relationship of OM with MTX metabolism time and other toxicities in childhood, cancer patients receiving high-dose of methotrexate (HD-MTX). Seventy-seven childhood patients receiving HD-MTX for treatment of leukaemia, osteosarcoma or lymphoma were evaluated. MTX serum level, hepatic and renal function parameters, and presence and intensity of OM were analysed. The patients were submitted to 255 cycles of chemotherapy. OM was diagnosed in 191 (74.9%) cycles. Of these, 119 (46.6%) presented ulcerative lesions. Lymphoma was associated with severe OM (P = .01). OM was associated with higher serum levels of aspartate aminotransferase (P = .006), alanine aminotransferase (P = .04) and creatinine (P = .008). Increase of one unit of total bilirubin and indirect bilirubin associated, respectively, with 11% and 39% higher prevalence of OM. For each increase of one unit of creatinine serum level, it was observed a 37% higher prevalence of OM in patients with lymphoma. No association was found between delayed excretion of MTX and OM development. OM is a prevalent complication of childhood cancer patients receiving HD-MTX. Renal and hepatic toxicity could be considered risk factors for OM, especially in patients with lymphoma.


Gonadotrophin-releasing hormone analogue-induced manipulation of testicular function in the monkey.
In this paper the properties of a novel group of compounds, gonadotrophin-releasing hormone antagonists, are used to study the regulation of testicular function. These studies provide the basis for new developments in male contraception.


Open-Loop Neurofeedback Audiovisual Stimulation: A Pilot Study of Its Potential for Sleep Induction in Older Adults.
This pilot study tested the efficacy of a 30-min audio-visual stimulation (AVS) program for the treatment of chronic insomnia in older adults. Chronic insomnia has been conceptualized as entailing increased cortical high frequency EEG activity at sleep onset and during NREM sleep. We hypothesized that an AVS program gradually descending from 8 to 1 Hz would potentially reduce the excessive cortical activation that is thought to contribute to difficulties with initiating and maintaining sleep. Accordingly, we conducted an intervention study of AVS using a pre-post design. Eight older adults (88 ± 8.7 years) complaining of chronic insomnia self-administered a 30-min AVS program nightly at bedtime for one month. Sleep was assessed at baseline and throughout the 4-week intervention. After using AVS for 4 weeks, significant improvement was reported in insomnia symptoms (ISI, p = 0.002) and sleep quality (PSQI, p = 0.004); with moderate to large effect sizes (Partial Eta2: 0.20-0.55)(Cohen's d: 0.7-2.3). The training effect (self-reported sleep improvement) was observed at the end of week one and persisted through the 1-month intervention. The results from this pilot study suggest that further exploration of AVS as a treatment for insomnia is warranted.


Rieger syndrome revisited: experimental approaches using pharmacologic and antisense strategies to abrogate EGF and TGF-alpha functions resulting in dysmorphogenesis during embryonic mouse craniofacial morphogenesis.
The major manifestations of Rieger syndrome (RS), an autosomal dominant disorder, include absent maxillary incisor teeth, malformations of the anterior chamber of the eye, and umbilical anomalies [Aarskog et al., 1983: Am J Med Genet 15:29-38; Gorlin et al., 1990: "Syndromes of the Head and Neck" 3rd ed.]. Linkage of RS to human chromosome 4q markers has been identified with tight linkage to epidermal growth factor (EGF) [Murray et al., 1992: Nat Genet 2:46-48]. Mutations associated with genes of the EGF superfamily are implicated in malformations arising from abnormal development of the first branchial arch [Ardinger et al., 1989: Am J Hum Genet 45:348-353; Sassani et al., 1993: Am J Med Genet 45:565-569]. Down-regulation of EGF during early mouse development results in ablation of tooth formation [Kronmiller et al., 1991: Dev Biol 147:485-488]. Since EGF, TGF-alpha, and EGF receptor (EGFr) transcripts are expressed in the mouse first branchial arch and derivatives, experimental strategies were employed to investigate the consequences of down-regulation of EGF translation and inhibition of EGF receptor during embryonic mandibular morphogenesis. Antisense inhibition of EGF expression produces mandibular dysmorphogenesis with decreased tooth bud size; these effects are reversed by the addition of exogenous EGF to the culture medium [Shum et al., 1993: Development 118:903-917]. Tyrphostin RG 50864, which inhibits EGF receptor kinase activity, inhibits EGF or TGF-alpha stimulation of tyrosine phosphorylation in a concentration-dependent manner and severely retards mandibular development [Shum et al., 1993: Development 118:903-917].(ABSTRACT TRUNCATED AT 250 WORDS)


