The performance of body mass component indices in detecting risk of musculoskeletal injuries in physically active young men and women.
Body composition indices can be related to musculoskeletal injuries (MI), particularly in physically active groups. However, little is known about the accuracy of these diagnoses as potential predictors of musculoskeletal injuries. Therefore, this study aims to indicate the cut-off points of relative body mass (BMI), fat mass index (FMI), skeletal muscle mass (SMI), and muscle to fat ratio (MFR) and establish its reliability in injury prediction for physically active men and women. The sample included 119 physically active individuals aged 23.72 ± 1.12 (66 men body height 1.79 ± 0.07 (m); body weight 80.51 ± 9.85 (kg) and 53 women body height 1.67 ± 0.08 (m); body weight 62 ± 10.72 (kg)), students at university of physical education in Poland. The participants' physical activity was measured with the International Physical Activity Questionnaire (IPAQ). The relevance of body mass index (BMI), fat mass index (FMI), skeletal muscle mass index (SMI), and muscle to fat ratio (MFR) in detecting injury risk was examined. Musculoskeletal injuries during 1 year before examination were registered using a self-reporting questionnaire. The areas under the curve (AUC) and Youden Index in the receiver operating characteristic curve (ROC) were calculated. The cut-off points used to classify the indices among men were BMI = 24.38; FMI = 3.74; SMI = 16.40; MFR = 3.70; and for women BMI = 20.90; FMI = 4.17; SMI = 8.96; MFR = 1.67. Results suggested the greatest reliability in the prediction of musculoskeletal injuries among men had BMI (AUC = 0.623; Youden = 0.30) and SMI (AUC = 0.608; Youden = 0.23) whereas among women, MFR (AUC = 0.628; Youden = 0.29) and FMI (AUC = 0.614; Youden = 0.32). BMI and SMI are the most appropriate indices to predict the risk of musculoskeletal injury in physically active men, whereas in women, MFR and FMI are more reliable. These results indicate that the indices with more muscle mass meaning are better in predicting injury among men. In contrast, indices with a higher contribution of fat are better for women. It indicates sex differentiation of injury risk conditions. Men should focus on developing muscle mass, whereas women should reduce body fat to decrease injury risk. However, widespread use seemed to be limited to the specific examined group. Therefore, cut-off points should be used with caution, and calculated values should be verified and confirmed in subsequent studies.


Determination of the mechanism of demethylenation of (methylenedioxy)phenyl compounds by cytochrome P450 using deuterium isotope effects.
The mechanism of demethylenation of (methylenedioxy)benzene (MDB), (methylenedioxy)amphetamine (MDA), and (methylenedioxy)methamphetamine (MDMA) by purified rabbit liver cytochrome P450IIB4 has been investigated by using deuterium isotope effects. A comparison of the magnitude and direction of the observed kinetic isotope effects indicates that the three compounds are demethylenated by different mechanisms. The different mechanisms of demethylenation have been proposed on the basis of comparisons of the observed biochemical isotope effects with the isotope effects from purely chemical systems.


Spindle cell subtype of pulmonary clear cell tumor with prominent calcification and malignant potential.
Perivascular epithelioid cell tumor of the lung, also known as clear cell "sugar" tumor, is a rare benign tumor arising from perivascular epithelioid cells. Herein, we present a case of spindle cell subtype of pulmonary perivascular epithelioid cell tumor with prominent calcification and malignant potential in a 49-year-old woman. Histologically, the striking feature of this lesion was attributed to the presence of spindle cells arranged in a diffuse pattern, which is a pitfall for diagnosis. However, some of the lesion contained polygonal tumor cells with clear abundant cytoplasm surrounded by thin-walled vascular spaces. The size of the tumor and its Ki-67 index suggested malignant potential, and calcification was another rare characteristic. Immunostaining indicated that the tumor cells were positive not only for HMB-45 and Melan A, but also for CD34 and CD1a. This tumor should be distinguished from tumors with rich spindle cells such as sarcoma, clear cell carcinoma, or metastatic tumors. The patient in this case was alive with no tumor recurrence or metastasis six months after lobectomy.


A survey and evaluation of population-based screening for gastric cancer.
Screening and early diagnosis of gastric cancer play important roles in reducing the mortality of gastric cancer. A vast amount of study data on gastric cancer screening and early diagnosis has been accumulated in and out of China in the past decades. The practice of gastric cancer screening has also been efficiently carried out in different countries and regions. However, no widely accepted principle of population screening for gastric cancer has been developed yet. Screening for gastric cancer requires extensive exploration both theoretically and practically. This article focuses on the method and program of gastric cancer screening based on population. Moreover, the current situation of gastric cancer screening and its evaluation are evaluated.


N,N-diethylaminobenzaldehyde (DEAB) as a substrate and mechanism-based inhibitor for human ALDH isoenzymes.
N,N-diethylaminobenzaldehyde (DEAB) is a commonly used "selective" inhibitor of aldehyde dehydrogenase isoenzymes in cancer stem cell biology due to its inclusion as a negative control compound in the widely utilized Aldefluor assay. Recent evidence has accumulated that DEAB is not a selective inhibitory agent when assayed in vitro versus ALDH1, ALDH2 and ALDH3 family members. We sought to determine the selectivity of DEAB toward ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH1L1, ALDH2, ALDH3A1, ALDH4A1 and ALDH5A1 isoenzymes and determine the mechanism by which DEAB exerts its inhibitory action. We found that DEAB is an excellent substrate for ALDH3A1, exhibiting a Vmax/KM that exceeds that of its commonly used substrate, benzaldehyde. DEAB is also a substrate for ALDH1A1, albeit an exceptionally slow one (turnover rate ∼0.03 min(-1)). In contrast, little if any turnover of DEAB was observed when incubated with ALDH1A2, ALDH1A3, ALDH1B1, ALDH2 or ALDH5A1. DEAB was neither a substrate nor an inhibitor for ALDH1L1 or ALDH4A1. Analysis by enzyme kinetics and QTOF mass spectrometry demonstrates that DEAB is an irreversible inhibitor of ALDH1A2 and ALDH2 with apparent bimolecular rate constants of 2900 and 86,000 M(-1) s(-1), respectively. The mechanism of inactivation is consistent with the formation of quinoid-like resonance state following hydride transfer that is stabilized by local structural features that exist in several of the ALDH isoenzymes.


Epidermal growth factor synergism with TGF-beta1 via PI-3 kinase activity in corneal keratocyte differentiation.
To investigate the action of epidermal growth factor (EGF) on corneal keratocyte differentiation and its effects in conjunction with transforming growth factor (TGF)-beta1. Rabbit corneal keratocytes (RCKs) were treated with EGF, TGF-beta1, or EGF plus TGF-beta1 in the presence or absence of inhibitors of EGF-receptor (EGF-R), neutralizing concentrations of EGF antibody and of signaling kinases for 2 days to 1 week. RCK differentiation to myofibroblasts was identified with anti-aldehyde dehydrogenase (ALDH)-1 and alpha-smooth muscle actin (alpha-SMA) antibodies. Cell proliferation was evaluated with anti-Ki-67 antibody. Extracellular matrix (ECM) components were assayed by immunochemistry and Western blot. Cell migration images were captured with a camera attached to the microscope, and the area of the wound was calculated using imaging software. RCKs cultured in serum-free DMEM/F12 without frequent changes of medium maintained the phenotype for more than 1 month. EGF stimulated differentiation into a proto-myofibroblast phenotype with the loss of dendritic shape and the expression of alpha-SMA. Treatment with TGF-beta1 stimulated 12% of the cells to differentiate to defined myofibroblasts, but in the presence of EGF, TGF-beta1 induced 90% of RCKs to transform into myofibroblasts. Inhibition of EGF-R activation and of the phosphatidylinositol-3 kinase (PI-3K)/Akt-1 pathway prevented the action of EGF on TGF-beta1 cell differentiation. TGF-beta1 in the presence of EGF also increased cell migration, which is inhibited by blocking EGF-R activation. These data show that EGF contributes to the differentiation and migration of myofibroblasts induced by TGF-beta1 through EGF-R activation and that it is an important modulator of wound healing and scar tissue formation.


Fourier phase analysis on equilibrium gated radionuclide ventriculography: Range of phase spread and cut-off limits in normal individuals.
To define the range of phase spread on equilibrium gated radionuclide ventriculography (ERNV) in normal individuals and derive the cut-off limit for the parameters to detect cardiac dyssynchrony. ERNV was carried out in 30 individuals (age 53±23 years, 25 males and 5 females) who had no history of cardiovascular disease. They all had normal left ventricular ejection fraction (LVEF 55-70%) as determined by echocardiography, were in sinus rhythm, with normal QRS duration (≤120 msec) and normal coronary angiography. First harmonic phase analysis was performed on scintigraphic data acquired in best septal view. Left and right ventricular standard deviation (LVSD and RVSD, respectively) and interventricular mechanical delay (IVMD), the absolute difference of mean phase angles of right and left ventricle, were computed and expressed in milliseconds. Mean + 3 standard deviation (SD) was used to derive the cut-off limits. Average LVEF and duration of cardiac cycle in the study group were 62.5%±5.44% and 868.9±114.5 msec, respectively. The observations of LVSD, RVSD and right and left ventricular mean phase angles were shown to be normally distributed by Shapiro-Wilk test. Cut-off limits for LVSD, RVSD and IVMD were calculated to be 80 msec, 85 msec and 75 msec, respectively. Fourier phase analysis on ERNV is an effective tool for the evaluation of synchronicity of cardiac contraction. The cut-off limits of parameters of dyssynchrony can be used to separate heart failure patients with cardiac dyssynchrony from those without. ERNV can be used to select patients for cardiac resynchronization therapy.


Urinary incontinence following surgery for BPH: the role of aging on the incidence of bladder dysfunction.
The reported incidence of urinary incontinence (UI) due to bladder dysfunction following surgery of BPH is variable. We described the causes of incontinence in a large group of men that developed this unusual complication and analyzed the influence of age on the prevalence of bladder dysfunction. We evaluated a total of 125 patients with urinary incontinence following surgical treatment for BPH: Transurethral resection of the prostate (81 men) and open prostatectomy (44 men). A third group of 21 patients with incontinence following radical prostatectomy was used for comparison. All patients underwent urodynamic analysis. Urethral Sphincter Insufficiency (USI) was defined as involuntary loss of urine induced by Valsalva maneuver in the absence of a detrusor contraction. Bladder dysfunction was defined as detrusor overactivity and/or decreased compliance. Urethral sphincter insufficiency was the most common etiology of urinary incontinence in the three groups of patients. However, bladder dysfunction was observed in 59.3%, 56.8% and 57.1% of patients who underwent transurethral resection, open prostatectomy and radical prostatectomy, respectively. Median patient age was 69 and 75 years for patients with and without bladder dysfunction, respectively. A logistic regression model for the presence of bladder dysfunction showed that age was a statistically significant predictor. Urethral Sphincter insufficiency is the main cause of incontinence following surgery for BPH. Bladder dysfunction may be the isolated cause of incontinence in approximately 25% of patients. The chances of bladder dysfunction rises 5.3% for each year added to patient age. Patients older than 70 years have twice the probability of post procedural incontinence.


