[The Emerging Interest in Breast Implant Illness and its impact on Patient Behavior].
Breast implant illness (BII) is a loosely defined term for a collection of non-specific systemic symptoms that are hypothesised to be associated with breast implants. BII symptoms include fatigue, hair loss, rashes, chronic pain, and others. However, conclusive evidence for a causal relationship between silicone implants and BII remains lacking. In the light of recent findings that textured implants can, in rare cases, lead to breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), a potential link between breast implants and BII is conceivable and justifies further investigation. We observe a growing number of patients seeking consultation and treatment for systemic symptoms related to breast implants, which is reflected in increasing interest in literature and social media. The aim of this work was to investigate the growing interest in BII. We now describe the clinical features of a patient who suffers from symptoms that are consistent with BII and contextualise clinical presentation in a review of literature and google trend analysis.


The death of King Charles XII--the forensic verdict.
King Charles XII of Sweden was killed in 1718 during his siege of the Danish fortress of Fredriksten. For 276 years, it remained an open question whether the lethal bullet came from the enemy or from a Swedish assassin. Now, a treatise published by a Swedish historian finally proves that the King's death was a case of political murder. Ballistic circumstances and the Danish ammunition then available are incompatible with a random shot from enemy quarters. Major-general Carl Cronstedt possessed the expertise needed to make an assassination look like a war casualty. It appears that the King was shot with a makeshift jacketed bullet long before jacketed bullets came into common use.


Determination of enantiomeric purity of ephedrine and pseudoephedrine by high-performance liquid chromatography with dual optical rotation/UV absorbance detection.
A reversed-phase high-performance liquid chromatography (HPLC) method with dual optical rotation/UV absorbance detection has been developed for the determination of enantiomeric purity of ephedrine hydrochloride and pseudoephedrine hydrochloride using an achiral column. The method gave a correlation coefficient of 0.9997 for the plot of log(optical rotation response) versus log (concentration) over the range of 0.06-10 mg ml(-1) of (+)-ephedrine hydrochloride (20 microliters injection). The limit of detection was 1.0 micrograms. Enantiomeric purity is shown to be most readily determined by measuring optical rotation, alpha, and absorbance, A, responses for standard and unknown samples, and using the equation (alpha/A)u/(alpha/A)s = (2xu - 1)/(2xs - 1), where x is the mole fraction of one of the enantiomers and subscripts s and u refer to standard and unknown, respectively. In blind trials using unknown mixtures of (+)- and (+/-)-ephedrine hydrochloride and a (+)-ephedrine hydrochloride standard, enantiomeric purities were determined to +/- 0.4% (95% confidence level) with five or six replicate 50 micrograms injections. The method has also been applied to the determination of the enantiomer mole fraction of (+)-pseudoephedrine hydrochloride in a cough linctus, giving xu = 0.99 +/- 0.01 with seven replicate injections of 20-fold diluted linctus samples containing 7.5 micrograms of the chiral compound being assayed. Unlike conventional polarimetry, the method does not require chemically-pure samples and can be orders of magnitude more economical in material.


Insulin resistance and adiposity in relation to serum β-carotene levels.
To determine the effects of placebo vs an encapsulated supplement of fruit and vegetable juice concentrate (FVJC) on serum β-carotene levels, insulin resistance, adiposity, and subclinical inflammation in boys. Thirty age-matched prepubertal boys (9 lean and 21 overweight (OW); age range, 6-10 years) were studied. All participants received nutrition counseling and were randomized to receive FVJC or placebo capsules for 6 months. Total cholesterol, triglycerides, lipid corrected β-carotene, serum retinol, glucose, insulin, retinol binding protein-4, leptin, adiponectin, leptin-to-adiponectin ratio, high-sensitivity C-reactive protein, and interleukin-6 were measured before and after the 6-month intervention. Homeostasis model assessment-insulin resistance (HOMA-IR), acute insulin response to intravenous glucose, along with abdominal fat mass (dual-energy x-ray absorptiometry) were also determined. Baseline β-carotene concentrations correlated inversely with HOMA-IR, leptin-to-adiponectin ratio, and abdominal fat mass (P ≤ .01). FVJC intake increased β-carotene concentrations (P ≤ .001) but did not influence retinol or retinol binding protein-4. Retinol insufficiency <1.047 μM was present in 18% of the entire cohort at baseline and in 37% at 6 months. HOMA-IR decreased after supplementation in the OW cohort, when adjusted for percent weight change (P = .014). The percent change in abdominal fat mass increased in the placebo group and decreased in the FVJC group (P = .029). A 6-month supplementation with FVJC in the presence of nutritional counseling was associated with an increase in serum β-carotene concentrations and a reduction in adiposity in conjunction with an improvement in insulin resistance in OW boys.


The targeted co-delivery of DNA and doxorubicin to tumor cells via multifunctional PEI-PEG based nanoparticles.
Co-delivery of nucleic acids and chemotherapeutics has a potential to efficaciously treat human diseases via their synergetic effects. Activable therapeutic tools at the nanoscale are suitable platforms for combination therapy. In this study, we have developed a multifunctional nanoscaled delivery system simultaneously integrated with passive and active tumor targeting, cell membrane translocation, pH-triggered drug release and co-delivery strategies. Poly (ethyleneimine) (PEI)-polyethylene glycol (PEG) copolymer was synthesized with coupling TAT to the distal end of PEG for membrane activity. The functional amino group of PEI was used to chemically conjugate doxorubicin (DOX) via a pH-sensitive hydrazone linkage. Meanwhile, the cationic PEI backbone could complex DNA to DOX loaded-TAT modified polyion complex micelles (NPIC). To achieve double targeting effect to tumor vascular endothelial cells and tumor cells either by active or passive targeting, a virus mimetic shell functioned with NGR was conferred by electrostatic adsorption of sulfamerazine (SA)-PEG-NGR on the surface of NPIC to obtain DOX loaded targeted PIC micelles (TPIC). The multifunctional nanoscaled delivery system was established to comprehensively improve the efficacy of cancer therapy through the synergistic effect of gene therapy with chemotherapy. Consequently, the system was shown to be a promising carrier for the co-delivery of DNA and DOX, leading to the efficiency of gene transfection and anti-tumor activity in vitro.


Occurrence and risk assessment of fullerene colloidal nanoparticles by ultrasonic-assisted dispersive liquid-liquid extraction and high-performance liquid chromatography in surface waters.
This paper presents a developed analytical technique for risk assessment of colloidal fullerene in surface waters by ultrasonic-assisted dispersive liquid-liquid extraction (UADLLE) and high-performance liquid chromatography ultraviolet-visible detector (HPLC-UV). Fullerene colloidal nanoparticles were synthesised and characterized by high-resolution transmission electron microscopy (HRTEM) and ultraviolet-visible spectroscopy (UV-Vis). Ultrasonication step, disperser solvent, and sodium chloride salt enhance the surface area of fullerene derivative aggregates for better contact and lowers the solubility of fullerene derivative to the aqueous solution, respectively promoting mass transfer of fullerene from aqueous into the organic phase. Several extraction parameters were optimized, and the optimal conditions were established: 5 mL toluene as extraction solvent (2 cycles); 200 mL water sample; 1% sodium chloride salt; 15 min ultrasonication, and 400 μL methanol as disperser solvent. The mean absolute recoveries established in drinking water, wastewater, and river water were 117%, 103%, and 93%, respectively. The proposed analytical technique was linear in the ranges between 0.25 μg L-1 - 250 μg L-1 with an r-squared of 0.9958. The limit of detection (LOD) determined from the signal-to-noise ratio of 3 was 0.11 μg L-1 and the limit of quantification (LOQ) from a signal-to-noise ratio of 10 was 0.38 μg L-1. The precision ranges from 2% to 11% and accuracy percent error ranged from 7%-14% for spiked concentration levels of 0.25 μg L-1, 50 μg L-1, and 250 μg L-1. The measured environmental concentration (MECs) for the fullerene in water samples ranged from not detected to 10.54 μg L-1 and ecological assessment showed the concentration level of the fullerene can pose risk. Overall, according to the author's knowledge, this is the earlier work on the occurrence and risk assessment of fullerene colloidal nanoparticles (C61-PCBM) in potable and wastewater on the African continent.


Mathematical assessment of the impact of human-antibodies on sporogony during the within-mosquito dynamics of Plasmodium falciparum parasites.
We develop and analyze a deterministic ordinary differential equation mathematical model for the within-mosquito dynamics of the Plasmodium falciparum malaria parasite. Our model takes into account the action and effect of blood resident human-antibodies, ingested by the mosquito during a blood meal from humans, in inhibiting gamete fertilization. The model also captures subsequent developmental processes that lead to the different forms of the parasite within the mosquito. Continuous functions are used to model the switching transition from oocyst to sporozoites as well as human antibody density variations within the mosquito gut are proposed and used. In sum, our model integrates the developmental stages of the parasite within the mosquito such as gametogenesis, fertilization and sporogenesis culminating in the formation of sporozoites. Quantitative and qualitative analyses including a sensitivity analysis for influential parameters are performed. We quantify the average sporozoite load produced at the end of the within-mosquito malaria parasite's developmental stages. Our analysis shows that an increase in the efficiency of the ingested human antibodies in inhibiting fertilization within the mosquito's gut results in lowering the density of oocysts and hence sporozoites that are eventually produced by each mosquito vector. So, it is possible to control and limit oocysts development and hence sporozoites development within a mosquito by boosting the efficiency of antibodies as a pathway to the development of transmission-blocking vaccines which could potentially reduce oocysts prevalence among mosquitoes and hence reduce the transmission potential from mosquitoes to human.


Effect of FSH receptor-binding inhibitor-8 on FSH-mediated granulosa cell signaling and proliferation.
Follicle-stimulating hormone is important for mammalian reproduction. It acts through specific receptors located on the plasma membrane of granulosa cells in ovaries and Sertoli cells in testes. The binding of follicle-stimulating hormone to its receptor activates intracytoplasmic signaling pathways leading to steroidogenesis. These steroids in turn regulate the follicle-stimulating hormone action from the anterior pituitary through exerting negative feedback effect. In addition to steroids, non-steroidal factors secreted by the ovaries are believed to modulate follicle-stimulating hormone action through autocrine/paracrine mode. One such low molecular weight peptide referred to as follicle-stimulating hormone receptor-binding inhibitor-8 purified from human follicular fluid has been extensively studied. Follicle-stimulating hormone receptor-binding inhibitor-8 has been shown to inhibit binding of follicle-stimulating hormone to its receptor. The present article describes the effect of follicle-stimulating hormone receptor-binding inhibitor-8 on follicle-stimulating hormone-induced signaling in rat granulosa cells. Follicle-stimulating hormone receptor-binding inhibitor-8 inhibited the follicle-stimulating hormone-induced cAMP, and the effect was observed to be mediated through the protein kinase A. Further, an inhibitory effect of follicle-stimulating hormone receptor-binding inhibitor-8 on the granulosa cell proliferation was evaluated using COV434 cell line which is derived from the human granulosa cell tumor. The effect of the peptide on the cell cycle analysis showed an increase in apoptotic population and the arrest of G1 phase. These findings suggest that follicle-stimulating hormone receptor-binding inhibitor-8 acts as a follicle-stimulating hormone antagonist and affects the follicle-stimulating hormone-mediated signaling and proliferation in the granulosa cells.