Immobilized Enzyme Pipette, Impette. Routine estimation of serum and urine urea.
This paper describes the preparation, properties, principles of operation and use of a new device, Immobilized Enzyme Pipette or Impette in routine determination of blood and urine urea. Clinical trials carried out in a medium sized hospital gave very reliable and reproducible results with a very high precision.


The mental health impact of parole on families of indeterminate-sentenced prisoners in England and Wales.
The indeterminate sentence of Imprisonment for Public Protection (IPP), was created in England and Wales in 2003. After its abolition in 2012, many IPP-prisoners have become stuck in the prison system, facing considerable problems of sentence progression. The extant literature makes clear that the uncertainty and hopelessness caused by the indeterminacy of the IPP sentence are compounded by the negative impacts experienced by families and others providing support to people serving these sentences. The mental strains caused for family members by the IPP sentence were examined. Of particular interest is the role and weight of the parole process experience, and its potential mental and physiological health impact on families. This article draws on findings from two qualitative research projects conducted with families of prisoners serving the IPP sentence in England and Wales. Their experiences will be examined by reference to literature on the mental health impact of indeterminate sentences on prisoners and their families and the wider literature on the symbiotic harms of imprisonment for families. The aim was to add to this by focusing on families' experiences of cumulative stress caused by the sentence. We demonstrate that the IPP parole process exerts specific weight and mental strains on family members occupying the negative end of the stress spectrum. Drawing on a body of neuroscientific, neuroendocrinological and criminological literature, we argue that these mental health impacts on families may represent a public health risk in need of practical and policy mitigation. There is a pressing need for recognition of what are often hidden symbiotic harms experienced by families of people sentenced to IPP. Families require more information as well as considerably greater practical and emotional support on an institutional and communal level.


Setting up a nurse-led anticoagulant clinic.
People on anticoagulation therapy need regular monitoring. With appropriate training, nurse specialists can improve patient care in anticoagulant clinics.


Improving ED Emergency Severity Index Acuity Assignment Using Machine Learning and Clinical Natural Language Processing.
Triage is critical to mitigating the effect of increased volume by determining patient acuity, need for resources, and establishing acuity-based patient prioritization. The purpose of this retrospective study was to determine whether historical EHR data can be used with clinical natural language processing and machine learning algorithms (KATE) to produce accurate ESI predictive models. The KATE triage model was developed using 166,175 patient encounters from two participating hospitals. The model was tested against a random sample of encounters that were correctly assigned an acuity by study clinicians using the Emergency Severity Index (ESI) standard as a guide. At the study sites, KATE predicted accurate ESI acuity assignments 75.7% of the time compared with nurses (59.8%) and the average of individual study clinicians (75.3%). KATE's accuracy was 26.9% higher than the average nurse accuracy (P <.001). On the boundary between ESI 2 and ESI 3 acuity assignments, which relates to the risk of decompensation, KATE's accuracy was 93.2% higher, with 80% accuracy compared with triage nurses 41.4% accuracy (P <.001). KATE provides a triage acuity assignment more accurate than the triage nurses in this study sample. KATE operates independently of contextual factors, unaffected by the external pressures that can cause under triage and may mitigate biases that can negatively affect triage accuracy. Future research should focus on the impact of KATE providing feedback to triage nurses in real time, on mortality and morbidity, ED throughput, resource optimization, and nursing outcomes.


