Enhancement of canine coronary collateral flow by nafazatrom.
The ability of oral nafazatrom treatment (10 mg/kg) 2 h preceding occlusion of the left anterior descending coronary artery for 6 h to limit expansion of myocardial injury was studied in anaesthetized canine hearts. Collateral blood flow was obtained with a load line analysis, employing aortic pressure, post-stenotic coronary pressure, and retrograde coronary flow from the occluded vessel. Contractile changes in the subendocardial ischemic perfused muscles were measured with ultrasonic techniques. Infarct size was determined post-mortem by a biochemical staining method and excision of necrosis. Post-stenotic coronary pressure was slightly below aortic pressure in both groups before coronary occlusion, and fell to 29 and 27% of aortic pressure in vehicle- and drug-treated hearts, respectively, after the insult. Retrograde flow was 2.4 +/- 0.6 vs. 4.1 +/- 0.7 ml/min in tylose- or nafazatrom-treated hearts. Collateral flow amounted to 1.5 +/- 0.06 vs. 2.5 +/- 0.04 ml/min in controls and drug-protected hearts. Contractility (dP/dtmax) and the %-segment shortening were greater in the ischaemic myocardium after nafazatrom treatment. Infarct size was 38 +/- 5.2 vs. 17 +/- 3.4 g/100 g left ventricle in the vehicle controls and nafazatrom group, respectively. Nafazatrom reduced infarct size by 46%. Besides other mechanisms, this was due to improved %-segment shortening and increased periinfarction collateral blood supply to jeopardized but viable myocardium. The drug may be of value in ischaemic heart disease as shown by the enhanced regional myocardial perfusion and improved contractility.


Prevalence of Polycystic Ovary Syndrome in Patients With McCune Albright Syndrome.
To identify polycystic ovarian syndrome (PCOS) in a population of female patients with McCune-Albright syndrome (MAS) by retrospective chart review. Retrospective study. Academic setting. All female patients with a prior diagnosis of MAS who were more than 12 years of age at the time of chart review. Only complete medical records from January 2009 to January 2020 were included in the analysis. None. Diagnosis of PCOS based on the Rotterdam 2003 criteria. Seventeen female patients with MAS were included in the analysis. PCOS appeared to be more prevalent in MAS patients than expected based on population estimates (exact binomial test = 0.353; CI = 0.142-0.617, P = .01). The average body mass index was not significantly different between MAS patients with and without PCOS (23.38 kg/m2 vs 23.44 kg/m2, 2-sample Wilcoxon rank-sum test with continuity correction, W = 29, P = 0.733). The majority of patients (71%) were treated with an aromatase inhibitor and/or a gonadotropin-releasing hormone (GnRH) agonist. The results of this study suggest that female individuals with MAS have a statistically higher prevalence of PCOS. These findings warrant further studies to determine whether the increased risk of PCOS may be associated with precocious puberty, treatment of precocious puberty, or other factors.


Morphogenesis of nuclear polyhedrosis virus from Autographa californica in a cell line from Mamestra brassicae (cabbage moth). Further aspects on baculovirus assembly.
Cultures of cell line IZD-MB 0503 from Mamestra brassicae were inoculated with nonoccluded nuclear polyhedrosis virus of Autographa californica (AcNOV). At 1 h postinoculation (p.i.) nucleocapsids were found in the cytoplasm near nuclear pores and within the nucleoplasm. Formation of virogenic stroma was observed at 7 h p.i. The first short empty capsids were seen at 10 h postinoculation (p.i.), followed by partially and completely filled nucleocapsids (11-12 h p.i.) with most capsids filled at 12 h and later. This suggests that nucleocapsid components, such as capsid and DNA-core, assemble in successive stages rather than simultaneously. Viral progeny, being released from the cells by budding, were observed at 13 h p.i.


Experience with the Russian model 249 suture gun for anastomosis of the rectum.
The Russian Model 249 circular suturing device used for rectal anastomoses in 62 patients undergoing high or low anterior resection or colectomy and ileorectal anastomosis was technically easy to use. The 38 high anastomoses were all shown to be intact by a Gastrografin, meglucomine diatrigoate, enema study 14 days after the operation. Of the 24 low anastomoses, six demonstrated small, 5 to 10 millimeters, dehiscences, two of the latter being evident also upon clinical examination. At least six of the low anastomoses were made at levels too low for hand suture from the abdomen. In three patients, moderate hemorrhage from the anastomotic site during the first two or three days complicated the situation; in all, it ceased spontaneously. In two patients, strictures developed, one of which rectified itself once the fecal stream was restored to the rectum on closing the transverse colostomy, the other was submitted to instrumental dilation, perhaps unnecessarily. The Model 249 circular suturing device provides colorectal anastomoses that are at least as secure as those done by hand suture and, sometimes, enables an anastomosis to be made at a lower level than would be possible by the conventional suture technique through the abdomen. Bleeding from the anastomotic site and subsequent stricture formation are rare complications of this technique.


An underestimated visual pathway in reptiles.
Field potentials evoked in the turtle general cortex by electric stimulation of the optic tectum were analyzed. Cathodal polarization and subtotal lesions of n. rotundus led to either facilitation or depression of later components of the cortical potential. On the contrary, cathodal polarization and lesions of n.geniculatus lateralis dorsalis similarly affected the initial component. After 21-23 months following eye enucleation or optic nerve section, the conduction of fast tectal volleys to the general cortex via n. geniculatus lateralis dorsalis was blocked, though the conduction of tectal impulses to the dorsal ventricular ridge via n.rotundus survived. It is concluded that in turtles one more visual channel, i.e., retino-tecto-geniculo-cortical, is functioning, in addition to well-known retino-tecto-rotundo-telencephalic and retino-geniculo-cortical channels.


A time-efficient protocol for transthoracic echocardiography during transfemoral transcatheter aortic valve implantation: early identification and effective management of intraprocedural complications.
Transfemoral transcatheter aortic valve implantation (TAVI) under conscious sedation is the most widely used method of implantation. Echocardiography is used to detect complications and to assess the implantation result. The aim of this paper is to provide a time-efficient protocol when transthoracic echocardiography (TTE) is used to guide TAVI procedures.


Arteriovenous fistula creation by nephrologist and its outcomes: a prospective cohort study from Vietnam.
Arteriovenous fistula (AVF) is the gold standard vascular access for effective hemodialysis. There is a growing interest in AVF creations performed by nephrologists to help reduce vascular surgeons' workload and enhance the timely treatment of patients with end-stage renal disease (ESRD). However, little is known about the feasibility and effectiveness of this approach in the low-resource settings. We examined the AVF surgical success and failure rates and associated predictors as well as early complications of AVF creations by a trained nephrologist with supports from vascular surgeons in Vietnam. A prospective cohort study was conducted on all adult ESRD patients at the Hemodialysis Department of Thong Nhat Hospital between April 2018 and October 2020. Information on demographic characteristics, comorbidities, and AVF creations was collected using a standardized questionnaire. All patients were followed up until 18 weeks post-surgery. Among 100 patients with a mean age of 61.22 ± 17.11 years old, male accounted for 54%. Common causes of ESRD included hypertension (57%) and diabetes (32%). Just more than half (52%) of them reported having an AVF creation prior to ESRD. The successful first-time AVF creation rate was 98% (13/99, 95%CI: 8.74-21.18%). The primary and secondary AVF failure rates were 13.13% (13/99, 95%CI: 8.74-21.18%) and 16.87% (14/83, 95%CI: 10.32-26.25%), respectively. Early complications included bleeding (1%) and early thrombosis of the anastomosis (2%). There was a statistically significant association between age and primary AVF failure (P = 0.005) and between operation time and secondary AVF failure (P = 0.038). AVF creations performed by well-trained and skilled interventional nephrologists with supports from vascular surgeons can result in favorable short- and long-term outcomes. It is important to follow up older patients and those with a long operation time to detect AVF failures. A standardized AVF creation training program and practice for nephrologists is needed to increase successful rates.


Immunity to tetanus and diphtheria in the UK in 2009.
This study aimed to estimate the immunity of the UK population to tetanus and diphtheria, including the potential impact of new glycoconjugatate vaccines, and the addition of diphtheria to the school leaver booster in 1994. Residual sera (n=2697) collected in England in 2009/10 were selected from 18 age groups and tested for tetanus and diphtheria antibody. Results were standardised by testing a panel of sera (n=150) to enable comparison with a previously (1996) published serosurvey. Data were then standardised to the UK population. In 2009, 83% of the UK population were protected (≥0.1 IU/mL) against tetanus compared to 76% in 1996 (p=0.079), and 75% had at least basic protection against diphtheria (≥0.01 IU/mL) in 2009 compared to 60% in 1996 (p<0.001). Higher antibody levels were observed in those aged 1-3 years in 2009 compared to 1996 for both tetanus and diphtheria. Higher diphtheria immunity was observed in those aged 16-34 years in 2009 compared to 1996 (geometric mean concentration [GMC] 0.15 IU/mL vs. 0.03 IU/mL, p<0.001). Age groups with the largest proportion of susceptible individuals to both tetanus and diphtheria in 2009 were <1 year old (>29% susceptible), 45-69 years (>20% susceptible) and 70+ years (>32% susceptible). Low immunity was observed in those aged 10-11 years (>19% susceptible), between the scheduled preschool and school leaver booster administration. The current schedule appears to induce protective levels; increases in the proportions protected/GMCs were observed for the ages receiving vaccinations according to UK policy. Glycoconjugate vaccines appear to have increased immunity, in particular for diphtheria, in preschool age groups. Diphtheria immunity in teenagers and young adults has increased as a result of the addition of diphtheria to the school leaver booster. However, currently older adults remain susceptible, without any further opportunities for immunisations planned according to the present schedule.


[Ultrasonic diagnostic measures in ambulant internal medical patients (author's transl)].
Ultrasonic investigation with the rapid B picture is a non-invasive method of examination which does not distress the patient and has no contraindications. It provides the examiner with abundant additional information, it is quickly performed without preparation and is therefore particularly to be recommended in ambulant patients. Ultrasonic investigation is no competitor to angiography or scintigraphy, but should be called on as a "forefield" diagnostic method before invasive methods. The various diagnostic possibilities are illustrated with some examples.