Bepridil reducing levothyroxine-induced enhancement of mitochondria Ca2+ Mg(2+)-ATPase activity in rat cerebrum.
To study if bepridil (Bep) could affect the enhancement of activity of cerebral mitochondria Ca2+ Mg(2+)-ATPase caused by levothyroxine (Lev) in relation to ischemic overload calcium cerebrum injury. The experimental hyperthyroidism model with ischemic cerebrum was developed in rats by ig Lev 1 mg.kg-1.d-1 for 7 d. Ca2+ Mg(2+)-ATPase activity and its kinetic parameters were assayed. The activity, Vmax and Km of cerebral mitochondria Ca2+ Mg(2+)-ATPase in control rats were 3.1 +/- 0.8, 5.1 +/- 2.3 mmol.P(i).h-1/g protein and 0.81 +/- 0.08 mmol.L-1 (ATP) respectively, whereas those of hyperthyroid rats were significantly altered to 4.6 +/- 0.5, 8.5 +/- 1.9 mmol.P(i).h-1/g protein and 0.49 +/- 0.11 mmol.L-1 (ATP) respectively. After treated with Bep 10 or 20 mg.kg-1.d-1 ig for 3 d, allabove 3 parameters of the enzyme were very significantly reduced vs those of either control or hyperthyroid. Bep, via decreasing Ca2+ Mg(2+)-ATPase activity and increasing the affinity of Ca2+ Mg(2+)-ATPase to ATP, could prevent rat cerebrum from ATP depletion and ischemic overload calcium injury.


Biomolecule-functionalized magnetic nanoparticles for flow-through quartz crystal microbalance immunoassay of aflatoxin B1.
A flow-through quartz crystal microbalance (QCM) immunoassay method has been developed based on aflatoxin B(1) antibody (anti-AFB(1))-functionalized magnetic core-shell Fe(3)O(4)/SiO(2) composite nanoparticles (bionanoparticles) in this study. To construct such an assay protocol, anti-AFB(1), as a model protein, was initially covalently immobilized onto the Fe(3)O(4)/SiO(2) surface, and then the functionalized nanoparticles were attached to the surface of the QCM probe with an external magnet. The binding of target molecules onto the immobilized antibodies decreased the sensor's resonant frequency, and the frequency shift was proportional to the AFB(1) concentration in the range of 0.3-7.0 ng/ml. The regeneration of the developed immunosensor was carried out via attaching or detaching the external magnet from the detection cell. In addition, the selectivity, reproducibility, and stability of the proposed immunoassay system were acceptable. Compared with the conventional ELISAs, the proposed immunoassay system was simple and rapid without multiple labeling and separation steps. Importantly, the proposed immunoassay method could be further developed for the immobilization of other antigens or biocompounds.


Aggressive Blood Pressure Lowing Therapy in Patients with Acute Intracerebral Hemorrhage is Safe: A Systematic Review and Meta-analysis.
The influence of blood pressure (BP) lowering on intracerebral hemorrhage (ICH) patients is unclear. To assess the safety and efficacy of aggressive antihypertensive therapies in acute ICH patients, we carried out a systematic review and meta-analysis. PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and VIP database up to July 2014 were searched. High-quality randomized controlled trials were included. Low-quality trials were excluded. Serious adverse events were defined as the primary outcome. The secondary outcomes were hematoma enlargement (HE) at 24 h after onset, mortality, and favorable clinical outcome at 90 days. Four high-quality trials involving a total of 1427 patients met the inclusion criteria and were analyzed. Odds ratios (ORs) of primary outcome was 0.96 (95% confidence interval [CI ]: 0.82-1.13, P = 0.61). ORs of HE at 24 h after onset, mortality and favorable clinical outcome at 90 days were 0.91 (95% CI: 0.72-1.17, P = 0.47), 0.97 (95% CI: 0.79-1.20, P = 0.81), 1.13 (95% CI: 0.98-1.30, P = 0.09) respectively. Aggressive BP management policies are safe and might have a potency of reducing HE and improving clinical outcome.


Synthesis, receptor binding and target-tissue uptake of carbon-11-labeled carbamate derivatives of estradiol and hexestrol.
Carbon-11-labeled estradiol and hexestrol derivatives were prepared via the reaction of [11C]ethylchloroformate with the 2- and 4-amino derivatives of estradiol, the 3'-amino derivatives of hexestrol, and the 1-aminophenoxy derivatives of hexestrol and 1-norhexestrol. The corresponding nonradioactive carbamates were prepared for chemical characterization and in vitro receptor binding assays. The positions of the substituents on the parent molecules were selected with a view to minimize interference with the receptor binding process. In spite of this, affinity for the estrogen receptor was strongly impaired for all carbamate derivatives. Likewise, in vivo, the [11C]carbamate analogs failed to localize in receptor rich tissue via an estrogen receptor mediated process.


Complementary and Integrative Medicine for Anxiety in Children, Adolescents, and Young Adults.
An integrative approach to treating anxiety in children and adolescents takes a biopsychosocial-spiritual approach. Early life stress may translate into anxiety via epigenetic mechanisms, the adoption of maladaptive coping tendencies (poor eating, sedentary lifestyle, substance use), and dysregulation of central autonomic nervous system function. Each of these mechanisms may increase inflammatory markers. This article will explore the efficacy of CIM interventions that work on these mechanisms through mind-body-medicine, acupuncture, nutrition, and supplements.


Takotsubo Cardiomyopathy and COVID-19: A Case Report and Literature Review.
Takotsubo cardiomyopathy is characterized by transient regional ventricular abnormalities in the absence of coronary artery disease and is reported as a complication of COVID-19. It can have a diverse clinical presentation, occasionally resembling an acute coronary syndrome, and progress to acute heart failure and cardiogenic shock, adversely affecting patients' prognosis. A high index of suspicion and a thorough diagnostic approach supported by ancillary studies like echocardiography and coronary angiography is key for an accurate diagnosis and correct medical treatment. Herein, we report a patient with severe COVID-19 who developed Takotsubo cardiomyopathy. We also present a detailed literature review regarding the relationship between COVID-19 and Takotsubo cardiomyopathy.


Enhanced technology for sewage sludge advanced dewatering from an engineering practice perspective: A review.
The increasing production of sludge poses significant environmental risks. Sludge disposal and transport are costly because of the high water content (WC). Reducing the WC of sludge is the most efficient strategy to decrease treatment costs. However, the sludge contains a large amount of hydrophilic organic matter, causing poor dewaterability. Therefore, research on preconditioning and mechanical dewatering has great significance for advanced sludge dewatering. In this study, the features of sludge, the advantages and disadvantages of preconditioning methods, and the action mechanisms (including physical, chemical, and biological preconditioning) are thoroughly described. In addition, the dewatering principle and engineering applications of mechanical dewatering techniques are introduced in this manuscript, especially the application of vacuum preloading as an in-situ dewatering technology in sludge. Finally, cost analysis of different conditioning and mechanical dewatering methods is conducted to explore their application feasibility. This manuscript provides new insights for engineering applications of preconditioning methods and mechanical dewatering technology.


Tissue organization of fasciated lateral roots of Arabidopsis mutants suggestive of the robust nature of outer layer patterning.
In three temperature-sensitive mutants of Arabidopsis, root redifferentiation 1 (rrd1), rrd2, and root initiation defective 4 (rid4), formation of fasciated lateral roots was previously observed under high temperature conditions of 28°C. When lateral roots were induced from explants of very young seedlings of these mutants by culture with exogenously supplied auxin at 28°C, expansion of lateral root primordia leading to lateral root fasciation occurred reproducibly and semi-synchronously with a high frequency. This experimental system allowed us to examine how radial organization of root tissues is altered in association with expansion of primordia. Analysis with various tissue-specific reporter genes indicated that in the fasciated lateral roots, cell files of the stele are increased markedly while the numbers of cortical and epidermal cell layers are not changed. This suggests that radial organization during root primordium development involves a mechanism that makes outer layer patterning more robust than inner layer patterning against unusual enlargement of the morphogenetic field.


Results of laparoscopic Nissen fundoplication at 2-8 years after surgery.
Although the long-term results of open fundoplication for gastro-oesophageal reflux disease are well documented, there have been few reports of the long-term results of laparoscopic fundoplication. Between January 1993 and July 1999, 179 consecutive patients underwent laparoscopic floppy Nissen fundoplication. Of these, 175 were available for long-term follow-up. Structured symptom questionnaires were completed by 140 patients (80 per cent) at 2-5 years (n = 92) or 5-8 years (n = 48) after operation. Patient satisfaction with surgery was 91 per cent at a median follow-up of 48 (range 24-99) months. Visick scores of I or II were recorded by 84 per cent. Ninety per cent of patients remained free from significant reflux symptoms. Side-effects were common (22 per cent) but rarely affected patient satisfaction. Of the 19 patients (14 per cent) taking regular antireflux medication, eight used it for non-reflux symptoms and 12 had normal postoperative pH tests. Laparoscopic floppy Nissen fundoplication is an effective and durable treatment for gastro-oesophageal reflux disease. Longer-term follow-up of patients operated on beyond the learning curve can be expected to show further improvements in surgical outcome.


