Medical, social, and legal implications of treating nausea and vomiting of pregnancy.
This article will deal with medical, social, and legal implications of treating nausea and vomiting of pregnancy (NVP). Clinical problems occur when the symptoms become exaggerated and result in debilitation, dehydration, and hospitalization. The treatment of NVP in its early stages has the implication that it will prevent the more serious complications, including hospitalization. Therapeutic modalities discussed in this conference that have been used or are being tested are primarily symptomatic treatments (antihistamines, Bendectin (Merrell Dow; Cincinatti, Ohio), phenothiazines, hypnosis, accupressure, relaxation behavioral modification, audiogenic feedback training, newer medications, diet, and nutritional support). Bendectin is probably the most studied medication with regard to its reproductive effects, and the studies clearly demonstrate that therapeutic doses of Bendectin have no measurable reproductive risks to the mother or the fetus. In spite of Bendectin's record of safety, numerous nonmeritorious congenital malformation lawsuits were filed and went to trial, and that junk science was presented at these trials. The Bendectin era focused our attention on the area of nonmeritorious litigation and junk science, which could have an effect on any new or less well-studied therapies, because such a high percentage of women are treated for NVP. Because 3% of the offspring will be affected with birth defects, the potential for litigation is immense. The solutions are (1) for legal problems, the medical community should focus their attention on junk scientists and their junk science, over which physicians should have some authority, and (2) for the treatment problem, it would seem most logical that a major research effort should be directed toward brain receptors that are involved in these physiologic effects. Furthermore, it would be imperative to study the array of molecules, both natural and manufactured, that can interact with these receptors for the amelioration of nausea. Until we understand the mechanism and specific therapy for NVP, it would appear that the reintroduction of Bendectin is the logical intermediate course to follow. We should also accompany the introduction of Bendectin with an educational campaign with regard to the lack of reproductive risks for this medication. The Food and Drug Administration has set the stage for the reintroduction of Bendectin by republishing their conclusion that Bendectin does not represent an increase in reproductive risks to the fetuses of pregnant women.


Diagnosis of Ewing's Sarcoma After a Fall.
A 21-year-old male Army basic trainee was evaluated in a direct-access physical therapy clinic for left-sided low back pain. Following examination, radiographs and a bone scan were ordered. The findings prompted referral for a computed tomography scan of the pelvis, which characterized an infiltrative soft tissue mass. The therapist immediately contacted an orthopaedic surgeon, who recommended that the physical therapist order immediate magnetic resonance imaging (STAT MRI). The patient underwent a tissue biopsy and subsequently was diagnosed with Ewing's sarcoma. J Orthop Sports Phys Ther 2020;50(5):276. doi:10.2519/jospt.2020.9109.


Association Of Serum Total Bilirubin Level With Diabetic Retinopathy In Type 2 Diabetes Mellitus.
Serum bilirubin has anti-inflammatory, antioxidant and immunological properties. It is considered a protective substance against atherosclerotic and microvascular complications of diabetes mellitus (DM). This study was designed to find the association between total serum bilirubin concentration and diabetic retinopathy (DR). This case control study was conducted in the Department of Endocrinology, Diabetes and Metabolic Diseases, Hayatabad Medical Complex, Peshawar. Type-2 DM patients more than 18 years of age of either gender with duration of T2DM more than 6 months were included and sub categorized in two groups. Cases (DM with DR) and Controls (DM without DR) while patients with acute and chronic liver diseases, haemolytic anaemia, history of chronic alcohol consumption, use of hepatotoxic drugs (anti-tuberculous, anti-epileptic), women on oral contraceptive pills were excluded. All participants underwent ophthalmic examination at diabetic retinopathy screening clinic followed by pre designed set of investigations. A total of 152 patients, 76 cases and 76 controls were included. Serum bilirubin concentration was found inversely and independently (p 0.000) associated and inversely co related (r -0.345and p 0.000) with prevalence of DR. Cases were concentrated in the lower quartiles of serum bilirubin concentration and vice versa. Low haemoglobin (p 0.00) and longer duration of DM (0.003) were independently and directly associated with prevalence of DR. Serum bilirubin concentration is inversely and independently associated and inversely correlated with the prevalence of DR and may predict progression of DR over time.


Low post-arthroplasty infection rate is possible in developing countries: long-term experience of local vancomycin use in Iran.
Utilizing intrawound vancomycin powder in TKA surgery has yielded rather contrasting results in the current literature. Furthermore, CDC criteria, although effective in general, are not specifically designed for post-TKA infections. Here, we present a 7-year experience of vancomycin use in primary TKA in a high-volume tertiary knee center in Iran. Also, new criteria are proposed to detect suspected superficial post-TKA infections. This is a retrospective analysis of primary total knee arthroplasties performed in a tertiary knee center, from March 2007 to December 2018, by a single senior knee surgeon. All patients with follow-up periods of less than 1 year were excluded from the study. Since March 2011, all patients received vancomycin (powder, 1 g) before water-tight closure of the joint capsule. A comparison was made between this group and historical control subjects (operated from March 2007 to March 2011). Altogether, 2024 patients were included in the study. The vancomycin and the control groups included 1710 and 314 cases respectively. Patients were mostly women (male to female ratio, 1 to 4), with a mean age of 65.20 (SD = 10.83) years. In the vancomycin group, the rate of suspected SII (1.87%) and PJI (0.41%) was significantly lower than the control group (P = 0.002). Our experience shows that application of local vancomycin during TKA surgery could be a reasonable infection prevention measure, although prospective randomized studies are required to evaluate its efficacy.


Outcome of common iliac arteries after straight aortic tube-graft placement during elective repair of infrarenal abdominal aortic aneurysms.
To determine the relative rates of common iliac artery (CIA) expansion after elective straight aortic tube-graft replacement of infrarenal abdominal aortic aneurysms (AAA). Five participating centers in this 2004 study entered patients they had managed by an aortoaortic tube graft for elective AAA repair. The procedures took place between January 1995 and December 2003. Postoperative computed tomography (CT) scans were obtained for all patients in 2004 to assess changes in CIA diameter. Measurements on preoperative and postoperative CT scans were all made at the same level using the same technique. Entered in the study were 147 patients (138 men, 9 women) with a mean age of 68 years. Mean follow-up from aortic surgery to verification of CIA diameter on the postoperative CT scan was 4.8 years. Mean preoperative CIA diameter was 13.6 mm vs 15.2 mm postoperatively. No patient developed occlusive iliac artery disease during follow-up. Three patients (2%) required repeat surgery during follow-up for a CIA aneurysm. The 147 patients were divided into three groups based on preoperative CIA diameter shown in CT scan: group A (n = 59, 40.1%), both CIA were of normal diameter; group B (n = 53, 36.1%), ectasia (diameter between 12 and 18 mm) of at least one CIA; group C (n = 35, 23.8%), an aneurysm (diameter >18 mm) of at least one CIA. CIA diameter increased by a mean of 1 mm (9.4%) over 5.5 years in group A vs 1.7 mm (12.1%) over 4.3 years in group B and 2.3 mm (12.7%) over 4.2 years in group C. The three patients who required repeat surgery for a CIA aneurysm during follow-up were all in group C. Four variables were associated with aneurysmal change in CIA: initial CIA diameter, celiac aorta diameter on the preoperative CT scan, a coexisting aneurysm site, and the follow-up duration. Tube-graft placement during AAA surgery is justified even for moderate CIA dilatation (<18 mm). CIA aneurysms with a preoperative diameter > or =25 mm enlarge more rapidly and warrant insertion of a bifurcated graft during the same surgical session as AAA repair. The evolutive potential of CIA between 18 mm and 25 mm in diameter justifies a bifurcated graft when the celiac aorta diameter is >25 mm or the patient's life expectancy is > or =8 years.


Bilateral upper limb amputations in victims of high tension electrical injuries: Three case studies.
Bilateral upper limb amputations result in severe disability. High voltage electrical injury is a rare cause of such an outcome and injuries often occur as occupational hazards. We present three case reports of accidental high voltage injuries that occurred in a non-occupational setting. Victims were all initially managed at other centres before referral to our hospital and all subsequently had bilateral upper limb amputations. The high cost of treatment, importance of prevention, and need for rehabilitation are highlighted.


[Cause of death of the working-age population of Ufa in relation to the area of residence].
Two districts, one with developed oil-processing and petrochemical industries and administrative one, were selected in Ufa city for 20-year study of mortality among able-bodied population. Both districts demonstrated a decreasing share of able-bodied people in mortality structure. However, mortality of able-bodied population in the industrial district tended to increase, in the administrative one--to decrease. The main death causes were traumatism, cardiovascular diseases, malignancies. Mean age at death among the able-bodied population was lower in the industrial district, among the people engaged into oil-processing and petrochemical industries, transport and building sector.


[Statin prescription in primary prevention: which cardiovascular risk score should be used in Switzerland?].
Primary prevention of cardiovascular disease by physicians is achieved by management of individual risk factors. The eligibility for treatment with statins is based on both an estimate of the risk of developing cardiovascular disease and the LDL-cholesterol. Three risk scores are commonly used: the PROCAM score, the Framingham score, and the European score. In Switzerland, the Swiss Group Lipids and Atherosclerosis (GSLA) recommends to use the PROCAM score with an adjustment of the level of risk for Switzerland. A survey also showed that PROCAM is the most used in Switzerland. In this article, the differences of these scores and their practical applications regarding the prescription of statins in primary prevention are discussed. The consequences and potential benefits of applying these scores in Switzerland are also discussed.


Taxonomy of Trichinella and the epidemiology of infection in the Southeast Asia and Australian regions.
Seven species belonging to the Trichinella genus (five with encapsulated larvae and two with non-encapsulated larvae in host muscles) and three additional genotypes have been described to date: T. spiralis (genotype T1), a cosmopolitan species with a high infectivity to swine and rats; T. nativa (T2), etiological agent of sylvatic trichinellosis in arctic and subarctic areas of the Holarctic region, and its related genotype (Trichinella T6), detected in Alaska, Idaho, Montana, Pennsylvania, Wyoming, and Ontario; T. britovi (T3), etiological agent of sylvatic trichinellosis in temperate areas of Europe and Asia, and its related genotypes Trichinella T9 in Japan and Trichinella T8 in South Africa and Namibia; T. murrelli (T5), etiological agent of sylvatic trichinellosis in temperate areas of the USA; T. nelsoni (T7), etiological agent of sylvatic trichinellosis in Africa south of the Sahara; T. pseudospiralis (T4), a non-encapsulated cosmopolitan species infecting both mammals and birds; and T. papuae (T10), a recently discovered non-encapsulated species in sylvatic swine of Papua New Guinea. In the Southeast Asia and Australian regions, T. spiralis, T. pseudospiralis and T. papuae have been detected in sylvatic and domestic animals and in humans. A focus of human trichinellosis due to T. papuae was recently discovered in Papua New Guinea, with a prevalence of 28.9%. Trichinellosis has also been documented in domestic animals and/or humans in Cambodia, Indonesia (Bali and Sumatra), Lao PDR, Malaysia, Myanmar, Thailand, and New Zealand, and in wildlife of Tasmania.