Killing of cultured hepatocytes by conjugates of asialofetuin and EGF linked to the A chains of ricin or diphtheria toxin.
A disulfide-linked conjugate between asialofetuin (ASF) and the toxic A chain (RTA) of ricin is as potent a toxin for cultured rat hepatocytes as our previously described conjugate between ASF and fragment A of diphtheria toxin (DTA). An RTA conjugate of epidermal growth factor (EGF) was a potent toxin for 3T3 cells. In contrast, EGF-DTA was essentially nontoxic for 3T3 cells. We have now examined the toxicity of EGF-RTA and EGF-DTA on cultured hepatocytes. The EGF-DTA conjugate, nontoxic to 3T3 cells, is also a potent toxin for hepatocytes. We also observed a decrease with time of culture in the sensitivity of hepatocytes to the ASF and EGF conjugates. This decrease is not a result of a decrease in EGF or asialoglycoprotein receptors.


Protein domain library generation by overlap extension (PDLGO): a tool for enzyme engineering.
We introduce an upgraded version of the error-prone polymerase chain reaction (epPCR) comprising three DNA polymerase-catalyzed steps. It improves the common epPCR strategy such that random mutations can be confined exactly to a distinct, but freely selectable, sequence region within a gene without the need for flanking restriction endonuclease sites. The new method is called protein domain library generation by overlap extension (PDLGO). To validate PDLGO, we generated a random library of EstE, a multidomain esterase from Xanthomonas vesicatoria. It was demonstrated that random mutations appear exclusively within the catalytic domains as intended. The domains of EstE flanking the catalytic domains are required for transport of EstE to the cell envelope and remain unaltered. Microplates with integrated pH sensors, providing a substrate-independent high-throughput screening tool, were used to analyze whole cells of E. coli expressing the variants of the EstE library. A variant (P286H) with substantially increased catalytic activity was identified. Our results indicate that combining PDLGO with microplates containing integrated pH sensors provides a simple and rapid toolbox for directed evolution of esterases.


Diagnosing women with HPV: the impact of diagnosis disclosure methods.
Little data exists on women's HPV diagnosis encounters. This research focuses on impacts of the communicative medium used to inform women of their HPV status. We conducted a qualitative study to identify the mediums used to communicate HPV diagnoses and the impact of each medium on the diagnosis experience. Twenty-five women with HPV completed semi-structured interviews, which we recorded and transcribed. We relied on grounded theory techniques in both data collection and analysis. There are three primary mediums health care providers use to inform women of their HPV diagnosis: phone calls, mailed letters/email, and face-to-face interactions. Implications regarding each medium are identified and discussed. There are drawbacks associated with the use of each medium that healthcare practitioners should be aware of and seek to avoid. Healthcare providers can utilize descriptions of diagnosis encounters and the recommendations accompanying them to understand and modify ways they choose to inform individuals of an HPV diagnosis.


Tn7 elements: engendering diversity from chromosomes to episomes.
The bacterial transposon Tn7 maintains two distinct lifestyles, one in horizontally transferred DNA and the other in bacterial chromosomes. Access to these two DNA pools is mediated by two separate target selection pathways. The proteins involved in these pathways have evolved to specifically activate transposition into their cognate target-sites using entirely different recognition mechanisms, but the same core transposition machinery. In this review we discuss how the molecular mechanisms of Tn7-like elements contribute to their diversification and how they affect the evolution of their host genomes. The analysis of over 50 Tn7-like elements provides insight into the evolution of Tn7 and Tn7 relatives. In addition to the genes required for transposition, Tn7-like elements transport a wide variety of genes that contribute to the success of diverse organisms. We propose that by decisively moving between mobile and stationary DNA pools, Tn7-like elements accumulate a broad range of genetic material, providing a selective advantage for diverse host bacteria.


A distribution-moment model of deactivation in cardiac muscle.
The Distribution Moment (DM) model has simulated experimental data on skeletal muscle, but it has not been used previously to study the mechanics of active contraction in cardiac muscle. In contrast to previous models of striated muscle contraction, all parameters have physical meaning and assumptions concerning biophysical events within the cell are consistent with available data. In order to simulate cardiac muscle deactivation using the DM model it was necessary to make the cross-bridge detachment rates large for large displacements from the neutral equilibrium position of a cross-bridge. To examine the effect of cooperativity on cardiac muscle contraction, we used the DM model's tight coupling scheme with binding of one or two calcium sites regulating contraction. As observed experimentally, our model predicted a reduction of isometric tension development following rapid shortening lengthening transients when contraction is regulated by either one or two calcium binding sites. The predicted deactivating effect increased if the transient was applied late in the twitch when contraction is regulated by two calcium binding sites, but not when it is regulated by one site. This is the first study in which deactivation has been simulated without making any provisions for length-dependent calcium trononin dissociation.