Mutagenic/carcinogenic agents in indoor pollutants; the dinitropyrenes generated by kerosene heaters and fuel gas and liquefied petroleum gas burners.
Incomplete combustion of kerosene heater, and fuel gas and liquefied petroleum gas-burner emissions produces indoor pollutants that may be carcinogenic. The incomplete-combustion products from each type of appliance were therefore collected by adsorption on about 3 g of XAD-2 resin, and were extracted with benzene-methanol as a solvent for determination and identification of mutagens in the Salmonella-microsome test system. Benzene-methanol extracts of the particulates generated by a heater and two burners showed extreme mutagenicity for strains TA97 and TA98 without S9 mix. Based on the results of analysis, a combination of high performance liquid chromatography (h.p.l.c.) and gas chromatography (GC), about 40-80% of the direct-acting mutagenicity in each crude extract showed the same h.p.l.c. and GC retention times as dinitropyrenes (1,3-, 1,6- and 1,8-isomers), and 1-nitropyrene. Moreover, other nitroarenes, 2-nitrofluorene, 1,5- and 1,8-dinitronaphthalene, and 4,4'-dinitrobiphenyl, were detectable in almost all samples, but their contribution to the mutagenicity of each extract was very low. Kerosene heaters were found to generate small amounts (0.2 ng/h) of dinitropyrenes, which are potential mutagens/carcinogens, only after 1 h of operation.


Evaluation of apoptosis and cell proliferation in experimentally induced renal cysts.
Cell proliferation and apoptosis in renal cysts induced by streptozotocin, alloxan and ferric-nitrilotriacetate were investigated in rats. In the kidneys of all treated animals dilated tubules at the cortico-medullary region, large cysts, glomerular cysts and tubular dilation in the medullary area were found. Both cell proliferation and apoptosis were increased in the epithelium of the non-dilated tubules, in the mesangial and interstitial cells. Cells lining the dilated tubules or cysts demonstrated apoptosis but their proliferating activity was low. By calculating the proliferation-apoptosis ratio we found that alloxan did not change the balance between the two mechanisms. Meanwhile streptozotocin resulted in an increased apoptosis and ferric-nitrilotriacetate in an increased cell proliferation. p53 expression might be responsible for the uncontrolled proliferation in rats treated with ferric-nitrilotriacetate as this oncoprotein was diffusely present in tubular cell nuclei. The observed apoptosis seemed to be independent of bcl-2 oncoprotein expression. We assume that the initial factor in such cystogenesis should be a cellular injury due to direct toxic or to the diabetogenic effect of the drugs. The latter is more likely as all the animals were hyperglycemic and insulin treatment following administration of streptozotocin prevented the morphologic changes.


Idiopathic catastrophic epileptic encephalopathy presenting with acute onset intractable status.
To delineate a catastrophic childhood epileptic syndrome of unknown cause presenting with persistent intractable multifocal status. Case note review. Six children aged 5 months to 6 years presented with focal seizures that progressed within days to intractable multifocal seizures with or without secondary generalisation, which recurred every few minutes and persisted for weeks. One developed impaired consciousness shortly before seizures started. The two younger children showed mild developmental delay before onset but the others were normal. The seizures were unresponsive to all conventional anticonvulsants, steroids or pyridoxine and could only be controlled with doses of thiopentone sufficient to cause electrical suppression. MRI scans were initially normal but later showed focal cortical swelling followed by generalised atrophy. Two developed hepatomegaly, with a normal liver biopsy in one and steatosis in the other. No cause has been found even after neuropathological investigation. Three have died, two within 3 months of onset, while the three survivors have very severe neurological impairment and continued seizures. The similarity of the clinical features suggests that this is a consistent clinical syndrome.


In Vivo Fluorescence Imaging in the Second Near-Infrared Window Using Carbon Nanotubes.
In vivo fluorescence imaging in the second near-infrared window (NIR-II window, 1000-1700 nm) is a powerful imaging technique that emerged in recent years. This imaging tool allows for noninvasive, deep-tissue visualization and interrogation of anatomical features and functions with improved imaging resolution and contrast at greater tissue penetration depths than traditional fluorescence imaging. Here, we present the detailed protocol for conducting NIR-II fluorescence imaging in live animals, including the procedures for preparation of biocompatible and NIR-II fluorescent carbon nanotube solution, live animal administration and NIR-II fluorescence image acquisition.


Effect of Different Types of Aerobic Exercise on Individuals With and Without Hypertension: An Updated Systematic Review.
High blood pressure (BP) is one of the main modifiable risk factors for cardiovascular disease (CVD) and preventing it greatly reduces the vascular consequences of aging and, along with intensive treatment of hypertension, eliminates a large portion of the burden of CVD-related mortality. Many meta-analyses and studies proved that regular aerobic exercise (AE) reduces BP but most of these studies consider only hypertensive populations or only AE but not resistant exercise or their combination. In this review, we aimed to study the effect of different types of physical activity (PA)/AE on various populations including normotensive, prehypertensive, primary hypertensive, and resistant hypertensive with different comorbidities. We searched PubMed, Web of Science, and Google Scholar for English articles with keywords for physical activity, aerobic exercise, and blood pressure from January 2010 until September 2021. Finally, 24 studies were included. Results showed that chronic or acute AE (long-term or short-term), either alone or as combined with different sessions and programs can reduce systolic and diastolic BP in every group including normotensive, prehypertensive, primary hypertensive, resistant hypertensive individuals and diabetic patients and those with kidney problems but not in people with chronic heart failure. Isometric exercise training showed to be useful in reducing BP in all groups either as low intensity or as high intensity but the rate of reduction was different in terms of gender. AE showed to be effective in terms of BP reduction in a different age range. It can be seen that different types and duration of AE independent of the modality and programs and independent of the BP medical situation of individuals have been successful in terms of BP reduction. For those with chronic heart failure, more concern and help might be needed to decrease BP via exercise.


Association between Pre-Existing Sleep Disorders and Survival Rates of Patients with Breast Cancer.
To investigate the effects of pre-existing sleep disorders on the survival outcomes of women receiving standard treatments for breast invasive ductal carcinoma (IDC). We recruited patients from the Taiwan Cancer Registry Database who had received surgery for clinical stage I-III breast IDC. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into those with and without sleep disorders (Groups 1 and 2, respectively) through propensity score matching. In the multivariate Cox regression analysis, the adjusted hazard ratio for all-cause mortality for Group 1 compared with Group 2 was 1.51 (95% confidence interval: 1.19, 1.91; p < 0.001). Our study demonstrated that the sleep disorder group had poorer survival rates than the non-sleep disorder group in breast cancer. Therefore, patients should be screened and evaluated for pre-existing sleep disorders prior to breast surgery, with such disorders serving as a predictor of survival in patients with breast cancer. Future studies may investigate the survival benefits of pharmacological and behavioral treatments for sleep problems in patients with breast cancer.


The associations of the BDNF and APOE polymorphisms, hippocampal subfield volumes, and episodic memory performance across the lifespan.
In this study, we explored the associations between the brain derived neurotrophic factor (BDNF) and the apolipoprotein E (APOE) polymorphisms and hippocampal subfields in 127 healthy participants (18-85 years). MRI datasets were collected on a 4.7 T system. Participants were administered the Wechsler Memory Scale to evaluate episodic memory function. Significant associations of both polymorphisms were present only in older adults (≥50 years). BDNF polymorphism was associated with larger dentate gyrus volumes within the anterior hippocampus (head) in Met-carriers compared to Val/Val homozygotes. We found that in Met-carriers total hippocampal volume predicted performance on visuospatial memory tasks. APOE polymorphism was associated with larger total hippocampal volume, especially in cornu ammonis 1-3 and subiculum in APOE ɛ2 carriers compared to both ɛ4 and ɛ3 carriers, while APOE ɛ3 and ɛ4 carriers did not differ from each other. APOE polymorphism was associated with better performance on visuospatial memory tasks in APOE ε2 carriers in comparison to ε4 carriers.


Molecular-scale observation of the surface of polystyrene particles by AFM.
The surface morphology of polystyrene particles prepared by soap-free emulsion polymerization was observed in situ using the tapping mode of an atomic force microscope (AFM). Here, the use of a cationic initiator enabled us to synthesize positively charged polystyrene, which then adsorbed electrostatically onto the negatively charged mica plate with molecular-scale smoothness. The following was found from AFM measurements in water. The surface of polystyrene particles changed from smooth to rough as the polymerization proceeded in the experimental condition, where the bulk generated tiny particles continuously, because of the heterocoagulation in the growth process between the newborn and tiny particles and the existing particles. However, it is easy to prepare the particles with smooth surfaces on the condition of rich monomers because the monomers in the bulk dissolve the polymers which form the surface morphology to be deformable and reduce the interfacial area.


Sequential photo electro oxidation and biodegradation of textile effluent: Elucidation of degradation mechanism and bacterial diversity.
Textile effluent contains a highly toxic and refractory azo dyes. Eco-friendly method for efficient decolorization and degradation of textile effluent is essential. In the present study, treatment of textile effluent was carried through sequential electro oxidation (EO) and photo electro oxidation (PEO) using RuO2-IrO2 coated titanium electrode as an anode and cathode followed by biodegradation. The pre-treatment of textile effluent by photo electro oxidation for 14 h exhibited 92% of decolorization. Subsequent biodegradation of the pre-treated textile effluent enhanced the reduction of chemical oxygen demand to 90%. Metagenomics results exhibited that Flavobacterium, Dietzia, Curtobacterium, Mesorhizobium, Sphingobium, Streptococcus, Enterococcus, Prevotellaand Stenotrophomonas bacterial communities majorly involved in the biodegradation of textile effluent. Hence, integrating sequential photo electro oxidation and biodegradation proposed an efficient and eco-friendly approach for treating textile effluent.


Lessons learned from lethal cardiac injury by nuss repair of pectus excavatum in a 16-year-old.
This report investigates cardiac injury and arrest during a Nuss repair of severe pectus excavatum in a 16-year-old boy in 2006. The injuries of the right atrial auricle and the right ventricle were sutured, and the patient was resuscitated. Ultimately he died on the 11th day of progressive malignant cerebral edema and respiratory distress syndrome despite cerebral decompression and hypothermia. Typical morphologic features of cardiac injuries are demonstrated, and strategies to avoid inadvertent organ injury in pectus operations are discussed.


