Dosimetric rationale and early experience at UFPTI of thoracic proton therapy and chemotherapy in limited-stage small cell lung cancer.
Concurrent chemoradiotherapy (CRT) is the standard of care in patients with limited-stage small cell lung cancer (SCLC). Treatment with conventional x-ray therapy (XRT) is associated with high toxicity rates, particularly acute grade 3+ esophagitis and pneumonitis. We present outcomes for the first known series of limited-stage SCLC patients treated with proton therapy and a dosimetric comparison of lung and esophageal doses with intensity-modulated radiation therapy (IMRT). Six patients were treated: five concurrently and one sequentially. Five patients received 60-66 CGE in 30-34 fractions once daily and one patient received 45 CGE in 30 fractions twice daily. All six patients received prophylactic cranial irradiation. Common Terminology Criteria for Adverse Events, v3.0, was used to grade toxicity. IMRT plans were also generated and compared with proton plans. The median follow-up was 12.0 months. The one-year overall and progression-free survival rates were 83% and 66%, respectively. There were no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis, and no other acute grade 3+ non-hematological toxicities were seen. One patient with a history of pulmonary fibrosis and atrial fibrillation developed worsening symptoms four months after treatment requiring oxygen. Three patients died: two of progressive disease and one after a fall; the latter patient was disease-free at 36 months after treatment. Another patient recurred and is alive, while two patients remain disease-free at 12 months of follow-up. Proton therapy proved superior to IMRT across all esophageal and lung dose volume points. In this small series of SCLC patients treated with proton therapy with radical intent, treatment was well tolerated with no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis. Dosimetric comparison showed better sparing of lung and esophagus with proton therapy. Proton therapy merits further investigation as a method of reducing the toxicity of CRT.


Free healthcare for some, fee-paying for the rest: adaptive practices and ethical issues in rural communities in the district of Boulsa, Burkina Faso.
In Burkina Faso, in July 2016, user fees were removed at all public healthcare facilities, but only for children under 60 months of age and for "mothers", i.e. for reproductive care. This study was conducted in five rural communities in Boulsa District (Burkina Faso) (1) to understand the perceptions and practices of stakeholders regarding compliance with eligibility criteria for free care and (2) to explore the ethical tensions that may have resulted from this policy. Semi-directed individual interviews (n = 20) were conducted with healthcare personnel and mothers of young children. Interviews were recorded and transcribed, and a thematic content analysis was conducted. The study reveals the presence of practices to circumvent strict compliance with the eligibility criteria for free access. These include hiding the exact age of children over 60 months and using eligible persons for the benefit of others. These practices result from ethical and economic tensions experienced by the beneficiaries. They also raise dilemmas among healthcare providers, who have to enforce compliance with the eligibility criteria while realizing the households' deprivation. Informal adjustments are introduced at the community level to reconcile the healthcare providers' dissonance. Local reinvention mechanisms help in overcoming ethical tensions and in implementing the policy.


Impact of hfq on the intrinsic drug resistance of salmonella enterica serovar typhimurium.
Salmonella enterica is an important enteric pathogen, and its various serovars cause both systemic and intestinal diseases in humans and domestic animals. The emergence of multidrug-resistant strains of Salmonella, leading to increased morbidity and mortality, has further complicated its management. Hfq is an RNA chaperon that mediates the binding of small RNAs to mRNA and assists in post-transcriptional gene regulation in bacteria. Although Hfq is related to important phenotypes including virulence in Salmonella, its role in the drug resistance of this organism is unknown. The aim of this study was to investigate the role of Hfq in intrinsic drug resistance of S. enterica serovar Typhimurium. hfq Mutant was susceptible to acriflavine. Although there is a relationship between the production of the AcrB multidrug efflux pump and Hfq in Escherichia coli, the deletion of the drug efflux acrB did not impair the effect of hfq deletion on Salmonella susceptibility. In contrast, the deletion of another drug efflux gene, smvA, impaired the effect of hfq deletion on acriflavine susceptibility. These results indicate that Hfq regulates the intrinsic drug resistance, and it may influence drug susceptibility by regulating SmvA in Salmonella.


Conversion of monoculture cropland and open grassland to agroforestry alters the abundance of soil bacteria, fungi and soil-N-cycling genes.
Integration of trees in agroforestry systems can increase the system sustainability compared to monocultures. The resulting increase in system complexity is likely to affect soil-N cycling by altering soil microbial community structure and functions. Our study aimed to assess the abundance of genes encoding enzymes involved in soil-N cycling in paired monoculture and agroforestry cropland in a Phaeozem soil, and paired open grassland and agroforestry grassland in Histosol and Anthrosol soils. The soil fungi-to-bacteria ratio was greater in the tree row than in the crop or grass rows of the monoculture cropland and open grassland in all soil types, possibly due to increased input of tree residues and the absence of tillage in the Phaeozem (cropland) soil. In the Phaeozem (cropland) soil, gene abundances of amoA indicated a niche differentiation between archaeal and bacterial ammonia oxidizers that distinctly separated the influence of the tree row from the crop row and monoculture system. Abundances of nitrate (napA and narG), nitrite (nirK and nirS) and nitrous oxide reductase genes (nosZ clade I) were largely influenced by soil type rather than management system. The soil types' effects were associated with their differences in soil organic C, total N and pH. Our findings show that in temperate regions, conversion of monoculture cropland and open grassland to agroforestry systems can alter the abundance of soil bacteria and fungi and soil-N-cycling genes, particularly genes involved in ammonium oxidation.