[Clinical application of grafts of cultured epidermis in burn patients. Apropos of 16 patients].
The authors report a series of 16 patients with extensive burns partially treated by epidermal culture between May 1985 and July 1988. This series consisted of 9 males and 7 females between the ages of 6 and 88 years (mean age: 34 years). The mean surface area of the burns was 66% (range: 30% to 92%). The technique of epidermis culture used was derived from that developed by Green and Rheinwald. A fragment of full-thickness skin taken from the patient was subjected to the action of trypsin. The keratinocytes were cultured on nutrient layers of 3T3 cells. After 10 days, the secondary cultures corresponded to stratified squamous epithelium with a differentiation similar to that of normal human epithelium. This cultured epithelium was used for autografts as well as allografts. Three deaths were related to septic or metabolic complications of the burn. The take rate of the initial graft was greater than 50% in 9 patients. In 3 patients the graft take rate was less than 50% and in 4 patients it was nil. The long-term evaluation of 12 patients revealed partial lysis of the grafts in 3 patients, a stable result in 6 patients and a healed surface greater than the grafted surface in three cases. The best results were obtained with autografts. The initial evaluation of taking of the graft is difficult, as the fine and shiny texture of the grafts is sometimes difficult to distinguish from non-covered zones. The good tolerance of cultured epidermis allografts is due to the fact that they are devoid of Langerhans cells. Although controversial, the reality of the taking of these allografts opens the way to establishing epidermis culture banks.(ABSTRACT TRUNCATED AT 250 WORDS)


Impact of amino acid substitutions near the catalytic site on the spectral properties of an O2-tolerant membrane-bound [NiFe] hydrogenase.
[NiFe] hydrogenases are widespread among microorganisms and catalyze the reversible cleavage of molecular hydrogen. However, only a few bacteria, such as Ralstonia eutropha H16 (Re), synthesize [NiFe] hydrogenases that perform H(2) cycling in the presence of O(2). These enzymes are of special interest for biotechnological applications. To gain further insight into the mechanism(s) responsible for the remarkable O(2) tolerance, we employ FTIR and EPR spectroscopy to study mutant variants of the membrane-bound hydrogenase (MBH) of Re-carrying substitutions of a particular cysteine residue in the vicinity of the [NiFe] active site that is characteristic of O(2)-tolerant membrane-bound [NiFe] hydrogenases. We demonstrate that these MBH variants, despite minor changes in the electronic structure and in the interaction behavior with the embedding protein matrix, display all relevant catalytic and noncatalytic states of the wild-type enzyme, as long as they are still located in the cytoplasmic membrane. Notably, in the oxidized Ni(r)-B state and the fully reduced forms, the CO stretching frequency increases with increasing polarity of the respective amino acid residue at the specific position of the cysteine residue. We purified the MBH mutant protein with a cysteine-to-alanine exchange to apparent homogeneity as dimeric enzyme after detergent solubilization from the membrane. This purified version displays increased oxygen sensitivity, which is reflected by detection of the oxygen-inhibited Ni(u)-A state, an irreversible inactive redox state, and the light-induced Ni(a)-L state even at room temperature.


Nursing leaders serving as a foundation for the electronic medical record.
Transitioning health care information to an electronic medical record is one of the newest policies to reach the health care agenda. Nursing leaders are at the forefront to affect the design, development, implementation, and reception of an electronic medical record. Because of their clinical workflow knowledge, decision-making capacity, and leadership role, nursing leaders are able to achieve high-quality EMRs. Being proactive in the reception, design, development, and implementation of an EMR plays a role in creating an organizational culture that allows for the flow of data efficiently and accurately.


Copper-catalyzed stereoselective aminoboration of bicyclic alkenes.
A copper-catalyzed aminoboration of bicyclic alkenes, including oxa- and azabenzonorbornadienes, has been developed. With this method, amine and boron moieties are simultaneously introduced at an olefin with exo selectivity. Subsequent stereospecific transformations of the boryl group can provide oxygen- and nitrogen-rich cyclic molecules with motifs that may be found in natural products or pharmaceutically active compounds. Moreover, a catalytic asymmetric variant of this transformation was realized by using a copper complex with a chiral bisphosphine ligand, namely (R,R)-Ph-BPE.


Propofol alternatives in gastrointestinal endoscopy anesthesia.
Although propofol has been the backbone for sedation in gastrointestinal endoscopy, both anesthesiologists and endoscopists are faced with situations where an alternative is needed. Recent national shortages forced many physicians to explore these options. A midazolam and fentanyl combination is the mainstay in this area. However, there are other options. The aim of this review is to explore these options. The future would be, invariably, to move away from propofol. The reason is not in any way related to the drawbacks of propofol as a sedative. The mandate that requires an anesthesia provider to administer propofol has been a setback in many countries. New sedative drugs like Remimazolam might fill this void in the future. In the meantime, it is important to keep an open eye to the existing alternatives.


JNK signaling in neomycin-induced vestibular hair cell death.
Mechanosensory hair cells are susceptible to apoptotic death in response to exposure to ototoxic drugs, including aminoglycoside antibiotics. The c-Jun n-terminal kinase (JNK) is a stress-activated protein kinase that can promote apoptotic cell death in a variety of systems. Inhibition of the JNK signaling pathway can prevent aminoglycoside-induced death of cochlear and vestibular sensory hair cells. We used an in vitro preparation of utricles from adult mice to examine the role of JNK activation in aminoglycoside-induced hair cell death. CEP-11004 was used as an indirect inhibitor of JNK signaling. Immunohistochemistry showed that both JNK and its downstream target c-Jun are phosphorylated in hair cells of utricles exposed to neomycin. CEP-11004 inhibited neomycin-induced phosphorylation of both JNK and c-Jun. CEP-11004 inhibited hair cell death in utricles exposed to moderate doses of neomycin. However, the results were not uniform across the dose-response function; CEP-11004 did not inhibit hair cell death in utricles exposed to high-dose neomycin. The CEP-11004-induced protective effect was not due to inhibition of PKC or p38, since neither Chelerythrine nor SB203580 could mimic the protective effect of CEP-11004. In addition, inhibition of JNK inhibited the activation of caspase-9 in hair cells. These results indicate that JNK plays an important role in neomycin-induced vestibular hair cell death and caspase-9 activation.


Increases from 2002 to 2015 in prescription opioid overdose deaths in combination with other substances.
Prescription opioid (PO) overdose deaths increased sharply over the last decade. Changes in PO deaths in combination with other psychoactive substances may provide a partial explanation. PO deaths from the National Multiple-Cause-of-Death Files for 2002-03 (N=15,973) and 2014-15 (N=41,491) were analyzed. We calculated (1) changes in proportions of deaths in combination with benzodiazepines, antidepressants, heroin, alcohol, cocaine between the two periods, and (2) proportions of increase in deaths attributable to each substance among PO and synthetic opioids other than methadone (SO-M) deaths, by age, gender, race/ethnicity. Between 2002-03 and 2014-15, PO deaths increased 2.6 times; SO-M deaths 5.6 times, especially for ages 18-34, males, African-Americans. For PO deaths, most frequent combinations at both periods were with benzodiazepines; for SO-M, benzodiazepines, antidepressants in 2002-03, heroin, benzodiazepines in 2014-15. The largest increases occurred in combination with heroin among all PO (4.6% to 15.4%, change ratio=3.3[95%CI=3.1-3.6]), but especially SO-M deaths (1.2% to 24.5%, change ratio=21.3[95%CI=15.0-30.3]). Deaths involving cocaine decreased among PO, increased among SO-M deaths. One-fifth of increased PO or SO-M deaths were attributable to any of the five substances. Increased PO deaths were equally attributable to benzodiazepines and heroin; deaths attributable to heroin were higher among ages 18-49, males, and non-Hispanic whites. Increased SO-M deaths were attributable mostly to heroin among all groups. Increased PO overdose deaths over the last decade may be partially explained by increased deaths in combination with other psychoactive substances. Use of other substances should be considered in efforts toward reducing prescription opioid overdoses.


[Immunological alterations after extensive burn injury].
It is recognized that extensively burned patients have an increased susceptibility to infection and often succumb to multiple organ failure related to sepsis. Numerous investigations performed over more than 30 years have demonstrated immunologic abnormalities in burn patients, including changes in serum immunoglobulin and opsonin levels, alterations in the complement system, impairment of phagocyte and neutrophil function, suppression of delayed hypersensitive reactions, and prolongation of allograft survival. Recent progress in immunology has shown that inadequate production of both cytokines and arachidonic acid derivatives is profoundly involved in immunosuppression after severe burn injury. A better understanding of immunologic status is necessary to reduce the mortality rate from infection in extensively burned patients. This may also lead to discovering the therapeutic control mechanisms for their immunity.


Simultaneous intervention against oxidative stress and inflammation by targeting Nrf2/ARE and NLRP3 inflammasome pathway mitigates thioacetamide-induced liver fibrosis in rat.
Liver fibrosis is a typical pathological state/stage involved in most chronic liver diseases and its persistence results in cirrhosis. Inflammasomes are cytoplasmic sensors that induce inflammation in response to stress. Glibenclamide (GLB) is an USFDA-approved drug for type 2 diabetes and is reported to possess anti-inflammatory activity by inhibiting inflammatory cytokines. Dimethyl fumarate (DMF) is an USFDA-approved drug for multiple sclerosis and has been reported to activate the Nrf2/ARE pathway to maintain the cellular antioxidant balance. A total of 36 rats were randomized into six groups (n = 6 each). The rats were injected with thioacetamide (TAA) 200 mg/kg, intraperitoneally every third day for eight consecutive weeks to induce liver fibrosis and oral treatment of GLB 0.5 mg/kg/day and DMF 25 mg/kg/day, and their combinations were provided for the last four consecutive weeks. Treatment with GLB, DMF, and GLB+DMF significantly protected against TAA-mediated oxidative stress and inflammatory conditions by improving hepatic function test, triglycerides, hydroxyproline, and histopathological alterations, by inhibiting the NLRP3 inflammasome signaling and fibrogenic markers, and by activating Nrf2/ARE pathway in Wistar rats. The present results suggest that simultaneous Nrf2/ARE activation and NLRP3 inflammasome inhibition could significantly contribute to developing a novel therapy for patients with liver fibrosis.