Incomitant strabismus: does extraocular muscle form denote function?
The paradigm that an "underacting" extraocular muscle is always atrophic or hypoplastic and that an overacting extraocular muscle should always be enlarged leads to inconsistencies with clinical observations. These include findings of "overacting" inferior oblique muscles, superior rectus muscle overaction or contracture syndrome, and normal extraocular muscle diameters in patients with apparent superior oblique muscle palsy, among other clinical entities. These inconsistencies can be reconciled if one accepts the possibility that extraocular muscle contractile activity may reflect a change in neural input to an anatomically normal muscle or that muscle contractile activity may be altered by shifts in fiber type and distribution within a normal-sized muscle. This remodeling may result from vergence adaptation or from any change in neural stimulus to the muscle. There is substantial evidence to suggest that both of these theoretical possibilities may likely occur.


Bariatric Surgery and the Mechanisms of Gastroesophageal Reflux Disease.
Introduction: The association between obesity and gastroesophageal reflux disease (GERD) is very well known and the pathophysiology of GERD is not completely understood but is likely to have a multifactorial nature especially after bariatric procedures. Methods: The current editorial summarizes the principal mechanisms involved in the reflux disease following different bariatric procedures. Results: Laparoscopic adjustable gastric banding could reduce the gastroesophageal reflux in the short term in some cases, but overeating will inevitably lead to enlargement of the pouch with loss of its antireflux properties. Although the laparoscopic Roux-en-Y gastric bypass was considered the gold standard procedure for obese patients with reflux disease, many patients had at least one complication within their follow-up period. One anastomosis gastric bypass remains a controversial procedure for GERD, especially when it is proposed as revisional surgery after laparoscopic sleeve gastrectomy. As revisional surgery, either single anastomosis duodeno-ileostomy (SADI) or duodenal switch (DS) have little or no impact on GERD and in our experience the indication for SADI/DS is a valid option in case of absence of any symptoms of reflux. The effect of sleeve for GERD is contradictory. Conclusion: For those with moderate reflux, since specific procedure guidelines are missing, surgical treatment for morbid obese patients must be selected according to the clinical characteristics of the patient, his eating habits and patient willingness. It should be based on a preoperative workup with shared decision making, with the double purpose of treating both GERD and obesity.


Body mass index and slipped capital femoral epiphysis.
Body mass index (BMI) as a predictor of slipped capital femoral epiphysis (SCFE) was studied. A total of 26 adolescent patients had complete annual height and weight measurements taken from birth to onset of slippage. These values were compared with those of the normal adolescent population. Patients with SCFE showed statistically higher BMI during growth than normal developing children. BMI gives more accurate data on body build than height and weight alone and may be a useful tool for evaluating risk factors in SCFE.


[Epidemiology of upper gastrointestinal bleeding in Gabon].
The department of internal medicine of the military hospital of Gabon managed 92 cases of upper gastrointestinal bleeding from April 2009 to November 2011. The frequency of these hemorrhages in the department was 8.2%; they occurred most often in adults aged 30-40 years and 50-60 years, and mainly men (74%). Erosive-ulcerative lesions (65.2%) were the leading causes of hemorrhage, followed by esophageal varices (15.2%). These results underline the importance of preventive measures for the control of this bleeding.


First results of electron temperature measurements by the use of multi-pass Thomson scattering system in GAMMA 10.
A multi-pass Thomson scattering (TS) has the advantage of enhancing scattered signals. We constructed a multi-pass TS system for a polarisation-based system and an image relaying system modelled on the GAMMA 10 TS system. We undertook Raman scattering experiments both for the multi-pass setting and for checking the optical components. Moreover, we applied the system to the electron temperature measurements in the GAMMA 10 plasma for the first time. The integrated scattering signal was magnified by approximately three times by using the multi-pass TS system with four passes. The electron temperature measurement accuracy is improved by using this multi-pass system.


Classification of vascular malformations of the central nervous system.
The ability to systematically and meaningfully classify a disease is in many ways a reflection of our overall understanding of it. Over time, nosologic schemes applied to any disease typically undergo a characteristic evolution from purely descriptive, to pathoanatomic and/or embryologic, to finally biological definitions. With the recent developments in further elucidating the pathophysiology, histopathology, natural history, and cellular biology of various vascular malformations occurring within the central nervous system, it is time to derive a more comprehensive and "universal" classification system that integrates classic pathoanatomic schemes with a biologically defined scheme previously developed for systematic vascular malformations. Such a system is proposed and discussed, including detailed review of important subtypes.


Long-term changes in corneal endothelial cell density after repeat penetrating keratoplasty in eyes with endothelial decompensation.
To compare the longitudinal changes in corneal endothelial cell density (ECD) and the incidence of postoperative complications between eyes with endothelial decompensation after repeat penetrating keratoplasty (RPK) and those after primary penetrating keratoplasty (PPK). Fifty-seven eyes with endothelial decompensation scheduled for RPK (RPK group) and 57 eyes with endothelial decompensation scheduled for PPK (PPK group) were enrolled. Corneal ECD was evaluated using a specular microscope at 1, 3, 6, 9, and 12 months, and every 6 months until 60 months postoperatively. Visual acuity (VA) and incidence of graft failure, graft rejection, or marked increase in intraocular pressure were examined. Corneal ECD decreased gradually and percentage of cell loss at 60 months was approximately 73% in both groups; these did not differ significantly between groups throughout the follow-up (P ≥ 0.2209). The incidence of graft failure (52.6% in the RPK group and 36.8% in the PPK group), immune rejection, and marked increase in intraocular pressure did not differ significantly between groups (P ≥ 0.0898), although corrected VA was worse in the RPK group. The most common cause of graft failure in both groups was late endothelial failure. The outcomes were not significantly different between eyes that underwent a first RPK and those that underwent a second or subsequent RPK. Corneal endothelial cell loss and complications are comparable between eyes with endothelial decompensation after RPK and those after PPK, although VA is worse in eyes after RPK. The outcomes after a first RPK did not differ from those after multiple RPKs.


Involvement of the ras genes in female genital tract cancer.
Human carcinogenesis is a multistep process involving complicated genetic events in which several onco-genes and oncosuppressor genes are implicated. The role of ras oncogenes in cellular transformation and apoptosis has been extensively examined and the dual role of ras as oncogene and oncosuppressor gene has been supported. Activation of ras occurs either by genomic alterations such as point mutations or by modulation of Ras protein expression. Many molecular and immunohistochemical studies have focused on ras activation in a wide range of human tumours. In this review, we summarize available information regarding the genomic and expression alterations of ras oncogenes in cervical, endometrial and ovarian cancer. Gynecological malignancies represent some of the most well- studied types of human cancer concerning ras activation and its possible use in clinical practice.


Focal defects on liver scintigraphy due to right ventricular failure.
A case of focal defects seen on liver scintigraphy on the basis of right ventricular failure is presented. The pattern bore a striking similarity to that seen in hepatic metastases.


Isolation and characterization of yeasts capable of efficient utilization of hemicellulosic hydrolyzate as the carbon source.
Few yeasts have shown the potential to efficiently utilize hemicellulosic hydrolyzate as the carbon source. In this study, microorganisms isolated from the Manaus region in Amazonas, Brazil, were characterized based on their utilization of the pentoses, xylose, and arabinose. The yeasts that showed a potential to assimilate these sugars were selected for the better utilization of lignocellulosic biomass. Two hundred and thirty seven colonies of unicellular microorganisms grown on hemicellulosic hydrolyzate, xylose, arabinose, and yeast nitrogen base selective medium were analyzed. Of these, 231 colonies were subjected to sugar assimilation tests. One hundred and twenty five of these were shown to utilize hydrolyzed hemicellulose, xylose, or arabinose as the carbon source for growth. The colonies that showed the best growth (N = 57) were selected, and their internal transcribed spacer-5.8S rDNA was sequenced. The sequenced strains formed four distinct groups in the phylogenetic tree, and showed a high percentage of similarity with Meyerozyma caribbica, Meyerozyma guilliermondii, Trichosporon mycotoxinivorans, Trichosporon loubieri, Pichia kudriavzevii, Candida lignohabitans, and Candida ethanolica. The discovery of these xylose-fermenting yeasts could attract widespread interest, as these can be used in the cost-effective production of liquid fuel from lignocellulosic materials.


Underdetermined DOA Estimation of Quasi-Stationary Signals Using a Partly-Calibrated Array.
Quasi-stationary signals have been widely found in practical applications, which have time-varying second-order statistics while staying static within local time frames. In this paper, we develop a robust direction-of-arrival (DOA) estimation algorithm for quasi-stationary signals based on the Khatri-Rao (KR) subspace approach. A partly-calibrated array is considered, in which some of the sensors have an inaccurate knowledge of the gain and phase. In detail, we first develop a closed-form solution to estimate the unknown sensor gains and phases. The array is then calibrated using the estimated sensor gains and phases which enables the improved DOA estimation. To reduce the computational complexity, we also proposed a reduced-dimensional method for DOA estimation. The exploitation of the KR subspace approach enables the proposed method to achieve a larger number of degrees-of-freedom, i.e., more sources than sensors can be estimated. The unique identification condition for the proposed method is also derived. Simulation results demonstrate the effectiveness of the proposed underdetermined DOA estimation algorithm for quasi-stationary signals.


Size and orientation cue figure-ground segregation in infants.
Adult perceivers segregate figure from ground based on image cues such as small size and main axis orientation. The current study examined whether infants can use such cues to perceive figure-ground segregation. Three- to 7-month-olds were familiarized with a pie-shaped stimulus in which some pieces formed a + and other pieces formed an x. The infants were then presented with a novelty preference test pairing the + and x. The bases for the pieces forming the + or x were size and orientation (Experiment 1), size (Experiment 2), and orientation (Experiment 3). In each experiment, infants responded as if they recognized as familiar the shape specified by small size, main axis orientation, or their combination. Control conditions showed that infant performance could not be attributed to spontaneous preference. The findings suggest that infants can achieve figure-ground segregation based on some of the same cues used by adults.