Role of taste preference on fluid intake during and after 90 min of running at 60% of VO2max in the heat.
The purpose of this study was to determine the relationship between taste preference and total fluid intake during a 90-min run at 60% VO2max as well as during a 90-min period of seated recovery under hyperthermic conditions (30 degrees C, 50% RH), comparing the ad libitum intake of water and two carbohydrate-electrolyte drinks (one containing 6% CHO and the other 8% CHO) randomized over three trails. Fifteen men runners and triathletes, 18 to 40 yr of age, completed an initial test to determine VO2max, a practice 90-min run at 60% VO2max, and three experimental 90-min run/90-min recovery trials on separate days approximately 1 wk apart. There were no differences across the three treatments in fluid intake, rectal temperature, or RPE during exercise, but subjects consumed 54% and 59% more fluid during recovery with the two carbohydrate-electrolyte drinks compared with water. When comparing the subjects' trials with the most liked versus the least liked of the three fluids, they consumed more of the most liked fluid during exercise (1.10 vs 0.97 L.90 min-1) but not during recovery (1.02 vs 0.90 L.90 min-1.ns). Thus, perceived taste of a beverage is important for fluid replacement during exercise.


Imipramine and buspirone in patients with panic disorder who are discontinuing long-term benzodiazepine therapy.
Pretreatment with imipramine, buspirone, or placebo was compared in 40 patients meeting the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria for panic disorder and in patients who were discontinuing long-term benzodiazepine use. The average duration of benzodiazepine use was 75 +/- 64 months, and the average benzodiazepine intake expressed as diazepam equivalents was 25.7 +/- 19 mg/d. We hypothesized that pretreatment with either imipramine or buspirone, in contrast to pretreatment with placebo, would lead to a significant decrease of symptoms of anxiety and depression before tapering benzodiazepines, thus making the taper process easier to complete. All 3 treatments (imipramine, buspirone, and placebo) caused a reduction in anxiety and depression symptoms as measured by changes in the Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale. Neither discontinuation severity nor taper-free status 12 weeks posttaper differed between the 3 treatment groups.


Quality of Life in Women with Polycystic Ovary Syndrome after a Program of Resistance Exercise Training.
Purpose Aerobic exercises may improve quality of life (QoL) in women with polycystic ovary syndrome (PCOS). However, there is no data on the effect of resistance exercise training (RET) programs on the QoL of women with PCOS. Thus, this study aimed to assess the effect of a 16-week RET program on QoL in PCOS women. Methods This 16-week case-control study enrolled 43 women with PCOS (PCOS group, PCOSG) and 51 healthy pre-menopausal controls aged 18 to 37 years (control group, CG). All women underwent a supervised RET program for 16 weeks, and were evaluated in two different occasions: week-0 (baseline), and week-16 (after RET). Quality of life was assessed using the 36-Item Short Form Health Survey (SF-36). Results Testosterone reduced significantly in both groups after RET (p < 0.01). The PCOSG had improvements in functional capacity at week-16 relative to week-0 (p = 0.02). The CG had significant improvements in vitality, social aspects, and mental health at week-16 relative to week-0 (p ≤ 0.01). There was a weak correlation between social aspects of the SF-36 domain and testosterone levels in PCOS women. Conclusion A 16-week RET program modestly improved QoL in women with PCOS.


[Role of flexible bronchoscopy in the diagnosis and treatment of refractory pneumonia in children].
To evaluate the effectiveness of the flexible bronchoscopy in the diagnosis and treatment of refractory pneumonia among children. Sixty children with refractory pneumonia were randomly divided into two groups: lavage and control (n=30 each). The control group received conventional medical treatment. The lavage group was given flexible bronchoscopy besides conventional medical treatment. The therapeutic effects were compared between the two groups. The results of bacterial culture and detection of antibodies against Mycoplasma pneumoniae in bronchoalveolar lavage fluid (BALF) were observed. The coincidence of bacterial culture results between BALF and sputum samples was 63.3%, and there were no significant differences in the positive bacterial culture results between them. The coincidence of PCR test for antibodies against Mycoplasma pneumoniae between BALF and serum samples was 73.3%. The results of Fisher's exact test showed the positive rate of Mycoplasma pneumoniae antibodies of BALF was higher than that of serum (P<0.05). The effective rate in the lavage group was significantly higher than that in the control group (97% vs 73%; P<0.01). The flexible bronchoscopy is useful for the diagnosis and treatment of refractory pneumonia in children.