Image encryption based on the pseudo-orbits from 1D chaotic map.
Chaotic systems have been extensively applied in image encryption as a source of randomness. However, dynamical degradation has been pointed out as an important limitation of this procedure. To overcome this limitation, this paper presents a novel image encryption scheme based on the pseudo-orbits of 1D chaotic maps. We use the difference of two pseudo-orbits to generate a random sequence. The generated sequence has been successful in all NIST tests, which implies it has adequate randomness to be employed in encryption process. Confusion and diffusion requirements are also effectively implemented. The usual low key space of 1D maps has been improved by a novelty procedure based on multiple perturbations in the transient time. A factor using the plain image is one of the perturbation conditions, which ensures a new and distinct secret key for each image to be encrypted. The proposed encryption scheme has been efficaciously verified using the Lena, Baboon, and Barbara test images.


Neuropathies in the rheumatoid patient: a case of the heavy hand.
Rheumatoid Arthritis (RA) is a common inflammatory arthritis' with pain and loss of function among its most disabling symptoms. These are mostly secondary to inflammation or mechanical damage to the joints. However it is also important to consider disease complications as a cause of symptoms, especially when the response to treatment is suboptimal. We report an RA patient whose symptoms were resistant to standard therapy, and were actually due to peripheral neuropathy.


Tongue strength of healthy young adults.
The measurement of tongue strength contributes to the study of oro-facial physiology. The objective of this study was to investigate the influence of gender on tongue strength in young adults and to determine the differences in this strength between tongue regions. This study was conducted on 50 healthy volunteers (17 men and 33 women) with a mean age of 23 years, with no oro-facial myofunctional alterations. The strength of the anterior portion and of the dorsum of the tongue was analysed with a calibrated electronic dynamometer. The subjects were asked to apply maximum force. Men showed higher tongue strength values than women both in the anterior portion and in the dorsum of the tongue (P<0·05), and the strength of the anterior portion of the tongue was lower than that of the dorsum in both genders (P<0·05). We conclude that gender and region influenced tongue strength.


Frequency stabilization of an internal mirror He-Ne laser with a high frequency reproducibility.
A method has been developed for the stabilization of an internal mirror He-Ne laser to achieve a high frequency reproducibility that is mainly influenced by the temperature of the stabilized laser. However, it is difficult to achieve a reproducible temperature in a short time under different ambient temperatures. In this paper, the He-Ne laser is stabilized based on the relationship between the laser mode number and the laser cavity temperature where a reproducible temperature can be rapidly achieved under different ambient temperatures, resulting in a high frequency reproducibility. Experiments have demonstrated that the He-Ne laser used can be stabilized in approximately 10 min, typically 6 min; the frequency stability is less than 2×10(-10); the frequency reproducibility is less than 1×10(-9).


[Retroperitoneoscopic radical nephrectomy with inferior vena cava thrombectomy].
Although laparoscopic radical nephrectomy has confidently established itself as the "gold standard" for treating renal cell carcinoma, reports on laparoscopic level II-III inferior vena cava (IVC) tumor thrombus thrombectomy are still lacking. From September 2013 through April 2015, three patients with renal cell carcinoma and level II IVC tumor thrombi underwent laparoscopic radical nephrectomy with IVC thrombectomy using a retroperitoneal approach. Tumor sized 10, 8, and 9 cm in the greatest dimension, the length of the IVC thrombi in proximal direction were 2.8, 4.1 and 3.5 cm, respectively. In all patients, the endoscopic interventions were completed successfully without conversion to open surgery. Blood loss was less than 450 ml. No significant intraoperative or postoperative complications were observed. The patients were discharged from the hospital in satisfactory condition at days 19, 7 and 14, respectively. One patient with multiple lung and bone metastases died 11 months after the operation. The two other patients showed no signs of disease progression during the follow-up (16 and 35 months). The retroperitoneal approach has certain advantages over the transperitoneal one. The method is relatively safe and reproducible. However, additional experience and further research are needed before the place of such operations in routine clinical practice can be assessed.


Case report study of the first five COVID-19 patients treated with remdesivir in France.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the virus responsible for the coronavirus disease 2019 (COVID-19) outbreak worldwide. Data on treatment are scare and parallels have been made between SARS-CoV-2 and other coronaviruses. Remdesivir is a broad-spectrum antiviral with efficient in vitro activity against SARS-CoV-2. Evidence of clinical improvement in patients with severe COVID-19 treated with remdesivir is controversial. The aim of this study was to describe the clinical outcomes and virological monitoring of the first five COVID-19 patients admitted to the intensive care unit of Bichat-Claude Bernard University Hospital, Paris, France, for severe pneumonia related to SARS-CoV-2 and treated with remdesivir. Quantitative reverse transcription PCR was used to monitor SARS-CoV-2 in blood plasma and the lower and upper respiratory tract. Among the five patients treated, two needed mechanical ventilation and one needed high-flow cannula oxygen. A significant decrease in SARS-CoV-2 viral load in the upper respiratory tract was observed in most cases, but two patients died with active SARS-CoV-2 replication in the lower respiratory tract. Plasma samples were positive for SARS-CoV-2 in only one patient. Remdesivir was interrupted before the initialy planned duration in four patients, two because of alanine aminotransferase elevations (3 to 5 normal range) and two because of renal failure requiring renal replacement. This case series of five COVID-19 patients requiring intensive care unit treatment for respiratory distress and treated with remdesivir, highlights the complexity of remdesivir use in such critically ill patients.


[Assistive technology devices for the elderly at home].
Using assistive technology (AT) to help the elderly and disabled overcome disabilities and attain their rehabilitation, learning, working and living potentials represents the mainstream trend in well-developed countries. According to data from Taiwan's Ministry of the Interior, Taiwan's senior citizen population exceeds two million. Proper application of AT can help achieve in Taiwan the goal of aging in place. Assistive technology devices can be divided into five categories, including barrier free environment (home modification), daily living aids, mobility aids, seating and positioning devices, and sensory aids. As of 2005, there were 16 senior care centers in Taiwan funded and administered by the Department of Health, all of which maintain interdisciplinary teams--comprising specialists in rehabilitation medicine, occupational therapy, physical therapy, speech therapy, nursing, education, social work and engineering--that provide service directly to persons with special needs and cooperate with manufactures to develop new assistive devices. Services provided by these centers include evaluation, design, customization, adaptation, maintenance, repair, therapy, training and technical assistance related to AT devices. The government has a legal responsibility to provide senior citizens in need with appropriate AT services. Service users, their families and professionals may contact centers directly for consultation.


Analysis of risk factors for postoperative pancreatic fistula following pancreaticoduodenectomy.
To explore the morbidity and risk factors of postoperative pancreatic fistula (POPF) following pancreaticoduodenectomy. The data from 196 consecutive patients who underwent pancreaticoduodenectomy, performed by different surgeons, in the General Hospital of the People's Liberation Army between January 1(st), 2013 and December 31(st), 2013 were retrospectively collected for analysis. The diagnoses of POPF and clinically relevant (CR)-POPF following pancreaticoduodenectomy were judged strictly by the International Study Group on Pancreatic Fistula Definition. Univariate analysis was performed to analyze the following factors: patient age, sex, body mass index (BMI), hypertension, diabetes mellitus, serum CA19-9 level, history of jaundice, serum albumin level, blood loss volume, pancreatic duct diameter, pylorus preserving pancreaticoduodenectomy, pancreatic drainage and pancreaticojejunostomy. Multivariate logistic regression analysis was used to determine the main independent risk factors for POPF. POPF occurred in 126 (64.3%) of the patients, and the incidence of CR-POPF was 32.7% (64/196). Patient characteristics of age, sex, BMI, hypertension, diabetes mellitus, serum CA19-9 level, history of jaundice, serum albumin level, blood loss volume, pylorus preserving pancreaticoduodenectomy and pancreaticojejunostomy showed no statistical difference related to the morbidity of POPF or CR-POPF. Pancreatic duct diameter was found to be significantly correlated with POPF rates by univariate analysis and multivariate regression analysis, with a pancreatic duct diameter ≤ 3 mm being an independent risk factor for POPF (OR = 0.291; P = 0.000) and CR-POPF (OR = 0.399; P = 0.004). The CR-POPF rate was higher in patients without external pancreatic stenting, which was found to be an independent risk factor for CR-POPF (OR = 0.394; P = 0.012). Among the entire patient series, there were three postoperative deaths, giving a total mortality rate of 1.5% (3/196), and the mortality associated with pancreatic fistula was 2.4% (3/126). A pancreatic duct diameter ≤ 3 mm is an independent risk factor for POPF. External stent drainage of pancreatic secretion may reduce CR-POPF mortality and POPF severity.


Porphyromonas gingivalis fimbriae proactively modulate beta2 integrin adhesive activity and promote binding to and internalization by macrophages.
In monocytes, the fimbriae of the oral pathogen Porphyromonas gingivalis activate cross talk signaling from Toll-like receptor 2 (TLR2) to the beta2 integrin CD11b/CD18, leading to the induction of the high-affinity state of the latter receptor. CD14 plays an important role in this "inside-out" proadhesive pathway by binding fimbriae and facilitating the activation of TLR2 and phosphatidylinositol 3-kinase signaling. In its high-affinity state, CD11b/CD18 mediates monocyte adhesion to endothelial cells and transmigration to sites of infection. We have now shown that P. gingivalis fimbriae function as both an activator and a ligand of CD11b/CD18; thus, fimbriae proactively promote their own binding to monocytes. Indeed, treatments that interfered with fimbria-induced activation of CD11b/CD18 (i.e., blockade of CD14, TLR2, or phosphatidylinositol 3-kinase signaling) also suppressed the cell binding activity of fimbriae, which was largely inducible and CD11b/CD18 dependent. Development of a recombinant inside-out signaling system in Chinese hamster ovary cells confirmed the ability of fimbriae to activate CD14/TLR2 signaling and induce their own CD11b/CD18-dependent binding. Induction of this proadhesive pathway by P. gingivalis fimbriae appeared to take place in lipid rafts. Indeed, methyl-beta-cyclodextrin, a cholesterol-sequestering agent that disrupts lipid raft organization, was found to inhibit the fimbria-induced assembly of CD14/TLR2 signaling complexes and the activation of the high-affinity state of CD11b/CD18. Experiments using macrophages from mice deficient in various pattern recognition receptors indicated that the receptors involved in the inside-out proadhesive pathway (CD14, TLR2, and CD11b/CD18) are important for mediating P. gingivalis internalization within macrophages. It therefore appears that P. gingivalis proactively modulates beta2 integrin adhesive activity for intracellular uptake.