The perspectives of people who use drugs regarding short term involuntary substance use care for severe substance use disorders.
In the Canadian Province of British Columbia (BC), the BC Mental Health Act permits involuntary care for treating mental disorders. However, the Act has also been applied to provide involuntary care to individuals with a primary substance use disorder, in the absence of specific guidelines and legislation, and with insufficient understanding of perspectives of people who use drugs (PWUD) regarding this approach. As part of a larger mixed-methods research project providing an overview of involuntary care for severe substance use disorders in BC, three focus groups were convened with: PWUD, families and caregivers, and Indigenous community stakeholders. This analysis examines perspectives from the focus group of PWUD, consisting of nine participants from local and regional drug user and advocacy organizations regarding involuntary care. A qualitative descriptive approach and thematic analysis were conducted, using a coding framework developed deductively and inductively, and participant perspectives were interpreted drawing on problematization theory. Participants did not endorse the use of involuntary care, instead emphasizing significant changes were needed to address shortcomings of the wider voluntary care system. When asked to conceptualize what an acceptable involuntary care scenario might look like (under hypothetical and ideal conditions), participants recommended it should include: individual control and autonomy, peer advocacy in decision-making, and elimination of police and criminal justice system involvement from treatment encounters. Participants saw involuntary care to be an inappropriate approach given the shortcomings of the current system, noting also problems inherent in its use to manage severe SUDs and imminent harm, and prioritized alternate approaches to offsetting risks. Improving voluntary care for substance use, along with addressing the social determinants of health that put individuals at risk of problematic substance use and harm, were prioritized in participant perspectives. Participant comments regarding the use of involuntary care bring forward alternate solutions in the context of the opioid overdose crisis, and a reconceptualization of the 'problem' of managing severe substance use disorders.


Soluble overexpression of a flagellin derivative from Salmonella enterica using synonymous codon substitutions of 5'-coding region in Escherichia coli.
To obtain a recombinant flagellin derivative CBLB502, expressed in functionally soluble form, the technology of library construction and screening of synonymous codon variants was employed, and its expression, solubility, and activity were assessed. We screened several synonymous codon variants scvCBLB502s with the enhanced solubility from the constructed library, harboring the random substitutions of the first ten amino acid residues of the parental CBLB502 with synonymous codons. Among them, scvCBLB502-5 was purified (> 8.4 mg/l) by single step procedure using an affinity chromatography without any ancillary treatment with protease inhibitor cocktail solution and/or boiling at 90 °C. Subsequent study showed that the recombinant protein scvCBLB502-5 distinctly induced the TLR5 (Toll-Like Receptor 5)-mediated NF-κB activation and also IL-8 production in HEK293-hTLR5 cells. Results showed that scvCBLB502-5, engineered through the synonymous codon substitutions, was easily expressed in functionally soluble form and maintained the proper folding to be recognized by TLR5, as an inducer for pathogen-associated molecular pattern (PAMP).


3,6'-disinapoyl sucrose attenuates Aβ1-42 - induced neurotoxicity in Caenorhabditis elegans by enhancing antioxidation and regulating autophagy.
The aggregation of β-amyloid (Aβ) has the neurotoxicity, which is thought to play critical role in the pathogenesis of Alzheimer's disease (AD). Inhibiting Aβ deposition and neurotoxicity has been considered as an important strategy for AD treatment. 3,6'-Disinapoyl sucrose (DISS), one of the oligosaccharide esters derived from traditional Chinese medicine Polygalae Radix, possesses antioxidative activity, neuroprotective effect and anti-depressive activity. This study was to explore whether DISS could attenuate the pathological changes of Aβ1-42 transgenic Caenorhabditis elegans (C. elegans). The results showed that DISS (5 and 50 μM) treatment significantly prolonged the life span, increased the number of egg-laying, reduced paralysis rate, decreased the levels of lipofuscin and ROS and attenuated Aβ deposition in Aβ1-42 transgenic C. elegans. Gene analysis showed that DISS could up-regulate the mRNA expression of sod-3, gst-4, daf-16, bec-1 and lgg-1, while down-regulate the mRNA expression of daf-2 and daf-15 in Aβ1-42 transgenic C. elegans. These results suggested that DISS has the protective effect against Aβ1-42 -induced pathological damages and prolongs the life span of C. elegans, which may be related to the reduction of Aβ deposition and neurotoxicity by regulating expression of genes related to antioxidation and autophagy.


Efficient charge generation and collection in organic solar cells based on low band gap dyad molecules.
Low band gap dyad molecules were prepared that have absorption spectra matched well with the solar spectrum, and the construction of efficient charge transport pathways was observed. Under AM 1.5 illumination, the devices have achieved the highest J(SC) (4.79 mA cm(2)) and FF (0.46) in dyad-based organic solar cells to date.


Sensory hybrid host materials for the selective chromo-fluorogenic detection of biogenic amines.
Pyrylium-containing mesoporous materials have been used for the chromo-fluorogenic sensing of biogenic amines in an aqueous environment.


Leber's hereditary optic neuropathy: a genetic disorder of the eye.
Leber's hereditary optic neuropathy is a rare, maternal linked, genetic disorder that is characterized by progressive bilateral optic nerve degeneration. Male offspring are predominately affected, and blindness occurs during the second or third decade of life. There is no known treatment; however, individuals affected early in life may show some visual recovery in later years. These patients require a supportive and caring environment to assist them, as this disease often results in devastating life style changes.


Anatomically Coiled Internal Carotid Artery Resulting in Severe Dysphagia and Burning Mouth Syndrome.
This is a report of a 65-year-old female presenting with symptoms of dysphagia due to a coiled left internal carotid artery, treated with resection and primary repair. Dysphagia lusoria is more commonly caused by aortic arch anomalies, aberrant subclavian or common carotid arteries. Internal carotid tortuosity as a cause of severe dysphagia and burning mouth syndrome is highly unusual. A literature review examines the etiology, natural history, and treatment options.


Malperfusion syndromes in acute type A aortic dissection do not affect long-term survival in Chinese population: A 10-year institutional experience.
Preoperative malperfusion of acute type A aortic dissection (ATAAD) remains a catastrophic complication that is associated with high postoperative morbidity and mortality. The relationship between malperfusion and long-term survival in the Chinese population is unknown. A total of 771 patients who underwent ATAAD surgery between January 2009 and December 2018 at our center were included. In-hospital mortality, complications, morbidity, and long-term survival were analyzed. Preoperative malperfusion was identified in 292 of 771 patients (37.9%), the in-hospital mortality rate was 20.9% in patients with preoperative malperfusion and 9.2% in those without. Independent predictors of in-hospital mortality included any malperfusion (odds ratio [OR], 5.132; p = .001), pericardial tamponade (OR, 1.808; p = .046), advanced age (OR, 1.028; p = .003), and cardiopulmonary bypass time (OR, 1.008; p = .001). Immediate emergency surgery (OR, 0.492; p = .007) and antegrade cerebral perfusion perioperatively (OR, 0.477; p = .020) were protective against postoperative mortality. The postoperative survival rates at 1, 3, and 5 years were 94.4% ± 1.5%, 91.9% ± 1.8%, and 83.0% ± 3.2% in patients with malperfusion and 94.7% ± 1.1%, 90.2% ± 1.7%, and 84.4% ± 2.7%, respectively, in those without. Preoperative malperfusion did not significantly affect the long-term outcomes of operative survivors (log-rank p = .601). Malperfusion resulted in an unfavorable prognosis in the short term, but showed almost equal long-term survival in patients without malperfusion of ATAAD. Emergency central repair might be considered to further improve the outcomes of ATAAD with malperfusion.


Health-Related Quality of Life Score and Outcomes in Living Donor Renal Transplant Recipients With COVID-19.
Renal transplant recipients with severe COVID-19 may have sequelae that can affect their quality of life and can have poor patient and graft outcomes. We conducted a prospective, observational study between April 1, 2020, and December 31, 2020, to assess patient and graft outcomes and quality of life using the EQ-5D quality of life survey score at baseline and at follow-up of at least 12 weeks. Of the 3100 renal transplant recipients with follow-up, 104 patients had COVID-19. Of these patients, 75 (72.1%) had mild-moderate disease and 29 (27.9%) had severe disease. In addition, 78 patients (75.0%) were hospitalized, with 43 patients (41.3%) in the intensive care unit. Remdesivir was used in 46 of the 78 hospitalized patients (58.9%) without any mortality benefitin the severe group. Sixteen patients (17.5%) were rehospitalized with opportunistic infection (n = 7), persistent graft dysfunction (n = 6), pulmonary sequelae (n = 2), and angina (n = 1). Thirteen patients (12.5%) died. On follow-up, the overall EQ-5D score was significantly lower, particularly the pain and anxiety/depression scores in patients with mild-moderate disease, whereas all components of the EQ-5D score were significantly affected in patients with severe COVID-19. Renal transplant recipients with severe COVID-19 are at high risk of mortality, acute graft dysfunction, and residual disability, severely affecting their quality of life score and requiring rehabilitation.


Kinetics of thermal oxidative degradation of poly (vinyl chloride) containing Ca and Sn at low temperature.
Calcium metal soap and polyol (dipentaerythritol) additives are replacing or partially replacing organotin in poly(vinyl chloride) (PVC) heat stabilizers due to their low cost, nontoxicity and safety. Therefore, investigating the low-temperature thermal oxidative degradation of stabilized plasticized PVC from the source is essential for recycling. This work uses isothermal thermogravimetry to investigate the thermal degradation process and isothermal discoloration of PVC/calcium metal soap/dipentaerythritol/organotin soft products with excellent heat resistance at 453-503 K and under air atmosphere. The chemical kinetics method is used to fit a single equation model of mass loss and time during the thermal oxidation degradation of PVC, and the kinetic equation obtained is: -ln(1 - α) = 3.83 × 103exp (-6834.4/T)t. When the temperature is 453-503 K, the calculation results are basically consistent with the experimental data and are independent of the heating rate and temperature changes. In addition, the isothermal discoloration of different PVC materials was tested under air atmosphere at 468 K. The results show that when the test material is PVC/calcium metal soap/dipentaerythritol/organotin, the heat aging time to become completely blackened is longer than that of the blank sample, which indicates a strong interaction occurs between Sn, Ca and dipentaerythritol complexes and PVC molecules, inhibiting the release of hydrogen chloride. At the same time, in order to recover PVC and prevent it from carbonization, if the temperature is set to 486 K, the thermal oxidation degradation time of PVC should be less than 130 min.