The Effect of Music Therapy in Patients with Huntington's Disease: A Randomized Controlled Trial.
Music therapy may have beneficial effects on improving communication and expressive skills in patients with Huntington's disease (HD). Most studies are, however, small observational studies and methodologically limited. Therefore we conducted a multi-center randomized controlled trial. To determine the efficacy of music therapy in comparison with recreational therapy in improving quality of life of patients with advanced Huntington's disease by means of improving communication. Sixty-three HD-patients with a Total Functional Capacity (TFC) score of ≤7, admitted to four long-term care facilities in The Netherlands, were randomized to receive either group music therapy or group recreational therapy in 16 weekly sessions. They were assessed at baseline, after 8, 16 and 28 weeks using the Behaviour Observation Scale for Huntington (BOSH) and the Problem Behaviour Assessment-short version (PBA-s). A linear mixed model with repeated measures was used to compare the scores between the two groups. Group music therapy offered once weekly for 16 weeks to patients with Huntington's disease had no additional beneficial effect on communication or behavior compared to group recreational therapy. This was the first study to assess the effect of group music therapy on HD patients in the advanced stages of the disease. The beneficial effects of music therapy, recorded in many, mainly qualitative case reports and studies, could not be confirmed with the design (i.e. group therapy vs individual therapy) and outcome measures that have been used in the present study. A comprehensive process-evaluation alongside the present effect evaluation is therefore performed.


Interaction of ezrin with the novel guanine nucleotide exchange factor PLEKHG6 promotes RhoG-dependent apical cytoskeleton rearrangements in epithelial cells.
The mechanisms underlying functional interactions between ERM (ezrin, radixin, moesin) proteins and Rho GTPases are not well understood. Here we characterized the interaction between ezrin and a novel Rho guanine nucleotide exchange factor, PLEKHG6. We show that ezrin recruits PLEKHG6 to the apical pole of epithelial cells where PLEKHG6 induces the formation of microvilli and membrane ruffles. These morphological changes are inhibited by dominant negative forms of RhoG. Indeed, we found that PLEKHG6 activates RhoG and to a much lesser extent Rac1. In addition we show that ezrin forms a complex with PLEKHG6 and RhoG. Furthermore, we detected a ternary complex between ezrin, PLEKHG6, and the RhoG effector ELMO. We demonstrate that PLEKHG6 and ezrin are both required in macropinocytosis. After down-regulation of either PLEKHG6 or ezrin expression, we observed an inhibition of dextran uptake in EGF-stimulated A431 cells. Altogether, our data indicate that ezrin allows the local activation of RhoG at the apical pole of epithelial cells by recruiting upstream and downstream regulators of RhoG and that both PLEKHG6 and ezrin are required for efficient macropinocytosis.


Utilization of gynecologic services in women with breast cancer receiving hormonal therapy.
The selective estrogen receptor modulator tamoxifen is now widely used for the treatment and prevention of breast cancer. Tamoxifen use has been associated with a variety of gynecologic problems. Despite the frequency with which hormonal therapy is used for the treatment of breast cancer, limited population-level data are available to describe the occurrence of gynecologic conditions and the use of surveillance testing in women receiving tamoxifen and aromatase inhibitors. We performed a population-based analysis among women with breast cancer receiving hormonal therapy with tamoxifen, a drug commonly used in premenopausal and sometimes postmenopausal women, to determine the frequency of gynecologic abnormalities and use of diagnostic and surveillance testing. We compared these findings to women treated with aromatase inhibitors, agents commonly used in postmenopausal women. The MarketScan database was used to identify women diagnosed with breast cancer from 2009 through 2013 who underwent mastectomy or lumpectomy. Women receiving tamoxifen (age <50 vs ≥50 years) were compared to women ≥50 years of age treated with aromatase inhibitors. We examined the occurrence of gynecologic symptoms and diseases (vaginal bleeding, endometrial polyps, endometrial hyperplasia, and endometrial cancer) and gynecologic procedures and interventions (transvaginal ultrasound, endometrial biopsy, hysteroscopy/dilation and curettage, and hysterectomy). Time-dependent analyses were performed to examine symptoms and testing. A total of 75,170 women, including 15,735 (20.9%) age <50 years treated with tamoxifen, 13,827 (18.4%) age ≥50 years treated with tamoxifen, and 45,608 (60.7%) age ≥50 years treated with aromatase inhibitors were identified. The cumulative incidence of any gynecologic symptom or pathologic diagnosis during the study period was 20.2%, 12.3%, and 3.5%, respectively (P < .001), while the cumulative incidence of any gynecologic procedure or intervention during the study period was 34.2%, 20.9%, and 9.0%, respectively (P < .0001). Among women without symptoms or pathology, interventions were performed in 20.0%, 11.0%, and 6.8%, respectively (P < .0001). Compared to women taking aromatase inhibitors, gynecologic symptoms, procedures, and pathology are higher for both premenopausal and postmenopausal women with breast cancer on tamoxifen. Increased efforts to curb use of gynecologic interventions in asymptomatic women are needed.


One-step silica coating of cetyltrimethyl ammonium bromide-stabilized alpha-Fe2O3.
The alpha-Fe2O3 nanoparticles were coated with silica using intermediated surfactant such as cetyltrimethyl ammonium bromide (CTAB). After the formation of a thin intermediate layer in basic solution without any purification, TEOS was added directly to the solution for further silica growing. Silica thickness can be controlled through the various synthetic conditions (5 to 50 nm). The synthesized powder was characterized by X-ray powder diffraction (XRD), transmission electron microscopy (TEM) and UV-visible spectroscopy. XRD and UV-visible spectroscopy of silica coated alpha-Fe2O3 is preserved constant after coating silica, suggesting that the SiO2 layers can be regarded as protecting layers without destroying the properties of the alpha-Fe2O3 nanoparticles.