Magnetic resonance imaging guided reirradiation of recurrent and second primary head and neck cancer.
To report a single-institutional experience using magnetic resonance imaging (MRI) guided radiation therapy for the reirradiation of recurrent and second cancers of the head and neck. Between October 2014 and August 2016, 13 consecutive patients with recurrent or new primary cancers of the head and neck that occurred in a previously irradiated field were prospectively enrolled in an institutional registry trial to investigate the feasibility and efficacy of MRI guided radiation therapy using a 0.35-T MRI scanner with a cobalt-60 radiation therapy source called the ViewRay system (ViewRay Inc., Cleveland, OH). Eligibility criteria included biopsy-proven evidence of recurrent or new primary squamous cell carcinoma of the head and neck, measurable disease, and previous radiation to >60 Gy. MRI guided reirradiation was delivered either using intensity modulated radiation therapy with conventional fractionation to a median dose of 66 Gy or stereotactic body radiation therapy (SBRT) using 7 to 8 Gy fractions on nonconsecutive days to a median dose of 40 Gy. Two patients (17%) received concurrent chemotherapy. The 1- and 2-year estimates of in-field control were 72% and 72%, respectively. A total of 227 daily MRI scans were obtained to guide reirradiation. The 2-year estimates of overall survival and progression-free survival were 53% and 59%, respectively. There were no treatment-related fatalities or hospitalizations. Complications included skin desquamation, odynophagia, otitis externa, keratitis and/or conjunctivitis, and 1 case of aspiration pneumonia. Our preliminary findings show that reirradiation with MRI guided radiation therapy results in effective disease control with relatively low morbidity for patients with recurrent and second primary cancers of the head and neck. The superior soft tissue resolution of the MRI scans that were used for planning and delivery has the potential to improve the therapeutic ratio.


Color Doppler sonography of focal lesions of the skin and subcutaneous tissue.
We evaluated with color Doppler sonography 71 visible and palpable nodules of the skin and subcutaneous tissue from 51 patients. The nodules were classified as avascular (type I), hypovascular with a single vascular pole (type II), hypervascular with multiple peripheral poles (type III), and hypervascular with internal vessels (type IV). Of the 32 malignant nodules, 9% showed a type I pattern, 50% had a type III pattern, and 41% had a type IV pattern; of the 39 benign nodules, 86% showed a type I pattern and 14% had a type II pattern. The sensitivity and specificity of hypervascularity in malignant lesions were 90% and 100%, respectively, whereas the sensitivity and specificity of hypovascularity in benign lesions were 100% and 90%, respectively. The authors conclude that color Doppler sonography is able to increase the specificity of ultrasonography in the evaluation of nodular lesions of the skin.


Impact of microbial efficiency to predict MP supply when estimating protein requirements of growing beef cattle from performance.
Data from 16 trials were compiled to calculate microbial CP (MCP) production and MP requirements of growing cattle on high-forage diets. All cattle were individually fed diets with 28% to 72% corn cobs in addition to either alfalfa, corn silage, or sorghum silage at 18% to 60% of the diet (DM basis). The remainder of the diet consisted of protein supplement. Source of protein within the supplement varied and included urea, blood meal, corn gluten meal, dry distillers grains, feather meal, meat and bone meal, poultry by-product meal, soybean meal, and wet distillers grains. All trials included a urea-only treatment. Intake of all cattle within an experiment was held constant, as a percentage of BW, established by the urea-supplemented group. In each trial the base diet (forage and urea supplement) was MP deficient. Treatments consisted of increasing amounts of test protein replacing the urea supplement. As protein in the diet increased, ADG plateaued. Among experiments, ADG ranged from 0.11 to 0.73 kg. Three methods of calculating microbial efficiency were used to determine MP supply. Gain was then regressed against calculated MP supply to determine MP requirement for maintenance and gain. Method 1 (based on a constant 13% microbial efficiency as used by the beef NRC model) predicted an MP maintenance requirement of 3.8 g/kg BW and 385 g MP/kg gain. Method 2 calculated microbial efficiency using low-quality forage diets and predicted MP requirements of 3.2 g/kg BW for maintenance and 448 g/kg for gain. Method 3 (based on an equation predicting MCP yield from TDN intake, proposed by the Beef Cattle Nutrient Requirements Model [BCNRM]) predicted MP requirements of 3.1 g/kg BW for maintenance and 342 g/kg for gain. The factorial method of calculating MP maintenance requirements accounts for scurf, endogenous urinary, and metabolic fecal protein losses and averaged 4.2 g/kg BW. Cattle performance data demonstrate formulating diets to meet the beef NRC model recommended MP maintenance requirement (3.8 g/kg S) works well when using 13% microbial efficiency. Therefore, a change in how microbial efficiency is calculated necessitates a change in the proposed MP maintenance requirement to not oversupply or undersupply RUP. Using the 2016 BCNRM to predict MCP production and formulate diets to meet MP requirements also requires changing the MP maintenance requirement to 3.1 g/kg BW.


[Malnutrition, environment and children's development].
Protein energy malnutrition (PME) affects negatively children's somatic and cognitive development. Micronutrient deficiencies which usually coexist with PEM also have a negative influence on the cognitive development of children. The social and familiar environment in which disadvantaged children usually grow is very poor from the point of view of psychological and sensorial stimulation. All these factors together severely impede the full expression of poor children's genetic potential.


Structure of the complete human c-fgr proto-oncogene and identification of multiple transcriptional start sites.
Here we report the isolation of cosmid clones containing the whole of the human c-fgr proto-oncogene. We have used these to determine the organization and nucleotide sequence of the exons upstream of exon 4, which have not previously been analysed. We show that, like exons 4 to 12, exon 3 closely resembles its counterpart in the avian c-src and murine lck genes. In contrast, the organization of the upstream exons of c-fgr differs markedly. In particular, the 5' untranslated regions of the c-fgr gene is interrupted by an extra intron. We have also mapped multiple transcriptional start sites within the 5' flanking region of the c-fgr gene and present an analysis of the nucleotide sequences within this region which may be responsible for regulating c-fgr expression.


Endoproteolysis by isolated membrane peptidases reveal metabolic stability of glucagon-like peptide-1 analogs, exendins-3 and -4.
These in vitro studies aimed to characterize the pattern and the kinetics of endoproteolysis of the insulinotropic hormone glucagon-like peptide-1 (GLP-1) and related peptides by native ectopeptidases. Peptides were incubated with isolated rat or pig kidney brush-border microvilli membranes, which are a rich source of the ectopeptidases that are responsible for the post-secretory metabolism of peptide hormones. The proteolytic products were separated by reversed-phase HPLC column chromatography and characterised by molecular mass and primary structure. The relative importance of specific peptidases was established by measuring the effects of specific peptidase inhibitors on the kinetics of proteolysis. Dipeptidyl-peptidase-IV was found to be rate-limiting in the endoproteolysis of GLP-1. GLP-1 homologs, exendins-3 and -4, exhibited exceptional stability in the presence of isolated kidney microvilli membranes. Our finding that exendin-4 is several orders of magnitude more stable than GLP-1 and Ser-8-GLP-1 is especially noteworthy given this peptide's widely reported insulinotropic potency.


Complete Genome Sequence of Spiroplasma sp. NBRC 100390.
Spiroplasma sp. NBRC 100390 was initially described as a duplicate of S. atrichopogonis GNAT3597T (=ATCC BAA-520T) but later found to be different in the 16S rDNA sequences. Here, we report the complete genome sequence of this bacterium to establish its identity and to facilitate future investigation.


Curcumin inhibits hepatocellular carcinoma growth by targeting VEGF expression.
Morbidity and mortality owing to hepatocellular carcinoma (HCC), the most common primary liver cancer, has increased in recent years. Curcumin is a polyphenol compound that has been demonstrated to exert effective antiangiogenic, anti-inflammatory, antioxidant, and antitumor effects. However, its clinical effects in HCC remain elusive. The main aim of the present study was to determine the antiangiogenic effects of curcumin in HCC. H22HCC cells were treated with different concentrations of curcumin in vitro. In addition, a mouse xenograft model was used and analyzed for expression levels of vascular endothelial growth factor (VEGF) protein and proteins of the phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase 1 (AKT) signaling pathway. Curcumin treatment inhibited H22 cell proliferation and promoted H22 cell apoptosis in a dose-dependent manner in vitro. In addition, curcumin treatment inhibited tumor growth in vivo at the concentrations of 50 and 100 mg/kg. Furthermore, curcumin treatment significantly decreased VEGF expression and PI3K/AKT signaling. The present findings demonstrated that curcumin inhibited HCC proliferation in vitro and in vivo by reducing VEGF expression.


Angiotensin-converting enzyme inhibitors--when to use?
Heart failure is difficult to define and quantify, and this makes it difficult to assess the relative value of different drug regimens. Although there are theoretical reasons suggesting that ACE inhibitors might be useful in all patients with heart failure, there are cogent arguments to the contrary. In practice, angiotensin-converting enzyme inhibitors have been shown to given considerable relief to patients with severe heart failure, but in patients who are only moderately ill these drugs may have less effect than increasing the dose of diuretics. Vasodilators in general probably reduce the fatality of patients with heart failure, but the effect is not specific to angiotensin-converting enzyme inhibitors.


Transfectomas expressing both secreted and membrane-bound forms of chimeric IgE with anti-viral specificity.
Because of the lack of a cell line expressing on surface and secreting human IgE of known Ag specificity, the construction of a transfectoma line possessing such properties would be useful for studying the roles of surface IgE and the effects of anti-IgE antibodies on IgE-producing B cells. Toward this goal, the human genomic DNA segment encompassing the two exons encoding the membrane anchor peptide of epsilon-chain and their flanking regions was sequenced. Hybrid epsilon and kappa genomic DNA comprising the C regions of human epsilon- and kappa-chains and the H and L chain V regions of the murine mAb BAT123, which reacts with the gp120 envelope protein of HIV-1, were constructed. Mammalian expression vectors containing these fusion genes were used to transfect murine myeloma Sp2/0 cells, and transfectants stably expressing on surface and secreting into culture medium chimeric IgE were obtained. The chimeric IgE showed identical Ag-binding properties as the murine mAb BAT123. Acting in concert with the specific peptide Ag polyvalently coupled to a protein carrier, the chimeric antibody could induce histamine release from human blood basophils. These results demonstrate the potential utility of the transfectoma cells and the chimeric IgE in studying the roles of membrane-bound IgE and effects of anti-IgE antibodies on IgE-producing B cells.