Biomarkers and heart failure events in patients with atrial fibrillation in the ARISTOTLE trial evaluated by a multi-state model.
Atrial fibrillation (AF) and heart failure (HF) often coexist. We investigated the prognostic impact of biomarkers on the development of HF and death in patients with AF and different left ventricular systolic function considering the influence of competing events. The study included 11,818 patients with AF from the ARISTOTLE trial who at entry had information on history of HF, an estimate of left ventricular function and plasma samples for determination of biomarkers representing cardiorenal dysfunction (NT-proBNP, troponin T, cystatin C) and inflammation (GDF-15, IL-6, CRP). Patients were categorized into: (I) HF with reduced ejection fraction (HFrEF, n = 2,048), (II) HF with preserved ejection fraction (HFpEF, n = 2,520), and (III) No HF (n = 7,250). Biomarker associations with HF hospitalization and death were analyzed using a multi-state model accounting also for repeated events. Baseline levels of NT-proBNP, troponin T, cystatin C, GDF-15, IL-6, and CRP were highest in HFrEF and lowest in No HF. During median 1.9 years follow-up, 546 patients were hospitalized at least once for HF and 819 died. Higher levels of all investigated biomarkers were associated with both outcomes (all P< .0001), with highest event rates in HFrEF and lowest in No HF. The associations remained after adjustments and were more pronounced for first than for recurrent events. In anticoagulated patients with AF, biomarkers indicating cardiorenal dysfunction and inflammation improve the identification of patients at risk of developing HF or worsening of already existing HF. These biomarkers might be useful for targeting novel HF therapies in patients with AF.


Rheological characterization of O/W emulsions incorporated with neutral and charged polysaccharides.
The effects of polysaccharides, including xyloglucan from Hymenaea courbaril (XG), galactomannans from Schizolobium parahybae (GMSP) and Mimosa scabrella (GMMS), xanthan gum (XT), sodium hyaluronate (HNa) and Fucogel(®) (FG), on the rheological behavior of cosmetic emulsions were evaluated. These incorporations gave rise to six emulsified systems, denoted XGE, GMSPE, GMMSE, XTE, HNaE and FGE, respectively. The emulsion consistency was found to follow the trend GMSPE>XGE>HNaE>FGE>XTE>GMMSE. In general, the addition of polysaccharides increased the viscoelastic properties of the emulsions and decreased the creep compliance. The neutral polysaccharides (GMSPE, GMMSE) led to better stability of the emulsions after storing for 20 days relative to charged polymers. It was found that polysaccharides XG, GMSP and GMMS, which come from the seeds of native Brazilian plant species, might be used to modify the flow properties and stabilities of oil-water emulsions.