The effect of photobiomodulation on human dental pulp-derived stem cells: systematic review.
This systematic review assessed if photobiomodulation of human dental pulp tissue improved cell viability, proliferation, and/or differentiation compared with a placebo. This systematic review was conducted in line with PRISMA. PICO question was established; inclusion and exclusion criteria were established before a search had begun. A literature search was conducted through PubMed, Scopus, and Cochrane. Studies were included if published within the last 20 years in English language, or where translation was available; laser parameters were mentioned; human dental pulp tissue was studied in vitro. Studies were excluded if non-human dental pulp tissue was studied and where the study was an in vivo study. Out of the total 121 studies found, 109 were excluded. Of the twelve included studies, three full-text articles were not available despite attempts made to contact the respective authors, leaving nine studies. Four of the included studies reported the use of stem cells derived from human deciduous teeth (SHEDs), and five used those from human permanent teeth (DPSCs). Most included studies utilized InGaAlP laser with wavelengths 660 nm, and one study with 610 nm. Other types of lasers included LED InGaN, and GaAlAs. Out of all included studies, two had a moderate risk of bias, and the rest had a low risk of bias. All studies confirmed positive effects on proliferation. One study also found improved osteogenic differentiation of the stem cells derived from stem cells of deciduous teeth. After assessing SHEDs and DPSCs separately, it is found that photobiomodulation improved cell proliferation in both subgroups. Due to heterogeneity in design protocols and laser parameters, it was not possible to compare the studies together. However, this study indicated that cell viability and proliferation did improve with photobiomodulation.


Nucleotide excision repair and neurological diseases.
This review will examine the known and postulated relationships between nucleotide excision repair (NER) and neurological diseases. We will begin with a description of NER and its subpathways: global genomic repair (GGR), transcription-coupled repair (TCR) and transcription domain-associated repair (DAR). As far as they are known, the underlying molecular mechanisms will be discussed. We will only briefly touch on the possible contribution of NER to neurodegenerative diseases such as Alzheimer's, but concentrate on neurological symptoms in NER-deficient patients. These are mainly observed in two clinical entities, Xeroderma pigmentosum (XP) and Cockayne syndrome (CS), and we shall try to understand why and how a deficit in DNA repair may result in neurological dysfunctions. The links between NER and neurological disease are also discussed in contributions by Brooks and by Niedernhofer, in this volume.


Reimagining Family Involvement in Residential Long-Term Care.
Although descriptions of family involvement in residential long-term care (RLTC) are available in the scientific literature, how family involvement is optimized in nursing homes or assisted living settings remains underexplored. During the facility lockdowns and visitor restrictions of the COVID-19 pandemic, residents experienced social deprivation that may have resulted in significant and adverse health outcomes. As with so many other critical issues in RLTC, the COVID-19 pandemic has magnified the need to determine how families can remain most effectively involved in the lives of residents. This article seeks to better understand the state of the science of family involvement in RTLC and how the COVID-19 pandemic has expedited the need to revisit, and reimagine, family involvement in RLTC.


Human placental apurinic/apyrimidinic endonuclease. Mechanism of action.
The mechanism of action of the homogeneous preparation of human placental apurinic/apyrimidinic (AP) endonuclease, described in the previous paper (Shaper, N. L., Grafstrom, R. H., and Grossman, L. (1982) J. Biol. Chem. 257, 13455-13458), has been investigated in detail. This enzyme cleaves apyrimidinic DNA both 5' and 3' to the site of damage in a ratio of 60:40, respectively. Even though this enzyme can cleave on both sides of an internal AP site, it does not release deoxyribose 5-phosphate from terminal AP sites. However, a compound, tentatively identified as alpha, beta unsaturated deoxyribose 5-phosphate, is nonenzymatically released only from 5'-terminal AP sites, presumably by a beta-elimination mechanism.


Successful treatment with infliximab and methotrexate of pyostomatitis vegetans associated with Crohn's disease.
A 35-year-old woman with severe fistulizing Crohn's disease presented with pyostomatitis vegetans affecting both the mouth and the vulva. The coalescing pustules transformed within several days into vegetating lesions on areas of inflammation. Microbial assessments revealed no pathogenic agent. Histology showed neutrophilic microabscesses, but no granulomas. Three injections of infliximab and maintenance therapy with methotrexate resulted in rapid and complete regression of both the pyostomatitis vegetans and the Crohn's disease. Infliximab and methotrexate may be a promising treatment for the rare cases of pyostomatitis vegetans associated with Crohn's disease.


Abnormal miRNAs Targeting Chromosome Open Reading Frame Genes were Enriched in Microvesicles Derived from the Circulation of HCC.
In this study, we detected the expression profiles of microRNAs (miRNAs) packaged within microvesicles (MVs) from blood samples of HCC patients and healthy donors. Using microarray analysis, there were 83 down-regulated and 92 over-expressed miRNAs in HCC circulation-derived MVs relative to control group. Then potential functions of the dysregulated MVs miRNAs were investigated with bioinformatic tools. We found that 664 Corf genes were targeted by 72 altered MVs miRNAs and some of these target genes were reported to be associated with tumorous activities. Gene Ontology annotation demonstrated that biological roles of the target Corf genes mainly contained the regulation of growth, cell death, macromolecule metabolism, etc. As regulated by abnormal MVs miRNAs, functions of target Corf genes might be interrupted, which were much likely to contribute to HCC occurrence and progression.


The correlation analysis between organizational justice, knowledge-hiding behaviour and Nurses' innovation ability: A cross-sectional study.
The aim of the study was to analyse the correlations among organizational justice, knowledge-hiding behaviour and nurses' innovation ability. A descriptive and cross-sectional design and the data were collected using questionnaires. Demographic information, professional data, innovation capacity scales, knowledge-hiding scales and organizational justice scales were used in this study. Using descriptive statistics, t-tests, one-way analysis of variance and Pearson's or Spearman's correlation analyses, we compared the differences and examined the correlations between participants' demographic and innovation capacity scales, and knowledge-hiding scales and organizational fairness scales. We received 1486 valid responses, with an effective response rate of 96.68%. We found team role, nursing age, number of training, literature-reading habits, organizational justice, information justice, fair distribution and deaf knowledge-hiding as the influencing factors of nurses' innovation. Nurses' sense of organizational fairness negatively correlated with knowledge concealment and positively correlated with innovation ability. Moreover, knowledge hiding negatively correlated with nurses' innovation ability. Furthermore, knowledge-hiding plays a partial intermediary role between organizational fairness and nurses' innovation ability.


Prevention of acute graft-versus-host disease in adult T-cell leukemia-lymphoma patients who received mogamulizumab before allogeneic hematopoietic cell transplantation.
Mogamulizumab (Mog) is effective against adult T-cell leukemia-lymphoma (ATL), but as we reported previously, Mog increases the incidence of severe acute GVHD when administered before allogeneic hematopoietic cell transplantation (allo-HCT). Here, we report the cases of two ATL patients who did not develop acute GVHD despite receiving Mog before allo-HCT. Case 1: a 63-year-old female who underwent allo-HCT from an HLA-matched donor 2 months after the last dose of Mog. Case 2: a 47-year-old male with ATL that relapsed 3 months after first allo-HCT. He received eight doses of Mog and underwent a second allo-HCT from a haploidentical donor 4 months after the last dose of Mog. Mog blood levels were measured and lymphocytes analyzed by mass cytometry. Mog blood levels measured before starting the conditioning regimens were low. A small proportion of regulatory T cells (Tregs) was detected before and shortly after allo-HCT. When using Mog before allo-HCT, it is important to consider the number of Mog doses and the interval from the last dose of Mog to allo-HCT. Analyzing Mog blood levels and Treg counts before and after allo-HCT should also be useful.


Role of mitochondria in alcoholic liver injury.
Oxidative stress and oxygen-derived free radicals are well known to play an important role in the pathogenesis of ethanol-associated liver injury. Active oxidants produced during ethanol metabolism induce mitochondrial membrane depolarization and permeability changes in cultured hepatocytes. These mitochondrial alterations (loss of DeltaPsim and mitochondrial permeability transition [MPT]) are now recognized as a key step in apoptosis. In recent studies, including ours, the MPT has been identified as a key step for the induction of mitochondrial cytochrome c release and caspase activation by ethanol. In addition, chronic and/or acute ethanol modulates intracellular, especially mitochondrial, antioxidant levels, leading to the increased susceptibility to alcoholic liver injury induced by several apoptotic stimuli. In this review, we address the mechanism of mitochondrial alterations and liver injury induced by ethanol.


Deuterium NMR studies of cerebroside-phospholipid bilayers.
2H-NMR was used to probe the interaction of non-hydroxy fatty acid cerebroside and 2-hydroxy fatty acid cerebroside with the polar head group and with the acyl chains of dipalmitoylphosphatidylcholine in unsonicated bilayers. It is shown that the interior of the bilayer exhibits uniformly increasing orientational order as the concentration of both types of cerebroside increases, whereas the surface of the bilayer, as reflected by the head group motion, becomes disordered. The extent of the disorder at the surface is dependent upon the type and concentration of the cerebroside. These results are discussed in terms of hydrogen-bonding interactions.


Three dimensional spatial-temporal convergence of otolith related signals in vestibular only neurons in squirrel monkeys.
Spatio-temporal convergence (STC) properties of 19 vestibular only neurons' responses to translational head movements were examined in an alert, behaving squirrel monkey. In addition to standard tests that included 1.2 Hz yaw/pitch/roll rotations and inter-aural/naso-occipital/dorso-ventral translations, we also observed responses to translations along multiple directions in several orthogonal planes. Neural responses were fitted first by a model that permitted STC in all planes, characterized by a non-zero minimum and a gradual shift of phase. We then evaluated statistically whether models with fewer independent dynamic parameters yielded equally satisfactory results. The responses of 13 neurons were adequately fit by simple cosine models (1-D) as well as models that allowed complex STC behavior. Of the six neurons exhibiting STC, five could be modeled with two independent phase parameters (2-D) while the remaining neuron required a model with three independent phase parameters (3-D). The maximum translation sensitivity and phase, Smax and varphimax, and minimum translation sensitivity and phase, Smin and varphimin, were estimated from the reconstructed sensitivity and phase surfaces. The tuning ratio, Smin/Smax, in STC neurons was>0.40 while in 1-D neurons it was <0.25. Furthermore, the maximum response vectors of most 1-D neurons lay within 20 degrees of either the horizontal or sagittal plane while those of STC neurons lay >20 degrees from both planes. No difference in other response properties, such as varphimax or rotational responses, was found between neurons exhibiting STC and the simple cosine tuning. Our results suggest that the STC behavior observed in otolith-related vestibular neurons probably arises from summing inputs from afferents, with diverse response dynamics, innervating different otolith macula.