Predictive role of human equilibrative nucleoside transporter 1 in patients with pancreatic cancer treated by curative resection and gemcitabine-only adjuvant chemotherapy.
The predictive roles of human equilibrative nucleoside transporter 1 (hENT-1) in patients who undergo curative resection and adjuvant chemotherapy with gemcitabine alone have not been established. The present study retrospectively analyzed the clinical data from 101 consecutive patients who underwent curative resection and who received gemcitabine adjuvant chemotherapy for the treatment of pancreatic cancer at Kanagawa Cancer Center (Yokohama, Japan) between 2005 and 2014. The associations between the hENT-1 status and the survival and clinicopathological features of the patients were investigated. Of the 101 patients, 60 patients (59.4%) had high levels of hENT-1 expression. A significant association was observed between hENT-1 status and sex; however, for all the other clinicopathological parameters, including tumor and node stages, no differences were observed between the high and low hENT-1 expression groups. The median follow-up period of the present study was 67.3 months. Between the high and low hENT-1 expression groups, there was a statistically significant difference in the 5-year overall survival (OS) rates following surgery (20.6 and 8.9%, respectively; P=0.019). In addition, a significant difference was observed in the recurrence-free survival (RFS) rates at 5 years following surgery (P=0.049). hENT-1 status was one of the important predictive factors for OS and RFS in patients with pancreatic cancer who underwent curative resection followed by adjuvant chemotherapy with gemcitabine. Adjuvant chemotherapy with gemcitabine alone may be insufficient, particularly in patients with certain relevant risk factors.


Male circumcision and prevalence of genital human papillomavirus infection in men: a multinational study.
Accumulated evidence from epidemiological studies and more recently from randomized controlled trials suggests that male circumcision (MC) may substantially protect against genital HPV infection in men. The purpose of this study was to assess the association between MC and genital HPV infection in men in a large multinational study. A total of 4072 healthy men ages 18-70 years were enrolled in a study conducted in Brazil, Mexico, and the United States. Enrollment samples combining exfoliated cells from the coronal sulcus, glans penis, shaft, and scrotum were analyzed for the presence and genotyping of HPV DNA by PCR and linear array methods. Prevalence ratios (PR) were used to estimate associations between MC and HPV detection adjusting for potential confounders. MC was not associated with overall prevalence of any HPV, oncogenic HPV types or unclassified HPV types. However, MC was negatively associated with non-oncogenic HPV infections (PR 0.85, 95% confident interval: 0.76-0.95), in particular for HPV types 11, 40, 61, 71, and 81. HPV 16, 51, 62, and 84 were the most frequently identified genotypes regardless of MC status. This study shows no overall association between MC and genital HPV infections in men, except for certain non-oncogenic HPV types for which a weak association was found. However, the lack of association with MC might be due to the lack of anatomic site specific HPV data, for example the glans penis, the area expected to be most likely protected by MC.


Fast affinity purification coupled with mass spectrometry for identifying organophosphate labeled plasma butyrylcholinesterase.
Classical plasma butyrylcholinesterase (BChE) purification involves dialysis and multiple steps of chromatography. We describe a procainamide affinity gel purification scheme that takes 15-30 min to purify BChE from 1 ml plasma. The method uses a microfuge spin column to build a 0.2 ml procainamide affinity column. The eluted BChE contains 3-4 microg of 500-fold purified BChE, free from 99% of contaminating plasma proteins. The BChE was further purified by gel electrophoresis. Tryptic peptides from the BChE containing gel electrophoresis band were prepared by in-gel digestion, separated by reverse phase liquid chromatography and identified by mass spectrometry. The 29 residue active site tryptic peptide labeled with the nerve agents soman or sarin was identified.


Metabolite changes in nine different soybean varieties grown under field and greenhouse conditions.
Global food security remains a worldwide concern due to changing climate, increasing population, and reduced agriculture acreages. Greenhouse cultivation increases productivity by extending growing seasons, reducing pest infestations and providing protection against short term drastic weather fluctuations like frost, heat, rain, and wind. In the present study, we examined and compared the metabolic responses of nine soybean varieties grown under field and greenhouse conditions. Extracts were assayed by GC-FID, GC-MS, and LC-MS for the identification of 10 primary (amino acids, organic acids, and sugars) and 10 secondary (isoflavones, fatty acid methyl esters) metabolites. Sugar molecules (glucose, sucrose, and pinitol) and isoflavone aglycons were increased but the isoflavones glucoside content decreased in the greenhouse cultivated soybeans. The amino acids and organic acids varied between the varieties. The results show that clustering (PCA and PLS-DA) patterns of soybean metabolites were significantly influenced by the genetic variation and growing conditions.


Increased plasma levels of soluble P-selectin in rheumatic mitral stenosis.
Previous studies have demonstrated that platelet activation occurs in peripheral blood of patients with rheumatic mitral stenosis (MS). However, in patients with MS, the plasma level of soluble P-selectin (a marker of platelet activation) remains unsettled. A total of 20 patients with symptomatic MS undergoing percutaneous transluminal mitral valvuloplasty (PTMV) were studied (group 1; 16 patients in permanent atrial fibrillation, and 4 patients in sinus rhythm). The plasma levels of soluble P-selectin in the femoral vein and artery, and right and left atria before PTMV and those in the peripheral venous blood at the 1-week and 4-week follow-ups after PTMV were determined by solid-phase, sandwich, enzyme-linked immunosorbent assay. The mitral valve area was calculated by means of the Doppler pressure half-time method. In addition, we measured plasma concentrations of soluble P-selectin in the peripheral venous blood samples obtained from 22 control patients (including 14 healthy volunteers in sinus rhythm [group 2] and 8 patients in permanent lone atrial fibrillation [group 3]). The plasma levels of soluble P-selectin were significantly elevated in group 1 patients (49.78 +/- 37.72 ng/mL) [mean +/- SD] compared with group 2 (25.52 +/- 15.38 ng/mL) and group 3 patients (32.17 +/- 14.18 ng/mL) [p < 0.005]. In group 1 patients, the plasma levels of soluble P-selectin in the left atrium did not significantly differ from those in the right atrium, femoral vein, or femoral artery (p = 0.05). The area of mitral valve increased significantly after PTMV (1.06 +/- 0.17 cm(2) vs 1.48 +/- 0.32 cm(2), p < 0.0001). The mean left atrial pressure fell significantly and immediately after PTMV (23.0 +/- 5.1 mm Hg vs 17.6 +/- 5.9 mm Hg, p < 0.0001). The peripheral venous plasma levels of soluble P-selectin obtained before PTMV did not significantly fall after PTMV (before, 49.8 +/- 37.7 ng/mL; 10 min after, 39.8 +/- 19.1 ng/mL; 1 week after, 46.1 +/- 20.8 ng/mL; and 4 weeks after, 41.2 +/- 15.9 ng/mL; p = 0.145). The venous plasma levels of soluble P-selectin in patients with moderate-to-severe MS were significantly higher than those in healthy volunteers or patients with lone atrial fibrillation. In addition, in patients with MS, there was no difference in the plasma levels of soluble P-selectin between the left and right atrial blood and between peripheral and atrial blood. Moreover, there was no change in soluble P-selectin levels as a result of PTMV.


Transcriptional map of respiratory versatility in the hyperthermophilic crenarchaeon Pyrobaculum aerophilum.
Hyperthermophilic crenarchaea in the genus Pyrobaculum are notable for respiratory versatility, but relatively little is known about the genetics or regulation of crenarchaeal respiratory pathways. We measured global gene expression in Pyrobaculum aerophilum cultured with oxygen, nitrate, arsenate and ferric iron as terminal electron acceptors to identify transcriptional patterns that differentiate these pathways. We also compared genome sequences for four closely related species with diverse respiratory characteristics (Pyrobaculum arsenaticum, Pyrobaculum calidifontis, Pyrobaculum islandicum, and Thermoproteus neutrophilus) to identify genes associated with different respiratory capabilities. Specific patterns of gene expression in P. aerophilum were associated with aerobic respiration, nitrate respiration, arsenate respiration, and anoxia. Functional predictions based on these patterns include separate cytochrome oxidases for aerobic growth and oxygen scavenging, a nitric oxide-responsive transcriptional regulator, a multicopper oxidase involved in denitrification, and an archaeal arsenate respiratory reductase. We were unable to identify specific genes for iron respiration, but P. aerophilum exhibited repressive transcriptional responses to iron remarkably similar to those controlled by the ferric uptake regulator in bacteria. Together, these analyses present a genome-scale view of crenarchaeal respiratory flexibility and support a large number of functional and regulatory predictions for further investigation. The complete gene expression data set can be viewed in genomic context with the Archaeal Genome Browser at archaea.ucsc.edu.


[The need for urodynamic tests].
Two hundred forty women were studied, who underwent symptomatological anamnesis, clinical examination and urodynamic investigations for female urinary incontinence. Our aim was to distinguish among the three main forms of incontinence (stress, urge and mixed incontinence). When only symptomatological anamnesis is considered, there is an incidence of error in nearly a third of the cases and, when further factors like menopause, prolapse and parity are considered, the incidence of error does not reduce. A correct diagnosis can be determined only by a combined use of clinical assessment and urodynamic investigations. (As regards clinical examination, a positive stress test leads to a diagnosis of stress incontinence. As regards urodynamic investigations a cystometry positive for instability of the detrusor muscle leads to a diagnosis of urge incontinence. If both clinical examination and urodynamic investigations are positive, the diagnosis is of mixed incontinence.) Our findings suggest that routinely it is sufficient to execute only cystometry among urodynamic investigations.


Catecholamine responses to acute and chronic exercise.
The body can adjust to a variety of stressors (physical activity, environmental, emotional, etc.) that are known to disrupt normal homeostatic conditions. Specific metabolic and physiological adaptations are required for both acute and chronic stimuli. The sympathoadrenal system is essential for such adjustments as they control and regulate a number of key bodily functions. In response to an acute bout of exercise, both central and peripheral alterations are elicited. The extent of these responses is dependent upon exercise intensity, duration, and tissue specificity. Further, endurance training results in adaptations that are tissue specific and enhance the ability for the maintenance of exercise energetics. While a number of markers are frequently used to assess the involvement of the sympathoadrenal response (plasma and tissue norepinephrine and epinephrine levels), it is important to examine more specific variables such as rates of turnover, synthesis and removal, and activity of key enzymes related to catecholamine metabolism.


Diabetes mellitus and periodontal disease.
A sample of 54 patients with diabetes mellitus were subjects to detailed assessment of periodontal disease levels using standard indices. In order to determine whether the severity of periodontal disease was related to the severity of diabets mellitus, a series of parameters of the diabetes mellitus population was simultaneously studied. There were no significant relationships between the levels of periodontal disease and the duration of diabetes, the type of treatment and the frequency of systemic complications. Periodontal disease in the diabetic appeared to the affected by the same etiologic factors [plaque, calculus, neglect] as would be expected in nondiabetic patients. Further studies with larger population samples would be appropriate.