Poisoning due to pyrethroids.
The first pyrethroid pesticide, allethrin, was identified in 1949. Allethrin and other pyrethroids with a basic cyclopropane carboxylic ester structure are type I pyrethroids. The insecticidal activity of these synthetic pyrethroids was enhanced further by the addition of a cyano group to give alpha-cyano (type II) pyrethroids, such as cypermethrin. The finding of insecticidal activity in a group of phenylacetic 3-phenoxybenzyl esters, which lacked the cyclopropane ring but contained the alpha-cyano group (and hence were type II pyrethroids) led to the development of fenvalerate and related compounds. All pyrethroids can exist as at least four stereoisomers, each with different biological activities. They are marketed as racemic mixtures or as single isomers. In commercial formulations, the activity of pyrethroids is usually enhanced by the addition of a synergist such as piperonyl butoxide, which inhibits metabolic degradation of the active ingredient. Pyrethroids are used widely as insecticides both in the home and commercially, and in medicine for the topical treatment of scabies and headlice. In tropical countries mosquito nets are commonly soaked in solutions of deltamethrin as part of antimalarial strategies. Pyrethroids are some 2250 times more toxic to insects than mammals because insects have increased sodium channel sensitivity, smaller body size and lower body temperature. In addition, mammals are protected by poor dermal absorption and rapid metabolism to non-toxic metabolites. The mechanisms by which pyrethroids alone are toxic are complex and become more complicated when they are co-formulated with either piperonyl butoxide or an organophosphorus insecticide, or both, as these compounds inhibit pyrethroid metabolism. The main effects of pyrethroids are on sodium and chloride channels. Pyrethroids modify the gating characteristics of voltage-sensitive sodium channels to delay their closure. A protracted sodium influx (referred to as a sodium 'tail current') ensues which, if it is sufficiently large and/or long, lowers the action potential threshold and causes repetitive firing; this may be the mechanism causing paraesthesiae. At high pyrethroid concentrations, the sodium tail current may be sufficiently great to prevent further action potential generation and 'conduction block' ensues. Only low pyrethroid concentrations are necessary to modify sensory neurone function. Type II pyrethroids also decrease chloride currents through voltage-dependent chloride channels and this action probably contributes the most to the features of poisoning with type II pyrethroids. At relatively high concentrations, pyrethroids can also act on GABA-gated chloride channels, which may be responsible for the seizures seen with severe type II poisoning. Despite their extensive world-wide use, there are relatively few reports of human pyrethroid poisoning. Less than ten deaths have been reported from ingestion or following occupational exposure. Occupationally, the main route of pyrethroid absorption is through the skin. Inhalation is much less important but increases when pyrethroids are used in confined spaces. The main adverse effect of dermal exposure is paraesthesiae, presumably due to hyperactivity of cutaneous sensory nerve fibres. The face is affected most commonly and the paraesthesiae are exacerbated by sensory stimulation such as heat, sunlight, scratching, sweating or the application of water. Pyrethroid ingestion gives rise within minutes to a sore throat, nausea, vomiting and abdominal pain. There may be mouth ulceration, increased secretions and/or dysphagia. Systemic effects occur 4-48 hours after exposure. Dizziness, headache and fatigue are common, and palpitations, chest tightness and blurred vision less frequent. Coma and convulsions are the principal life-threatening features. Most patients recover within 6 days, although there were seven fatalities among 573 cases in one series and one among 48 cases in another. Management is supportive. As paraesthesiae usually resolve in 12-24 hours, specific treatment is not generally required, although topical application of dl-alpha tocopherol acetate (vitamin E) may reduce their severity.


Dietary palmitic acid raises plasma LDL cholesterol relative to oleic acid only at a high intake of cholesterol.
Using a crossover design, the effects of exchanging up to 10% dietary energy (%en) between oleic (18:1) and palmitic acid (16:0) on plasma lipoprotein metabolism was investigated in 12 normocholesterolemic cebus monkeys, both in the absence and presence of dietary cholesterol (0.3%, w/w). In all the purified diets, which contained 33%en as fat blends, myristic acid (14:0) and linoleic acid (18:2) were held constant at 0.3%en and 3.7%en, respectively. Cholesterol-free diets containing either high 18:1 (19%en), roughly equivalent levels of 16:0 and 18:1 (12 and 15%en, respectively), or a high level of 16:0 (18%en), generated similar values for total plasma cholesterol (TC), HDL-C and LDL-C. Plasma triacylglycerol concentrations (TG) were significantly higher when monkeys were fed the 16: 0-rich diet than when fed the 18: 1-rich diet (75 +/- 6 vs. 52 +/- 8 mg/dl; P < 0.05). LDL and HDL kinetic parameters (assessed after simultaneous injection of homologous 131I-LDL and 125I-HDL) revealed no significant differences between the 18: 1-rich or 16: 0-rich diets. By contrast, with added dietary cholesterol (0.78 mg/kcal) the 16: 0-rich diet resulted in significantly higher TC (318 +/- 20 vs. 299 +/- 20 mg/dl; P < 0.05) and LDL-C (136 +/- 10 vs. 117 +/- 10 mg/dl; P < 0.05) in comparison to the 18: 1-rich diet. HDL-C was unaffected (159 +/- 8 vs. 156 +/- 5 mg/dl), but plasma TG concentrations also tended to be higher (70 +/- 8 vs. 60 +/- 6 mg/dl, P < 0.08). Kinetic studies revealed that the higher LDL-C concentration was associated with an elevated pool size of LDL apo B (40 +/- 2 vs. 34 +/- 2 mg/kg body weight; P < 0.005), the latter attributed to decreased FCR (1.06 +/- 0.07 vs. 1.27 +/- 0.12 pools/day; P < 0.04) with no effect on the transport rate of LDL apo B (41 +/- 2 vs. 42 +/- 3 mg/kg body weight per day). HDL kinetic parameters were comparable during the 16: 0 and 18: 1 dietary periods, but dietary cholesterol caused an increase in apo A-I pool size and transport rate without impacting FCR. In this study a palmitic acid-rich diet failed to alter plasma or LDL-C when compared to an oleic acid-rich diet, unless the diet also contained cholesterol. In the latter case, 16: 0 increased LDL-C, which reflected a decrease in the efficiency of LDL apo B removal.