Intrauterine administration of peripheral blood mononuclear cells activated by human chorionic gonadotropin in patients with repeated implantation failure: A meta-analysis.
The purpose of this study was to assess whether intrauterine administration of peripheral blood mononuclear cells (PBMCs) activated by human chorionic gonadotropin (hCG) could improve the pregnancy and live birth rates in women with repeated implantation failure (RIF), and whether the parameters of co-culture of hCG and PBMCs would affect the clinical outcomes. Six databases (PubMed, Ovid, Medline, NCBI, Cqvip and Wanfang) were searched up to October 2020 by two independent reviewers. Seven studies were included according to specific inclusion and exclusion criteria. A meta-analysis showed that the pregnancy and live birth rates were significantly increased in the case group compared with the control group (odds ratio [OR]: 3.43, 95 % confidence interval [CI]: 1.78-6.61; P = 0.0002 and OR: 2.79, 95 % CI: 1.09-7.15; P = 0.03), especially when hCG was cultured with PBMCs for 48 h or PBMCs administration was performed two or three days before embryo transfer (ET). Neither the dosage of the hCG co-cultured with PBMCs nor the mean concentration of the administered PBMCs appeared to influence the therapeutic efficiency. In conclusion, intrauterine administration of PBMCs co-cultured with hCG for 48 h, conducted two or three days before ET, could be an effective therapy for women experiencing RIF. Due to the limitations of sample size and quality of the included studies, further high-quality studies with large sample sizes are warranted to optimize the parameters of hCG and PBMC co-culture to help more RIF patients benefit from this therapy.


Calmodulin binds to Drosophila TRP with an unexpected mode.
Drosophila TRP is a calcium-permeable cation channel essential for fly visual signal transduction. During phototransduction, Ca2+ mediates both positive and negative feedback regulation on TRP channel activity, possibly via binding to calmodulin (CaM). However, the molecular mechanism underlying Ca2+ modulated CaM/TRP interaction is poorly understood. Here, we discover an unexpected, Ca2+-dependent binding mode between CaM and TRP. The TRP tail contains two CaM binding sites (CBS1 and CBS2) separated by an ∼70-residue linker. CBS1 binds to the CaM N-lobe and CBS2 recognizes the CaM C-lobe. Structural studies reveal the lobe-specific binding of CaM to CBS1&2. Mutations introduced in both CBS1 and CBS2 eliminated CaM binding in full-length TRP, but surprisingly had no effect on the response to light under physiological conditions, suggesting alternative mechanisms governing Ca2+-mediated feedback on the channel activity. Finally, we discover that TRPC4, the closest mammalian paralog of Drosophila TRP, adopts a similar CaM binding mode.


A case of thyroid storm caused by Graves' disease misdiagnosed as panic attack due to panic disorder.
Graves' disease is characterized by hyperthyroidism and its symptoms often overlap with those of panic disorder, which may make it difficult to distinguish between the two conditions. In this report, we describe how proper diagnosis of thyroid disease in patients with mental illness can lead to appropriate treatment. We encountered a 34-year-old woman in whom thyroid crisis from Graves' disease was misdiagnosed as panic attack. The patient was being managed as a case of panic disorder and bipolar disorder in a psychiatric outpatient setting. About 6 months before presentation she had lost about 16 kg in weight, and a month before presentation she developed several unpleasant symptoms as her condition worsened. Several weeks before she had had severe palpitations, tachycardia, and discomfort in her throat. She became unable to eat solids, ate only yogurt and gelatin, and felt it difficult to take psychiatric drugs. She visited our emergency outpatient department on a Sunday morning, presenting with nausea, severe tachycardia, fever, and restlessness with anxiety. We treated her as panic disorder with fever, but noted proptosis and considered the possibility of Graves' disease. Thyroid function tests were performed even though data from her clinic was not available because it was a weekend. Because there was no improvement in her condition after her first visit, she returned to our hospital early the next morning. We had misdiagnosed her as having severe panic attacks due to panic disorder, and after a diazepam injection had allowed her to go home. Later that day, the thyroid function test results became available, and her symptoms and the results strongly indicated a thyroid storm. The endocrinology department was consulted immediately, and she was referred for hospitalization the next day. During hospitalization, she was treated with steroid and radioactive iodine therapy and was discharged from hospital in 3 weeks. Psychiatrists and doctors engaged in psychosomatic medicine need to consider the possibility of severe hyperthyroidism as a differential diagnosis of panic disorder.


Clinical pearl: Expanding knowledge of emergency contraception among dermatologists.
Dermatologists prescribe teratogenic or potentially teratogenic medications to treat a variety of skin diseases, including spironolactone for hormonal dysregulation in hidradenitis suppurativa or isotretinoin for severe acne. Although contraceptive options are regularly discussed, dermatologists must also be familiar with emergency contraceptive methods in the case that patients receiving teratogenic medications engage in unprotected sexual intercourse and do not desire pregnancy. A lack of knowledge regarding emergency contraceptive options may represent a practice gap for dermatologists.


Anterior Cruciate Ligament Reconstructed Patients Who Recovered Normal Postural Control Have Dissimilar Brain Activation Patterns Compared to Healthy Controls.
Postural control, which is a fundamental functional skill, reflects integration and coordination of sensory information. Damaged anterior cruciate ligament (ACL) may alter neural activation patterns in the brain, despite patients' surgical reconstruction (ACLR). However, it is unknown whether ACLR patients with normal postural control have persistent neural adaptation in the brain. Therefore, we explored theta (4-8 Hz) and alpha-2 (10-12 Hz) oscillation bands at the prefrontal, premotor/supplementary motor, primary motor, somatosensory, and primary visual cortices, in which electrocortical activation is highly associated with goal-directed decision-making, preparation of movement, motor output, sensory input, and visual processing, respectively, during first 3 s of a single-leg stance at two different task complexities (stable/unstable) between ACLR patients and healthy controls. We observed that ACLR patients showed similar postural control ability to healthy controls, but dissimilar neural activation patterns in the brain. To conclude, we demonstrated that ACLR patients may rely on more neural sources on movement preparation in conjunction with sensory feedback during the early single-leg stance period relative to healthy controls to maintain postural control. This may be a compensatory protective mechanism to accommodate for the altered sensory inputs from the reconstructed knee and task complexity. Our study elucidates the strategically different brain activity utilized by ACLR patients to sustain postural control.


Testicular cultivation of Treponema pallidum (Nichols strains) facilitated by sustained-release steroid administration.
Treponema pallidum cultivation is facilitated by substitution of methylprednisolone acetate suspension for hydrocortisone administration during rabbit testicular infection. Methylprednisolone suspension reduces testicular mononuclear cell infiltration and should benefit future studies of virulent T. pallidum.


A multifocal schwannoma of the masseteric nerve causing hemicrania.
A case is reported of schwannoma of the right masseteric nerve, invading the pterygopalatine fossa and the parapharyngeal space through the mandibular notch in a 61-year-old woman. The tumor in this case was composed of four various-sized interconnected nodules, simulating a string of beads. The tumor was the cause of the patient's chronic hemicrania, as confirmed by the relief from and disappearance of head pain after surgical removal of the tumor. The most important aspects of this case are the anatomic site of the schwannoma and its uncommon clinicopathologic manifestations; this tumor originated from the masseteric nerve and is the first case reported to straddle the mandibular notch.


A triple combination gemcitabine + romidepsin + cisplatin to effectively control triple-negative breast cancer tumor development, recurrence, and metastasis.
Triple-negative breast cancer (TNBC) is an aggressive, lethal, heterogeneous type of breast cancer (BC). TNBC tends to have a lower response rate to chemotherapy and a lower 5-year survival rate than other types of BC due to recurrence and metastasis. Our previous study revealed that a combination of gemcitabine, romidepsin, and cisplatin was efficacious in controlling TNBC tumor development. In this study, we extended our investigation of gemcitabine + romidepsin + cisplatin in controlling TNBC tumor recurrence and metastasis. We investigated the ability of gemcitabine + romidepsin + cisplatin to control cell survival and invasiveness using cell viability, soft agar colony formation, and transwell invasion assays. We determined the efficacy of gemcitabine + romidepsin + cisplatin in controlling tumor recurrence and metastasis using cell-derived xenograft animal models. We used immunoblotting to study signaling modulators regulated by gemcitabine + romidepsin + cisplatin in TNBC cells and tumor tissues. Treatment with gemcitabine + romidepsin + cisplatin reduced the TNBC MDA-MB231 and MDA-MB468 cell survival to ~ 50% and ~ 15%, as well as invasiveness to ~ 31% and ~ 13%, respectively. Gemcitabine + romidepsin + cisplatin suppressed modulators involved in epithelial-mesenchymal transition in an ROS-dependent manner. Controlling tumor recurrence, the Gem plus Rom + Cis regimen (~ 112%) was more efficacious than the Gem plus Cis regimen (~ 21%) in tumor growth inhibition. The Gem plus Rom + Cis regimen efficaciously reduced the development of metastatic nodules to 20% in animals. The gemcitabine plus romidepsin + cisplatin regimen was highly efficacious in controlling TNBC tumor development, recurrence, and metastasis in animals. The combination regimen should be poised for efficient translation into clinical trials for controlling the recurrence and metastasis, ultimately contributing to reducing mortality and improving TNBC patients' quality of life.


Conditions for metachronal coordination in arrays of model cilia.
On surfaces with many motile cilia, beats of the individual cilia coordinate to form metachronal waves. We present a theoretical framework that connects the dynamics of an individual cilium to the collective dynamics of a ciliary carpet via systematic coarse graining. We uncover the criteria that control the selection of frequency and wave vector of stable metachronal waves of the cilia and examine how they depend on the geometric and dynamical characteristics of a single cilium, as well as the geometric properties of the array. We perform agent-based numerical simulations of arrays of cilia with hydrodynamic interactions and find quantitative agreement with the predictions of the analytical framework. Our work sheds light on the question of how the collective properties of beating cilia can be determined using information about the individual units and, as such, exemplifies a bottom-up study of a rich active matter system.


[Chronic obstructive pulmonary disease: the right treatment for the right patient].
In recent years, large treatment studies have been published in the field of chronic obstructive pulmonary disease (COPD) and were supplemented by several post-hoc analyses in 2020. The new evidence was incorporated into the 2021 update of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) report. This article describes the updated fundamentals of and recommendations for the treatment of COPD. Indications for inhaled corticosteroids (ICS), long-acting muscarinic antagonists (LAMA), and/or long-acting beta-mimetics (LABA) will be addressed. The treatment of COPD is contrasted with that of bronchial asthma. The impact of a concomitant asthma component on the treatment strategy for COPD is also discussed. In addition, the article focuses on triple therapy with LAMA, LABA, and ICS, for which the evidence and indications are described. Bronchodilation remains the foundation of COPD therapy. For patients with clustered exacerbations, triple therapy with LAMA + LABA + ICS confers a mortality benefit. Further analysis or studies are needed to clarify whether this effect is more pronounced for specific subgroups.