Positive regulation of the Hrp type III secretion system in Pseudomonas syringae pv. phaseolicola.
Disease in compatible hosts and induction of the hypersensitive response in resistant plants by most plant-pathogenic bacteria require a functional type III secretion system (T3SS). Expression of T3SS genes responds to host and environmental factors and is induced within the plant. In Pseudomonas syringae, expression of the T3SS requires HrpL, which is transcriptionally upregulated by HrpR and HrpS. In some pathovars, expression of the hrpRS genes is upregulated by the GacA/S two-component system. Additionally, HrpA, the major component of the T3SS pilus, has also been linked to the regulation of the hrpRS gene expression. Previous studies concerning regulation of hypersensitive response and pathogenesis/hypersensitive response conserved (hrp/hrc) gene expression have used mostly in vitro inducing conditions, different pathovars, and methodology. Here, we analyze the roles of HrpL, GacA, and HrpA in the bean pathogen, using single, double, and triple mutants as well as strains ectopically expressing the regulators. We use real-time polymerase chain reaction analysis in vitro and in planta to quantify gene expression and competitive indices and other assays to assess bacterial fitness. Our results indicate that i) HrpL acts as a general virulence regulator that upregulates non-T3SS virulence determinants and downregulates flagellar function; ii) GacA modulates the expression of hrpL, and its contribution to virulence is entirely HrpL dependent; iii) there is a basal HrpL-independent expression of the T3SS genes in rich medium that is important for full activation of the system, maybe by keeping the system primed for rapid activation upon contact with the plant; and iv) HrpA upregulates expression of the T3SS genes and is essential to activate expression of the hrpZ operon upon contact with the plant.


Underreporting of alcohol use in pregnancy.
Studies of alcohol-related birth defects in humans rely heavily on maternal self-reports of alcohol use. The accuracy of self-reports, and thus of related risk levels, is of concern to investigators, to public health professionals, and to persons advising pregnant women. We contrasted quantitative reports of drinking in pregnancy by 238 women with retrospective reports obtained 5 years later. Although correlated (r = 0.67, p less than 0.0001), marked discrepancies suggested underreporting during pregnancy by a significant proportion of the women. The validity of the retrospective index was indicated in that it was somewhat more highly related to scores on the Michigan Alcoholism Screening Test (MAST) and to a tally of alcohol-related craniofacial anomalies in the neonate than was the in-pregnancy index. Furthermore, the retrospective index and the MAST score were significant predictors of other neonatal anomalies; the in-pregnancy index was not. The only variable related to underreporting was MAST score, i.e., the higher the MAST score the greater the underreporting. The results suggest that previously reported thresholds of effect based on self-report data may be underestimates. The results also suggest that questions regarding alcohol-related problems may be more effective than direct consumption questions in the identification of women who drink heavily in pregnancy.


Peritoneal tuberculosis in an immunocompetent, unknown risk patient.
A 36-year-old man with no significant past medical history presented with two-month abdominal distention, night sweats, and weight loss of 15 Ib. He had no known exposure to tuberculosis. PPD test was negative prior to the hospital admission. Physical examination was notable for new onset ascites, but no superficial lymphadenopathy or stigmata of chronic liver disease was found. CT scan demonstrated enlarged mesenteric lymph nodes, and prominent retroperitoneal lymph nodes along with moderate ascites and omental infiltration. Diagnostic paracentesis yielded WBC of 295/mm(3), lymphocytic predominance (70%), and serum ascitic albumin gradient of 0.1, consistent with exudate. Both the ascitic culture and AFB smear were negative, and ascitic cytology revealed nonmalignant cells. Exploratory laparoscopy for excisional biopsy of mesenteric lymph nodes was performed. Pathologic findings revealed caseous granulomas with scattered multinucleated giant cells. Mesenteric lymph node tissue culture subsequently grew Mycobacterium tuberculosis complex and the diagnosis of peritoneal tuberculosis was confirmed. The patient was started on quadruple therapy. A couple of days after the antibiotics were started, the small bowel obstruction started to resolve with resumption of bowel movements and tolerance of oral intake. A week later, ascites stopped accumulating and fever was no longer noted. He has been well and continues to be under observation.


Exposure to tobacco and nicotine product advertising: Associations with perceived prevalence of use among college students.
The purpose of this study was to examine the relationship between exposure to tobacco marketing and perceptions of peer tobacco use among college students. Participants were 5,767 undergraduate students from 19 colleges/universities in the State of Texas. Students completed an online survey, in the spring of 2016, that assessed past 30 day exposure to e-cigarette, cigar, smokeless tobacco, and traditional cigarette advertising across multiple marketing channels, past 30 day use of each product, and perceived prevalence of peer use. Multi-level linear regression models were run to examine the associations between exposure to tobacco advertising and perceptions of peer tobacco use controlling for age, gender, race/ethnicity, use and school. Greater exposure to advertising was associated with greater perceived prevalence of peer use. Given the normative effects of advertising on perceived peer tobacco use, college tobacco initiatives should include descriptive norms education to counteract inaccurate perceptions.