Cyclic stretch induces the release of growth promoting factors from cultured neonatal cardiomyocytes and cardiac fibroblasts.
Growth factors and hormones may play an autocrine/paracrine role in mechanical stress-induced cardiac hypertrophy. Using an in vitro model of mechanical stress, i.e. stretch of cardiomyocytes and cardiac fibroblasts, we tested the involvement of growth factors and hormones in this process. We found that conditioned medium (CM) derived from 4 h cyclicly (1 Hz) stretched cardiomyocytes increased the rate of protein synthesis in static cardiomyocytes by 8 +/- 3%. Moreover, CM derived from 2 h stretched fibroblasts increased the rate of protein synthesis in static fibroblasts as well as in static cardiomyocytes by 8 +/- 2 and 6 +/- 2%, respectively. Analysis of CM using size-exclusion HPLC showed that cardiomyocytes and fibroblasts released at least three factors with MW < or = 10 kD, their quantities being time-dependently increased by stretch. Subsequent analyses using immunoassays revealed that cardiomyocytes released atrial natriuretic peptide (ANP) and transforming growth factor-beta1 (TGFbeta1) being increased by 45 +/- 17 and 21 +/- 4% upon 4 h of stretch, respectively. Fibroblasts released TGFbeta1 and very low quantity of endothelin-1 (ET-1). The release of TGFbeta1 was significantly increased by 18 +/- 4% after 24 h of stretch in fibroblasts. Both cell types released no detectable amount of angiotensin II (Ang II). In conclusion, upon cyclic stretch cardiomyocytes and fibroblasts secrete growth factors and hormones which induce growth responses in cardiomyocytes and fibroblasts in an autocrine/paracrine way. TGFbeta secreted by cardiomyocytes and fibroblasts, and ANP secreted by cardiomyocytes are likely candidates. We found no evidence for the involvement of Ang II and ET-1 in autocrine/paracrine mechanisms between cardiac cell types.


[Effects of needle knife relaxing therapy on tension of local soft tissue and pain of osteoarthritis of knee].
To probe into the mechanism and methods of needle knife relaxing therapy for treatment of osteoarthritis of knee from biomechanical view. Needle knife relaxing therapy was given to 92 pain points around the knee joint in 14 cases of osteoarthritis of knee, and the displacement of the local pain point under the stress of 500 g (L500 g) was measured and the VAS scores were recorded before and after treatment. L500 g of the pain point was (4.72+/-1.03) mm before treatment and (5.39+/-1.01) mm after treatment with a very significant difference before and after treatment (P<0.01), and VAS score was (7.10+/-1.49) points before treatment and (1.49+/-1.24) points after treatment with a very significant difference before and after treatment (P<0.01), and there was a linear correlation between the changes of L500 g and VAS scores. There was close connection between the local pain and tension of local soft tissue in knee osteoarthritis. The needle knife relaxing therapy can relieve the neurovascular compression or traction syndrome by relaxing the local contracted, adhesive soft tissue, so as to relieve tension pain and finally recover internal force equilibrium of the knee joint.


Educators' Interprofessional Collaborative Relationships: Helping Pharmacy Students Learn to Work with Other Professions.
Similar to other professions, pharmacy educators use workplace learning opportunities to prepare students for collaborative practice. Thus, collaborative relationships between educators of different professions are important for planning, implementing and evaluating interprofessional learning strategies and role modelling interprofessional collaboration within and across university and workplace settings. However, there is a paucity of research exploring educators' interprofessional relationships. Using collaborative dialogical inquiry we explored the nature of educators' interprofessional relationships in a co-located setting. Data from interprofessional focus groups and semi-structured interviews were interpreted to identify themes that transcended the participants' professional affiliations. Educators' interprofessional collaborative relationships involved the development and interweaving of five interpersonal behaviours: being inclusive of other professions; developing interpersonal connections with colleagues from other professions; bringing a sense of own profession in relation to other professions; giving and receiving respect to other professions; and being learner-centred for students' collaborative practice. Pharmacy educators, like other educators, need to ensure that interprofessional relationships are founded on positive experiences rather than vested in professional interests.


Characterization of a copper-resistant symbiotic bacterium isolated from Medicago lupulina growing in mine tailings.
A root nodule bacterium, Sinorhizobium meliloti CCNWSX0020, resistant to 1.4 mM Cu2+ was isolated from Medicago lupulina growing in mine tailings. In medium supplied with copper, this bacterium showed cell deformation and aggregation due to precipitation of copper on the cell surface. Genes similar to the copper-resistant genes, pcoR and pcoA from Escherichia coli, were amplified by PCR from a 1.4-Mb megaplasmid. Inoculation with S. meliloti CCNWSX0020 increased the biomass of M. lupulina grown in medium added 0 and 100 mg Cu2+ kg(-1) by 45.8% and 78.2%, respectively, and increased the copper concentration inside the plant tissues grown in medium supplied with 100 μM Cu2+ by 39.3%, demonstrating that it is a prospective symbiotic system for bioremediation purposes.


HLA-B27 subtypes in Japanese with seronegative spondyloarthropathies and healthy controls.
To determine HLA-B27 subtype frequencies in Japanese patients with seronegative spondyloarthropathies (SpA) and healthy controls. We determined HLA-B27 subtypes of 20 Japanese patients with ankylosing spondylitis and one with Reiter's syndrome, and 11 healthy Japanese individuals using a polymerase chain reaction sequence specific oligonucleotide hybridization method specifically designed for the discrimination of B*2701-09. 14 of 21 (67%) patients and 9 of 11 (82%) controls were typed as B*2704. The remainder were B*2705. HLA-B*2704 and B*2705 are present in the Japanese population, the former being the predominant subtype of HLA-B27. Both subtypes are associated with SpA.


Central command suppresses pressor-evoked bradycardia at the onset of voluntary standing up in conscious cats.
What is the central question of this study? Standing up can cause hypotension and tachycardia. Accumulated evidence poses the simple question, does the cardiac baroreflex operate at the onset of standing up? If the cardiac baroreflex is suppressed, what mechanism is responsible for baroreflex inhibition? What is the main finding and its importance? In cats, we found blunting of cardiac baroreflex sensitivity in the pressor range at the onset of voluntary hindlimb standing, but not of passive hindlimb standing. This finding suggests that central command suppresses pressor-evoked bradycardia at the onset of standing up, probably in advance, to prevent or buffer orthostatic hypotension. It remains unclear whether cardiac baroreflex function is preserved or suppressed at the onset of standing up. To answer the question and, if cardiac baroreflex is suppressed, to investigate the mechanism responsible for the suppression, we compared the sensitivity of the arterial cardiac baroreflex at the onset of voluntary and passive hindlimb standing in conscious cats. Cardiac baroreflex sensitivity was estimated from the maximal slope of the baroreflex curve between the responses of systolic arterial blood pressure and heart rate to a brief occlusion of the abdominal aorta. The systolic arterial blood pressure response to standing up without aortic occlusion was greater in the voluntary case than in the passive case. Cardiac baroreflex sensitivity was clearly decreased at the onset of voluntary standing up compared with rest (P = 0.005) and the onset of passive standing up (P = 0.007). The cardiac baroreflex sensitivity at the onset of passive standing up was similar to that at rest (P = 0.909). The findings suggest that central command would transmit a modulatory signal to the cardiac baroreflex system during the voluntary initiation of standing up. Furthermore, the present data tempt speculation on a close relationship between central inhibition of the cardiac baroreflex and the centrally induced tachycardiac response to standing up.


The possible role of meiotic pairing anomalies in the atresia of human fetal oocytes.
Following a previous study of human fetal oocytes analysed by light and electron microscope microspreading (Speed 1985), a further and more extensive analysis has now been carried out at electron microscope (EM) level. Some new anomalies not previously observed are described. More than one-third of all pachytene oocytes show degeneration (Z-cells) or synaptic errors which might lead to germ cell death. Meiotic pairing anomalies appear to be much more common among oocytes than spermatocytes, and could be significant factor in the high rate of atresia found between mid-term and birth in the human ovary.


Supersonic Dislocation Bursts in Silicon.
Dislocations are the primary agents of permanent deformation in crystalline solids. Since the theoretical prediction of supersonic dislocations over half a century ago, there is a dearth of experimental evidence supporting their existence. Here we use non-equilibrium molecular dynamics simulations of shocked silicon to reveal transient supersonic partial dislocation motion at approximately 15 km/s, faster than any previous in-silico observation. Homogeneous dislocation nucleation occurs near the shock front and supersonic dislocation motion lasts just fractions of picoseconds before the dislocations catch the shock front and decelerate back to the elastic wave speed. Applying a modified analytical equation for dislocation evolution we successfully predict a dislocation density of 1.5 × 10(12) cm(-2) within the shocked volume, in agreement with the present simulations and realistic in regards to prior and on-going recovery experiments in silicon.


The ultrastructure of cones in the walleye retina.
The ultrastructure of single and twin cone photoreceptors in the retina of the walleye was analyzed by scanning and transmission electronmicroscopy. The outer segment disks resemble those of other vertebrates. An accessory outer segment arises from the inner segment, makes frequent contacts with the outer segment proper, and may thus provide a bridge for signal transmission from outer to inner segment. A palisade of some 30 calycal processes surrounds and may provide structural support for the outer segment. The region of apposition between the inner segments of twin cones consists of a space of some 28 nm with no indication of gap junctions. The proximal quarter of the inner segment displays a profusion of some 50 lateral fins which increase the inner segment surface by 3-4 X and do not contact fins of neighboring cones. The fins surround a profusion of Müller cell microvilli and probably promote metabolic exchange between cones and Müller cells. Apart from differences in size and the presence of apposed inner segments, twin and single cones appear to be morphologically similar.


Intoxication in manic patients following chaotic self-administration of lithium.
Intoxication is a serious complication of lithium therapy. Suicides attempted by depressive patients or excessive serum levels due to reduced renal elimination are typical causes of these intoxications. So far, lithium intoxications following excessive intake by patients with manic disorders have not been reported. We present 4 case histories of manic patients in whom the diagnosis of lithium intoxication was delayed, even though their affective disorders and medication were known. Lithium should be determined immediately on a routine basis in all patients who, on the basis of their history, are known to receive or who, considering the underlying mental illness, possibly receive lithium therapy.