Macrophage polarization by MSC-derived CXCL12 determines tumor growth.
Phenotypic and functional heterogeneity of macrophages is known to be the main reason for their ability to regulate inflammation and promote tumorigenesis. Mesenchymal stem cells (MSCs) are one of the principal cells commonly found in the tumor stromal niche, with capability of macrophage phenotypic switching. The objective of this study was to evaluate the role of C-X-C motif chemokine ligand 12 (CXCL12) produced by marrow-derived MSCs in the phenotypic and functional pattern of bone marrow-derived macrophages (BMDMs). First, the CRISPR/Cas9 system was used for the CXCL12 gene knock-out in MSCs. Then, coculture systems were used to investigate the role of MSCsCXCL12-/- and MSCsCXCL12+/+ in determination of macrophage phenotype. To further analyze the role of the MSC-derived CXCL12 niche, cocultures of 4T1 mammary tumor cells and macrophages primed with MSCsCXCL12-/- or MSCsCXCL12+/+ as well as in-vivo limiting dilution assays were performed. Our results revealed that the expression of IL-4, IL-10, TGF-β and CD206 as M2 markers was significantly increased in macrophages co-cultured with MSCsCXCL12+/+ , whereas the expression of IL-6, TNF-α and iNOS was conversely decreased. The number and size of multicellular tumor spheroids were remarkably higher when 4T1 cells were cocultured with MSCCXCL12+/+-induced M2 macrophages. We also found that the occurrence of tumors was significantly higher in coinjection of 4T1 cells with MSCCXCL12+/+-primed macrophages. Tumor initiating cells were significantly decreased after coinjection of 4T1 cells with macrophages pretreated with MSCsCXCL12-/-. In conclusion, our findings shed new light on the role of MSC-derived CXCL12 in macrophage phenotypic switching to M2, affecting their function in tumorigenesis.


Estimation of cancer risks during mammography procedure in Saudi Arabia.
The aims of the present work were to quantify radiation doses arises from patients' exposure in mammographic X-ray imaging procedures and to estimate the radiation induced cancer risk. Sixty patients were evaluated using a calibrated digital mammography unit at King Khaled Hospital and Prince Sultan Center, Alkharj, Saudi Arabia. The average patient age (years) was 44.4 ± 10 (26-69). The average and range of exposure parameters were 29.1 ± 1.9 (24.0-33.0) and 78.4 ± 17.5 (28.0-173.0) for X-ray tube potential (kVp) and current multiplied by the exposure time (s) (mAs), respectively. The MGD (mGy) per single projection for craniocaudal (CC), Medio lateral oblique (MLO) and lateromedial (LM) was 1.02 ± 0.2 (0.4-1.8), 1.1 ± 0.3 (0.5-1.8), 1.1 ± 0.3 (0.5-1.9) per procedure, in that order. The average cancer risk per projection is 177 per million procedures. The cancer risk is significant during multiple image acquisition. The study revealed that 80% of the procedures with normal findings. However, precise justification is required especially for young patients.


Bilobed Flap in Hand Clinodactyly Reconstruction: Technique Description and Result Appraisal.
Objective Clinodactyly is a congenital hand deformity that is characterized by coronal angular deviation and may occur in thumbs or fingers. Surgical treatment is indicated for severe angulations. Among the described techniques, one of the options consists of bone alignment by wedge-shaped addition osteotomy of the anomalous phalanx. Such alignment maneuver creates a problem in skin cover, along with soft-tissue tension at the concave aspect of the deformity. Hence, some sort of skin flap is required for the adequate operative wound closure. We aim to demonstrate the aforementioned technique and to assess the results of bilobed flap in the treatment of hand clinodactyly. Methods Retrospective study conducted between January 2008 and January 2015. Five patients were included in the study, including nine operated digits. Surgical indication consisted of angular deviations ˃ 30 o . Neither patients with thumb deformities nor those with deformities associated to syndromes were excluded from the study. We assessed the functional and cosmetic outcomes of the technique, as well as complications and the satisfaction rates of the family. Results All patients had satisfactory functional and cosmetic results, with a mean skin healing of 18.6 days. Among nine operated digits, only one of the patients presented vascular compromise at the distal portion of the first flap lobe, albeit without necrosis or the need for any additional procedure. Patients were followed up on a minimum of 12-month interval. No deformity recurred during the observation period. Conclusion Bilobed flap for the treatment of hand clinodactyly is a good option for skin cover after the osteotomy.


Induction of gene conversion in diploid yeast by chemicals: correlation with mutagenic action and its relevance in genotoxicity screening.
More than 200 chemicals, comprising drugs, pesticides, herbicides, industrial chemicals, food additives, etc. tested by various workers for their ability to induce gene conversion in diploid yeast, have been reviewed. This review shows that a strong correlation exists between the convertogenic and mutagenic abilities of these chemicals. This conclusion confirms the earlier one by Zimmermann which was based on fewer mutagenic chemicals. Published data have further been analysed to confirm quantitatively Zimmermann's other important conclusion that gene conversion is not mutagen-specific. This is a positive advantage in using gene conversion in preliminary screening of chemicals because it reduces the chances of false negatives.


A survey on endoparasites and ectoparasites of stray cats from Mashhad (Iran) and association with risk factors.
As there appeared to be no data available on parasite infection of stray cats in the region and considering the potential threat of stray cats for animal and public health, the present study was carried out using biological samples and necropsy finding collected from cats captured in Mashhad city in the northeast of Iran. From a total 52 stray cats examined, 18 (34.6%) were male and 34 (65.4%) were female. Ten species of endoparasites including helminthes and protozoa and two species of ectoparasites were detected in the examined cats. There were two protozoa, five cestodes, three nematodes and two arthropods. Overall 46 cats (88.46%) have been infected with at least one of the parasites. The following parasites, with their respective prevalence, were found; Nematoda: Toxocara cati 28.84%, Toxocara leonina 7.69%, Physaloptera praeputialis 3.84%; Cestoda: Dipylidium caninum 23.08%, Mesocestoides lineatus 13.46%, Taenia taeniaformis 9.6%, Joyeuxiella echinorhyncoides 7.6% and Taenia hydatigena 1.92%; Protozoa: I. felis 23.7%, Haemobartonella felis 1.92%; Arthropoda: Ctenocephalides felis 1.92% and Cheyletiella blakei 1.92%. Based on our data, there was no significant difference in infection rate between male and female animals. However, the age of the cats were found to be an important risk factor associated with parasitic infection. Our results revealed that zoonotic agents, namely T. cati were present in stray cat colonies in the investigated area. In this respect, appropriate control measures should be taken and it is recommended to determine the most appropriate preventive methods.


Revolution or redux? Assessing IQOS through a precursor product.
Philip Morris International (PMI) currently claims that its heated tobacco product, IQOS, reduces health risk by reducing users' exposure to harmful and potentially harmful constituents present in tobacco smoke. Given the tobacco industry's long history of misrepresenting and obfuscating research, independent assessment of PMI's claims is important. Analysis of Accord, a failed but strikingly similar precursor to IQOS, may help contextualise PMI's claims in its Modified Risk Tobacco Product (MRTP) application. We analysed previously secret internal Philip Morris (PM) and PMI documents, public communications and MRTP application. PM marketed Accord as a 'cleaner' tobacco product in an attempt to address smokers' growing health concerns without making explicit health claims. While PM communications asserted that Accord reduced users' exposure to harmful constituents, company scientists and executives consistently stressed to both regulators and the public that such reductions did not render Accord safer. IQOS's design and marketing are similar to Accord's. On the basis of aerosol chemistry data, IQOS reduces user exposure to some compounds compared with Accord but raises them for others. IQOS appears to be a variant of Accord without consistent improvements in exposure to aerosol toxic compounds. In contrast to PM's past claims for Accord, PMI now claims in its MRTP application that IQOS reduces health risk. This shift in stance is likely not the result of any toxicological difference between Accord and IQOS, but rather a change in the social and regulatory landscape permitting these claims.


Increased angiogenic sprouting in poor prognosis FL is associated with elevated numbers of CD163+ macrophages within the immediate sprouting microenvironment.
Follicular lymphoma has considerable clinical heterogeneity, and there is a need for easily quantifiable prognostic biomarkers. Microvessel density has been shown to be a useful prognostic factor based on numerical assessment of vessel numbers within histologic sections in some studies, but assessment of tumor neovascularization through angiogenic sprouting may be more relevant. We therefore examined the smallest vessels, single-staining structures measuring less than 30 microm(2) in area, seen within histologic sections, and confirmed that they were neovascular angiogenic sprouts using extended focal imaging. Tissue microarrays composing diagnostic biopsies from patients at the extremes of survival of follicular lymphoma were analyzed with respect to numbers of these sprouts. This analysis revealed higher angiogenic activity in the poor prognostic group and demonstrated an association between increased sprouting and elevated numbers of infiltrating CD163(+) macrophages within the immediate microenvironment surrounding the neovascular sprout.


Multi-wavelength laser treatments of spider nevi.
Spider nevi (SN) are one of common vascular diseases. Different treatment techniques have been described for SN previously, including electrocoagulation, argon laser, pulsed dye lasers (PDL), pulsed potassium titanylphosphate laser (KTP), and 1064-nm neodymium yttrium-aluminum-garnet (Nd:YAG) laser. These methods are effective but may require good technical management, multiple treatments, and often result in scarring or pigmentation. Multi-wavelength laser combined with 595-nm PDL followed by 1064-nm Nd:YAG and can be selectively absorbed by hemoglobin in vessels. The 595-nm laser can target shallow vessels whereas the 1064-nm laser may target deeper vessels due to the different penetration capacities of these wavelengths. Moreover, Nd:YAG absorption is remarkable increased following by PDL treatment. Multi-wavelength laser treatments have been successfully used for vascular diseases but there is little experience in SN therapy. Consequently, these treatment parameters have not been established for SN, particularly in Asian patients with Fitzpatrick skin type (FST) IV. Report experience with using multi-wavelength laser for SN treatment in Asian patients with FST IV. Forty-three SN lesions received multi-wavelength laser treatments via a PDL followed by an Nd:YAG laser. The treatment was performed at 7 mm spot size at 9.5-11 J/cm2, 10 ms with PDL, followed by Nd:YAG at 40-50 J/cm2, 15 ms. The laser treatments were performed with a single pass without overlap. Complete resolution was observed in 40 lesions and an 80-90% improvement in the other three lesions after one treatment session. One patient had superficial scarring. Four patients had hyperpigmentation that resolved within 3 months. Multi-wavelength laser treatments are fast and effective interventions for SN treatment in Asian patients with minimal adverse effects when appropriate parameters are set.