Effects of heat treatment on sound absorption coefficients in nanosilver-impregnated and normal solid woods.
Effects of impregnation with silver nano-suspension as well as heat-treatment on sound absorption coefficients (AC) were studied in tangential direction of five different solid woods based on their importance. AC was measured at two frequencies of 250 and 500 Hz. A 400 ppm nanosuspension was used for the impregnation; silver nanoparticles had a size range of 30-80 nm. Based on the obtained results, the species reacted significantly different in absorbing sound at the two frequencies. Impregnation with nano-suspension substantially decreased AC at the lower frequency of 250 Hz; it did not show any particular trend when AC was measured at the frequency of 500 Hz. Heat treatment significantly increased AC at the frequency of 250 Hz. ACs of mulberry tended to be similar at the two frequencies; in the other four species though, ACs were significantly different. High significant correlations were found in the hardwoods between the ACs measured at the two frequencies.


Intact cell evidence for the early synthesis, and subsequent late apopain-mediated suppression, of poly(ADP-ribose) during apoptosis.
Poly(ADP-ribose) polymerase (PARP), which is catalytically activated by DNA strand breaks, has been implicated in apoptosis, or programmed cell death. A protease (CPP32) responsible for the cleavage of PARP and necessary for apoptosis was recently purified and characterized. The coordinated sequence of events related to PARP activation and cleavage in apoptosis has now been examined in individual cells. Apoptosis was studied in a human osteosarcoma cell line that undergoes a slow (8 to 10 days), spontaneous, and reproducible death program in culture. Changes in the abundance of intact PARP, poly(ADP-ribose) (PAR), and a proteolytic cleavage product of PARP that contains the DNA-binding domain were examined during apoptosis in the context of individual, whole cells by immunofluorescence with specific antibodies. The synthesis of PAR from NAD increased early, within 2 days of cell plating for apoptosis, prior to the appearance of internucleosomal DNA cleavage and before the cells become irreversibly committed to apoptosis, since replating yields viable, nonapoptotic cells. Strong expression of full-length PARP was also detected, by immunofluorescence as well as by Western analysis, during this same time period. However, after approximately 4 days in culture, the abundance of both full-length PARP and PAR decreased markedly. After 6 days, a proteolytic cleavage product containing the DNA-binding domain of PARP was detected immunocytochemically and confirmed by Western analysis, both in the nuclei and in the cytoplasm of cells. A recombinant peptide spanning the DNA-binding domain of PARP was expressed, purified, and biotinylated, and was then used as a probe for DNA strand breaks. Fluorescence microscopy with this probe revealed extensive DNA fragmentation during the later stages of apoptosis. This is the first report, using individual, intact cells, demonstrating that poly(ADP-ribosyl)ation of nuclear proteins occurs prior to the commitment to apoptosis, that inactivation and cleavage of PARP begin shortly thereafter, and that very little PAR per se is present during the later stages of apoptosis, despite the presence of a very large number of DNA strand breaks. These results suggest a negative regulatory role for PARP during apoptosis, which in turn may reflect the requirement for adequate NAD and ATP during the later stages of programmed cell death.


Examination of Host Phenotypes in Gambusia affinis Following Antibiotic Treatment.
The commonality of antibiotic usage in medicine means that understanding the resulting consequences to the host is vital. Antibiotics often decrease host microbiome community diversity and alter the microbial community composition. Many diseases such as antibiotic-associated enterocolitis, inflammatory bowel disease, and metabolic disorders have been linked to a disrupted microbiota. The complex interplay between host, microbiome, and antibiotics needs a tractable model for studying host-microbiome interactions. Our freshwater vertebrate fish serves as a useful model for investigating the universal aspects of mucosal microbiome structure and function as well as analyzing consequential host effects from altering the microbial community. Methods include host challenges such as infection by a known fish pathogen, exposure to fecal or soil microbes, osmotic stress, nitrate toxicity, growth analysis, and measurement of gut motility. These techniques demonstrate a flexible and useful model system for rapid determination of host phenotypes.


Use of colour duplex ultrasound to diagnose giant cell arteritis in a case of visual loss of uncertain aetiology.
Giant cell arteritis is a common condition that can result in permanent visual loss. It has traditionally been diagnosed by invasive temporal artery biopsy in cases of clinical suspicion. The findings of colour duplex ultrasound have recently been described. We report the use of duplex ultrasound to diagnose temporal arteritis, with clinicopathological correlation, and discuss the possible application of this non-invasive technique to the management of giant cell arteritis.


Balloon Expandable Transcatheter Aortic Valve Implantation in Failing Self-Expandable Transcatheter Valve in Degenerated Surgical Bioprosthesis: Valve-in-Valve-in-Valve Implantation for the Treatment of Early Degenerative Prosthetic Insufficiency.
Background: Transcatheter aortic valve implantation (TAVI) has emerged as the standard of care for patients with severe aortic stenosis who are at high surgical risk. However, transcatheter valves can degenerate, and redo TAVI has been reported after surgical aortic valve implantation and post initial TAVI. Case Report: We describe the case of a 70-year-old male who presented with decompensated heart failure secondary to severe prosthetic valve insufficiency. The patient had a history of distant triple coronary artery bypass surgery in 2004, surgical ascending aortic aneurysm repair and stentless aortic valve replacement in 2012, and transcatheter CoreValve (Medtronic) implantation in 2015 for the failing stentless aortic valve. In 2019, the patient presented with heart failure symptoms. A 29-mm SAPIEN 3 valve (Edwards Lifesciences) was implanted for the third time (valve-in-valve-in-valve) with excellent clinical and echocardiographic results and no evidence of coronary obstruction. Conclusion: Early (<5 years) bioprosthetic valve insufficiency after initial valve-in-valve implantation can be successfully treated with a second TAVI.