Mercury-induced motor and sensory neurotoxicity: systematic review of workers currently exposed to mercury vapor.
The neurotoxicity of elemental mercury (Hg0) is well-recognized, but it is uncertain whether and for how long neurotoxicity persists; among studies that evaluated previously exposed workers, only one examined workers during and also years after exposure ceased. The aim of this review is to document the type, frequency, and dose-relatedness of objective neurological effects in currently exposed mercury workers and thereby provide first approximations of the effects one would have expected in previously exposed workers evaluated during exposure. We systematically reviewed studies of neurotoxicity in currently exposed mercury workers identified by searching MEDLINE (1950-2015), government reports, textbook chapters, and references cited therein; dental cohorts were not included. Outcomes on physical examination (PE), neurobehavioral (NB) tests, and electrophysiological studies were extracted and evaluated for consistency and dose-relatedness. Forty-five eligible studies were identified, comprising over 3000 workers chronically exposed to a range of Hg0 concentrations (0.002-1.7 mg/m3). Effects that demonstrated consistency across studies and increased frequency across urine mercury levels (<50; 50-99; 100-199; ≥200 μg/L) included tremor, impaired coordination, and abnormal reflexes on PE, and reduced performance on NB tests of tremor, manual dexterity and motor speed. The data suggest response thresholds of UHg ≈275 μg/L for PE findings and ≈20 μg/L for NB outcomes. These results indicate that PE is of particular value for assessing workers with UHg >200 μg/L, while NB testing is more appropriate for those with lower UHg levels. They also provide benchmarks to which findings in workers with historical exposure can be compared.


Involvement of granulin in estrogen-induced neurogenesis in the adult rat hippocampus.
Recent studies have demonstrated the presence of neurogenesis in the adult mammalian hippocampus, and it has been suggested that estrogen and various growth factors influence the processes of adult neurogenesis. The present study assessed cell proliferation in the dentate gyrus and the mRNA expression levels of granulin, insulin-like growth factor-I (IGF-I), and brain-derived neurotrophic factor (BDNF) in the hippocampus 4 h after treatment with estradiol benzoate (EB) in 3- and 12-month old ovariectomized rats. At 3 months of age, mRNA expression of granulin precursor and cell proliferation were increased by EB treatment, although the mRNA expressions of IGF-I and BDNF remained unchanged. At 12 months of age, however, neither mRNA expression of the three genes nor cell proliferation in the dentate gyrus were affected by EB treatment. In addition, 17beta-estradiol enhanced the proliferation of neural progenitor cells derived from hippocampal tissue of 3-month-old female rats in vitro; this was inhibited by neutralization of granulin with specific antibody. These results suggest that estrogen induces granulin gene expression in the hippocampus and that the product of this gene is involved in the mitogenic effects of estrogen in the dentate gyrus, although the responses to estrogen decline with age.


Comparing dual phase Tl-201 thyroid scan and fine-needle aspiration cytology to detect follicular carcinoma.
It remains difficult to pre-operatively differentiate follicular carcinoma and adenoma even under intraoperative investigations including histopathologic diagnosis of frozen sections. We retrospectively compared dual phase thallium (Tl-201) thyroid scan and fine-needle aspiration (FNA) cytology to detect follicular carcinoma in 12 patients with cold thyroid nodules. Fine-needle aspiration cytology results were assessed and categorized by experienced pathologists into benign, suspicious, and malignant. Dual phase Tl-201 thyroid scan including an early (10-min) image and a delayed (3-hour) image were acquired after 2 mCi (74 MBq) of Tl-201 was injected intravenously. Dual phase Tl-201 thyroid scan findings were visually interpreted as positive and negative results. Based on FNA cytologic interpretation criteria, three nodules were diagnosed as benign, five nodules were diagnosed as suspicious, and four nodules were diagnosed as malignant. However, based on dual phase Tl-201 thyroid scan interpretation criteria, all of the 12 nodules could accurately diagnose as malignant. We conclude that dual phase Tl-201 thyroid scan was more accurate in diagnosing follicular carcinoma when comparing with FNA cytology.


Association between influenza vaccination, all-cause mortality and cardiovascular mortality: a protocol for a living systematic review and prospective meta-analysis.
Influenza virus infection is known to increase the risk of cardiovascular events, especially in populations with pre-existing cardiovascular disease (CVD). Considering that influenza is vaccine preventable, international guidelines recommend high-risk populations with CVD receive an influenza vaccine every year. However, there are various classifications of recommendations and levels of evidence. Previous systematic reviews concluded uncertain evidence on influenza vaccine efficacy for preventing cardiovascular events in the general population or in populations with pre-existing CVD. Limited safety data of influenza vaccines were reported for populations with pre-existing CVD. Randomised controlled trials with larger sample sizes relative to previous studies are emerging, the findings of these trials are likely to be highly influential on summary efficacy estimates. We aim to perform a living systematic review and a prospective meta-analysis to evaluate the efficacy and safety of influenza vaccines compared with no vaccines or placebo for preventing mortality or CVD events in the general population and in populations with pre-existing CVD. Any types of randomised controlled trial and observational study meeting the Population, Intervention, Comparator, Outcome and Study design criteria for the research question will be selected for inclusion. The living systematic review status will be maintained for 3 years with an update for every 6 months. Mainstream medical literature databases will be independently searched by two authors with predefined strategies. Two authors will perform the risk of bias assessment with consensus. Narrative synthesis and meta-analyses will be performed to summarise the results. Formal ethical review is not required as this study does not involve primary data collection. We will publish results of the living systematic review and prospective meta-analysis in a peer-reviewed journal. Findings will also be presented at relevant meetings. CRD42021222519.


Antenatal plasma exchange therapy.
A 22-year-old primigravida with severe mesangiocapillary gomerulonephritis presented at 10 weeks gestation for antenatal care. Delivery of a small health infant was achieved by caesarean section at term. The successful outcome of this pregnancy was attributed to the careful control of anaemia, oedema, and hypertension; and to the use of plasma-exchange therapy throughout the third trimester. The value of plasma exchange therapy in pregnancies which are complicated by renal disease is discussed.


Effects of progesterone on the oviductal epithelium in estrogen-primed prepubertal beagles: light and electron microscopic observations.
A total of 45 prepubertal beagles 6 to 8 weeks of age were used to study the cytological changes that accompany regression of the oviductal epithelium. The oviductal epithelium in untreated pups consisted of undifferentiated low cuboidal cells that measured 10.3 +/- 2.0 microns in height. In response to estradiol (E2), low cuboidal cells underwent hypertrophy, hyperplasia, and cytodifferentiation and gave rise to columnar ciliated and secretory cells. After 12 days of E2 treatment the epithelium was fully differentiated and measured 29.4 +/- 2.6 microns in height with 56% of the cells possessing cilia. When E2 treatment was continued for an additional 12 days, the epithelium was maintained in a differentiated state. However, if E2 treatment was terminated or progesterone (P) given alone or in conjunction with E2, the oviductal epithelium regressed and after 6 days was composed of low cuboidal cells that ranged in height from 9 to 14 microns with approximately 25% of the cells possessing cilia. A variety of cytological changes characterized the process of regression. The most immediate signs that regression was underway was a reduction in the height of the epithelium and the presence of cells with shrunken, pleomorphic nuclei that lacked prominent nucleoli. Degenerative events included: pinching off and shedding of the apical cytoplasm of cells comprising the epithelium, extrusion of whole cells and/or nuclei, and resorption of cilia and basal bodies. During the first 6 days following E2 withdrawal or P treatment, macrophages and cellular debris were frequently present within the lumen of the oviduct. The process of regression did not proceed synchronously throughout the ampulla of the oviduct, nor did all cells appear to degenerate in the same manner. The cytological changes that accompanied oviductal regression following P treatment were identical to those observed following E2 withdrawal. Results from experiments conducted in the present study show that: E2 induces the oviductal epithelium to differentiate and is required to maintain the epithelium in a differentiated state, E2 withdrawal or P treatment causes the oviductal epithelium to regress, at least three distinct degenerative processes are involved in the transition of columnar ciliated and secretory cells into low cuboidal cells, and regression does not occur synchronously throughout the ampulla region of the oviduct.


The millipede Craspedosoma raulinsii Leach, 1814 (Chordeumatida: Craspedosomatidae) in North America with comments on the derivation of its binomial name.
The millipede Craspedosoma raulinsii (Craspedosomatidae) is widespread in Central Europe from Belarus and southern Scandinavia west to Britain and Ireland. Although the species is often not common and rarely encountered (Blower 1985, Hoffman 1999, Lee 2006), Kime (2004) reports C. raulinsii as the third most widespread millipede in Belgium. Shelley (1990) reported C. raulinsii (as C. rawlinsii) for the first time from North America (from Gatineau Park, Quebec, Canada) and noted the occurrence is the first introduction of a representative of the order Chordeumatida in the New World. Here we report new records that suggest widespread occurrence of this introduced millipede in eastern Canada and comment on the commonly-applied spelling of the specific epithet of the species. Vouchers have been deposited in the collections of the New Brunswick Museum (NBM).


Sexual and reproductive health communication intervention for caretakers of adolescents: a quasi-experimental study in Unguja- Zanzibar.
Caretakers/parents or parents figure need to be trained to promote effective communication about sexual and reproductive health to their adolescents. This study assessed the effect of an intervention aiming to improve caretaker-adolescent communication on sexual and reproductive health matters through improving information, motivation, and behavioral skills related to sexual health communication. The study also evaluated the relationship of information, motivation, and behavioral skills model-constructs with communication practice. Information-Motivation-Behavioural skills model was used as a framework to guide the intervention implementation and evaluation process. This is a quasi-experimental non-randomized controlled pre- and post-test study which involved one thousand caretakers of adolescents in all the six districts of Unguja-Zanzibar. All participants completed interviewer-administered structured pre-test questionnaire. The experimental group then received sexual health communication intervention addressing the information, motivation, and behavioral skills related to sexual health communication, while the control group received the sexual health information only. All participants were then reassessed for their information, motivation, behavioral skills and their sexual health communication after 1 month, 6 months and at 1 year following the intervention. To evaluate the effect of intervention at the post-test measures, Univariate Analyses of Covariance was performed whereby the pre-test score and variables on which the groups differed were considered as covariates. Standardized mean difference statistics of Cohen's d was used to calculate the effect size, and the cut-off point for the level of significance was set at two-sided, p-value < 0.05. Results shows that the immediate post-test sexual health communication, motivation and behavioral skills scores were statistically significantly higher in the experimental group compared to control group (p < 0.05). Moreover, sexual health communication score after 6 months and at 1 year were statistically significantly higher in the experimental group compared to control group (p < 0.05). Information construct however did not differ between groups in post-test measures. Furthermore, results revealed that communication practice is statistically significantly associated with information, motivation and behavioural skills in post-test measures. The findings provided preliminary evidence for the effectiveness of SRH communication intervention and supported the significance of IMB model-constructs to inform the SRH-communication intervention and to guide the intervention evaluation.