Identifying the 'inorganic gene' for high-temperature piezoelectric perovskites through statistical learning.
This paper develops a statistical learning approach to identify potentially new high-temperature ferroelectric piezoelectric perovskite compounds. Unlike most computational studies on crystal chemistry, where the starting point is some form of electronic structure calculation, we use a data-driven approach to initiate our search. This is accomplished by identifying patterns of behaviour between discrete scalar descriptors associated with crystal and electronic structure and the reported Curie temperature (TC) of known compounds; extracting design rules that govern critical structure-property relationships; and discovering in a quantitative fashion the exact role of these materials descriptors. Our approach applies linear manifold methods for data dimensionality reduction to discover the dominant descriptors governing structure-property correlations (the 'genes') and Shannon entropy metrics coupled to recursive partitioning methods to quantitatively assess the specific combination of descriptors that govern the link between crystal chemistry and TC (their 'sequencing'). We use this information to develop predictive models that can suggest new structure/chemistries and/or properties. In this manner, BiTmO3-PbTiO3 and BiLuO3-PbTiO3 are predicted to have a TC of 730°C and 705°C, respectively. A quantitative structure-property relationship model similar to those used in biology and drug discovery not only predicts our new chemistries but also validates published reports.


On the role of epigallocatechin-3-gallate in protecting phospholipid molecules against UV irradiation.
Catechin molecules such as epigallocatechin-3-gallate (EGCG) are capable of attenuating the biomolecular damage induced by UV radiation, possibly through molecular mechanisms involving the cell membranes. In this study, we confirmed the protective role of EGCG against UV of 1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1-glycerol) (sodium salt) (DPPG) in liposomes and cast films. The incorporation of EGCG increased the stability of DPPG liposomes as indicated by UV-vis absorption spectra. Using 2D correlation spectroscopy to analyse the spectra, we found that DPPG and EGCG are co-helpers and complement each other against degradation induced by UV. At the molecular level, UV irradiation affects the phosphate and carbonyl groups of DPPG, in addition to triggering the oxidation and opening of the pyrogallol ring of EGCG. Since EGCG can be incorporated into liposomes and is a strong shield against UV radiation, one may envisage its use in anti-ageing and sunscreen creams, and in dermal drug delivery.


Complete genome sequence analysis of a novel citlodavirus isolated from the leaves of Myrica rubra in Yunnan.
Through high-throughput sequencing, a novel citlodavirus, tentatively named "Myrica rubra citlodavirus 1" (MRV1, accession no. OP374189), was isolated from the leaves of Myrica rubra in Yunnan exhibiting narrow deformity of leaf tips, shrinkage, and chlorosis along the veins. The complete genome sequence was determined and analyzed using cloning and Sanger sequencing. MRV1 is a single-stranded circular non-enveloped DNA virus with a genome size of 3775 nucleotides and contains six open reading frames (ORFs). The virion-sense genome strand encodes a coat protein (CP, nt 750-1,493, 247 aa), two hypothetical movement proteins (V3, nt 382-666, 94 aa; and V2, nt 461-895, 144 aa), and one movement protein (MP, nt 1,527-2,438, 303 aa). The complementary strand of the genome encodes two replication proteins (RepA, nt 3,712-2,834, 292 aa; Rep, nt 2,867-2,553, 104 aa). The MRV1 genome contains the stem-loop motif 5'-TAATATTAC-3', which is a highly conserved nonanucleotide motif found in the origin of virion-strand replication in geminiviruses. Genome sequence alignment analysis showed that citrus chlorotic dwarf associated virus (CCDaV, accession no. JQ920490) shared the highest nucleotide sequence similarity (66.10% identity) with MRV1. Phylogenetic analysis showed that CCDaV is the closest known relative of MRV1, and that these viruses clustered in a single branch within a clade consisting of citlodaviruses. These results indicate that MRV1 should be regarded as a new species of the genus Citlodavirus in the family Geminiviridae.


Asymmetric synthesis of 2-arylpyrrolidines starting from gamma-chloro N-(tert-butanesulfinyl)ketimines.
The enantioselective reductive cyclization of gamma-chloro N-(tert-butanesulfinyl)ketimines towards the short and efficient synthesis of (S)- and (R)-2-arylpyrrolidines (ee >99%) is described for the first time by treatment with LiBEt(3)H and subsequent acid deprotection.


Effects of Combined Transcranial Direct Current Stimulation with Cognitive Training in Girls with Rett Syndrome.
Transcranial Direct Current Stimulation (tDCS) combined with traditional rehabilitative techniques has not been widely applied to Rett Syndrome (RTT). The aim of this study was to examine the effects of combined cognitive traditional training with tDCS applied to attention and language measures in subjects with RTT. 31 subjects with RTT were randomly allocated into two groups: non-sham tDCS (n = 18) and sham tDCS (n = 13). The former received the integrated intervention non-sham tDCS plus cognitive empowerment during the treatment phase. The latter received sham stimulation plus cognitive empowerment. All participants underwent neurological and cognitive assessment to evaluate attention and language measures: before integrated treatment (pre-test phase), at the conclusion of the treatment (post-test phase), and at 1 month after the conclusion of the treatment (follow-up phase). the results indicated longer attention time in the non-sham tDCS group compared to the sham tDCS group with a stable trend also in the follow-up phase; an increase of the number of vowel/phoneme sounds in the non-sham tDCS group; and an improvement in the neurophysiological parameters in the non-sham tDCS group. This study supports the use of tDCS as a promising and alternative approach in the RTT rehabilitation field.


Correction to Multifunctional Alginate Hydrogel Protects and Heals Skin Defects in Complex Clinical Situations.
[This corrects the article DOI: 10.1021/acsomega.0c01108.].


Investigation on the influence of time-of-day on benzene metabolic pharmacokinetics by direct breath analysis in mice.
Benzene, well known as a ubiquitous environmental pollutant, can lead to increasing risk of cancer, bone marrow failure as well as other serious diseases. Benzene has been classified as carcinogenic to humans with no recommended safe level of exposure. In this study, the influence of time-of-day on benzene metabolism has been tentatively explored in a mouse model based on direct real-time breath analysis by using membrane inlet single photon ionization time of flight mass spectrometry (MI-SPI-TOFMS). The exhaled breath of eight mice was monitored at a time resolution of less than 20 s after intraperitoneal (I.P.) injection of benzene in the morning, afternoon and evening on different days, and two rounds of experiments were carried out in total. The pharmacokinetic parameters such as total exposure AUC0-∞ (h ng/mL), peak level Cmax (ng/mL), time of peak level tmax (h), and terminal half-life t1/2z (h) were calculated and discussed. The values of individual parameter varied greatly among the eight mice, e.g., AUC0-∞ in the morning of the first round of experiment ranged from 10.66 to 162.17 h ng/mL and the mean ± SD was 103.72 ± 99.72 h ng/mL (n = 8). Significant difference has also been observed between two rounds of experiments, implying the damage in the liver caused by the benzene exposure. However, there is no significant difference among the results from the morning, afternoon and evening for each round of the experiment. In our follow-up study, the influence of time-of-day will be further investigated, in which the metabolites of benzene as well as endogenous metabolites will be considered.


Assessment of a serum calcification propensity test for the prediction of all-cause mortality among hemodialysis patients.
Vascular calcification is a major contributor to the high cardiac burden among hemodialysis patients. A novel in vitro T50-test, which determines calcification propensity of human serum, may identify patients at high risk for cardiovascular (CV) disease and mortality. We evaluated whether T50 predicts mortality and hospitalizations among an unselected cohort of hemodialysis patients. This prospective clinical study included 776 incident and prevalent hemodialysis patients from 8 dialysis centers in Spain. T50 and fetuin-A were determined at Calciscon AG, all other clinical data were retrieved from the European Clinical Database. After their baseline T50 measurement, patients were followed for two years for the occurrence of all-cause mortality, CV-related mortality, all-cause and CV-related hospitalizations. Outcome assessment was performed with proportional subdistribution hazards regression modelling. Patients who died during follow-up had a significantly lower T50 at baseline as compared to those who survived (269.6 vs. 287.7 min, p = 0.001). A cross-validated model (mean c statistic: 0.5767) identified T50 as a linear predictor of all-cause-mortality (subdistribution hazard ratio (per min): 0.9957, 95% CI [0.9933;0.9981]). T50 remained significant after inclusion of known predictors. There was no evidence for prediction of CV-related outcomes, but for all-cause hospitalizations (mean c statistic: 0.5284). T50 was identified as an independent predictor of all-cause mortality among an unselected cohort of hemodialysis patients. However, the additional predictive value of T50 added to known mortality predictors was limited. Future studies are needed to assess the predictive value of T50 for CV-related events in unselected hemodialysis patients.


The Bengali Short Form-36 was acceptable, reliable, and valid in patients with rheumatoid arthritis.
To develop a culturally adapted Bengali version of the Short Form-36 (SF-36) Health Survey and to test its acceptability, reliability, and validity in patients with rheumatoid arthritis (RA). The US English SF-36 was translated into Bengali after established cross-cultural adaptation procedures. The questionnaire was interviewer administered to 125 consecutive outpatients with RA and readministered after 2 weeks to 40 randomly selected patients. Most participants (86.4%) did not have any problem in understanding the Bengali SF-36 and 98.4% of the questionnaires were fully completed. Only the role-physical and role-emotional scales showed substantial floor and ceiling effects. Principal component analysis confirmed that the hypothesized two-factor structure and tests of scaling assumptions were 100% successful for all eight scales expect physical functioning (98.8%) and general health (77.5%). Cronbach's α was higher than 0.78 and the test-retest reliability was high (r>0.82) for all scales. Correlations with other disease activity parameters were generally as expected and summary scores were able to discriminate between relevant subgroups. The interviewer-administered Bengali SF-36 appears to be an acceptable, reliable, and valid instrument for measuring health-related quality of life in Bangladeshi patients with RA. The questionnaire should be further evaluated in people from the general population and in patients with different medical conditions.


Telemedicine Pays: Billing and Coding Update.
Telemedicine is a rapidly growing healthcare sector that can improve access to care for underserved populations and offer flexibility and convenience to patients and clinicians alike. However, uncertainty about insurance coverage and reimbursement policies for telemedicine has historically been a major barrier to adoption, especially among physicians in private practice (the majority of practicing allergists). The COVID-19 public health emergency has highlighted the importance of telehealth as a safe and effective healthcare delivery model, with governments and payers rapidly expanding coverage and payment in an effort to ensure public access to healthcare in the midst of an infectious pandemic. This comprehensive review of updated telemedicine coverage and payment policies will include a tabular guide on how to appropriately bill and optimize reimbursement for telemedicine services. This review of current trends in telemedicine coverage, billing, and reimbursement will outline the historical and current state of telemedicine payment policies in the USA, with special focus on recent policy changes implemented in light of COVID-19. The authors will also explore the potential future landscape of telehealth coverage and reimbursement beyond the resolution of the public health emergency.