Effect of dietary fish oil on renal function and rejection in cyclosporine-treated recipients of renal transplants.
Dietary fish oil exerts effects on renal hemodynamics and the immune response that may benefit renal-transplant recipients treated with cyclosporine. To evaluate this possibility, we studied the effect of fish oil on renal function, blood pressure, and the incidence of acute rejection episodes in cyclosporine-treated recipients of renal transplants. In a randomized, double-blind trial, 33 recipients of first cadaveric kidney transplants who were treated with cyclosporine and prednisolone ingested 6 g of fish oil daily during the first postoperative year (the fish-oil group), whereas another 33 renal-graft recipients treated with cyclosporine and prednisolone ingested 6 g of coconut oil daily for three months after which time it was stopped (the control group). One year after transplantation, the fish-oil group had higher median values than the controls for glomerular filtration rate (53 vs. 40 ml per minute per 1.73 m2, P = 0.038) and effective renal plasma flow (214 vs. 178 ml per minute per 1.73 m2, P = 0.023) and lower mean arterial pressure (103 vs. 118 mm Hg, P = 0.0011). The cyclosporine doses in the two groups were similar. The cumulative number of rejection episodes was 20 in the controls, as compared with 8 in the fish-oil group (P = 0.029). One-year graft survival also tended to be better in the fish-oil group, (97 vs. 84 percent, P = 0.097). The daily administration of 6 g of fish oil during the first postoperative year has a beneficial effect on renal hemodynamics and blood pressure in renal-transplant recipients treated with cyclosporine. Although the fish-oil group had significantly fewer rejection episodes than the control group, graft survival at one year was not significantly better in the fish-oil group.


Digging up the roots of an insular hotspot of genetic diversity: decoupled mito-nuclear histories in the evolution of the Corsican-Sardinian endemic lizard Podarcis tiliguerta.
Mediterranean islands host a disproportionately high level of biodiversity and endemisms. Growing phylogeographic evidence on island endemics has unveiled unexpectedly complex patterns of intra-island diversification, which originated at diverse spatial and temporal scales. We investigated multilocus genetic variation of the Corsican-Sardinian endemic lizard Podarcis tiliguerta with the aim of shedding more light on the evolutionary processes underlying the origin of Mediterranean island biodiversity. We analysed DNA sequences of mitochondrial (12S and nd4) and nuclear (acm4 and mc1r) gene fragments in 174 individuals of P. tiliguerta from 81 localities across the full range of the species in a geographic and genealogical framework. We found surprisingly high genetic diversity both at mitochondrial and nuclear loci. Seventeen reciprocally monophyletic allopatric mitochondrial haplogroups were sharply divided into four main mitochondrial lineages (two in Corsica and two in Sardinia) of Miocene origin. In contrast, shallow divergence and shared diversity within and between islands was observed at the nuclear loci. We evaluated alternative biogeographic and evolutionary scenarios to explain such profound discordance in spatial and phylogenetic patterning between mitochondrial and nuclear genomes. While neutral models provided unparsimonious explanations for the observed pattern, the hypothesis of environmental selection driving mitochondrial divergence in the presence of nuclear gene flow is favoured. Our study on the genetic variation of P. tiliguerta reveals surprising levels of diversity underlining a complex phylogeographic pattern with a striking example of mito-nuclear discordance. These findings have profound implications, not only for the taxonomy and conservation of P. tiliguerta. Growing evidence on deep mitochondrial breaks in absence of geographic barriers and of climatic factors associated to genetic variation of Corsican-Sardinian endemics warrants additional investigation on the potential role of environmental selection driving the evolution of diversity hotspots within Mediterranean islands.


Late graft dysfunction after liver transplantation for primary biliary cirrhosis: disease recurrence versus chronic graft rejection.
Possible recurrence of primary biliary cirrhosis (PBC) in the transplanted liver has been reported. We discuss a case of presumed PBC recurrence after liver transplantation. However, the patient's full documented 9-yr follow-up after liver transplantation confirmed the diagnosis of chronic liver graft rejection instead of recurrent disease. This case report underlines not only the difficult differential diagnosis between recurrent PBC and chronic rejection, but it also stresses that complete follow-up, including strict morphological follow-up, is necessary before definitive conclusions can be drawn.


Chromatographic analysis of methylglyoxal and other α-dicarbonyls using gas-diffusion microextraction.
Many α-dicarbonyl compounds such as methylglyoxal, diacetyl and pentane-2,3-dione are important quality markers of processed foods. They are produced by enzymatic and chemical processes, the Maillard reaction is the most known chemical route for α-dicarbonyl formation. In the case of methylglyoxal, there are obstacles to be overcome when analysing this compound due to its high reactivity, low volatility and low concentration. The use of extraction techniques based on the volatilization of methylglyoxal (like solid-phase microextraction) showed to be ineffective for the methylglyoxal extraction from aqueous solutions. Therefore, derivatization is typically applied to increase analyte's volatility. In this work a new methodology for the extraction and analysis of methylglyoxal and also diacetyl and pentane-2,3-dione from selected food matrices is presented. It is based on a gas-diffusion microextraction step followed by high performance liquid chromatographic analysis. It was successfully applied to port wines, black tea and soy sauce. Methylglyoxal, diacetyl and pentane-2,3-dione were quantified in the following concentration ranges: 0.24-1.74 mg L(-1), 0.1-1.85 mg L(-1) and 0.023-0.15 mg L(-1), respectively. The main advantages over existing methodologies are its simplicity in terms of sample handling, not requiring any chemical modification of the α-dicarbonyls prior to the extraction, low reagent consumption and short time of analysis.