Extracellular calcium results in a conformational change in Mac-1 (CD11b/CD18) on neutrophils. Differentiation of adhesion and phagocytosis functions of Mac-1.
Mac-1 is a leukocyte integrin involved in multiple adhesion phenomena and also in the phagocytosis of particles that are bound via CR1 and the IgG FcR. We examined the divalent cation requirements for the Mac-1-dependent processes of adhesion and receptor-mediated phagocytosis. With phorbol ester stimulation, both processes occurred in the absence of extracellular Ca+2. In Ca+2-containing buffer, IB4, an anti-beta 2 mAb, inhibited both adhesion and CR1-mediated ingestion. In the absence of Ca+2, IB4 no longer had any effect on ingestion, although it continued to inhibit adhesion to protein-coated plastic completely. This demonstrates that the role of Mac-1 in adhesion is distinct from its role in phagocytosis. In addition, 1) IB4 did not change intracellular Ca+2 homeostasis; 2) as little as 300 nM free extracellular Ca+2 could restore the ability of IB4 to inhibit ingestion; and 3) in the absence of extracellular Ca+2, Mac-1 was more susceptible to enzymatic cleavage. Together these data suggest a Ca+2-dependent conformational change in Mac-1, which allows distinction of the roles of Mac-1 in phagocytosis and adhesion.


Recent developments in cathepsin K inhibitor design.
Cathepsin K is abundantly and selectively expressed in osteoclasts where it plays a critical role in bone degradation. Cathepsin K inhibitors are the first antiresorptive agents that prevent bone loss while allowing bone formation to continue, thereby enhancing the quality and ultimately the strength of bone. The development of cathepsin K inhibitors requires appropriate cell-based assays and animal models. Advances in reversible cathepsin K inhibitor design from January 2004 are reviewed herein.


[Optimization of 131I ablation in patients with differentiated thyroid carcinoma: comparison of early outcomes of treatment with 100 mCi versus 60 mCi].
The aim of this study was to compare the early outcomes between two groups of patients with differentiated thyroid carcinoma (DTC) who received 60 or 100 mCi of (131)I for remnant ablation. 224 DTC patients with primary tumor > 1 cm of diameter or multifocal were randomised into prospective clinical trial. Patients with extrathyroideal extension of primary tumor and nodal metastases or M1 were not enrolled. 99 patients received 60 mCi, and 125--100 mCi of radioiodine as the first ablative dose. The effectiveness of thyroid ablation was evaluated after one year, during endogenous TSH (thyroid stimulating hormone) stimulation, and after two years during Lthyroxine therapy. Whole body scintigraphy (WBS) was performed under thyroxine withdrawal and thyroglobulin serum level was assessed. Distant micrometastases were detected in 9.8% of patients by post-therapy WBS, 11 patients in group A treated with 60 mCi and 11 in group B treated with 100 mCi. In other patients no symptoms of persistent disease were detected. At one year follow up full remission was diagnosed in 176 patients: 76 in group A and 100 in group B. The remaining ones, 13.3% and 11.2% respectively, received the second course of (131)I for remnant ablation. There were no statistically significant differences in Tg (thyroglobulin) serum level either 12 or 24 months after 131I treatment. Our evaluation of early efficacy of adjuvant radioiodine treatment in low risk DTC patients shows no differences between two radioiodine activities - 60 and 100 mCi in relation to thyroid ablation. Thus, the activity of 60 mCi is recommended.


Three-Year Clinical Outcome After 2nd-Generation Cryoballoon-Based Pulmonary Vein Isolation for the Treatment of Paroxysmal and Persistent Atrial Fibrillation - A 2-Center Experience.
Pulmonary vein isolation (PVI) using the 2nd-generation cryoballoon (CB2) for the treatment of atrial fibrillation (AF) has demonstrated encouraging acute and mid-term results. However, follow-up data on outcomes beyond 1 year are sparse. We investigated the 3-year outcome after PVI using the CB2.Methods and Results:100 patients with paroxysmal (PAF, 70/100 [70%] patients) or persistent AF (pAF, 30/100 [30%] patients) underwent CB2-based PVI in 2 experienced centers in Germany. Freeze-cycle duration was 240 s. After successful PVI a bonus freeze-cycle of the same duration was applied in the first 71 patients but was omitted in the following 29 patients. Phrenic nerve palsy occurred in 3 patients (3%); 2 patients were lost to follow-up. After a median follow-up of 38 (29-50) months, 59/98 (60.2%) patients remained in stable sinus rhythm (PAF: 48/70 (69%), pAF: 11/28 (39%) P=0.0084). In 32/39 (77%) patients with arrhythmia recurrence, a second ablation procedure using radiofrequency energy was conducted. Persistent PVI was noted in 76/125 (61%) PVs. After a mean of 1.37±0.6 procedures and a median follow-up of 35 (25-39) months, 77/98 (78.6%) patients remained in stable sinus rhythm (PAF: 56/70 (80%), pAF: 20/28 (71%), P=0.0276). CB2-based PVI resulted in a 60.2% single-procedure and a 78.6% multiple-procedure success rate after 3 years. Repeat procedures demonstrated a high rate of durable PVI.


A process model of attachment-friend linkages: hostile attribution biases, language ability, and mother-child affective mutuality as intervening mechanisms.
This study identified mechanisms through which child-mother attachment security at 36 months was associated with mother- and teacher-reported friendship quality at 3rd grade. Data from a subsample of 1,071 children (536 boys) participating in the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development were used. Separate structural equation models were tested for mother and teacher reports of peer functioning. For both models, the total indirect effect between attachment security and friendship quality was significant. Tests of specific indirect effects indicated that attachment security was associated with friendship quality via greater mother-child affective mutuality and better language ability at 54 months and fewer hostile attributions (teacher model only) and greater peer competence at first grade. The findings highlight interpersonal and intrapersonal mechanisms of attachment-friend linkages.


Effects of proprioceptive neuromuscular facilitation on the initiation of voluntary movement and motor evoked potentials in upper limb muscles.
To better understand the mechanisms behind proprioceptive neuromuscular facilitation (PNF), an important method in motor rehabilitation, we investigated the effects of assuming a PNF posture relative to a neutral posture on the initiation of voluntary movement (Experiment 1) and the excitability of the motor cortex (Experiment 2) using a wrist extension task. The initiation of voluntary wrist movement was operationalized in terms of the electromyographic reaction time (EMG-RT), and the excitability of the motor cortex in terms of motor evoked potentials (MEPs). Compared to the neutral position, we found that (1) the facilitation position changed the muscle discharge order enhancing the movement efficiency of the joint, (2) the facilitation position led to a reduction in EMG-RT, the magnitude of which depended on the proximity of the muscle to the movement joint, and (3) MEP amplitude increased and MEP latency decreased in the facilitation position as a function of the proximity of the muscle to the joint. These findings corroborate the presumed effects of PNF and provide insights into the neurophysiological mechanisms underlying the PNF method.


[Treatment techniques of harvesting injury of donor renal blood vessels].
To study the treatment technique for harvesting injury of donor blood vessels for the clinic application. The data of 32 renal transplantation patients with injury of graft blood vessels were retrospectively reviewed. 60 renal transplantation patients with non-injury during the same term were selected as the control group. The treatment techniques for harvesting injury of graft blood vessels mainly includes end-to-end anastomosis of graft artery, side-to-side anastomosis of branch artery, end-to-side anastomosis of branch artery to the main renal artery, reconstruction of multiple segmental arteries by using iliac arterial grafts from cadaveric donors or recipients on the workbench, repairs of injuries for the smaller segmental/polar arteries by using inferior epigastric artery, end-to-end anastomosis of the lower thick segmental/polar arteries with the iliac internal arterial by placing kidney upside down. Those injured included 28 arterial and 4 venous. Average bench surgery time was 42 minutes. Mean warm ischemic time was 31 minutes. No death occurred at an average follow-up of 3.5 years (1 - 5 years). There was no statistical difference in the 1-year graft survival, postoperative 1-year acute rejection, delayed graft function (DGF) and the incidence of constriction of vascular anastomosis rate (96.9%, 12.5%, 21.9%, 3.1%, respectively) compared with non-reconstructed kidneys during the same term (98.3%, 11.7%, 18.3%, 1.7%, P > 0.05, respectively). The flexible and appropriate application of different vascular reconstruction means and satisfactory surgery techniques play an important role in assuring quality of kidney with harvesting blood vessels injury and donor kidney availability.


Synthesis of benzofused five-ring sultams via Rh-catalyzed C-H olefination directed by an N-Ac-substituted sulfonamide group.
A Rh-catalyzed N-Ac-sulfonamide group directed C-H olefination-cyclization to afford benzofused five-ring sultam is described with high yield and a wide range of substrate scope. The N-acetyl group is a key for this transformation implying that N-H acidity is the major influence. The acetyl group is removed under mild conditions in excellent yield to provide NH-free sultam that can be transformed into various benzofused five-ring sultam analogues via acylation, nucleophilic substitution, and Mitsunobu alkylation.


Analysis of T-cell receptor Vbeta gene from infiltrating T cells in insulitis and myocarditis in encephalomyocarditis virus-infected BALB/C mice.
Encephalomyocarditis (EMC) virus induces insulin-dependent diabetes and myocarditis in several strains of mice. The T-cell receptor (TCR) Vbeta genes of infiltrating T cells in the pancreas and myocardium of BALB/C mice infected with EMC virus D-variant (EMC-D virus) were analyzed. Using a nested two-step polymerase chain reaction (PCR), TCR Vbeta cDNAs were cloned and sequenced. Two and four kinds of TCR Vbeta clones were obtained from T cells infiltrating into the pancreas and myocardium of BALB/C mice infected with EMC-D virus, respectively. The infiltrating lymphocytes in the diabetic mice expressed Vbeta 8.1, 8.2, and 8.3 genes predominantly. Previously, the use of Vbeta 8.2 has been reported in autoimmune diseases such as murine experimental allergic encephalomyelitis (EAE) and non-obese diabetic (NOD) mouse. This study suggests that mice infected with EMC virus are a useful animal model for autoimmune diseases such as insulin-dependent diabetes.