Effects of ethanol and acetaldehyde on collagen synthesis, prostaglandin release and resorption of fetal rat bone in organ culture.
We tested the effect of ethanol and its metabolite, acetaldehyde, on bone formation as measured by [3H]proline incorporation into collagenase digestible protein (CDP) and noncollagen protein (NCP), and on DNA synthesis as measured by [3H]thymidine (TdR) incorporation in fetal rat calvaria. We also determined the effects of ethanol and acetaldehyde on prostaglandin E2 (PGE2) release from calvaria and on bone resorption as measured by 45Ca release from fetal rat long bones. Bones were cultured in multiwell plastic dishes (open system) or in stoppered Erlenmeyer flasks (closed system) for 24 to 96 h. In the open system, 1% ethanol (v/v; 172 mM) resulted in a 31% decrease in TdR incorporation at 24 h with no effect on CDP and NCP. At 0.1% (17.2 mM), ethanol increased TdR by 22%, CDP by 73% and NCP by 67% at 24 h, but these effects were not sustained at 96 h. At 24 h, 1% and 0.3% ethanol decreased PGE2 release by 88% and 75% respectively. This effect was sustained for 96 h only at the higher concentration. In the closed system, 0.1% ethanol increased TdR incorporation by 38% at 24 h. However, there was no effect on the labeling of CDP or NCP. Because its boiling point is 21 degrees C, acetaldehyde could only be tested in the closed system. Acetaldehyde markedly inhibited bone metabolism. At 24 h, 0.003% (0.54 mM) to 0.01% (1.79 mM) acetaldehyde caused a dose-related inhibition of TdR incorporation from 23 to 45%. At 0.01% and 0.03% acetaldehyde inhibited proline incorporation into CDP by 48% and 94% and NCP by 40% and 74% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Clinical characteristics and risk factors for mortality in children with Pseudomonas aeruginosa bacteraemia: A retrospective review at a paediatric tertiary centre.
The objective of this study was to describe clinical features and to assess the risk factors associated with mortality in Pseudomonas aeruginosa bacteraemia in a tertiary Japanese paediatric care hospital. Patients diagnosed with P. aeruginosa bacteraemia at our hospital between 2007 and 2018 were analysed in a retrospective case series. Inadequate initial therapy for P. aeruginosa bacteraemia was defined as initial treatment without antipseudomonal antibiotics or an administration of antipseudomonal agent to which the causative strain was resistant. Bacteraemia-related death was defined as all deaths occurring within 7 days after the onset of bacteraemia. Overall, 41 patients with 42 P. aeruginosa bacteraemia episodes were identified. The most common underlying condition was malignancy (27%), followed by congenital heart disease (20%) and preterm birth (17%). Among the 42 P. aeruginosa clinical isolates, 24% were resistant to at least one of the antipseudomonal agents and 10% were resistant to more than one agent. The susceptibility levels for piperacillin, fourth-generation cephalosporins and ciprofloxacin were higher than that for carbapenems. Bacteraemia-related death was observed in 43% of episodes. The 30-day all-cause mortality was 50% (standard error 8%). Neonates, intensive care, mechanical ventilation, afebrile episodes, septic shock, hypoxia, renal injury and inadequate initial therapy were associated with bacteraemia-related death episodes. We found that childhood P. aeruginosa bacteraemia is still a high mortality disease. Our results imply the importance of the identification of high-risk patients and the establishment of adequate empirical antibiotic therapy.


Combined Ultrasound and Photoacoustic Image Guidance of Spinal Pedicle Cannulation Demonstrated With Intact ex vivo Specimens.
Spinal fusion surgeries require accurate placement of pedicle screws in anatomic corridors without breaching bone boundaries. We are developing a combined ultrasound and photoacoustic image guidance system to avoid pedicle screw misplacement and accidental bone breaches, which can lead to nerve damage. Pedicle cannulation was performed on a human cadaver, with co-registered photoacoustic and ultrasound images acquired at various time points during the procedure. Bony landmarks obtained from coherence-based ultrasound images of lumbar vertebrae were registered to post-operative CT images. Registration methods were additionally tested on an ex vivo caprine vertebra. Locally weighted short-lag spatial coherence (LW-SLSC) ultrasound imaging enhanced the visualization of bony structures with generalized contrast-to-noise ratios (gCNRs) of 0.99 and 0.98-1.00 in the caprine and human vertebrae, respectively. Short-lag spatial coherence (SLSC) and amplitude-based delay-and-sum (DAS) ultrasound imaging generally produced lower gCNRs of 0.98 and 0.84, respectively, in the caprine vertebra and 0.84-0.93 and 0.34-0.99, respectively, in the human vertebrae. The mean ± standard deviation of the area of -6 dB contours created from DAS photoacoustic images acquired with an optical fiber inserted in prepared pedicle holes (i.e., fiber surrounded by cancellous bone) and holes created after intentional breaches (i.e., fiber exposed to cortical bone) was 10.06 ±5.22 mm 2 and 2.47 ±0.96 mm 2, respectively (p 0.01). Coherence-based LW-SLSC and SLSC beamforming improved visualization of bony anatomical landmarks for ultrasound-to-CT registration, while amplitude-based DAS beamforming successfully distinguished photoacoustic signals within the pedicle from less desirable signals characteristic of impending bone breaches. These results are promising to improve visual registration of ultrasound and photoacoustic images with CT images, as well as to assist surgeons with identifying and avoiding impending bone breaches during pedicle cannulation in spinal fusion surgeries.


MAM and C99, key players in the pathogenesis of Alzheimer's disease.
Inter-organelle communication is a rapidly-expanding field that has transformed our understanding of cell biology and pathology. Organelle-organelle contact sites can generate transient functional domains that act as enzymatic hubs involved in the regulation of cellular metabolism and intracellular signaling. One of these hubs is located in areas of the endoplasmic reticulum (ER) connected to mitochondria, called mitochondria-associated ER membranes (MAM). These MAM are transient lipid rafts intimately involved in cholesterol and phospholipid metabolism, calcium homeostasis, and mitochondrial function and dynamics. In addition, γ-secretase-mediated proteolysis of the amyloid precursor protein 99-aa C-terminal fragment (C99) to form amyloid β also occurs at the MAM. Our most recent data indicates that in Alzheimer's disease, increases in uncleaved C99 levels at the MAM provoke the upregulation of MAM-resident functions, resulting in the loss of lipid homeostasis, and mitochondrial dysfunction. Here, we discuss the relevance of these findings in the field, and the contribution of C99 and MAM dysfunction to Alzheimer's disease neuropathology.


The impact of renal denervation procedure on use of antihypertensive drugs in the real-life setting.
Purpose. Randomised controlled trials have shown that renal denervation lowers office and ambulatory blood pressure. The aim of the present study was to evaluate whether patients undergoing renal denervation procedure in a real-life setting have a reduction in antihypertensive drug prescription over the subsequent years.Material and methods. Using the healthcare utilisation database of the Lombardy Region (Italy), the 136 patients who, during the period 2011-2016, were prescribed four or more antihypertensive drugs and underwent renal denervation were included in the study cohort. The number and type of antihypertensive drugs were assessed over the year before and during the three-year period after renal denervation.Results. The median age of the patients was 67 years and 68% of them were men. Based on a multisource comorbidity score, about 40% of patients showed a poor or very poor clinical status. Before renal denervation, the majority of the patients were prescribed four or five antihypertensive drugs. The number of drugs decreased after the denervation and reached 55% after three years. Over the same period, patients prescribed six drugs decreased from 18% to 2%. All antihypertensive drugs were less prescribed throughout the post denervation period. Compared to the year before the denervation, after three years prescription of diuretics was reduced by 15%, calcium channel blockers by 21%, ACE-inhibitors by 32%, angiotensin receptor blockers by 22%, beta-blockers by 20%, and alfa-blockers by 30%. Use of antihypertensive drugs exhibited a reduction also in an age, sex, and clinically matched control group with no renal denervation to an extent, however, much lower than in denervated patients (p-value = 0.013).Conclusion. In the real-life setting, patients who underwent renal denervation had a clearcut reduction in antihypertensive drug prescription over the following years.Plain Language SummaryPatients exhibited a reduction in the prescription of antihypertensive drugs during the three years that followed the denervation procedureThe decrease in the number of antihypertensive drugs was marked, started after a relatively short time (six months), and involved all drugs prescribed before the denervationThe number of hospitalisations for a cardiovascular event was similar before and after renal denervationAlbeit blood pressure values were not recorded in our database, all these findings taken together suggest the renal denervation procedure has a favourable influence on blood pressure control and is not associated with an increase in the risk of major cardiovascular complications.


Direct observation of optically injected spin-polarized currents in semiconductors.
Quantum interference of one- and two-photon excitation of unbiased semiconductors yields ballistic currents of carriers. The magnitudes and directions of the currents and the spin orientations of the carriers are controlled by the polarization and relative phase of the exciting femtosecond laser fields. We provide direct experimental evidence for the spin polarization of the optically injected spin currents by detecting a phase-dependent spatial shift of the circularly polarized photoluminescence in cubic ZnSe.


Mechanistic insight into the degradation of 1H-benzotriazole and 4-methyl-1H-benzotriazole by •OH-based advanced oxidation process and toxicity assessment.
Benzotriazoles (BTs) are highly produced chemicals that are commonly used in the manufacture of aircraft de-icing/antifreeze fluids (ADAFs), coolants, etc. BTs have been detected in a variety of water environments, causing health hazards to aquatic species and humans. In this study, 1H-benzotriazole (BTri) and 4-methyl-1H-benzotriazole (4-TTri) were selected to investigate their degradation mechanisms in the aqueous phase initiated by ·OH using a theoretical calculation method. Addition reactions are the main type of reactions of ·OH with BTri and 4-TTri. The total rate constants for the reactions of BTri and 4-TTri with ·OH at 298 K are 8.26 × 109 M-1 s-1 and 1.81 × 1010 M-1 s-1, respectively. The reaction rate constants increase as the temperature rises, indicating that rising temperatures promote the degradation of BTri and 4-TTri. 7-hydroxy-1H-benzotriazole (1-P1) and 4-hydroxy-benzotriazoles (1-P2) produced via multiple reaction pathways are important transformation products of BTri. After successive reactions with ·OH, 1-P1 and 1-P2 can be successively converted to 4,7-dihydroxy-1H-benzotriazole (1-P7), 4,7-dione-1H-benzotriazole (1-P8), and 1,2,3-triazole-4,5-dicarboxylic acid (1-P9), which is consistent with the product compositions detected in the experiments. The toxicity assessment indicated that the acute toxicity and chronic toxicity of the resulting transformation products are significantly reduced compared to BTri as the degradation process progressed, and ultimately showed no harm to all three aquatic organisms (fish, daphnia, and green algae). Hence, advanced oxidation processes (AOPs) can not only effectively remove BTs from water, but also reduce their toxic effects on aquatic organisms.