Postoperative necrotizing fasciitis in children.
Necrotizing fasciitis is a rapidly progressive soft tissue infection, involving the skin, subcutaneous tissue, and superficial fascia. It is a rare but life-threatening complication in the postoperative patient. In the last 7 years, we have treated four children in whom necrotizing fasciitis developed after appendectomy for ruptured appendix, bilateral inguinal herniorrhaphy, or gastrostomy closure. These four patients and seven well-described children from the literature with necrotizing fasciitis following surgery form the basis of this review. The ages ranged from six days to 15 years (mean 4.5 years). There were eight boys and three girls. There were five clean, five clean-contaminated, and one contaminated surgical procedures. No patient had evidence of malignancy or diabetes. Two of our four patients had evidence of failure to thrive. Only one patient had an intraabdominal abscess. In ten, the infection started in the abdominal wall; in one, the infection started in the chest wall. In our four patients, three had neutropenia and fever, four had tachycardia, and two had wound crepitation and radiographic evidence of subcutaneous gas. Cultures of all ten wounds were positive for bacteria; six were positive for more than one organism. Blood culture results were positive in five of five patients who died and in only two of five patients who survived. All survivors had wide surgical debridement and were treated with broad-spectrum antibiotics. The mortality rate was 45% in the whole series.(ABSTRACT TRUNCATED AT 250 WORDS)


High-Throughput Analysis Reveals Seasonal Variation of the Gut Microbiota Composition Within Forest Musk Deer (Moschus berezovskii).
The gut microbiota plays a key role in the nutritional ecology of ruminants, and host diet has a significant effect on these microbial communities. Longitudinal studies assessing variation of seasonal microbiota in animals can provide a comparative context for interpreting the adaptive significance of such changes. However, few studies have investigated the effects of seasonally-related dietary shifts on the gut microbial communities of endangered forest musk deer (FMD), and the national breeding programs need this information to promote the growth of captive populations. The present study applied bacterial 16S rRNA genes based on high-throughput sequencing to profile the fecal microbial communities of FMD across four seasons. Microbial diversity was higher in seasons with dry leaf diets (winter and spring) compared to seasons with fresh leaf diets (summer and autumn). The dominant microbial phyla were Firmicutes and Bacteroidetes, and the core bacterial taxa also comprised mostly (94.40% of shared OTUs) Firmicutes (37 taxa) and Bacteroidetes (6 taxa), which were relatively stable across different seasons. The Firmicutes-Bacteroidetes ratio declined in seasons with fresh leaf diets relative to seasons with dry leaf diets, and the dominant genera among the four seasons showed no significant variation in abundance. This work explores the seasonal variation in the microbial communities of FMD for the first time, and reveals how gut microbial community dynamics vary seasonally in accordance with differences in dietary plants (fresh and dry leaf). These results indicate that the annual cyclic reconfiguration of FMD gut microbiota could be associated with shifts in dietary nutrients, which is important information to inform captive FMD management.


Two cases of coronary artery spasm induced by indocyanine green.
There is no evidence in the literature that coronary artery spasm is induced by indocyanine green (ICG). In the present report, we describe 2 cases who developed chest pain with transient ST elevation on electrocardiograms after intravenous administration of ICG.


Vocal and verbal expression of postoperative pain in preschoolers.
The purpose of this study was to examine the development and construction of vocal and verbal expression of postoperative pain in young children with limited linguistic abilities. The main objective was to highlight specific pain vocalizations, which may lead to easy and quick detection and assessment of postoperative pain relative to the age of the suffering child. Forty-seven children aged 1 to 6 years were observed during two periods of surgical hospitalization: a preoperative and a postoperative period. The results showed that there was a significant relation between their age and the types of vocalization they expressed during the postoperative period. Regarding the development in relation to certain contexts, a minor modification seems to be concerned not with the type but with the frequency of the items of vocalizations. The study confirms earlier observations and clinical experience that an efficient and reliable assessment of pain in infants and young children necessitates taking several factors into account, such as the developmental age of the children, and especially a consideration of the whole spectrum of pain markers present in the child's behavior and captured by the assessment tools.


Fabrication of gallic acid loaded Hydroxypropyl methylcellulose nanofibers by electrospinning technique as active packaging material.
The objective of this study was to encapsulate gallic acid in Hydroxypropyl methylcellulose (HPMC)/ polyethylene oxide (PEO) blend nanofiber by using electrospinning and examine the usage of nanofibers as active packaging materials. Gallic acid loaded nanofibers showed homogenous morphology. Gallic acid was loaded into nanofibers efficiently and nanofibers showed strong antioxidant activity. As the gallic acid amount increased, the TGA curves had shifted one stage to two stage degradation and degradation temperature (Td) of gallic acid decreased from 275 °C to 250 °C due to the crystalline structure change. Interaction between gallic acid and HPMC/PEO nanofiber demonstrated that gallic acid successfully embedded into the nanofibers. Gallic acid loaded nanofibers decreased the oxidation of walnut during storage. Overall, electrospinning technique was proved to be an efficient method to encapsulate bioactive compounds and gallic acid loaded nanofibers showed promissory results that can be suggested as great potential to active packaging material.


The levonorgestrel-releasing intrauterine system: its effect on the number of hysterectomies performed in perimenopausal women with uterine fibroids.
This prospective observational study was designed to determine the percentage of hysterectomies avoided following insertion of a levonorgestrel-releasing intrauterine system (LNG-IUS) in perimenopausal women with uterine fibroids and a prior indication for surgery. The study also compared the progress of patients using the LNG-IUS with those submitted to hysterectomy, with particular emphasis on the patient's satisfaction with treatment. Sixty perimenopausal patients with uterine fibroids and excessive bleeding referred for hysterectomy were included. After counseling on the possibility of non-surgical treatment, 39 patients opted to use an LNG-IUS while 21 opted for hysterectomy. Continuation of LNG-IUS use and the patient's satisfaction with the chosen procedure were assessed. A secondary analysis evaluated hemoglobin levels, clinical complications, bleeding patterns and uterine volume at ultrasonography over time. After 24 months of follow-up, four of the patients who had opted to use an LNG-IUS were submitted to surgery, while 35 continued using the device, thus avoiding hysterectomy in 89.5% of cases. LNG-IUS users were more satisfied with treatment (p = 0.02) compared to those submitted to hysterectomy. In conclusion, the use of the LNG-IUS enables the number of hysterectomies to be reduced in women with uterine fibroids and is associated with greater satisfaction compared to surgical treatment.


[Polymorphic genes of xenobiotic-metabolizing enzymes associated with bronchial asthma in genetically predisposed children].
The frequencies of the CYP1A1 valine allele, homozygous deletions of GSTM1 and GSTT1, and two point mutations of the NAT2 gene, (C481-->T) and S2 (G590-->A), were compared in healthy children and children having bronchial asthma. The S1 mutation was associated with resistance, and all of the other traits, with predisposition to the disease. In families of patients with diseased progenitors and in those with healthy progenitors, the estimates of the asthma risk were similar. In both groups, parameters of the trait association with the disease depended on passive smoking. At passive smoking, a trend to an overrepresentation (high odds ratio, OR) of the GSTM1 null genotype and S2 mutation of the NAT2 gene was observed, whereas the odds ratio of the GSTT1 null genotype decreased, and those of the CYP1A1 and S1 mutation of the NAT2 gene remained unchanged. The highest OR = 36.25 (P < 0.01) was characteristic of the GSTT1 null genotype in nonsmoking hereditary burdened patients. The results obtained suggest an important role of xenobiotic-metabolizing enzymes in development of bronchial asthma.


Pancreatic heterotopia: a reappraisal and clinicopathologic analysis of 32 cases.
A total of 32 histologically documented cases of heterotopic pancreas was found in a review of the records of the department of pathology at the Chang Gung Memorial Hospital between 1977 and 1987. This review was done to ascertain the clinical significance of this uncommon entity. In 14 patients (44%), the aberrant pancreatic tissue was symptomatic; in the other 18 (56%), it was found incidentally. In the symptomatic group, the heterotopic pancreatic tissue was found in a duplication cyst of the ileum in one patient, in the common bile duct in one, in a Meckel's diverticulum in four, in the stomach in three, in a congenital duodenal diaphragm in one, in the duodenum in three, and in the ileum in one. The majority of heterotopic pancreatic tissue in the asymptomatic group was encountered in the jejunum (15 patients). Symptoms were related to complications, including obstruction of the common bile duct, mucosal ulcer with hemorrhage, intussusception, and intestinal obstruction, but not to pathologic conditions of the pancreas itself, such as pancreatitis or pancreatic cyst or neoplasm. In all of the clinically significant cases, the clinical symptoms disappeared completely after surgical removal of the aberrant tissue. In 28 cases (87%), diagnosis was made by frozen section during operation. Preoperative diagnosis of aberrant pancreas was not made in any of the cases. Histologically, all cases showed pancreatic excretory ducts; in 31 cases (97%), exocrine glands were present, and in 27 cases (84%), islets of Langerhans were discernible. There was no relationship between symptoms and the presence of islets, acini, or ducts. Mallory's phosphotungstic acid-hematoxylin stain was used to demonstrate zymogen granules in the acinar cells, and insulin, glucagon, and somatostatin were demonstrated with the horseradish peroxidase-antihorseradish peroxidase immunocytochemical staining technique; islets of Langerhans were also identified. Technetium Tc 99m scintigraphy was used to detect the bleeding source in a Meckel's diverticulum and an enteric duplication associated with ectopic gastric mucosa.