Compression inhibits aggregation of human platelets under high hydraulic pressure.
It has been found in our laboratory that compression induces disaggregation and decompression induces aggregation of human platelets. The experimental design was based on the premise that oppositely charged amino acid residues of fibrinogen are juxtaposed in the specific adhesive site(s). This can be explained by the principle of Le Chateller. Under compression, electrically charged groups gain layers of water molecules which are radially oriented and pulled in closer to the center of the charge, thus making the layer more compact. This increases the thickness of the shield, thus inactivating or disaggregating the platelets. Conversely, decompression drives the water away from the compact shield; water molecules are randomized into the bulk phase; the shield becomes thinner, thus permitting spontaneous aggregation of platelets. It is well known that increasing the concentration of neutral salt can inhibit platelet aggregation. This is due to the increase of ionic strength which attenuates the electric charge and thickens the shield. Molecules having a large electric dipole moment can inhibit platelet aggregation by a similar mechanism. It is generally accepted that fibrinogen is involved in platelet aggregation. However, it is not known whether or not fibrinogen is essential for platelet aggregation inducible by decompression. Here we present data indicating that fibrinogen is essential in decompression-inducible platelet aggregation. We also present experimental data which show that high hydraulic pressure inhibits platelet aggregation, consistent with our premise that electrically charged groups are involved in the initial phase of platelet aggregation.


Uptake and kinetics of Tc-99m hexakis 2-methoxy isobutyl isonitrile in benign and malignant lesions in the lungs.
Kinetics of Tc-99m MIBI uptake was studied in 19 patients with lung lesions (6 benign, 13 malignant). Two dynamic studies were acquired after the I.V. injection of 10-15mCi (370-550 MBq); the first was every second for 60 seconds, followed by a second one every minute for 30 minutes. Delayed images were acquired at two and three hours. By assigning regions of interest (ROI) over the lung lesions (TR), contralateral normal lung (NL) and the heart (Ht), time activity curves (TAC) were generated and time to peak activity was calculated as well as the ratios of TR/NL, Ht/TR and Ht/NL. The Ht/NL ratio was also assessed in five patients referred with diagnosis of ischaemic heart disease (IHD) for myocardial imaging. There was a localized increase of Tc-99m MIBI uptake in ten patients with untreated malignant tumours of the lung. No localized uptake was found in one patient with untreated poorly differentiated squamous cell carcinoma, two treated lung cancer and four patients with non-malignant lesions of the lungs. Two patients with fibrosing alveolitis showed diffuse increase lung uptake. In all positive studies peak tumour was reached within the first minute. There was no statistical difference in the ratio of Ht/NL between all groups except in patients with fibrosing alveolitis. There was no significant difference between the ratios TR/NL, Ht/TR and Ht/NL at 5-10 minutes and 25-30 minutes. The ratio of TR/NL at 25-30 minutes was 1.58 +/- 0.36 in the positive cases versus 1 +/- 0.22 in the negative ones.(ABSTRACT TRUNCATED AT 250 WORDS)


Keratinocyte-specific deletion of the receptor RAGE modulates the kinetics of skin inflammation in vivo.
The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor causally related to the pathogenesis of acute and chronic inflammation. In a mouse model of inflammation-driven skin carcinogenesis, RAGE deletion conferred protection from the development of skin tumors due to a severely impaired cutaneous inflammation. Although the impact of RAGE expression in immune cells was shown to be essential for the maintenance of a cutaneous inflammatory reaction, the role of RAGE in keratinocytes remained unsolved. Using mice harboring a keratinocyte-specific deletion of RAGE, we analyzed its role in the regulation of an acute inflammatory response that was induced by topical treatment of the back skin with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA). We show that RAGE expression in cutaneous keratinocytes modulates the strength and kinetics of acute inflammation and supports the maintenance of epidermal keratinocyte activation. To address the underlying molecular mechanism, we isolated interfollicular epidermis by laser microdissection for gene expression analysis, and identified RAGE as a regulator in the temporal control of TPA-induced epidermal tumor necrosis factor alpha transcript levels. In summary, our data demonstrate that RAGE expression in keratinocytes is critically involved in the perpetuation of acute inflammation and support the central role of RAGE in paracrine communication between keratinocytes and stromal immune cells.


Comparison of singleton and multiple pregnancies in in vitro fertilization (IVF) and embryo transfer (ET).
The purpose of this study was to analyze factors associated with multiple gestations in IVF-ET. Twenty-seven multiple gestations conceived following IVF-ET resulted in the delivery of 20 sets of twins and three sets of triplets. One quadruplet pregnancy was terminated due to heavy bleeding. There were four "vanishing sacs," two of which resulted in a twin pregnancy and two in singletons. These were compared to 88 singleton IVF-ET gestations. The only significant difference found was the higher numbers of embryos transferred in the multiple gestation group. No difference was found between the two groups in diagnosis, stimulation protocol, estradiol, response, number of eggs, fertilization, and cleavage rate. Maternal age was younger in the multiple-gestation group, though not statistically significant. It is thus suggested that limitation of the number of embryos transferred is the only means to reduce the incidence of multiple gestations in IVF-ET.


Chemical synthesis and calcium release activity of N(1)-ether strand substituted cADPR mimic.
8-Chloro cyclic inosine 5'-diphosphate ethoxymethyl ether 3 was synthesized by means of chemical method from protected inosine via phenylthio-type biphosphate substrate. The detection of Ca(2+) release activity shows that 3 is a potent agonist of cADPR and has activity in intact Hela cells.


Ambulatory management of burns in children.
A randomized trial of three treatment methods for the ambulatory management of minor burns in children has shown Op-site to be superior. The dressing is cost-effective and well tolerated, with the advantage that children can return to their normal activities without jeopardizing the healing process.


Protein biosynthesis in organelles requires misaminoacylation of tRNA.
In the course of our studies on transfer RNA involvement in chlorophyll biosynthesis, we have determined the structure of chloroplast glutamate tRNA species. Barley chloroplasts contain in addition to a tRNA(Glu) species at least two other glutamate-accepting tRNAs. We now show that the sequences of these tRNAs differ significantly: they are differentially modified forms of tRNA(Gln) (as judged by their UUG anticodon). These mischarged Glu-tRNA(Gln) species can be converted in crude chloroplast extracts to Gln-tRNA(Gln). This reaction requires a specific amidotransferase and glutamine or asparagine as amide donors. Aminoacylation studies show that chloroplasts, plant and animal mitochondria, as well as cyanobacteria, lack any detectable glutaminyl-tRNA synthetase activity. Therefore, the requirement for glutamine in protein synthesis in these cells and organelles is provided by the conversion of glutamate attached to an 'incorrectly' charged tRNA. A similar situation has been described for several species of Gram-positive bacteria. Thus, it appears that the occurrence of this pathway of Gln-tRNA(Gln) formation is widespread among organisms and is a function conserved during evolution. These findings raise questions about the origin of organelles and about the evolution of the mechanisms maintaining accuracy in protein biosynthesis.


Attempted suicide leading to acquired brain injury: a scoping review.
Objective: Conduct a scoping review of literature surrounding acquired brain injury (ABI) sustained secondary to a suicide attempt to establish the current body of research on injury outcomes and rehabilitative needs for this population.Methods: A systematic search of the literature was conducted. Searches were conducted using terms relating to this injury etiology and search results with original or secondary data on individuals with an ABI were included for review.Results: Thirty-two articles were reviewed. Limited data characterizing this population exists in the literature. Findings indicate that this population have generally poorer injury outcomes compared with ABI sustained through other means. Rehabilitative needs are rarely addressed, but limited commentary suggests that extensive pre-morbid conditions, severity of injuries and psychosocial support needs of this population present implications for rehabilitative supports.Conclusion: There is a relative dearth of research examining ABI sustained secondary to a suicide attempt. Collated findings suggest these individuals are rarely recognized in the literature as a distinct ABI population with rehabilitative needs specific to this etiology. Future research should aim to address the gaps identified in the literature, including characterizing the population, establishing pre-morbid conditions and developing tailored rehabilitative support to address complex needs.


Improving cup positioning using a mechanical navigation instrument.
Although surgical navigation reduces the rate of malpositioned acetabular cups in total hip arthroplasty (THA), its use has not been widely adopted. As a result of our perceived need for simple and efficient methods of navigation, we developed a mechanical navigation device for acetabular cup orientation. We assessed accuracy of cup orientation (mean error of cup inclination and anteversion) of a novel mechanical navigation device, percentage of outliers, length of operation, and compared the results with a series of CT-based computer-assisted THAs. Cup orientation of 70 THAs performed using the mechanical navigation device was compared with a historical control group of 146 THAs performed using CT-based computer navigation. Postoperative cup orientation was measured using a validated two-dimensional/three-dimensional matching method. An outlier was defined outside a range of ± 10° from the planned inclination and/or anteversion. Using the mechanical navigation device, we observed a decrease in the errors of inclination (1.3° ± 3.4° [range, -6.6° to 8.2°] versus 3.5° ± 4.2° [-12.7° to 6.9°]), errors of anteversion (1.0° ± 4.1° [-8.8° to 9.5°] versus 3.0° ± 5.8° [-11.8° to 19.6°]), percentages of outliers (0% versus 9.6%), and length of operation (112 ± 22 [78-184] minutes versus 132 ± 18 [90-197] minutes) compared with CT-based navigation. Compared with CT-based surgical navigation, navigation of acetabular cup orientation using a mechanical device can be performed in less time, lower mean errors, and minimal equipment.


Shape-controlled synthesis and influence of W doping and oxygen nonstoichiometry on the phase transition of VO2.
Monoclinic VO2(M) in nanostructure is a prototype material for interpreting correlation effects in solids with fully reversible phase transition and for the advanced applications to smart devices. Here, we report a facile one-step hydrothermal method for the controlled growth of single crystalline VO2(M/R) nanorods. Through tuning the hydrothermal temperature, duration of the hydrothermal time and W-doped level, single crystalline VO2(M/R) nanorods with controlled aspect ratio can be synthesized in large quantities, and the crucial parameter for the shape-controlled synthesis is the W-doped content. The dopant greatly promotes the preferential growth of (110) to form pure phase VO2(R) nanorods with high aspect ratio for the W-doped level = 2.0 at% sample. The shape-controlled process of VO2(M/R) nanorods upon W-doping are systematically studied. Moreover, the phase transition temperature (Tc) of VO2 depending on oxygen nonstoichiometry is investigated in detail.


C reactive protein and skin temperature post total knee replacement.
We prospectively assessed 20 patients following uncomplicated total knee replacement (TKR). Clinical status, skin temperature and C-reactive protein (CRP) were measured preoperatively and at intervals up to 18 weeks. The CRP rose postoperatively up to 5-7 days but returned to normal values by 6 weeks. The skin temperature remained elevated up to 18 weeks. We concluded that in uncomplicated cases, the CRP should be within normal limits by 6 weeks after operation, but skin temperature may remain elevated up to 18 weeks. A sustained rise in these values may indicate the development of a complication such as infection and the patient must be closely monitored.