Breast Ultrasound Volume Sweep Imaging: A New Horizon in Expanding Imaging Access for Breast Cancer Detection.
The majority of people in the world lack basic access to breast diagnostic imaging resulting in delay to diagnosis of breast cancer. In this study, we tested a volume sweep imaging (VSI) ultrasound protocol for evaluation of palpable breast lumps that can be performed by operators after minimal training without prior ultrasound experience as a means to increase accessibility to breast ultrasound. Medical students without prior ultrasound experience were trained for less than 2 hours on the VSI breast ultrasound protocol. Patients presenting with palpable breast lumps for standard of care ultrasound examination were scanned by a trained medical student with the VSI protocol using a Butterfly iQ handheld ultrasound probe. Video clips of the VSI scan imaging were later interpreted by an attending breast imager. Results of VSI scan interpretation were compared to the same-day standard of care ultrasound examination. Medical students scanned 170 palpable lumps with the VSI protocol. There was 97% sensitivity and 100% specificity for a breast mass on VSI corresponding to 97.6% agreement with standard of care (Cohen's κ = 0.95, P < .0001). There was a detection rate of 100% for all cancer presenting as a sonographic mass. High agreement for mass characteristics between VSI and standard of care was observed, including 87% agreement on Breast Imaging-Reporting and Data System assessments (Cohen's κ = 0.82, P < .0001). Breast ultrasound VSI for palpable lumps offers a promising means to increase access to diagnostic imaging in underserved areas. This approach could decrease delay to diagnosis for breast cancer, potentially improving morbidity and mortality.


Neutralizing EBV-specific IgA in throat washings of nasopharyngeal carcinoma (NPC) patients.
Throat washings from 26 nasopharyngeal carcinoma (NPC) patients from Hong Kong and Tunisia were studied for the presence of transforming EBV. Only six (23%) were found positive which led to the hypothesis of a neutralizing factor in such salivas. The search for EBV-specific antibodies showed that NPC saliva contained neutralizing VCA and EA IgA (54 and 27% respectively) and VCA and EA IgG (73 AND 54% respectively). Both transforming and non-transforming throat washings contained virus particles as visualized by electron microscopy, but in non-transforming salivas (containing IgA and IgG) the particles were found to be clumped. Comparative study of throat washings from patients with Burkitt's lymphoma (BL); infectious mononucleosis (IM), immunodeficiencies, other cancers, and healthy subjects showed that IgA were restricted to NPC cases.


Drivers of Palatability for Cats and Dogs-What It Means for Pet Food Development.
The pet food industry is an important sector of the pet care market that is growing rapidly. Whilst the number of new and innovative products continues to rise, research and development to assess product performance follows traditional palatability methodology. Pet food palatability research focuses on the amount of food consumed through use of one-bowl and two-bowl testing, but little understanding is given to why differences are observed, particularly at a fundamental ingredient level. This review will highlight the key differences in feeding behaviour and nutritional requirements between dogs and cats. The dominant pet food formats currently available and the ingredients commonly included in pet foods are also described. The current methods used for assessing pet food palatability and their limitations are outlined. The opportunities to utilise modern analytical methods to identify complete foods that are more palatable and understand the nutritional factors responsible for driving intake are discussed.


Characterization of the promoter for the human long pentraxin PTX3. Role of NF-kappaB in tumor necrosis factor-alpha and interleukin-1beta regulation.
The "long pentraxins" are an emerging family of genes that have conserved in their carboxy-terminal halves a pentraxin domain homologous to the prototypical acute phase protein pentraxins (C-reactive protein and serum amyloid P component) and acquired novel amino-terminal domains. In this report, a genomic fragment of 1371 nucleotides from the human "long pentraxin" gene PTX3 is characterized as a promoter on tumor necrosis factor-alpha (TNFalpha) and interleukin (IL)-1beta exposure in transfected 8387 human fibroblasts by chloramphenicol acetyltransferase and RNase protection assays. In the same cells, the PTX3 promoter does not respond to IL-6 stimulation. Furthermore, IL-1beta and TNFalpha responsiveness is not seen in the Hep 3B hepatoma cell line. The minimal promoter contains one NF-kappaB element which is shown to be necessary for induction and able to bind p50 homodimers and p65 heterodimers but not c-Rel. Mutants in this site lose the ability to bind NF-kappaB proteins and to respond to TNFalpha and IL-1beta in functional assays. Sp1- and AP-1 binding sites lying in proximity to the NF-kappaB site do not seem to play a major role for cytokine responsiveness. Finally, cotransfection experiments with expression vectors validate that the natural promoter contains a functional NF-kappaB site.


Liposomal Nanomedicine: Applications for Drug Delivery in Cancer Therapy.
The increasing prevalence of cancer, a disease in which rapid and uncontrollable cell growth causes complication and tissue dysfunction, is one of the serious and tense concerns of scientists and physicians. Nowadays, cancer diagnosis and especially its effective treatment have been considered as one of the biggest challenges in health and medicine in the last century. Despite significant advances in drug discovery and delivery, their many adverse effects and inadequate specificity and sensitivity, which usually cause damage to healthy tissues and organs, have been great barriers in using them. Limitation in the duration and amount of these therapeutic agents' administration is also challenging. On the other hand, the incidence of tumor cells that are resistant to typical methods of cancer treatment, such as chemotherapy and radiotherapy, highlights the intense need for innovation, improvement, and development in antitumor drug properties. Liposomes have been suggested as a suitable candidate for drug delivery and cancer treatment in nanomedicine due to their ability to store drugs with different physical and chemical characteristics. Moreover, the high flexibility and potential of liposome structure for chemical modification by conjugating various polymers, ligands, and molecules is a significant pro for liposomes not only to enhance their pharmacological merits but also to improve the effectiveness of anticancer drugs. Liposomes can increase the sensitivity, specificity, and durability of these anti-malignant cell agents in the body and provide remarkable benefits to be applied in nanomedicines. We reviewed the discovery and development of liposomes focusing on their clinical applications to treat diverse sorts of cancers and diseases. How the properties of liposomal drugs can be improved and their opportunity and challenges for cancer therapy were also considered and discussed.


[Transformation of mouse lymphocytes stimulated by phytohemagglutin depending on their cultivation conditions].
Conditions were elaborated to cultivate splenocytes of mice in medium-199 (Soviet production) changed a little by the addition of 200 mM of glutamine, 6 mM glucose, 60 unit/l of insulin, 5.10(-5) M 2-mercaptoethanol (final concentration), and of 5% serum of new-born calf. In such conditions of cultivation the value of the lymphocyte transformation coefficient lies within 3 and 10.


The impacts of mining on soil pollution with metal(loid)s in resource-rich Mongolia.
As Mongolia is considered one of the most resource extraction-dependent countries globally, significant mining-related environmental and human health risks are expected. The aim of this study was to (I) assess the impacts of mining on soil pollution with metals in Mongolia's key coal mining towns (Baganuur, Nalaikh and Sharyn Gol) and (II) review the current knowledge on soil pollution with metal(loid)s and related health risks in Mongolia. The results showed predominantly low soil contents of Cd, Cu, Pb and Zn and a related absence of severe pollution and potential health risk in the coal mining towns. Urban design, rather than the presence of mines, controlled the pollution distribution. Despite the methodological shortcomings of several studies on soil pollution in Mongolia, their results suggest a similarly low threat in the three largest cities (Ulaanbaatar, Darkhan, Erdenet) and several mining areas. While the generally highlighted risk of As seems like an artificially escalated issue, the content of Cr in urban soil may be a neglected threat. Further pollution research in Mongolia should focus on street dust and drinking water pollution.


Probing ion channel neighborhoods using proximity proteomics.
Protein-protein interactions are critically important for cellular functions, including regulation of ion channels. Ion channels are typically part of large macromolecular complexes that impact their function. These complexes have traditionally been elucidated via standard biochemical techniques including immunoprecipitation, pull-down assays and mass spectrometry. Recently, several methods have been developed to provide a more complete depiction of the microenvironment or "neighborhood" of proteins of interest. These new methods, which fall broadly under the category of proximity-dependent labeling techniques, aim to overcome the limitations imposed by antibody-based techniques and mass spectrometry. In this chapter, we describe the use of proximity labeling to elucidate the cardiac CaV1.2 macromolecular complex under basal conditions and after β-adrenergic stimulation. Using these methodologies, we have identified the mechanism underlying adrenergic stimulation of the Ca2+ current in the heart.


3D Electron Diffraction Structure Determination of Terrylene, a Promising Candidate for Intermolecular Singlet Fission.
Herein we demonstrate the prowess of the 3D electron diffraction approach by unveiling the structure of terrylene, the third member in the series of peri-condensed naphthalene analogues, which has eluded structure determination for 65 years. The structure was determined by direct methods using electron diffraction data and corroborated by dispersion-inclusive density functional theory optimizations. Terrylene crystalizes in the monoclinic space group P21 /a, arranging in a sandwich-herringbone packing motif, similar to analogous compounds. Having solved the crystal structure, we use many-body perturbation theory to evaluate the excited-state properties of terrylene in the solid-state. We find that terrylene is a promising candidate for intermolecular singlet fission, comparable to tetracene and rubrene.


Mosaic genome evolution in a recent and rapid avian radiation.
Recent genomic analyses of evolutionary radiations suggest that ancestral or standing genetic variation may facilitate rapid diversification, particularly in cases involving convergence in ecological traits. Likewise, lateral transfer of alleles via hybridization may also facilitate adaptive convergence, but little is known about the role of ancestral variation in examples of explosive diversification that primarily involve the evolution of species recognition traits. Here, we show that genomic regions distinguishing sympatric species in an extraordinary radiation of small finches called munias (genus Lonchura) have phylogenetic histories that are discordant with each other, with the overall pattern of autosomal differentiation among species, and with sex-linked and mitochondrial components of the genome. Genome-wide data for 11 species sampled in Australia and Papua New Guinea indicate substantial autosomal introgression between sympatric species, but also identify a limited number of divergent autosomal regions, several of which overlap known colour genes (ASIP, EDN3, IGSF11, KITLG, MC1R and SOX10). Phylogenetic analysis of these outlier regions shows that different munia species have acquired unique combinations of alleles across a relatively small set of phenotypically relevant genes. Our results demonstrate that the recombination of ancestral genetic variation across multiple loci may be an important mechanism for generating phenotypic novelty and diversity.