HOXD3-overexpression increases integrin alpha v beta 3 expression and deprives E-cadherin while it enhances cell motility in A549 cells.
We have previously shown that transduction of HOXD3, one of homeobox genes, into human lung cancer A549 cells enhances cell motility, invasion and metastasis. In the present study, we examined the roles of integrin beta3 which was up-regulated by HOXD3-overexpression in the HOXD3-induced motility of A549 cells. We first established integrin beta3-transfectants and compared their motile activity to those of the HOXD3-transfected, control-transfected and parental cells by three different assays. The integrin beta3-transfectants as well as the HOXD3-transfectants formed heterodimer with integrin alphav subunit, and showed highly motile activities assessed by haptotaxis or phagokinetic track assay compared to the control transfectants or parental cells. In vitro wound-healing assay revealed that migratory activities were graded as the HOXD3-transfectants > the integrin beta3-transfectants > the control transfectants or parental cells. E-cadherin was expressed in the integrin beta3-transfectants but not expressed in the HOXD3-transfectants. An addition of function-blocking antibody to E-cadherin into the wound-healing assay promoted the migratory activity of the integrin beta3-transfectants, suggesting that E-cadherin prevented the cells from dissociating from the wound edges. These results indicate that increased expression of integrin alphav beta3 and loss of E-cadherin by HOXD3-overexpression are responsible for the enhanced motility and dissociation.


A low-count reconstruction algorithm for Compton-based prompt gamma imaging.
The Compton camera is an imaging device which has been proposed to detect prompt gammas (PGs) produced by proton-nuclear interactions within tissue during proton beam irradiation. Compton-based PG imaging has been developed to verify proton ranges because PG rays, particularly characteristic ones, have strong correlations with the distribution of the proton dose. However, accurate image reconstruction from characteristic PGs is challenging because the detector efficiency and resolution are generally low. Our previous study showed that point spread functions can be incorporated into the reconstruction process to improve image resolution. In this study, we proposed a low-count reconstruction algorithm to improve the image quality of a characteristic PG emission by pooling information from other characteristic PG emissions. PGs were simulated from a proton beam irradiated on a water phantom, and a two-stage Compton camera was used for PG detection. The results show that the image quality of the reconstructed characteristic PG emission is improved with our proposed method in contrast to the standard reconstruction method using events from only one characteristic PG emission. For the 4.44 MeV PG rays, both methods can be used to predict the positions of the peak and the distal falloff with a mean accuracy of 2 mm. Moreover, only the proposed method can improve the estimated positions of the peak and the distal falloff of 5.25 MeV PG rays, and a mean accuracy of 2 mm can be reached.


Zwitterionic Phosphorylcholine-TPE Conjugate for pH-Responsive Drug Delivery and AIE Active Imaging.
Polymeric micelles have emerged as a promising nanoplatform for cancer theranostics. Herein, we developed doxorubicin (DOX) encapsulated pH-responsive polymeric micelles for combined aggregation induced emission (AIE) imaging and chemotherapy. The novel zwitterionic copolymer poly(2-methacryloyloxyethylphosphorylcholine-co-2-(4-formylphenoxy)ethyl methacrylate) (poly(MPC-co-FPEMA)) was synthesized via RAFT polymerization and further converted to PMPC-hyd-TPE after conjugation of tetraphenylethene (TPE, a typical AIE chromophore) via acid-cleavable hydrazone bonds. The AIE activatable copolymer PMPC-hyd-TPE could self-assemble into spherical PC-hyd-TPE micelles, and DOX could be loaded through hydrophobic interactions. The zwitterionic micelles exhibited excellent physiological stability and low protein adsorption due to the stealthy phosphorylcholine (PC) shell. In addition, the cleavage of hydrophobic TPE molecules under acidic conditions could induce swelling of micelles, which was verified by size changes with time at pH 5.0. The in vitro DOX release profile also exhibited accelerated release rate with pH value decreasing from 7.4 to 5.0. Fluorescent microscopy and flow cytometry studies further demonstrated fast internalization and accumulation of drug loaded PC-hyd-TPE-DOX micelles in HepG2 cells, resulting in considerable time/dose-dependent cytotoxicity. Meanwhile, high-quality AIE imaging of PC-hyd-TPE micelles was confirmed in HepG2 cells. Notably, ex vivo imaging study exhibited efficient accumulation and drug release of PC-hyd-TPE-DOX micelles in the tumor tissue. Consequently, the multifunctional micelles with combined nonfouling surface, AIE active imaging, and pH-responsive drug delivery showed great potential as novel nanoplatforms for a new generation of cancer theranostics.


Erzhi Tiangui Granules Improve In Vitro Fertilization Outcomes in Infertile Women with Advanced Age.
The fertility of females with advanced age declines with aging. Therefore, for medical and social reasons, it is important to establish mechanisms to protect and improve the fertility of such populations. With widespread use of traditional Chinese medicine (TCM) in in vitro fertilization (IVF), studies have evaluated their impact on improving the fertility of females with advanced age. In this study, we performed proteomic analysis of follicular fluid to reveal mechanisms of the Erzhi Tiangui (EZTG) granule (Chinese herbs for replenishing vital essence to tonify the kidney) in improving the outcomes of IVF in infertile women with advanced age. This was a randomized, double-blind, and placebo-controlled trial in which 100 patients with advanced age were divided into the EZTG group and the placebo group by the random number table plus envelope method. Both groups were subjected to controlled ovarian stimulation with a GnRH antagonist regimen. Differences between the two groups were evaluated, including the TCM syndrome score after treatment, gonadotrophin (Gn) days and Gn doses, the number of retrieved oocytes, 2 pronucleus (PN) fertilization, 2PN cleavage, and high-quality embryos. Differentially expressed proteins were identified using the LC-MS/MS method, and their functions were determined through bioinformatics analyses. The number of high-quality embryos in the placebo group was significantly lower than that in the EZTG group (2.88 ± 1.85 vs. 4.13 ± 2.83, p=0.011). Eleven differentially expressed proteins were identified between the two groups. Four proteins were highly expressed, whereas seven were suppressed in the control group, compared to the EZTG group. The overall trend suggested that the apoptotic effect in the follicular fluid of the EZTG group was downregulated. Treatment with the EZTG granule can improve embryo quality in IVF of advanced age females with both kidney Qi and Yin deficiency syndromes. The mechanism is attributed to downregulation of apoptotic-effector protein expressions in the follicular fluid. This trial is registered with ChiCTR1900025139.


Upregulation of Phosphatase 1 Nuclear-Targeting Subunit (PNUTS) Is an Independent Predictor of Poor Prognosis in Prostate Cancer.
Protein phosphatase 1 nuclear-targeting subunit (PNUTS) is ubiquitously expressed and associates with PTEN and protein phosphatase 1 (PP1) to control its activity. The role of PNUTS overexpression has hardly been studied in cancer. In this study, we used immunohistochemistry to quantitate PNUTS expression on a tissue microarray containing 17,747 clinical prostate cancer specimens. As compared to normal prostate epithelium, PNUTS expression was often higher in cancer. Among 12,235 interpretable tumors, PNUTS staining was negative in 21%, weak in 34%, moderate in 35%, and strong in 10% of cases. High PNUTS expression was associated with higher tumor stage, classical and quantitative Gleason grade, nodal stage, surgical margin, Ki67 labeling index, and early biochemical recurrence (p < 0.0001 each). PNUTS expression proved to be a moderate prognostic parameter with a maximal univariable Cox proportional hazard for PSA recurrence-free survival of 2.21 compared with 5.91 for Gleason grading. It was independent from established prognostic parameters in multivariable analysis. Comparison with molecular data available from earlier studies using the same TMA identified associations between high PNUTS expression and elevated androgen receptor expression (p < 0.0001), presence of TMPRSS2:ERG fusion (p < 0.0001), and 8 of 11 chromosomal deletions (3p13, 5q21, 8p21, 10q23, 12p13, 13q14, 16q24, and 17p13; p < 0.05 each). Particularly strong associations with PTEN and 12p13 deletions (p < 0.0001 each) may indicate a functional relationship, which has already been established for PNUTS and PTEN. PNUTS had no additional role on outcome in PTEN-deleted cancers. In conclusion, the results of our study identify high PNUTS protein levels as a predictor of poor prognosis possibly linked to increased levels of genomic instability. PNUTS measurement, either alone or in combination, might be of clinical utility in prostate cancers.


Effect of belly dancing on urinary incontinence-related muscles and vaginal pressure in middle-aged women.
[Purpose] This study examined the effect of belly dancing on the urinary incontinence-related muscles and vaginal pressure in middle-aged women to provide fundamental data for establishing an effective training program focusing on mitigating and preventing urinary incontinence. [Subjects and Methods] The subjects included 24 middle-aged women, who have been diagnosed with urinary incontinence. The subjects were randomly divided into two groups, viz. the experimental group (N=12) and control group (N=12). The experimental group underwent a belly dancing program focusing on pelvis moves. [Results] In the experimental group, the urinary incontinence-related muscle strength and vaginal pressure were increased, while the control group showed no significant change. [Conclusion] Belly dancing focusing on pelvis moves had a positive effect on the urinary incontinence-related muscle strength and vaginal pressure, suggesting that a recreational dance program focusing on pelvic exercise can be used to prevent and relieve the symptoms of urinary incontinence as a non-surgical treatment.


Evolutionary dynamics of the ABCA chromosome 17q24 cluster genes in vertebrates.
ABCA is a subfamily of ATP-binding-cassette (ABC) transporter genes. In this subfamily, it was found that five ABCA genes cluster in a head-to-tail pattern in the human and mouse genomes, but only one was found in fish. To understand better the evolution of this cluster of genes, we screened 11 vertebrate genome sequences and newly identified 28 ABCA cluster genes. Comparative genomic analysis reveals that the ABCA5 gene is relatively evolutionarily conserved. In contrast, the repertoires of the other ABCA genes in this cluster diverge tremendously among species, which is due mainly to postspeciation duplications. In addition, maximum likelihood analysis reveals that positive selection is acting on the paralogous genes ABCA6 and Abca8a, suggesting that these two genes have possibly acquired new functions after duplication. Because most eukaryotic ABC proteins integrate into the cytoplasmic membrane and transport a wide range of substrates across it, we conjecture that newly duplicated ABCA cluster genes are under diversifying selection for the ability to recognize a diverse array of substrates.


Metastatic Choriocarcinoma of the Breast: A Rare Entity.
Breast neoplasms are becoming more common in the last few years. Among these masses, metastasis to the breast is rare. Extra-gestational choriocarcinoma is extremely rare among breast neoplasms. We intend to present a case of a 30-year-old female with complaints of breast and axillary lumps. She had a history of a previously treated uterine trophoblastic tumor. Subsequently, she underwent a trucut biopsy of the breast mass and the axillary node, revealing metastatic choriocarcinoma.