Long noncoding RNA expression profile and functional analysis in psoriasis.
Long noncoding RNAs (lncRNAs) serve important roles in the biology of autoimmune diseases and immune‑associated disorders. To identify lncRNAs specifically associated with psoriasis, the expression of lncRNAs from biopsies obtained from patients with psoriasis were compared with samples obtained from healthy volunteers using a microarray. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to detect the expression of 10 identified dysregulated lncRNAs. Cis‑ and trans‑regulated target genes of lncRNAs were predicted. The results of microarray analysis indicated that 2,194 lncRNAs and 1,725 mRNAs were significantly dysregulated. Gene Ontology and pathway analyses among the dysregulated genes were performed. Co‑expression network analysis was also performed to study molecular interactions. Several identified pathways were associated with psoriasis. Among the 2,194 dysregulated lncRNAs, 1,549 of these had cis‑ or trans‑regulated predicted target genes. Among the 1,725 dysregulated mRNAs, 289 of the cis‑regulated target genes and 262 of the trans‑regulated target genes may be regulated by the differentially expressed lncRNAs; 10 differentially expressed lncRNAs were randomly selected and then validated. Of these lncRNAs, 7 exhibited the same expression profile as determined via microarray analysis, of which 3 lncRNAs were upregulated and 4 lncRNAs were downregulated. To the best of our knowledge, the present study is the first in which a microarray has been used to investigate the expression profile of lncRNAs associated with psoriasis. Additionally, the expression levels of the 10 aforementioned lncRNAs associated with psoriasis were validated in the present study for the first time using RT‑qPCR. The findings demonstrated that lncRNAs may contribute to the pathogenesis of psoriasis and suggested their potential diagnostic and therapeutic value. Furthermore, the findings of the present study suggest that the combined actions of several lncRNAs may contribute to the pathogenesis of psoriasis.


SIRT6 inhibits hypoxia-induced pulmonary arterial smooth muscle cells proliferation via HIF-1α/PDK4 signaling.
SIRT6 is an NAD+-dependent protein that plays a vital role in regulating the cell proliferation, differentiation and apoptosis. Abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) in peripheral vascular is one of the major pathological findings of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). However, whether SIRT6 is involved in hypoxia-induced proliferation of PASMCs and its possible mechanisms remain unknown. In the present study, we found that the expression of SIRT6 was decreased in both hypoxia-induced PAH rats model and HPASMCs. Hypoxia promoted the proliferation of HPASMCs in a time-dependent manner, inhibited the activity of caspase-3 and the production of PDH, increased the activity of LDH, ROS level, mitochondrial membrane potential(MMP) and the expression of HIF-1α and PDK4, which induced glycolysis. SIRT6 over-expression could inhibit the proliferation of HPASMCs and increase the apoptosis rate, impelled the retardation of cell cycle in phase G1. Meanwhile, SIRT6 over-expression reduced LDH activity, the levels of ROS and MMP, which simultaneously increased the production of PDH, the expression of HIF-1α, PDK4, Cyclin D1 and PCNA in hypoxia-induced HPASMCs. Moreover, SIRT6 over-expression inhibited the transcriptional activation of HIF-1α/PDK4 signaling. In addition, SIRT6 knockdown with SIRT6 siRNA exhibited the same effect as hypoxia. Together, our results indicated that SIRT6 was participant in regulating hypoxia-induced imbalance of proliferation and apoptosis of HPASMCs, which was associated with the activation of HIF-1α/PDK4 signaling pathway. Targeting at SIRT6 gene and regulating the downstream metabolism signaling pathway may be a novel strategy for the treatment of hypoxia-induced PAH.