Increased levels of antibodies to heat shock proteins with increasing age in Mrl/Mp-lpr/lpr mice.
Approximately 30% of human patients with systemic lupus erythematosus (SLE) develop IgG autoantibodies to the highly conserved 90 kDa heat shock protein (hsp90). The development of anti-hsp90 antibodies is shown here to be paralleled in the Mrl/lpr mouse, which is an acknowledged model for SLE, but not in control BALB/c mice (P = 0.005). The generation of these antibodies appears to be closely linked to the onset of disease and titres of these antibodies increase with age, but there is no correlation with well-established clinical parameters of disease. Antibodies to hsp70 and hsp65 are also observed in the Mrl/lpr model; these antibodies appear to be unrelated to the pathogenesis of the disease.


Prolonged post-vagotomy gastric atony treated by oxytocin.
Persistent and complete post-vagotomy gastric atony was treated in 3 patients by intravenous infusion of oxytocin. Despite failure of both conventional treatment with gastric aspiration and intravenous fluids or jejunal feeding, as well as the reported trials with bethanechol chloride and metaclopramide, these patients promptly responded to oxytocin. It appears that the latter may represent a solution to this uncommon but recalcitrant complication of peptic ulcer surgery.


Mycotoxins in house dust - an underestimated problem?
People in developed countries spend up to 90% of their time indoors. This led to an increased awareness for problems regarding indoor environment in recent years. It is known that especially spores, mycelia and organic compounds released by the microbial colony e.g. mycotoxins and microbial volatile organic compounds (MVOCs) can be harmful to human health. The aim of a pilot program is to investigate mould-dependent health complaints in a burdened population of the city of Leipzig, Germany. Phase 1 of the investigation includes inspection of dwellings, determination of exposure and clinical examination of exposed persons. In phase 2 it is planned to analyse the influence of burdens with mould spores and their metabolites like mycotoxins on health complaints. House dust seems to be a representative sample medium for sedimented spores and mycelia which may contain mycotoxins. The analysis will be performed by LC-MS-MS after extraction of the crude dust samples by accelerated solvent extraction. The qualitative proof of mycotoxins in house dust was successful in a case study with a high burden.


Author Correction: Identification and characterization of Colletotrichum species causing apple bitter rot in New York and description of C. noveboracense sp. nov.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


What a 31-yr multibreed herd taught us about the influence of B. indicus genetics on reproductive performance of cows.
Bos taurus × Bos indicus crosses are widespread in tropical and subtropical regions, nonetheless, quantitative information about the influence of B. indicus genetics on the reproductive performance of beef cattle is lacking. Herein, we determined the association between level of B. indicus genetics and reproduction from a 31-yr dataset comprising sequential breeding seasons of the University of Florida multibreed herd (n = 6,503 Angus × Brahman cows). The proportion of B. indicus genetics in this herd is evenly distributed by each 1/32nd or approximately 3-percentage points. From 1989 to 2020, the estrous cycle of cows was synchronized for artificial insemination (AI) based on detected estrus or timed-AI (TAI) using programs based on gonadotropin-releasing hormone and prostaglandin, and progestin/progesterone. All cows were exposed to natural service after AI and approximately 90-d breeding seasons, considering the day of AI as day 0. The proportion of B. indicus genetics of cows was associated negatively with pregnancy per AI, ranging from 51.6% for cows with 0%-19% of B. indicus genetics to 37.4% for cows with 81%-100% of B. indicus genetics. Similar association was found for estrous response at the end of the synchronization protocol, ranging from 66.3% to 38.4%, respectively. This reduced estrous response helped to explain the pregnancy results, once the pregnancy to AI of cows showing estrus was 2.3-fold greater than for those not showing estrus and submitted to TAI. Despite reduced pregnancy per AI, the increase in the proportion of B. indicus genetics of cows was not associated with a reduction in the proportion of pregnant cows at the end of the breeding season. Nevertheless, the interval from entering the breeding season to pregnancy was lengthened as the proportion of B. indicus genetics of cows increased. The median days to pregnancy was extended by 25 when the proportion of B. indicus genetics surpassed 78% compared with less than 20%. Thus, the increase in the proportion of B. indicus genetics of cows was related to a reduction in pregnancy per AI and lengthening the interval to attain pregnancy during the breeding season, but not with the final proportion of pregnant cows. As a result, reproductive management strategies directed specifically to cows with a greater proportion of B. indicus genetics are needed to improve the rate of pregnancy in beef herds.


Health-related quality of life in sickle cell disease.
Advances in drug therapy, hematopoietic stem cell transplantation, and technology have improved the morbidity and survival for those with sickle cell disease. The effect of this modern therapy on the health-related quality of life (HRQL) of those with sickle cell disease is not known. HRQL provides an assessment of how an illness, its complications, and its treatment are experienced by a patient. This review will examine prior work in HRQL in sickle cell disease and the rationale for utilizing HRQL as an outcome to measure impact of treatment. In addition, issues to consider when reporting HRQL will be presented.


[Use of the leukomobilizing capacity of dextran sulfate for assessing the severity of an ionizing radiation lesion].
It was shown that the number of lymphocytes migrating to the blood 3 h after the administration of dextran sulphate (DS) is a function of the radiation dose absorbed (up to 1.5 Gy). It is supposed that 3 populations of lymphocytes varying in radiosensitivity are present in the blood. The authors suggest that it is possible to estimate the degree of the radiation damage according to the number of lymphocytes circulating in the blood under the effect of DS. It was also shown that the number of CFUc in the blood after the injection of DS is a function of the radiation dose absorbed.


An additional marker for familial hypertrophic cardiomyopathy?
Family screening for hypertrophic cardiomyopathy using conventional techniques yields some equivocal cases. Although mutations in the beta-cardiac myosin heavy-chain gene (MYH7) have been demonstrated in some patients, additional diagnostic methods are desirable to clarify the equivocal cases until the full genetic spectrum is characterized. Because coronary flow reserve is reduced in patients with typical hypertrophic cardiomyopathy independent of the severity of left ventricular hypertrophy, this measurement may help to identify patients with equivocal features of the disease. Coronary flow reserve was measured in two subjects: one with a MYH7 mutation but without typical diagnostic features of hypertrophic cardiomyopathy, and one with borderline left ventricular hypertrophy but no mutation in the MYH7 gene. Both subjects underwent screening for hypertrophic cardiomyopathy because of a family history of the disease. Positron-emission tomography was performed to measure myocardial blood flow (MBF) with oxygen-15 labeled water. MBF was measured at baseline and during coronary vasodilatation obtained by intravenous dipyridamole (0.56 mg/kg body weight infused over 4 minutes). Coronary flow reserve was expressed as the ratio MBF-dipyridamole/MBF-baseline. Coronary flow reserve was 1.69 and 1.12 in the two subjects. Both of these values are 2 SD below that (3.87 +/- 1.08) measured in 17 normal subjects using the same method. Noninvasive quantification of coronary flow reserve by positron-emission tomography may have a role in identifying patients with equivocal hypertrophic cardiomyopathy and should be further explored.


Brainstem monoamine pathology of neonatal hypoxic-ischemic brain damage: a model of acute stage of neonatal asphyxia.
Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the most severe perinatal diseases and leads to high mortality and sometimes severe neurological sequelae. At the acute stage of HIE, it is thought to be the damage of catecholaminergic system in the brainstem. And then, HIE reflects mental development throughout the norepinephrine and serotonin systems, which mainly originates in the brainstem. Therefore, we studied both systems in the brainstem of neonatal HIE model rats with tyrosine hydroxylase (TH) and tryptophan hydroxylase (TpH) immunohistochemistry and a high-performance liquid column (HPLC) to measure norepinephrine and serotonin and their metabolism. As a result, the TH-positive and TpH-positive cell numbers significantly decreased 2 days after hypoxic-ischemic (HI) insult (n=10). However, 7 days after insult (n=10), the TH-positive and TpH-positive cell numbers had recovered in most regions. HPLC demonstrated a significant difference in the norepinephrine concentration 2 days after HI insult, but not in the other monoamines.


The effect of indwelling endoprosthesis on stone size or fragmentation after long-term treatment with biliary stenting for large stones.
Endoscopic biliary stenting is often used for large or difficult common bile duct (CBD) stones, but the effect of indwelling endoprosthesis on size or fragmentation of stones after long-term treatment with biliary stenting has not been formally established. We compared the stone size or fragmentation of common bile duct stones after a long period of biliary stenting. Endoscopic biliary endoprosthesis was performed for 49 high-risk patients with CBD stones too large or difficult to be extracted by conventional endoscopic means. Bile duct drainage was established in all the patients without complications. Of the patients, 24 died with endoprosthesis in situ all from causes unrelated to biliar disease; 22 underwent a second and three patients a third attempt at stone extraction. The largest stone diameter was >12 mm in all patients. In 11 of 25 patients (44%) the endoprosthesis allowed resolution of the problem of unextractable common bile duct stones. Four patients showed no existence of stent, and ERCP complete stone clearance from the CBD on programmized appointment after endoprosthesis insertion. Reduced size or fragmentation of stones was obtained in seven patients, and the stones could be removed endoscopically. The remaining 14 patients demonstrated no significant change in the size or fragmentation of their stones, and endoprostheses were replaced. These results suggest that endoscopic endoprosthesis for large or difficult CBD stones is an effective method to clear the duct in selected cases, as well as an important definitive treatment in high-risk patients.


Toxicity studies of select ionic liquids (1-ethyl-3-methylimidazolium chloride, 1-butyl-3-methylimidazolium chloride, 1-butyl-1-methylpyrrolidinium chloride, and n-butylpyridinium chloride) administered in drinking water to Sprague Dawley (Hsd:Sprague Dawley SD) rats and B6C3F1/N mice.
Ionic liquids (ILs) are synthetic solvents with applications in a variety of industrial and chemical industries. Human exposure to this diverse chemical class is primarily through dermal or oral routes. Research suggests toxicity may be associated with IL structural characteristics, including the type of cation base or alkyl chain substitutions associated with the cation. To further investigate this hypothesis, the National Toxicology Program (NTP) conducted 3-month toxicity studies in male and female Sprague Dawley (Hsd:Sprague Dawley SD) rats and B6C3F1/N mice (n = 10/sex/exposure group; 3 exposure concentrations per IL) to compare the relative toxicities of four ILs administered via drinking water-1-ethyl-3-methylimidazolium chloride (Emim-Cl), 1-butyl-3-methylimidazolium chloride (Bmim-Cl), 1-butyl-1-methylpyrrolidinium chloride (Bmpy-Cl), and n-butylpyridinium chloride (NBuPy-Cl). (Abstract Abridged).