Description of Candidatus Bartonella fadhilae n. sp. and Candidatus Bartonella sanaae n. sp. (Bartonellaceae) from Dipodillus dasyurus and Sekeetamys calurus (Gerbillinae) from the Sinai Massif (Egypt).
Bartonella spp. are parasites of mammalian erythrocytes and endothelial cells, transmitted by blood-feeding arthropod ectoparasites. Different species of rodents may constitute the main hosts of Bartonella, including several zoonotic species of Bartonella. The aim of this study was to identify and compare Bartonella species and genotypes isolated from rodent hosts from the South Sinai, Egypt. Prevalence of Bartonella infection was assessed in rodents (837 Acomys dimidiatus, 73 Acomys russatus, 111 Dipodillus dasyurus, and 65 Sekeetamys calurus) trapped in 2000, 2004, 2008, and 2012 in four dry montane wadis around St. Katherine town in the Sinai Mountains. Total DNA was extracted from blood samples, and PCR amplification and sequencing of the Bartonella-specific 860-bp gene fragment of rpoB and the 810-bp gene fragment of gltA were used for molecular and phylogenetic analyses. The overall prevalence of Bartonella in rodents was 7.2%. Prevalence differed between host species, being 30.6%, 10.8%, 9.6%, and 3.6% in D. dasyurus, S. calurus, A. russatus, and A. dimidiatus, respectively. The phylogenetic analyses of six samples of Bartonella (five from D. dasyurus and one from S. calurus) based on a fragment of the rpoB gene, revealed the existence of two distinct genetic groups (with 95-96% reciprocal sequence identity), clustering with several unidentified isolates obtained earlier from the same rodent species, and distant from species that have already been described (90-92% of sequence identity to the closest match from the GenBank reference database). Thus, molecular and phylogenetic analyses led to the description of two species: Candidatus Bartonella fadhilae n. sp. and Candidatus Bartonella sanaae n. sp. The identification of their vectors and the medical significance of these species need further investigation.


Nonstranger and Stranger Sexual Homicides in Mainland China: Comparing the Modus Operandi of Male Sexual Murderers.
Although studies have been made of different subtypes of individuals who committed sexual homicides, the research into nonstranger and stranger sexual homicides remains limited. This study therefore aimed to examine whether those who sexually murder nonstrangers differ from those who kill strangers. Data derived from police records, court documents, and published case reports spanning a 31 year period (1988-2018) in mainland China were used to examine the modus operandi of 127 males who committed sexual homicides (45 nonstranger and 82 stranger cases). Relative to nonstranger sexual homicides, stranger sexual homicides were more likely to have been committed by individuals with a previous sexual offense conviction and the victims were more likely to have been single and employed at the time of the offense. Furthering the analysis, a logistic regression found that individuals who targeted strangers were significantly more likely to have committed their homicide at an outdoor location, to have been sexually motivated, and to have used murder weapons that required more physical strength than those who killed nonstranger victims. These findings can be informative to law enforcement agents and security professionals in their investigative processes.


Distribution of High Risk Human Papillomavirus Types in Western Kazakhstan - Retrospective Analysis of PCR Data.
Virtually all cases of cervical cancer are caused by persistent infections with a restricted set of human papillomaviruses (HPV). Cancer of the cervix is the third or even the second most common cancer in women worldwide, more than 85% of the cases occurring in developing countries, such as China and India, including the Republic of Kazakhstan. The purpose was to determine the HPV type distribution to evaluate efficacy of vaccination and adjust cancer prevention strategy in Western Kazakhstan in the future. A retrospective analysis was conducted of data obtained from PCR laboratories in 4 regional centers for the time period covering 12 months, 2013-2014, using AmpliSens® Real-Time PCR kits for HPV testing of 12 genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59). A total of 1,661 persons were HPV tested within 2013-14, but a proprotion examined for 16 and 18 genotypes only (563) was not been included for statistic analysis of distribution and ratio of the most common genotypes. Males accounted for only a small number (N=90 in total). Total number of the HPV-positive appeared to be 26.0%, or 286 of N=1098. Types distribution was as follows: type 16 (10.7%), 39 (5.83%), 51 (5.27%), 31 (4.85%), 56 (4.58%), 18 (3.61%), 59 (2.64%), 58 (2.22%), 35 (1.94%), 33 (1.25%). Overall the HPV infection was highest in 16-29 years old (62.4%) and decreased with age. Total prevalence of the HR-HPVs amongst male population was 21.4% with top five types 16, 18, 39, 51, 31. Trends forcorrelations between Aktau site and type 33 (Cramer's V 0.2029), between Caucasian ethnicity and type 33 (Cramer's V .1716), and between European ethnicities in Uralsk and type 45 (Cramer's V .1752) were found. Of N 563 tested separately for 16 or 18 types, 13.6% were positive. As a whole, the distribution of 16/18 types had a ratio of 3.53:1. Given the vaccine-targeted type 16 is widely spread amongst this regional population, HPV immunization program of adolescent girls 10-13 years should be implemented appropriately.


The LNLS soft X-ray spectroscopy beamline.
The soft X-ray spectroscopy beamline installed at a bending-magnet source at the LNLS is described. The optics are designed to cover energies from 800 to 4000 eV with good efficiency. The focusing element is a gold-coated toroidal mirror with an angle of incidence of 17 mrad. The UHV double-crystal monochromator has three pairs of crystals, Si (111), InSb (111) and beryl (101;0), that can be selected by a sliding movement. The UHV workstation is equipped with an ion gun, an electron gun, an electron analyser, LEED optics, an open channeltron and a photodiode array. This beamline is intended for photoemission, photoabsorption, reflectivity and dichroism experiments.


[Changes in the receptor function of Na,K-ATPase during hypoxia and ischemia].
Na,K-ATPase maintains sodium and potassium homeostasis. It is the only known receptor for cardiotonic steroids such as ouabain. Binding of ouabain to Na,K-ATPase leads to the activation of Src kinase and the subsequent initiation of intracellular signaling pathways, including the induction of apoptosis. Changes in Na,K-ATPase activity is one of the earliest responses to hypoxia and is most critical for cell survival. However, it is not known how the hypoxia affects the functioning of Na,K-ATPase as a receptor. We have shown that, under the conditions of hypoxia and ischemia, ouabain is less toxic for murine fibroblast cells (SC-1 cell line) and ouabain does not cause an increase in the level of reactive oxygen species, which is typically observed at 20% pO2. Under hypoxia, the treatment of cells with ouabain also does not lead to the activation of Na,K-ATPase-associated Src kinase. Thus, at low oxygen content, the receptor function of Na,K-ATPase is altered, and cells become less sensitive to cardiotonic steroids. The decrease in sensitivity to cardiotonic steroids, which is evident at hypoxic conditions, should be taken into account in clinical practice. At the same time, in the presence of ouabain the cells are less sensitive to hypoxia, which indicates that cardiotonic steroids can be protective in acute ischemia.


Restriction fragment length polymorphism analysis of ribosomal DNA intergenic regions is useful for differentiating strains of Trichophyton mentagrophytes.
Twenty isolates of Tricophyton mentagrophytes var. mentagrophytes and 47 isolates of T. mentagrophytes var. interdigitale, identified by morphological characteristics, were screened by restriction fragment length polymorphism (RFLP) analysis of the PCR-amplified internal transcribed spacer (ITS) region of ribosomal DNA (rDNA). Sixty isolates (14 of 20 T. mentagrophytes var. mentagrophytes isolates and 46 of 47 T. mentagrophytes var. interdigitale isolates) shared an identical ITS RFLP profile and were further investigated by using a probe targeted to the rDNA nontranscribed spacer (NTS) region. Polymorphisms were observed in the NTS regions of both T. mentagrophytes var. mentagrophytes and T. mentagrophytes var. interdigitale isolates. Twenty-three individual RFLP patterns (DNA types P-1 to P-12 and A-1 to A-11) were recognized and divided into two groups depending on the presence (P) or absence (A) of a 2.5-kb band, which correlated to a large extent with the morphological variety. Eleven of 14 T. metagrophytes var. mentagrophytes isolates were A types, and all of the 46 T. mentagrophytes var. interdigitale isolates were P types. A majority of strains (23 of 60 [38.3%]) were characterized by one RFLP pattern (pattern P-1), and eight types (P-1 to P-6, P-8, and P-9) accounted for 75% (45 of 60) of all strains, including all of the T. mentagrophytes var. interdigitale isolates. The remaining 15 types were represented by one only isolate and included all of the T. mentagrophytes var. mentagrophytes isolates. We conclude that RFLP analysis of the rDNA NTS region is a valuable technique for differentiation of T. mentagrophytes strains. Furthermore, by use of this method, there appears to be a greater degree of diversity among T. mentagrophytes var. mentagrophytes isolates than among T. mentagrophytes var. interdigitale isolates.


Effect of lizards on spider populations: manipulative reconstruction of a natural experiment.
Which species affect one another, how intensely, and the mechanisms of those effects are crucial data for understanding how ecological communities work. Tropical islands without lizards, the major top predators, have about ten times as dense web spider populations as those with lizards; processes responsible for this effect were experimentally simulated by removing lizards from randomly selected mainland plots. Spider densities in removal plots averaged 2.5 times as high as controls. Spider survival, prey abundance, and prey consumption were all negatively affected by lizards. Contrary to most studies, predator removal caused an increase in the number of spider species.


Compassionate use of Pulmonary Vasodilators in Acute Severe Hypoxic Respiratory Failure due to COVID-19.
There have been over 200 million cases and 4.4 million deaths from COVID-19 worldwide. Despite the lack of robust evidence one potential treatment for COVID-19 associated severe hypoxaemia is inhaled pulmonary vasodilator (IPVD) therapy, using either nitric oxide (iNO) or prostaglandins. We describe the implementation of, and outcomes from, a protocol using IPVDs in a cohort of patients with severe COVID-19 associated respiratory failure receiving maximal conventional support. Prospectively collected data from adult patients with SARS-CoV-2 admitted to the intensive care unit (ICU) at a large teaching hospital were analysed for the period 14th March 2020 - 11th February 2021. An IPVD was considered if the PaO2/FiO2 (PF) ratio was less than 13.3kPa despite maximal conventional therapy. Nitric oxide was commenced at 20ppm and titrated to response. If oxygenation improved Iloprost nebulisers were commenced and iNO weaned. The primary outcome was percentage changes in PF ratio and Alveolar-arterial (A-a) gradient. Fifty-nine patients received IPVD therapy during the study period. The median PF ratio before IPVD therapy was commenced was 11.33kPa (9.93-12.91). Patients receiving an IPVD had a lower PF ratio (14.37 vs. 16.37kPa, p = 0.002) and higher APACHE-II score (17 vs. 13, p = 0.028) at ICU admission. At 72 hours after initiating an IPVD the median improvement in PF ratio was 33.9% (-4.3-84.1). At 72 hours changes in PF ratio (70.8 vs. -4.1%, p < 0.001) and reduction in A-a gradient (44.7 vs. 14.8%, p < 0.001) differed significantly between survivors (n = 33) and non-survivors (n = 26). The response to IPVDs in patients with COVID-19 associated acute hypoxic respiratory failure differed significantly between survivors and non-survivors. Both iNO and prostaglandins may offer therapeutic options for patients with severe refractory hypoxaemia due to COVID-19. The use of inhaled prostaglandins, and iNO where feasible, should be studied in adequately powered prospective randomised trials.