Effect of Heat Stress on Dairy Cow Performance and on Expression of Protein Metabolism Genes in Mammary Cells.
The aim of this study was to assess the effect of heat stress on dairy cow performance and on the expression of selected genes involved in milk protein metabolism. Eight Italian Holstein Friesian cows were kept under thermoneutral conditions (temperature-humidity index (THI) < 72, CON) for 8 days and under mild heat stress conditions (72 < THI < 78, HS) for an additional 8 days. The rectal temperature, feed intake, and milk yield were recorded during the last 3 days of the CON and HS periods. During the same time period, milk samples were collected to assess the composition and expression of selected genes involved in milk protein metabolism. Gene expression analyses were performed on somatic cells from milk, which are representative of mammary tissue. In terms of dairy cow performance, HS resulted in lower milk and protein yields and feed intake but higher rectal temperature than for CON (p < 0.05). Under HS, there were greater abundances of HSPA1A (p < 0.05) and BCL2 (p < 0.05), compared to CON, but similar levels of CSN2 (p > 0.05), CSN3 (p > 0.05), HSPA8 (p > 0.05), and STAT5B (p > 0.05) mRNA. Mild heat stress reduced the performance of dairy cows without affecting the expression of genes coding for caseins.


The diagnostic utility of zinc E-box 1 (ZEB1) transcription factor for identification of pulmonary sarcomatoid carcinoma in cytologic and surgical specimens.
Although uncommon, pulmonary sarcomatoid carcinoma carries a worse prognosis due to poor chemotherapeutic response. Currently, a histologic spindle and/or giant cell component indicates sarcomatoid differentiation, with zinc E-box binding homeobox 1 (ZEB1) implicated in promoting epithelial-mesenchymal transition. However, diagnostic use of ZEB1 in limited specimens, including cell block (CB) preparations, remains unclear. Pulmonary sarcomatoid (SARC, n = 15), typical (TC, n = 10) and atypical carcinoid (AC, n = 10), small cell (SCLC, n = 8) and large cell neuroendocrine carcinoma (LCNEC, n = 9), squamous cell carcinoma (SQ, n = 7), and adenocarcinoma (ADC, n = 7) CBs along with 69 SARCs, 20 TCs, 21 ACs, 9 SCLCs, 10 LCNECs, 71 SQs, 402 ADCs, 16 large cell carcinoma (LCC) and 17 other thoracic tumor (OT) surgical specimens between 2007 and 2018 were retrieved. ZEB1 (Sigma Aldrich, St. Louis, Mo and Novus Biological, Centennial, Colo) immunohistochemistry was graded 1+ to 3+, with ≥1+ and >5% staining considered positive. Nuclear ZEB1 was seen in 80% SARC (12/15), 0% TC (0/10), 0% AC (0/10), 12.5% SCLC (1/8) and 11.1% LCNEC (1/9), 0% SQ (0/7), and 0% ADC (0/7) CBs. In surgical specimens, 75.4% SARCs (52/69), 0% TCs (0/20), 0% ACs (0/21), 11.1% SCLCs (1/9), 30% LCNECs (3/10), 0% SQs (0/71), 0.2% ADCs (1/402), 12.5% LCCs (2/16), and 11.8% OTs (2/17) demonstrated ZEB1. ZEB1 sensitivity and specificity in cytology and surgical specimens were 80% and 96.1%, and 75.4% and 98.1%, respectively. ZEB1 is sensitive and highly specific for pulmonary sarcomatoid carcinoma in limited cytologic and surgical specimens. Diagnostic pitfalls include high-grade neuroendocrine tumors and large cell carcinoma, which are resolvable by morphologic considerations.