Normative scores for the Timed Up & Go in a Spanish sample of community-dweller adults with preserved functionality.
Our aim was to calculate the 'Timed Up & Go' (TUG) normative scores in a Spanish sample composed of functional older adults. The TUG test provides a measure of global ambulation skills and its total score has been successfully related with functionality and other important health variables in older adults. Reliable norms are needed for adults 50 years and older that allow the early identification and intervention in motor disturbances. The study was carried out with adults from Galicia and Valencia living in the community. A total of 314 Spanish community-living participants, aged from 50 to 90 years and functionality preserved were assessed through the implementation of a cross-sectional design. Health, comorbidity, physical activity, cognitive status, functionality measures and TUG test scores were obtained. TUG scores were successfully predicted by age and gender, and significantly correlated with cognitive status and comorbidity. TUG norms were calculated by age-group for women and men. TUG normative scores were below 13s and slightly lower in men. Normative scores for women and men were lower than those proposed in studies carried-out in our context. Our norms showed risk reference scores close to those obtained by meta-analytical procedures.


[Search for an Optimal Formula for Calculation of the Corrected QT Interval in Children Based on Data of Clinical-Epidemiological Study].
The aim of the study was to compare different types of QT correction, establish age norms of QT duration, and assess associations between QT duration and heart rate (HR) in children. The sample comprised 0-18-year-old children (n=5909) selected from general population. The study examined several existing formulas of corrected QT (Bazett, Fridericia, Framingham, and Hodges) and modified Bazett formula developed for healthy children. The analysis demonstrated that neither formula enabled complete exclusion of the correlation between QT and RR intervals. Among existing formulas, Bazett formula provided maximum possible elimination of the HR influence on QT duration. Modified Bazett formula, developed by us, provided even less correlation of QT and RR intervals. Therefore, we recommend implementing modified Bazett formula to pediatric practice.


Student nurses' attitudes toward dying patients in central Anatolia.
This study was descriptively conducted to explore attitudes of nursing students related to caring for dying patients in central Anatolia. The study was completed with 222 third-year students of nursing school originating from three universities in Turkey. It was explored that Frommelt Attitudes Toward Care of the Dying Scale (FATCOD) scores of the students who had previously cared for terminal patients at the clinics were significantly higher, and the scores of those who regarded themselves as nonbeliever in terms of religion were significantly lower (p < .05). It was seen that nursing students' FATCOD scores were at a moderate level. We are of the opinion that it will be helpful that nursing students should be trained about the care for dying patients during their formal education.


[Search for potential gastric cancer biomarkers using low molecular weight blood plasma proteome profiling by mass spectrometry].
Gastric cancer, one of the most widespread malignant tumors, still lacks reliable serum/plasma biomarkers of its early detection. In this study we have developed, unified, and tested a new methodology for search of gastric cancer biomarkers based on profiling of low molecular weight proteome (LMWP) (1-17 kDa). This approach included three main components: sample pre-fractionation, matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS), data analysis by a bioinformatics software package. Applicability and perspectives of the developed approach for detection of potential gastric cancer markers during LMWP analysis have been demonstrated using 69 plasma samples from patients with gastric cancer (stages I-IV) and 238 control samples. The study revealed peptides/polypeptides, which may be potentially used for detection of this pathology.


Interaction of activated Rab5 with actin-bundling proteins, L- and T-plastin and its relevance to endocytic functions in mammalian cells.
Rab5 is a GTP-binding protein that is crucial for endocytic machinery functions. We previously identified L-plastin as a binding protein for Rab5, using an affinity column with constitutively active Rab5. L- and T-plastin are isoforms of a plastin protein family belonging to actin-bundling proteins that are implicated in the regulation of cell morphology, lamellipodium protrusion, bacterial invasion and tumor progression. However, the physiological relevance of Rab5 binding to plastin has remained unclear. Here, we show that L- and T-plastin interacted only with activated Rab5 and that they co-localized with Rab5 on the plasma membrane and endosome. Rab5 activity was also higher in both L- and T-plastin over-expressing Cos-1 cells. Furthermore, expression of L- and T-plastin increased the rate of fluid-phase endocytosis. These findings imply that the Rab5 is either activated or the activity is sustained by interaction with plastin, and that this interaction influences endocytic activity.


Human PXR-mediated transcriptional activation of CYP3A4 by 'Fuzi' extracts.
This study focused on determining whether the 'Fuzi' (FZ) extracts from different extraction methods are related to pregnane X receptor (PXR) and cytochrome P450 3A4 (CYP3A4), and explore the mechanism. FZ was extracted under various conditions, and the components were identified by Ultra Performance Liquid Chromatography/Quad Time of Flight Mass Spectrometry (UPLC/Q-TOF-MS). Annexin V-FITC and propidium iodide staining assays were used to measure the cell cytotoxicity of these extracts. Real-time PCR, western blot analysis and reporter gene assay were used to detect the expression changes of PXR and CYP3A4. FZ extracts were found to contain high levels of monoester-diterpene alkaloids (MDAs) and diester-diterpene alkaloids (DDAs). FZ extracts were cytotoxic. Interestingly, we found that FZ extracts and DDAs can induce the expressions of PXR and CYP3A4. And the MDAs can inhibit the expressions of PXR and CYP3A4. Different extracts of FZ can induce the expressions of PXR and CYP3A4 in different degrees. This may be related to the drug-drug interactions.


[The influence of completely ligated ureters on the regeneration of tubulus cells after diversion of the urine by ureterocystoneostomy (author's transl)].
After a complete destruction of the ureter, renal function recovers more completely after diversion of the urine by splints than by ureterocystoneostomy. After a longer period of obstruction and successive restoration of urinary diversion by ureterocystoneostomy a relative increase in pressure of the ureter continues. This is the result of a functional obstruction, caused by disintegration of the muscle cells by connective tissue. The proliferation of connective tissue is probably induced and maintained by extravasation of urine into the layers of the ureter and that after abolition of the special function of the tunica mucosa. The defects of the mucosa are probably caused by metabolic disturbance after a pressure-induced decrease of blood supply.


A neurofibromatosis type 1 patient with thoracic encapsulated fluid and intracranial hypotension syndrome: a case report.
Spinal meningoceles are uncommon entities, mostly associated with neurofibromatosis type 1 (NF-1). Their intrusion into the thoracic cavity, which compresses lung tissue, is quite often mistaken as a "pleural effusion." The withdrawal of a large amount of "pleural effusion" can lead to the intracranial hypotension syndrome (IHS), herniation, or even death. A 43-year-old woman, with NF-1 and a large "pleural effusion" which compressed lung tissue, was admitted to the Thoracic Department due to the patient's shortness of breath during her physical activities. The patient complained of headache shortly after withdrawal of about 250 mL of "pleural effusion." She was diagnosed with IHS according to the typical symptoms of postural headache, low cerebrospinal fluid (CSF) pressure and magnetic resonance imaging findings of diffuse pachymeningeal gadolinium enhancement. The "pleural effusion" was examined and found to be CSF. The reported case is the first 1 in the literature in which the intrusion of the NF-1 patient's spinal meningoceles into the thoracic cavity was diagnosed as a "pleural effusion" and large CSF withdrawal led to IHS. We highlight the possibility that thoracic meningoceles can coexist with a thoracic spinal deformity and the caution that needs to be taken when cases with similar symptoms are subjected to withdrawal of fluid.


Repeated short periods of regional myocardial ischemia: effect on local function and high energy phosphate levels.
The effect of recurrent periods of ischemia on the myocardium was investigated in 15 open-chest dogs. Ischemia was produced by 3 minutes of proximal occlusion of the left anterior descending coronary artery. Each occlusion was followed by reperfusion of 3 minutes duration. Forty occlusions with a total of 120 minutes of ischemia were performed, and regional function (sonomicrometry) as well as high energy phosphates (needle biopsies) were determined at the end of the 5th, 20th, and 40th period of ischemia and reperfusion. The first periods of ischemia had a cumulative effect both on regional postischemic function (44% and 59% respectively of preischemic control after 20 occlusions) and on the ATP content, but with increasing number of occlusions the additive effects became smaller (ATP reduction/mumol/g w w/per occlusion). The ATP breakdown per occlusion was diminished with increasing number of periods of ischemia, and no significant adenosine was measured in the ischemic myocardium. Higher than normal postischemic creatine phosphate levels (9.1 mumol/g w w at the 40th reperfusion vs. 6.7 mumol/g w w control) indicated a functioning oxidative phosphorylation in the presence of an ATP utilization problem at the sarcomere level, because indicators of the cellular energy level (energy charge, free energy change of ATP hydrolysis) quickly normalized during reperfusion. Stunned myocardium is therefore not a problem of energy supply but rather of energy utilization. Reduced ATP utilization and regional dysfunction are the expressions of the same cellular defect which resides either in the ATP-splitting contractile apparatus or in the electromechanical coupling. Contractile dysfunction during reperfusion protects the heart against subsequent periods of ischemia because ATP turnover is reduced.


Treatment of Plants with Gaseous Ethylene and Gaseous Inhibitors of Ethylene Action.
The gaseous nature of ethylene affects not only its role in plant biology but also how you treat plants with the hormone. In many ways, it simplifies the treatment problem. Other hormones have to be made up in solution and applied to some part of the plant hoping the hormone will be taken up into the plant and translocated throughout the plant at the desired concentration. Because all plant cells are connected by an intercellular gas space the ethylene concentration you treat with is relatively quickly reached throughout the plant. In some instances, like mature fruit, treatment with ethylene initiates autocatalytic synthesis of ethylene. However, in most experiments, the exogenous ethylene concentration is saturating, usually >1 μL L-1, and the synthesis of additional ethylene is inconsequential. Also facilitating ethylene research compared with other hormones is that there are inhibitors of ethylene action 1-MCP (1-methylcyclopropene) and 2,5-NBD (2,5-norbornadiene) that are also gases wherein you can achieve nearly 100% inhibition of ethylene action quickly and with few side effects. Inhibitors for other plant hormones are applied as a solution and their transport and concentration at the desired site is not always known and difficult to measure. Here, our focus is on how to treat plants and plant parts with the ethylene gas and the gaseous inhibitors of ethylene action.