Exercise-induced urinary abnormalities in long-distance runners.
The post-exercise urine samples from 122 long-distance runners showed evident abnormalities upon microscopic examination in 95% of all subjects. Proteinuria, alone or with microscopic hematuria, was frequently found. Macroscopic hematuria was a rare occurrence. The urine samples collected in 30 runners before, immediately after the race, and 6, 12, 24, 36, and 48 h later showed a significant post-race decrease in the osmolarity and a significant increase in gamma-glutamyl transferase and N-acetyl-beta-glucosaminidase enzyme activity. Plasma renin activity and plasma aldosterone, determined before and after the race in nine runners, showed a significant increase in the post-race samples. The abnormal urinary findings disappeared in all cases within 24-36 h. It can be concluded that urinary abnormalities are very common after exercise. These abnormalities are most often of a "renal" origin, probably due to a temporary hemodynamic impairment, partially of glomerular but principally of tubular function.


[Localization of type I, III, IV collagen and fibronectin in benign tumors and epitheliomas of the human breast].
Fibronectin and types I, III and IV collagens were localized by an indirect immunofluorescence technique in 10 fibro-adenomas and 27 mammary adenocarcinomas. In the benign lesions, a densification of a type III collagen meshwork was noted around galactophoric channels. In carcinomas, various patterns of connective tissue proteins distributions were observed depending upon the histological types of lesions. Connective tissue proteins are restricted to the perivascular areas in mucinous carcinomas. Type III collagen is largely distributed in the stroma of poorly differentiated tumors. In differentiated carcinomas, discontinuous linear deposits of type IV collagen or fibronectin are localized at the border of epithelial proliferations. They probably represent the remmants of epithelial basement membrane. In intra- canalar adenocarcinomas, type IV collagen and fibronectin form irregular and discontinuous depositifs . These finding indicate that extensive connective tissue remodelling is observed during neoplastic infiltration. The type of stroma and connective tissue proteins distributed in these epithelial proliferations depends primarily upon the histological type of malignant infiltrating carcinomas.


Characterization of monoclonal antibodies against the second-generation schizonts of Leucocytozoon caulleryi.
Monoclonal antibodies (MAbs), R1 and M5, were established against the second-generation schizont of Leucocytozoon caulleryi (L. caulleryi). Both antibodies reacted to membrane and internal structure proteins of the second-generation schizont by immunofluorescence microscopy. Molecular weight of the second-generation schizont (2GS) antigen was analyzed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. At least 40 protein bands were detected in 2GS antigen by SDS-PAGE under reduced condition and ranged from 10 to 270 kDa. MAb R1 reacted to polypeptides of 150-268 kDa in 2GS antigen, whereas MAb M5 did with that of 66 kDa. Injection with a protein of 2GS antigen fractionated by affinity chromatography using MAbs R1 and M5 protected chickens against challenge with sporozoites of L. caulleryi. These results suggest that MAbs, R1 and M5, recognize 2GS antigen of L caulleryi.


Effect of physiological concentration of urea on the conformation of human serum albumin.
We report that the presence of very low concentrations (<0.1 M) of urea, a widely used chemical denaturant, induces structure formation in the water-soluble globular protein human serum albumin (HSA) at pH 7. We have presented results suggesting an almost 8% and 5% increase in alpha-helix in the presence of 10 mM urea (U) and 20 mM monomethylurea (MMU), respectively. Far and near-UV circular dichroism studies along with tryptophan fluorescence and 1-anilino-8-naphthalenesulphonicacid (ANS) binding support our view. We hypothesize that both U and MMU, at such low concentrations, modify the solvent structure, increase the dielectric constant and consequently increase hydrophobic forces resulting in enhanced alpha-helical content. The implications of these results of the lower urea regime are significant because the physiological blood urea ranges from 2.5 to 7.5 mM.


Mapping the connectome in awake surgery for gliomas: an update.
The traditional principle underlying oncological neurosurgery is to remove a tumor mass displacing the brain in order to increase survival. Recently, advances in connectomics enabled an improved understanding of cerebral processing, and led to a paradigmatic shift in tumor surgery based upon interactions between neurooncology and cognitive neurosciences. First, glioma is not a focal tumor invaginated within the parenchyma but a diffuse neoplastic disease migrating in the brain. This concept resulted in a new surgical ideology, i.e., to maximally resect the invaded nervous system on the condition that eloquent neural networks are spared. Second, this led to determine what structures are crucial to preserve the quality of life (QoL) versus those that can be compensated by means of neuroplasticity. Because limitations of functional remodelling are mainly represented by the subcortical connectivity, mapping the connectome during surgery is a priority. Neurosurgeons have to switch from an image-guided surgery to a functional mapping-guided resection, namely, from a technological guidance into the operating theater to a philosophy based on the investigation of the dynamics of delocalized neural circuits throughout resection. Indeed, awake mapping with real-time monitoring of sensorimotor, visuospatial, language, executive and behavioral functions allowed an optimization of the onco-functional balance. Third, surgery should not be seen in isolation, but integrated in a global multistep therapeutic management, especially in low-grade gliomas, opening the window to repeat resections thanks to the potential of remapping over years. Such a "cognitive neurooncological surgery" which aims to improve both QoL and survival must become a "connectomal neurosurgery".


Total synthesis of chaetoquadrins A-C.
The first total synthesis of the monoamine oxidase inhibitors chaetoquadrins A-C has been accomplished. Key steps in the synthesis include an aromatic Claisen rearrangement, asymmetric boron aldol reaction and acid-mediated spiroketalization. Comparison of spectral data for the synthetic spiroketals confirmed the proposed structure for these natural products.


Minichromosome maintenance protein 7 regulates phagocytosis in kuruma shrimp Marsupenaeus japonicas against white spot syndrome virus.
Minichromosome maintenance protein (MCM7) belongs to the MCM protein family and participates in the MCM complex by playing a role in the cell replication cycle and chromosome initiation of eukaryotes. Previously, we found that several genes, including MCM7, were over-expressed in Drosophila melanogaster after white spot syndrome virus (WSSV) infection. In this study, we aimed to further research the MCM7 of kuruma shrimp, Marsupenaeus japonicus (mjMCM7) and determine its role in the innate immune system. To this end, we cloned the entire 2307-bp mjMCM7 sequence, including a 1974-bp open reading frame (ORF) encoding a 658-aa-long protein. Real-time PCR showed that the gene was primarily expressed in the hemolymph and hepatopancreas and over-expressed in shrimp challenged with WSSV. Gene function study was carried out by knocking down the expression of MCM7 using small interference RNA (siRNA). The results revealed that β-actin, hemocyanin, prophenoloxidase (proPO) and tumor necrosis factor-α (TNF-α) were up-regulated while the cytoskeleton proteins such as myosin and Rho were significantly down-regulated at 24 h after treatment. The results indicate a possible relationship between mjMCM7 and the innate immune system, and suggest that mjMCM7 may play a role in phagocytosis. After WSSV challenge, WSSV copies and mortality count were both higher in the MCM7-siRNA-treated groups at 60 h after treatment, and the mortality count approached that of the control groups over time. The phagocytosis rate was significantly lower in the MCM7-siRNA-treated group than in the WSSV group. The findings of this study confirm that mjMCM7 positively regulates phagocytosis and plays an important role against WSSV. These results could help researchers to further understand the function of the MCM7 protein and reveal its potential role in the innate immunity of invertebrates.


The effect of L-thyroxine treatment on ventricular dysfunction and pulmonary arterial stiffness in patients with subclinical hypothyroidism.
In our study, we aimed at evaluating the change in biventricular functions and pulmonary arterial stiffness (PAS) in patients with subclinical hypothyroidism (SH) in whom euthyroidism was achieved with L-thyroxine therapy. 70 SH patients and 75 healthy volunteers were included in our study consecutively. Baseline demographic and echocardiographic data of the participants were recorded. The data obtained in the control evaluation 6 months after the euthyroidism were achieved in the SH group patients started on L-thyroxine treatment and then compared with the baseline measurements. The mean age of patients in the SH group was 44.1 ± 9.4 years and 47.1% were women. Euthyroidism in SH patients was achieved with a mean daily L-thyroxine treatment of 59 µg/day for a mean of 16.1 ± 4.5 weeks. Positive changes in metabolic and hormonal profiles were achieved after L-thyroxine treatment in SH patients. It was determined that left ventricular and right ventricular isovolumetric relaxation and myocardial performance index were higher in SH patients compared to the control group, and these measurements were observed to decrease significantly with L-thyroxine treatment (p < 0.05 for each). While PAS was 16.9 ± 3.1 kHz/ms in the control group, it was 25.2 ± 5.3 kHz/ms in the SH group (p < 0.05). After L-thyroxine treatment, PAS measurements decreased to 17.2 ± 3.2 kHz/ms (p < 0.05) in the SH group and showed a positive change. Thyroid-stimulating hormone (TSH) change (Δ TSH) with Δ E/A ratio (r: -0.407, p < 0.001), right ventricular myocardial performance index (Δ RV MPI) change (r: 0.404, p < 0.001) and PAS change (Δ PAS) (r: 0.458, p < 0.001) found to be correlated. SH is associated with dysfunction in the biventricular and pulmonary vascular bed. Biventricular functions and PAS change positively in SH patients with L-thyroxine treatment.


Random Deep Belief Networks for Recognizing Emotions from Speech Signals.
Now the human emotions can be recognized from speech signals using machine learning methods; however, they are challenged by the lower recognition accuracies in real applications due to lack of the rich representation ability. Deep belief networks (DBN) can automatically discover the multiple levels of representations in speech signals. To make full of its advantages, this paper presents an ensemble of random deep belief networks (RDBN) method for speech emotion recognition. It firstly extracts the low level features of the input speech signal and then applies them to construct lots of random subspaces. Each random subspace is then provided for DBN to yield the higher level features as the input of the classifier to output an emotion label. All outputted emotion labels are then fused through the majority voting to decide the final emotion label for the input speech signal. The conducted experimental results on benchmark speech emotion databases show that RDBN has better accuracy than the compared methods for speech emotion recognition.