Agomelatine treatment with adolescents with ADHD.
Antidepressants, in particular Atomextine, along with stimulants have demonstrated benefit in the treatment of ADHD. Agomelatine is a new antidepressant with additional affinities to the melatonergic system. As ADHD has been associated with sleep disorders, it is assumed that Agomelatiine might serve as a therapeutic alternative to treat patients with the ADHD refractory to first line medications. Ten late adolescents were evaluated in a placebo controlled manner. Agomelatine's effect was superior to that of placebo but appeared to be less than that of first line medications such as methylphenidate. Agomelatine may be a useful second line medication for individuals with ADHD, particularly if they suffer from additional sleep disorders.


Effects of lingual strength training on lingual strength and articulator function in stroke patients with dysarthria.
[Purpose] This study investigated the effects of lingual strength training (LST) on lingual strength and articulator function in stroke patients with dysarthria. [Subjects and Methods] 16 stroke patients with dysarthria were randomly assigned into two groups: the experimental group (n=8) or the control group (n=8). Both groups received the conventional rehabilitation therapy at 30 min/day, 5 times for week, and during 4 weeks, and the experimental group received an additional 30 min of LST using the Iowa Oral Performance Instrument (IOPI). The Maximum Isometric Tongue Pressures (MIPs) was used to assess the lingual strength and the Alternating-Motion Rate (AMR) and Sequential-Motion Rate (SMR) were used to measure the articulator function. [Results] After the intervention, the experimental group showed a significant improvement in MIPs and AMR (/tə/) than the control group. [Conclusion] Findings of this study suggest that LST provides positive effects on lingual strength and articulator function, and thus can be used as an interventional method in stroke patients with dysarthria.


MicroRNA-597 inhibits NSCLC progression through negatively regulating CDK2 expression.
Previous studies have shown that microRNA-597 serves as a tumor suppressor gene. However, the role of microRNA-597 in non-small cell lung cancer (NSCLC) has not been fully elucidated. Therefore, the aim of this study was to investigate the expression of microRNA-597 in NSCLC, and to further explore the possible underlying mechanism. Real-time quantitative polymerase chain reaction (qPCR) was performed to examine microRNA-597 level in tumor tissues and para-cancerous normal tissues collected from 50 patients with NSCLC. The interplay between microRNA-597 expression and clinical indicators, as well as prognosis of NSCLC patients, was analyzed. Meanwhile, qPCR was used to verify microRNA-59 level in NSCLC cell lines. Subsequently, microRNA-597 overexpression and knockdown models were constructed using lentivirus in NSCLC cell lines (including H1299 and PC-9). The impacts of microRNA-597 on the biological functions of NSCLC cells were evaluated using cell counting kit-8 (CCK-8), colony formation, and 5-Ethynyl-2'-deoxyuridine (EdU) assay, respectively. Finally, luciferase reporter gene assay and recovery experiment were performed to investigate the underlying molecular mechanism. QPCR results indicated that microRNA-597 level in NSCLC tissues was remarkably lower than that of adjacent normal tissues, and the difference was statistically significant (p<0.05). Compared with patients with high expression of microRNA-597, patients with low expression of microRNA-597 exhibited significantly higher incidence of pathological stage and lower overall survival rate (p<0.05). Similarly, compared with NC group, the proliferation ability of NSCLC cells was remarkably weakened in microRNA-597 overexpression group (p<0.05). However, the opposite results were observed in microRNA-597 inhibitor group (p<0.05). CDK2 expression was found remarkably elevated in NSCLC cell lines as well as in tissue samples CDK2 expression. Meanwhile, CDK2 expression was negatively correlated with microRNA-597 expression. Luciferase reporter gene assay demonstrated that overexpression of CDK2 could significantly attenuate the luciferase activity of wild-type microRNA-597 vector without attenuating that of mutant vector CDK2 expression. This further suggested that microRNA-597 could target bind to CDK2. Furthermore, cell recovery experiment revealed that CDK2 could reverse the impact of microRNA-597 on the malignant progression of NSCLC. MicroRNA-597 expression was significantly down-regulated in NSCLC tissues, as well as cell lines. Meanwhile, microRNA-597 expression was associated with the pathological staging and poor prognosis of patients with NSCLC. In addition, microRNA-597 might suppress the malignant progression of NSCLC through the regulation of CDK2.