[The determination of activity of low-molecular heparins against activated factor Xa by means of the diagnostic kit "Reachrom-Heparin" (scientific-production association "Renam")].
It is possible to successfully determine both the activity against activated factor Xa in animals plasma after heparins administration and specific activity against activated factor Xa of new anticoagulants by means of the domestic diagnostic kit "Reachrom-Heparin" developed by the company "Renam". It was compared to the similar kit "Berichrom heparin" (Dade Behring). No statistically significant differences were detected.


Strategies to manage the difficult colonoscopy.
During endoscopy, an endoscopist is inevitably faced with the occasional "difficult colonoscopy," in which the endoscopist finds it challenging to advance the endoscope to the cecum. Beyond optimization of technique, with minimized looping, minimal insufflation, sufficient sedation, and abdominal splinting when needed, sometimes additional tools may be needed. In this review, we cover available techniques and technologies to help navigate the difficult colonoscopy, including the ultrathin colonoscope, rigidizing overtube, balloon-assisted colonoscopy and the abdominal compression device.


Hand infections due to non-cholera Vibrio after injuries from St Peter's fish (Tilapia zillii).
We report 49 patients with a wide variety of hand infections, which developed after injuries from St Peter's fish (Tilapia zillii). Twenty-eight of 36 patients who had been operated on had non-cholera Vibrio infections, all identified as Vibrio vulnificus. The course in these patients was characterized by rapid spread of the infection with progressive necrosis of the tendon sheath, subcutaneous tissues and the skin. Two of them required amputations but the others had satisfactory functional results. Thirteen other patients were managed nonoperatively with intravenous antibiotics and all of them recovered completely.


A novel I247T missense mutation in the haptoglobin 2 beta-chain decreases the expression of the protein and is associated with ahaptoglobinemia.
We have identified a novel base substitution at codon 247 in the beta-chain of the haptoglobin 2 ( Hp(2)) allele in a Ghanaian with the Hp0 (ahaptoglobinemic) phenotype. The heterozygous T-->C substitution caused reduced expression of the protein when the mutant was transfected into COS7 cells. The base substitution resulted in a missense change of the non-polar amino acid isoleucine to the polar amino acid threonine at a position in the beta-chain that is highly conserved among several species. We had previously identified a mutation in the Hp gene promoter region for the same individual, which gives her genotype as -61C Hp(2)/-61C Hp(2)(I247T). Since the -61C mutation also leads to low Hp expression, the genotype represents the first and most definitive ahaptoglobinemic case reported in Africa.


Major surgery in patients with chronic renal failure.
To determine the risks of performing major surgical procedures on patients with chronic renal failure, the charts of twenty-nine hemodialysis patients who underwent thirty-eight elective and nine emergency operations were reviewed. Preoperative preparation included adequate hemodialysis of the patients, 88 per cent of whom were dialyzed within 24 hours of surgery. Azotemia was well controlled prior to administration of anesthesia. The average preoperative hematocrit was 26 per cent, and only one patient was hyperkalemic preoperatively. There were no intraoperative complications attributable to the patients' impaired renal function. Postoperative complications were frequent and are discussed in detail. Hemodialysis was done immediately postoperatively in five patients and on the first postoperative day in twenty-three additional patients with no problems. There were only two deaths (4.3 per cent) in the series. With careful monitoring during the perioperative period, major surgical procedures can safely be performed on patients with chronic renal failure.


Identification of susceptibility variants to benign childhood epilepsy with centro-temporal spikes (BECTS) in Chinese Han population.
Benign Childhood Epilepsy with Centro-temporal Spikes (BECTS) is the most common form of idiopathic epilepsy in children, accounting for up to 23% of pediatric epilepsy. The pathogenesis of BECTS is unknown, but it is thought that genetic factors play a role in susceptibility to the disease. To investigate the role of common genetic variants in BECTS pathogenesis, a 2-stage genome-wide association study (GWAS) was performed in 1,800 Chinese Han BECTS patients, and 7,090 healthy controls. Genetic findings were used in a Mendelian Randomization study in the UK Biobank dataset to investigate the potential role of smoking in BECTS. Definitive evidence of a role for common-variant heritability was demonstrated, with heritability of BECTS of >10% observed even with conservative disease prevalence assumptions. Although no individual locus achieved genome-wide significance, twelve loci achieved suggestive evidence of association (5 × 10-8<P<10-5). Using combined genetic and brain tissue gene expression data analyzed by Summary-data-based Mendelian Randomization (SMR), causative association of BECTS was demonstrated with SNP rs1948 and the CHRNA5 t3603436 transcript (Peqtl = 2·10 × 10-12, Psmr = 7·9 × 10-5). This finding indicates rs1948 is significantly associated with BECTS through effects on expression of CHRNA5 in brain tissue. The identification of novel loci suggests involvements of KALRN and the CHRNA5-A3-B4 cluster in BECTS. Using a generalized SMR approach we demonstrate that maternal smoking around birth is significantly associated with increased risk of BECTS (odds ratio = 3·90, P = 0·0099). This study shows that BECTS risk is at least partially heritable and due to common genetic variants. Additionally, we demonstrate that BECTS risk is substantially increased by maternal smoking around birth.


Clinical value of prolactin bioassay in euprolactinemic reproductive disorders.
To examine the disparity between clinical presentation and prolactin (PRL) measured by radioimmunoassay (RIA), serum samples from 128 patients with galactorrhea and/or reproductive disorders were evaluated by RIA for immunoassayable PRL (RIA-PRL) and by Nb2 lymphoma cell proliferation assay for bioassayable PRL (bioassay-PRL). One hundred fifteen patients had normal RIA-PRL and 13 patients had high RIA-PRL (greater than 25 ng/ml). Twenty patients had galactorrhea, two of whom had hyperprolactinemia. The reproductive disorders in female patients included infertility, amenorrhea, oligomenorrhea, irregular menstrual cycles, and luteal phase defects. Six oligospermic males also were studied. Twenty-three male and female volunteers with no evidence of reproductive disorders served as controls. Appropriate comparisons showed that PRL bioassay/RIA ratio, an index of agreement between the two assay systems, did not differ for the various patient groups compared with controls. It is concluded that Nb2 lymphoma bioassay does not provide additional diagnostic value to RIA in defining the cause of euprolactinemic galactorrhea and/or reproductive disorders.


Application of 18F-PSMA-1007 PET/MR Imaging in Early Biochemical Recurrence of Prostate Cancer: Results of a Prospective Study of 60 Patients with Very Low PSA Levels ≤ 0.5 ng/mL.
The use of 18F-PSMA-1007 and the role of PET/MR in the diagnosis of prostate cancer are not conclusively confirmed. There are reports indicating the potential pros and cons of using 18F-PSMA-1007 as well as the PET/MR technique in prostate cancer recurrence, but they are not yet included in the EAU guidelines. The aim of the study was to assess the effectiveness of 18F-PSMA-1007 PET/MR in detecting BCR lesions at very low PSA levels <0.5 ng/mL. Sixty patients with BCR after radical prostatectomy (RP) with PSA ranged 0.1-0.5 ng/mL were enrolled in a prospective study. All patients underwent simultaneous whole-body and pelvic 18F-PSMA-1007 PET/MR. The obtained results were verified by 12-month follow-up. Fifty-three lesions were detected in 45 patients with 75% detection rate. The mean PSA value was 0.31 ng/mL. Of all PSMA-positive foci, 91% were localized in the pelvis, and only 9% of lesions were located in the extrapelvic region. Local recurrences were detected in 29%, PSMA-positive lymph nodes were detected in 64% of patients and bone metastases lesions were detected in 7% of patients. 18F-PSMA-1007 PET/MR seems to be an excellent diagnostic tool in patients with early BCR with very low PSA levels, especially with dt PSA < 6 months. The synergistic effect of combining 18F-PSMA-1007 and whole-body PET/MR with precise multiparametric assessment of pelvic lesions is of particular benefit in early BCR.


Assessing cognitive alignment in different types of dialog by means of a network model.
We present a network model of dialog lexica, called TiTAN (Two-layer Time-Aligned Network) series. TiTAN series capture the formation and structure of dialog lexica in terms of serialized graph representations. The dynamic update of TiTAN series is driven by the dialog-inherent timing of turn-taking. The model provides a link between neural, connectionist underpinnings of dialog lexica on the one hand and observable symbolic behavior on the other. On the neural side, priming and spreading activation are modeled in terms of TiTAN networking. On the symbolic side, TiTAN series account for cognitive alignment in terms of the structural coupling of the linguistic representations of dialog partners. This structural stance allows us to apply TiTAN in machine learning of data of dialogical alignment. In previous studies, it has been shown that aligned dialogs can be distinguished from non-aligned ones by means of TiTAN -based modeling. Now, we simultaneously apply this model to two types of dialog: task-oriented, experimentally controlled dialogs on the one hand and more spontaneous, direction giving dialogs on the other. We ask whether it is possible to separate aligned dialogs from non-aligned ones in a type-crossing way. Starting from a recent experiment (Mehler, Lücking, & Menke, 2011a), we show that such a type-crossing classification is indeed possible. This hints at a structural fingerprint left by alignment in networks of linguistic items that are routinely co-activated during conversation.


Fragile X syndrome carrier screening accompanied by genetic consultation has clinical utility in populations beyond those recommended by guidelines.
Fragile X syndrome (FXS) is the most common inherited form of intellectual disability. Many providers offer preconception or prenatal FXS carrier screening. However, guidelines recommend screening only for those with a family history or undergoing fertility evaluation. Wider screening has been resisted because of concerns about patient understanding of FXS-associated inheritance patterns and phenotypes. Additionally, the clinical utility has been questioned. We addressed these concerns by analyzing reproductive decision-making and pregnancy management informed by post-test genetic consultation among 122 FMR1 premutation carriers identified by expanded carrier screening. Sixty-three percent of those screened met guidelines screening criteria; the remaining 37% did not. Ninety-eight percent had undergone post-test genetic consultation. Of respondents screened preconceptionally, 74% reported planning or pursuing actions to reduce the risk of an affected pregnancy; the extent to which couples planned/pursued these actions was not significantly different between those meeting either screening criterion (76%) versus those meeting neither criterion (55%). Of respondents screened prenatally, 41% pursued prenatal diagnostic testing; the extent to which couples pursued prenatal diagnosis was not significantly different between those who met either screening criterion (37%) versus those who met neither criterion (31%). These results support the expansion of FXS screening criteria in guidelines.