Inverse horse-shoe technique for the phacoemulsification of posterior polar cataract.
To study a new technique of controlled hydrodelineation followed by viscodelineation and viscodissection during phacoemulsification in eyes with posterior polar cataracts and to report its effectiveness in preserving the posterior capsule. Prospective interventional study. Twenty-eight eyes of 22 patients with posterior polar cataracts. All patients underwent phacoemulsification under topical anaesthesia with controlled hydrodelineation, viscodelineation, and viscodissection with minimal stress on the posterior capsule. Hydrodissection was not done. The preoperative complications and visual outcome were recorded. The mean follow-up time was 8 months (range 2-24 months). Posterior capsule rupture occurred only in 2 eyes (7.1%); neither of the 2 had any vitreous prolapse, so anterior vitrectomy was not required. Mean visual acuity improved significantly after surgery (p = 0.0001, paired t test). The causes of the low postoperative visual acuity were amblyopia in 3 eyes (10.7%) and age-related macular degeneration in 1 (3.6%). This inverse horse-shoe technique of controlled viscodelineation and viscodissection markedly reduced the risk of posterior capsule rupture. Moreover, if it occurred, the anterior vitreous face remained intact, so the IOL could be implanted in the sulcus without resorting to anterior vitrectomy.


Ultrafast DNA Sensors with DNA Framework-Bridged Hybridization Reactions.
Intracellular DNA-based hybridization reactions generally occur under tension rather than in free states, which are spatiotemporally controlled in physiological conditions. However, how nanomechanical forces affect DNA hybridization efficiencies in in-vitro DNA assays, for example, biosensors or biochips, remains largely elusive. Here, we design DNA framework-based nanomechanical handles that can control the stretching states of DNA molecules. Using a pair of tetrahedral DNA framework (TDF) nanostructured handles, we develop bridge DNA sensors that can capture target DNA with ultrafast speed and high efficiency. We find that the rigid TDF handles bind two ends of a single-stranded DNA (ssDNA) and hold it in a stretched state, with an apparent stretching length comparable to its counterpart of double-stranded DNA (dsDNA) via atomic force microscopy measurement. The DNA stretching effect of ssDNA is then monitored using single-molecule fluorescence energy transfer (FRET), resulting in decreased FRET efficiency in the stretched ssDNA. By controlling the stretching state of ssDNA, we obtained significantly improved hybridization kinetics (within 1 min) and hybridization efficiency (∼98%) under the target concentration of 500 nM. The bridge DNA sensors demonstrated high sensitivity (1 fM), high specificity (single mismatch mutation discrimination), and high selectivity (suitable for the detection in serum and blood) under the target concentration of 10 nM. Controlling the stretching state of ssDNA shows great potential in biosensors, bioimaging, and biochips applications.


Maternal serum alpha-fetoprotein levels in pregnancies complicated by diabetes: implications for screening programs.
Maternal serum alpha-fetoprotein may be reduced in diabetic pregnancies, but the association with elevated glycosylated hemoglobin has been controversial. We tested the hypothesis that reductions in maternal serum alpha-fetoprotein may reflect the same phenomena that can also impair normal rates of embryo growth in the presence of poorly compensated maternal diabetes. If so, associations would be expected among maternal serum alpha-fetoprotein, embryo rates of growth, and levels of glycosylated hemoglobin reflective of regulation of maternal diabetes during the period of organogenesis. We found maternal serum alpha-fetoprotein levels in 93 pregnant patients with diabetes to be negatively associated with the earliest (4 to 12 weeks) glycosylated hemoglobin determinations. At glycosylated hemoglobin values greater than 9.6% (which approximates the upper quartile), all maternal serum alpha-fetoprotein values fell below the median for patients without diabetes (below 0.8 multiple of the median after weight adjustment). Moreover, there was a trend for pregnancies with lower maternal serum alpha-fetoprotein levels and higher glycosylated hemoglobin values to also demonstrate early fetal growth delay as measured by ultrasonography.


Identification and profiling of circulating antigens by screening with the sera from schistosomiasis japonica patients.
Schistosomiasis is a chronic disease caused by trematode flatworms of the genus Schistosoma. The disease remains a serious public health problem in endemic countries and affects at least 207 million people worldwide. A definite diagnosis of the disease plays a key role in the control of schistosomiasis. The detection of schistosome circulating antigens (CAs) is an effective approach to discriminate between previous exposure and current infection. Different methods have been investigated for detecting the CAs. However, the components of the schistosome CAs remain unclear. In this study, we analyzed the CAs in sera of patients infected with Schistosoma japonicum. The parasites were collected from the infected rabbits for preparing the adult worm antigen (AWA). The hyline hens were immunized subcutaneously with AWA to produce anti-AWA IgY. The IgY was purified by water-dilution and ammonium sulfate precipitation method and identified by ELISA and Western blotting. After purification and characterization, IgY was immobilized onto the resin as a capture antibody. The circulating antigens were immune-precipitated from patients' serum samples by direct immunoprecipitation. The precipitated proteins were separated by one-dimensional electrophoresis and analyzed by LC-MS/MS. Firstly, the IgY against AWA was produced from the eggs of immunized hens by AWA, which gave a titer of 1:12800. The purified IgY was used as the capture antibody to enrich the CAs in sera of S. japonicum infected patients through immunoprecipitation. The CAs were determined by LC-MS/MS. There were four proteins, including protein BUD31 homolog, ribonuclease, SJCHGC06971 protein and SJCHGC04754 protein, which were identified among the CAs. We developed a novel method based on IgY for identification and profiling CAs in sera of S. japonicum infected patients. Four new CAs were identified and have potential value for further development of an antigen assay.


On Quality Thresholds for the Clustering of Molecular Structures.
It has been recently suggested that diametral (so-called quality) similarity thresholds are superior to radial ones for the clustering of molecular three-dimensional structures (González-Alemán et al., 2020). The argument has been made for two clustering algorithms available in various software packages for the analysis of molecular structures from ensembles generated by computer simulations, attributed to Daura et al. (1999) (radial threshold) and Heyer et al. (1999) (diametral threshold). Here, we compare these two algorithms using the root-mean-squared difference (rmsd) between the Cartesian coordinates of selected atoms as pairwise similarity metric. We discuss formally the relation between these two methods and illustrate their behavior with two examples, a set of points in two dimensions and the coordinates of the tau polypeptide along a trajectory extracted from a replica-exchange molecular-dynamics simulation (Shea and Levine, 2016). We show that the two methods produce equally sized clusters as long as adequate choices are made for the respective thresholds. The real issue is not whether the threshold is radial or diametral but how to choose in either case a threshold value that is physically meaningful. We will argue that, when clustering molecular structures with the rmsd as a metric, the simplest best guess for a threshold is actually radial in nature.


Production of cyanophycin, a suitable source for the biodegradable polymer polyaspartate, in transgenic plants.
The production of biodegradable polymers in transgenic plants in order to replace petrochemical compounds is an important challenge for plant biotechnology. Polyaspartate, a biodegradable substitute for polycarboxylates, is the backbone of the cyanobacterial storage material cyanophycin. Cyanophycin, a copolymer of l-aspartic acid and l-arginine, is produced via non-ribosomal polypeptide biosynthesis by the enzyme cyanophycin synthetase. A gene from Thermosynechococcus elongatus BP-1 encoding cyanophycin synthetase has been expressed constitutively in tobacco and potato. The presence of the transgene-encoded messenger RNA (mRNA) correlated with changes in leaf morphology and decelerated growth. Such transgenic plants were found to produce up to 1.1% dry weight of a polymer with cyanophycin-like properties. Aggregated material, able to bind a specific cyanophycin antibody, was detected in the cytoplasm and the nucleus of the transgenic plants.


Mechanisms underlying helminth- induced Th2 polarization: default, negative or positive pathways?
Since the initial description of Th1 and Th2 subsets in the 1980s, there has been enormous progress in identifying the molecular events and the transcriptional factors that regulate Th differentiation in response to a specific stimulus (e.g. antigen dose, co-receptors, cytokines). Although TCR cross-linking and engagement of co-stimulatory molecules are necessary for activation of CD4+ lymphocytes, these two events do not appear in themselves to explain Th1/Th2 commitment. Among pathogens, helminths are the main examples of Th2-cell inducers in both humans and experimental models. This review will focus on our recent findings on the requirements for Th2 polarization by the parasitic trematode Schistosoma mansoni. In particular, we will address the ongoing controversy as to whether Th2 development depends on positive vs. negative vs. the absence of signals from antigen-presenting cells. In addition, we will discuss the similarities between the pathways involved in parasite- and allergen-induced Th2 differentiation.


Modified activities of macrophages' deubiquitinating enzymes after Francisella infection.
Francisella tularensis influences several host molecular/signaling pathways during infection. Ubiquitination and deubiquitination are among the most important regulatory mechanisms and respectively occur through attachment or removal of the ubiquitin molecule. The process is necessary not only to mark molecules for degradation, but also, for example, to the activation of signaling pathways leading to pro-inflammatory host response. Many intracellular pathogens, including Francisella tularensis, have evolved mechanisms of modifying such host immune responses to escape degradation. Here, we describe that F. tularensis interferes with the host's ubiquitination system. We show increased total activity of deubiquitinating enzymes (DUBs) in human macrophages after infection, while confirm reduced enzymatic activities of two specific DUBs (USP10 and UCH-L5), and demonstrate increased activity of USP25. We further reveal the enrichment of these three enzymes in exosomes derived from F. tularensis-infected cells. The obtained results show the regulatory effect on ubiquitination mechanism in macrophages during F. tularensis infection.


Production of superoxide through NADH oxidase in thick ascending limb of Henle's loop in rat kidney.
We recently reported that NADH oxidase is one of the major enzymes responsible for superoxide (O(2)(-)*) production in the rat kidney. However, the functional significance of NADH oxidase-mediated O. production and the mechanisms regulating this enzyme activity are poorly understood. Using fluorescence microscopic imaging analysis, the present study demonstrated that thick ascending limbs of Henle's loop (TALHs) exhibited red fluorescence when incubated with dihydroethidium (DHE), suggesting that O(2)(-)* is produced in this tubular segment. Compared with other nephron segments, TALHs from both renal cortex and medulla showed the highest fluorescence intensity. By incubating cortical TALHs (cTALHs) with the substrates of NADH oxidase, xanthine oxidase, nitric oxide synthase, arachidonic acid-metabolizing enzymes, and intramitochondrial oxidases, NADH oxidase was found to be one of the most important enzymes for O(2)(-)* production in this tubular segment. The NADH oxidase inhibitor diphenyleneiodonium (DPI; 100 microM) completely blocked NADH-induced O(2)(-)* production in cTALHs. Exposure of cTALHs to low PO(2) (5-10 Torr) significantly increased O(2)(-)* production regardless of the absence or presence of NADH. Furthermore, angiotensin II (100 nM) increased NADH oxidase activity by 32%, which was completely blocked by DPI. These results suggest that NADH oxidase is a major enzyme responsible for O(2)(-)* production in the TALHs and that the production of O(2)(-)* via NADH oxidase may be regulated by renal tissue oxygenation and circulating hormones.