The morphometry of the laryngeal phonatory system - base of the anatomical study of the voice aptitudes.
Speaking is one of the characteristics of the human race and the main factor that has marked our progress over time. The singing voice is the crowning of the speech act and the main component of the lyrical manifestation of personality. Doctors in various fields, but especially anatomists have been concerned about discovering how the voice and the substrate of its variability are formed, but these aspects have not yet been fully deciphered. This study is the starting point in our research on the phonation system, organized on three levels: laryngeal, oral, palatinal, pharyngeal, epiglottal and nasal. We performed the dissection of seven embalmed anatomical parts, on which, we made measurements of the anatomical elements involved in the phonation. We performed the same measurements on a batch of seven adults investigated by magnetic resonance imaging (MRI). The results were entered into the statistical calculation formulas and compared with each other and with the literature. The results of the study show that certain values resulting from the calculation formulas remain constant and others vary greatly from each individuals and gender.


Perindopril and losartan attenuate pro-coagulation factors in human adipocytes exposed to SARS-CoV-2 spike protein.
Thrombotic events are highly prevalent in coronavirus disease 2019 (COVID-19), especially in patients presenting with risk factors of adverse outcomes such as obesity. Recently, the associations between the angiotensin converting enzyme 2 (ACE2) pathway and thrombosis have been reported. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARBs) are widely used cardiovascular pharmacologic agents that upregulate ACE2 levels. An observation of the alterations in pro-coagulation factors after exposure to ACEIs and ARBs may provide valuable insight into the thrombosis mechanism and how it may relate to ACE2. This study use adipose tissue harvested from an obese male donor was isolated and exposed to perindopril, losartan, and ACE2 recombinant as binding assay, following exposure with 10 nm of SARS-CoV-2 S1 spike protein. After 48 hours, tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) as pro-coagulation factors as well as ACE2 levels and binding evaluated. The results shows TF level was significantly reduced in Perindopril group compared to control (4.834; p=0.005), while a non-significant reduction was observed in Losartan group (5.624; p=0.111). However, Losartan group showed a better reduction of PAI-1 levels (2.633; p≤0.001) than Perindopril group (3.484; p=0.001). These findings were consistent with the observations in ACE2 recombinant group, suggesting that both drugs lowered the bindings of ACE2 and SARS-CoV-2 spike proteins. This study indicated that both perindopril and losartan may attenuate pro-coagulation factors in human adipocytes exposed to SARS-CoV-2 spike proteins, and therefore showcased a potential role of ACE2 in the mechanism of COVID-19-related thrombosis. Further investigation in non-COVID-19 populations should commence and may be of value to expanding this potential in general cardiovascular diseases.


Acute puerperal breast abscesses: US-guided drainage.
Breast abscesses typically develop in lactating women. The recommended treatment is surgical incision and drainage with the patient under general anesthesia. Ultrasonically guided percutaneous drainage with local anesthesia was performed in 19 consecutive patients referred for treatment because of clinical signs of acute puerperal breast abscess. Eighteen of the 19 patients (95%) were successfully treated. Long-term follow-up (median, 12 months) did not show any recurrences, and the cosmetic results were excellent. Eight of the 19 patients (42%) continued nursing during and after treatment. Ten of the 19 (53%) were treated on an outpatient basis. On the basis of these results, the authors recommend ultrasonically guided percutaneous treatment for use in patients with acute puerperal breast abscesses.


Mitochondrial haplogroup X is associated with successful aging in the Amish.
Avoiding disease, maintaining physical and cognitive function, and continued social engagement in long-lived individuals describe successful aging (SA). Mitochondrial lineages described by patterns of common genetic variants ("haplogroups") have been associated with increased longevity in different populations. We investigated the influence of mitochondrial haplogroups on SA in an Amish community sample. Cognitively intact volunteers aged ≥80 years (n = 261) were enrolled in a door-to-door survey of Amish communities in Indiana and Ohio. Individuals scoring in the top third for lower extremity function, needing little assistance with self-care tasks, having no depression symptoms, and expressing high life satisfaction were considered SA (n = 74). The remainder (n = 187) were retained as controls. These individuals descend from 51 matrilines in a single 13-generation pedigree. Mitochondrial haplogroups were assigned using the ten mitochondrial single nucleotide polymorphisms (mtSNPs) defining the nine most common European haplogroups. An additional 17 mtSNPs from a genome-wide association panel were also investigated. Associations between haplogroups, mtSNPs, and SA were determined by logistic regression models accounting for sex, age, body mass index, and matriline via generalized estimating equations. SA cases were more likely to carry Haplogroup X (OR = 7.56, p = 0.0015), and less likely to carry Haplogroup J (OR = 0.40, p = 0.0003). Our results represent a novel association of Haplogroup X with SA and suggest that variants in the mitochondrial genome may promote maintenance of both physical and cognitive function in older adults.


Comparison of 3 methods of selenium assessment in cattle.
Three tests are routinely done to assess blood status of selenium in cattle: serum selenium, whole blood selenium, and glutathione peroxidase. The objective of this study was to compare the various analytical methods for determining blood selenium status in groups of mature cows and beef calves. Twenty to 30 blood samples per herd were collected from 8 beef herds in central Alberta and 1 dairy in Alberta herd twice a year from the spring of 1992 through the fall of 1995, and once from 185 spring calves in 2 beef herds in Saskatchewan. Serum and whole blood samples were submitted to 1 laboratory and whole blood samples were submitted to a 2nd laboratory. Samples for glutathione peroxidase determinations were submitted to a 3rd laboratory. Pearson's correlation coefficients and Cohen's kappa were calculated for each possible comparison among the different measures. The best agreement was observed between serum and whole blood analysis within Laboratory A. The remaining comparisons reflected poor agreement. Comparison of herd-level assessment resulted in better agreement than comparison of individual sample results among laboratories and procedures for all combinations tested. Serum selenium analysis was the only laboratory procedure for which external reference material was utilized. Serum selenium, whole blood selenium, and glutathione peroxidase measure different compartments of the blood selenium pool. The time frame of interest, supplementation practices, and the stability of recent dietary intake determine the optimum assessment method for individual animals or herds. Determination of the serum status or of blood selenium is more consistently measured at the herd-level than for individual samples.


Effect of age at menopause and menopause itself on high sensitivity C-reactive protein, pulse wave velocity, and carotid intima-media thickness in a Chinese population.
Potential associations between menopause, age at menopause, and clinical indicators related to cardiovascular disease (CVD) have not been elucidated. To identify the risk of CVD early and contribute to its prevention and intervention, the present study used relevant biomarkers to evaluate the risk of CVD among pre- and postmenopausal women. An overall population of 816 women (aged 40-60 y) was evaluated as premenopause, natural early menopause, or natural late menopause (ages ≤ 48 and ≥52 y), with ages 49-51 years as reference (natural menopause). High-sensitivity C-reactive protein, carotid intima-media thickness, and brachial-ankle pulse wave velocity were measured. Triglycerides (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (LDL-C) of the postmenopausal group were each significantly higher than that of the premenopausal. However, the 3 menopausal groups were similar regarding hypertension, diabetes, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. In the logistic regression model, the CRP, brachial-ankle pulse wave velocity, and carotid intima-media thickness levels were similar among the premenopause and early and late menopause groups. These results were unchanged after further adjustment for multiple confounders including age, smoking, drinking, salt intake habits, presence of hypertension, or diabetes mellitus. Menopause itself is a more important risk factor for CVD compared with menopause that begins at early or late age.


Predicted endurance times during overhead work: influences of duty cycle and tool mass estimated using perceived discomfort.
A need for overhead work remains in several industries and such work is an important risk factor for shoulder musculoskeletal problems. In this study, we evaluated the effects of duty cycle and tool mass on endurance times during overhead work. A psychophysical approach was used, via a new methodology that was implemented to more efficiently estimate endurance times (rather than through direct measurements). Participants performed a simulated overhead task in specified combinations of tool mass and duty cycle. Both duty cycle and tool mass have substantial effects on the development of fatigue and estimated endurance times, though the former was more substantial and an interactive effect was evident. Gender differences were not substantial, except when using the largest tool mass. We recommend that, for two-hour periods of overhead work, tool masses greater than 1.25 kg should be avoided, as should duty cycles greater than 50%. Practitioner Summary: The current results may facilitate enhanced design and evaluation of overhead work tasks. In addition, the new estimation approach that was employed may enhance the efficiency of future studies using a psychophysical approach (ie using extrapolation of patterns of reported discomfort to predict longer term outcomes).


Estimated genetic parameters for growth-related traits in large yellow croaker Larimichthys crocea using microsatellites to assign parentage.
To estimate the heritabilities of growth-related traits in large yellow croaker, Larimichthys crocea, three independent full-factorial crosses were created by crossing four males × four females, seven males × three females and four males × three females (set 1, set 2 and set 3). At 13 months post-hatch, the juveniles were collected from three cross sets and measured for body mass (M), standard length (L(S)) and body height (H(B)). In addition, the parentage of the juveniles was assigned by genotyping six or seven polymorphic microsatellite loci. Out of the 959 juveniles, 99·6% could be assigned to a single parental pair. Heritabilities of growth-related traits were estimated for individual and combined sets with the pedigrees reconstructed by using microsatellite genotypes. The heritability estimates at 13 month-old were 0·02-0·30 for M, 0·02-0·25 for L(S) and 0·03-0·36 for H(B). These results showed that the heritabilities of M, L(S) and H(B) were different among three sets, which suggested that different breeding strategies should be adopted for different sets.


The human metallothionein gene family: structure and expression.
Metallothioneins (MTs) are encoded by a multigene family in man. We have isolated those genes and analyzed the structure of some of them. The MT-II variant is encoded by a single functional gene: MT-IIA. The MT-IIB gene is a processed pseudogene derived from a reverse transcript of MT-II mRNA. On the other hand, the MT-I class of variants are encoded by a large number of genes, arranged in tandem. The MT-IIA and the MT-IA genes show a differential response to glucocorticoid hormones and heavy metals, yet they are both expressed in primary human fibroblasts and in HeLa cells. Expression of both of those genes, in high level after transfer on bovine papilloma virus vectors, leads to increased resistance of the host cells to cadmium-induced toxicity.


Lactoperoxidase, a dithionite ion dismutase.
The dithionite ion is catalytically disproportionated by lactoperoxidase with Km = 0.36 mM in 100 mM glycine HCl pH 3.0. The products formed are thiosulfate and hydrogensulfite ions. The rate of reaction is considerably increased at low pH with a pKa at 3-3.5 possibly indicating the involvement of a carboxyl group. The reaction is competitively inhibited by hydrogensulfite, Ki = 5.5 mM in 100 mM glycine HCl pH 3.50. Four different spectral forms of reduced lactoperoxidase appear during the reaction. The first two forms are found during the lag phase of the reaction. The third form, which is interpreted as a ternary complex, exists under the dismutation phase. After exhaustion of the substrate a visible spectrum similar to that of lactoperoxidase H2O2 compound III appears. A mechanistic model for the lactoperoxidase dismutation of the dithionite ion is proposed and discussed.