Renal function in patients with β-thalassaemia major: a long-term follow-up study.
Little information is available about the kidney's involvement in patients with β-thalassaemia major (TM). In particular, there are no studies reporting the outcome of renal function over time. In this retrospective study, we evaluated the changes in estimated glomerular filtration rate (eGFR) in 81 adult patients with TM followed for 10 years. Only patients who had an eGFR of >90 mL/min/1.73 m(2) at presentation were admitted to the study. All patients were regularly followed for at least 10 years. At 10 years, 66 patients showed a mild decline in eGFR that remained, however, within a normal range (from 119.9 to 113.6 mL/min/1.73 m(2), P = 0.636). In the remaining 15 patients (18.5%), eGFR decreased to <90 mL/min (from 98.1 to 78.2 mL/min/1.73 m(2); P = 0.004). The repeated-measures models showed that the decline in eGFR over time was significantly higher (P = 0.0068) in patients with baseline phosphaturia >1000 mg/24 h (P = 0.0068), while eGFR tended to decline more rapidly in patients with baseline uricuria >700 mg/24 h than in those with lower uricuria (P = 0.0783). Univariate Cox's proportional regression models showed that abnormal levels of calcaemia were associated with the risk of kidney damage [hazard ratio (HR) 0.30, 95% confidence interval 0.09-0.97 for calcaemia 8.4-10.2 mg/dL versus HR not estimable for calcaemia <8.4 or >10.2 mg/dL]. In most adults with TM, the eGFR tends to remain within a normal range after 10 years. However, patients with elevated phosphaturia, elevated uricuria and/or abnormal levels of calcaemia show a significant decline in eGFR over time, suggesting that tubular damage acquired in childhood caused by either TM or its treatment may eventually result in abnormal eGFR. Further studies in a larger cohort of TM patients are needed to further elucidate the long-term impact of TM on renal function.


The effect of miR-579 on the PI3K/AKT pathway in human glioblastoma PTEN mutant cell lines.
Glioblastoma multiform (GBM) is a type of aggressive brain cancer with limited success in standard treatment. MicroRNAs are one of the most beneficial tools for diagnosis, prognosis, and treatment of cancer. This study aimed to investigate the effect of miR-579 on cellular behaviors and expression of PI3K/AKT signaling pathway in GBM cell lines. In the present study, miR-579 was overexpressed in U251 and A-172 cell lines by using lentil vector, and its effect on cellular behavior such as proliferation and migration was investigated by the cell cycle, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Annexin V, colony formation, Transwell and wound healing assays. MiR-579 predicted target genes (AKT1, Rheb, PDK1, and a few others) were also evaluated by real-time polymerase chain reaction or luciferase assay and Western blot analysis. Our results represented that overexpression of miR-579 could inhibit proliferation, migration, cell cycle and also promoted the apoptosis of GBM cell lines. The luciferase reporter assay showed miR-579 directly targets the 3 UTR of mTOR, Rheb, and PDK1 and repressed their expressions. Furthermore, the Western blot analysis showed that miR-579 could downregulate the AKT1 and Rheb protein expression. Overall, our findings propose that miR-579 functions as a novel tumor suppressor gene in GBM by regulating the PI3K/AKT signaling pathway and may serve as a therapeutic target for clinical therapy of glioblastoma multiform.


Effector T cell analysis of melanoma tumor-infiltrating lymphocyte cultures using HLA-ABC semimatched melanoma cell lines.
The generation of T cells with specific reactivity against tumor-associated antigens is prerequisite for adoptive transfer therapy. Melanoma-specific lymphocyte cultures can be established from tumor-infiltrating lymphocytes (TILs) by in vitro culture with high levels of interleukin-2. In this report, we present TIL data originating from 728 attempted cultures from 33 consecutive melanoma biopsy specimens originating from 30 patients. Cultures were analyzed for the presence of interferon gamma (IFNgamma)-producing cells upon stimulation with a panel of HLA-ABC semimatched melanoma cell lines. We sought to find whether such cell lines could be used to analyze TIL reactivity. Cell lines were used as stimulators to circumvent the need for autologous primary tumor cells. Melanoma-reactive cultures were identified by flow cytometry in 25 of the 30 patients. Four hundred forty-four of 728 (60.9%) cultures contained TILs at the end of experiment. Ninety-one of 318 cultures (28.6%) contained IFNgamma-producing cells after stimulation. In HLA-A*0201 patients IFNgamma analysis was complemented with melanoma-specific tetramer staining. All but one HLA-A*0201 patient had MART-1/Melan-A27-35-directed TILs, with frequencies ranging from 0.1% to 90% of CD8 cells. In addition, tetramer analysis also identified TILs directed against gp100, Tyrosinase, and Her2Neu. Tumor material was collected via needle biopsy in 16 cases and surgery in 18 cases. Overall, surgical material generated more cultures positive for T cells. The described methods are efficient in characterizing clinically relevant melanoma-reactive TILs.


Sialic acid containing substrates as intracellular calcium receptors involved in transmitter release.
The possible function of sialic acid containing substrates in the synaptic terminals was studied by intracellular injection of ruthenium red (RuR) and neuraminidase (NAA). When injected into cholinergic and non cholinergic neurons of Aplysia, NAA and RuR, known to have similar molecular targets, blocked synaptic transmission. The subcellular sites of action of these molecules were investigated. 1. ACh receptors are not affected by RuR. 2. An intracellular site of action of RuR is likely, as less was necessary to block transmission when injected into the presynaptic cell than when applied in the bath. 3. Ca++ channels are not blocked by RuR or neuraminidase. 4. Transmission block is not due to an axonal conduction block, since strong somatic depolarization is not able to induce transmitter release in the presence of RuR. 5. Biochemical analysis of pools of 3H ACh was performed in controls and after injection of RuR. RuR appeared to significantly increase the cytoplasmic ACh pool without any change of the vesicular ACh pool. 6. Quantal release of transmitter was analysed with a current fluctuation method. There were no changes in the amplitude or decay time (tau) of miniataure postsynaptic potentials, but a decrease in the quantal content of the synapse was found.


Mapping lubricin in canine musculoskeletal tissues.
Lubricin, also known as superficial zone protein or PRG4, has many distinct biological functions, including lubrication, antiadhesion, and as a regulator of cell growth. This study investigated lubricin in canine musculoskeletal tissues using RT-PCR and immunohistochemistry. One or more variants were noted in canine flexor digitorum profundus (FDP) tendon, Achilles tendon, patellar tendon, A2 pulley, anterior cruciate ligament (ACL), knee lateral collateral ligament (LCL), articular cartilage, meniscus, muscle, and skin. We found 6 N-terminal lubricin splicing variants. The variants with larger sizes were identified in FDP tendon, ACL, LCL, A2 pulley, and cartilage. Lubricin was distributed both on the tissue surfaces and at the interface of fiber bundles within tissues, but this distribution varied by tissue type. We conclude that lubricin is present in many tissues; variations in splicing and physical distribution suggest that the variants of lubricin may play different roles in different locations.


Benign metastasizing leiomyomatosis: case report and review.
The authors report an interesting case of a minimally symptomatic 23-year-old African American woman who was found to have extensive diffuse reticulonodular opacities of the lungs on a routine chest radiograph. She had a hysterectomy 5 years previously for multiple leiomyomas of the uterus. She had no history of any prior exposure to dusts or toxins. Collagen vasculitides and bacterial, mycobacterial, and fungal infectious causes were excluded through standard testing, and a bronchoscopic lung biopsy was nonspecific. An open lung biopsy revealed multiple nodules of proliferating smooth muscle cells intermixed with irregular areas of epithelial-lined spaces. Histologically, the muscle cells appear benign with a very low mitotic rate, and the pathologic findings were consistent with benign metastasizing leiomyomatosis (BML). Staining for estrogen and progesterone receptors, actin, and c-kit were performed. This case and the review of the medical literature support the concept that BML originates from an antecedent leiomyoma of the uterus in virtually all cases with rare exceptions. It appears that tumor metastasizes to lungs or other extrauterine tissues via hematogenous spread. However, the origin of the tumor remains controversial. BML is a rare entity, with only a handful of reports in the medical literature. The authors report an interesting case of BML in a 23-year-old patient who, to their knowledge, is the youngest such patient described and who, at 13 years, has the longest period of clinical follow-up. In this article, the authors review the pathogenesis, cytogenetics, histologic markers, and management options of this rare entity.


A first principles study of thiol-capped Au nanoparticles: structural, electronic, and magnetic properties as a function of thiol coverage.
We have studied the stability of thiolated Au38 nanoparticles (NPs) via density functional theory based calculations varying the coverage from 0 up to 32 molecules. Three different initial core arrangements were considered for the cluster, spherical, tubular, and bi-icosahedral, while thiol groups were attached to the cluster via the sulfur atom either as single molecules or forming more complex staple motifs. After molecular dynamics runs several metastable configurations are found at each coverage thus allowing to analyze the properties of the NPs in the form of ensemble averages. In particular, we address the structural and electronic properties as a function of the number of thiols. The study emphasizes the strong influence of the core structure on the stability of the NPs, and its interplay with the thiol coverage and adsorption geometries. The magnetic properties of the NPs have also been explored via spin-polarized calculations including spin-orbit coupling. No evidence for the existence of a robust intrinsic ferromagnetism is found in any of the structures.


Giving Time Purpose: The Synechococcus elongatus Clock in a Broader Network Context.
Early research on the cyanobacterial clock focused on characterizing the genes needed to keep, entrain, and convey time within the cell. As the scope of assays used in molecular genetics has expanded to capture systems-level properties (e.g., RNA-seq, ChIP-seq, metabolomics, high-throughput screening of genetic variants), so has our understanding of how the clock fits within and influences a broader cellular context. Here we review the work that has established a global perspective of the clock, with a focus on (a) an emerging network-centric view of clock architecture, (b) mechanistic insights into how temporal and environmental cues are transmitted and integrated within this network,