Coffee drinking and the risk of epithelial ovarian cancer.
The relation between ovarian cancer and coffee drinking habits was evaluated in a case-control study of 247 histologically confirmed epithelial ovarian cancers and 494 age-matched controls, admitted to hospital for acute conditions apparently unrelated to coffee consumption. Compared to rates for women who had never drunk coffee, the crude relative risk estimates for those who drank less than two, two or three, and four or more cups per day were 1.3, 1.5 and 1.4 respectively; however, when allowance was made for smoking habits, these risk estimates became 1.3, 1.7 and 1.8 respectively, and a significant linear trend of increasing risk with more elevated coffee consumption was evident. These results were not explained by various other potential confounding factors, including the major risk factors for ovarian cancer, but we had no information on dietary variables. The relative risk, however, did not increase with increasing duration of use. The findings of this study give apparent support in favour of the hypothesis that coffee consumption, or related dietary variables, may be associated with the risk of epithelial ovarian cancer. Further studies in different settings, however, are required in order to establish whether this association is real, and if so, whether it is causal.


Distribution of high-dimensional entanglement via an intra-city free-space link.
Quantum entanglement is a fundamental resource in quantum information processing and its distribution between distant parties is a key challenge in quantum communications. Increasing the dimensionality of entanglement has been shown to improve robustness and channel capacities in secure quantum communications. Here we report on the distribution of genuine high-dimensional entanglement via a 1.2-km-long free-space link across Vienna. We exploit hyperentanglement, that is, simultaneous entanglement in polarization and energy-time bases, to encode quantum information, and observe high-visibility interference for successive correlation measurements in each degree of freedom. These visibilities impose lower bounds on entanglement in each subspace individually and certify four-dimensional entanglement for the hyperentangled system. The high-fidelity transmission of high-dimensional entanglement under real-world atmospheric link conditions represents an important step towards long-distance quantum communications with more complex quantum systems and the implementation of advanced quantum experiments with satellite links.


Radioactive quality evaluation and cross validation of data from the HJ-1A/B satellites' CCD sensors.
Data from multiple sensors are frequently used in Earth science to gain a more complete understanding of spatial information changes. Higher quality and mutual consistency are prerequisites when multiple sensors are jointly used. The HJ-1A/B satellites successfully launched on 6 September 2008. There are four charge-coupled device (CCD) sensors with uniform spatial resolutions and spectral range onboard the HJ-A/B satellites. Whether these data are keeping consistency is a major issue before they are used. This research aims to evaluate the data consistency and radioactive quality from the four CCDs. First, images of urban, desert, lake and ocean are chosen as the objects of evaluation. Second, objective evaluation variables, such as mean, variance and angular second moment, are used to identify image performance. Finally, a cross validation method are used to ensure the correlation of the data from the four HJ-1A/B CCDs and that which is gathered from the moderate resolution imaging spectro-radiometer (MODIS). The results show that the image quality of HJ-1A/B CCDs is stable, and the digital number distribution of CCD data is relatively low. In cross validation with MODIS, the root mean square errors of bands 1, 2 and 3 range from 0.055 to 0.065, and for band 4 it is 0.101. The data from HJ-1A/B CCD have better consistency.


Layers of interstitial fluid flow along a "slit-shaped" vascular adventitia.
Interstitial fluid (ISF) flow through vascular adventitia has been discovered recently. However, its kinetic pattern was unclear. We used histological and topographical identification to observe ISF flow along venous vessels in rabbits. By magnetic resonance imaging (MRI) in live subjects, the inherent pathways of ISF flow from the ankle dermis through the legs, abdomen, and thorax were enhanced by paramagnetic contrast. By fluorescence stereomicroscopy and layer-by-layer dissection after the rabbits were sacrificed, the perivascular and adventitial connective tissues (PACTs) along the saphenous veins and inferior vena cava were found to be stained by sodium fluorescein from the ankle dermis, which coincided with the findings by MRI. The direction of ISF transport in a venous PACT pathway was the same as that of venous blood flow. By confocal microscopy and histological analysis, the stained PACT pathways were verified to be the fibrous connective tissues, consisting of longitudinally assembled fibers. Real-time observations by fluorescence stereomicroscopy revealed at least two types of spaces for ISF flow: one along adventitial fibers and another one between the vascular adventitia and its covering fascia. Using nanoparticles and surfactants, a PACT pathway was found to be accessible by a nanoparticle of <100 nm and contained two parts: a transport channel and an absorptive part. The calculated velocity of continuous ISF flow along fibers of the PACT pathway was 3.6‒15.6 mm/s. These data revealed that a PACT pathway was a "slit-shaped" porous biomaterial, comprising a longitudinal transport channel and an absorptive part for imbibition. The use of surfactants suggested that interfacial tension might play an essential role in layers of continuous ISF flow along vascular vessels. A hypothetical "gel pump" is proposed based on interfacial tension and interactions to regulate ISF flow. These experimental findings may inspire future studies to explore the physiological and pathophysiological functions of vascular ISF or interfacial fluid flow among interstitial connective tissues throughout the body.


CREPT expression correlates with poor prognosis in patients with retroperitoneal leiomyosarcoma.
Retroperitoneal leiomyosarcomas (LMSs) are rare gynecological malignancies that display poor prognosis and high mortality. Cell cycle-related and expression-elevated protein in tumor (CREPT) is an oncogene that is involved in the regulation of many cell cycle-related proteins. However, its distribution and clinical significance in retroperitoneal LMS remains poorly understood. This study assessed the histological classifications of postoperative tumor samples from 71 cases of retroperitoneal LMS that were collected at The General Hospital of the People's Liberation Army from January 1998 to December 2012. We found that more than half of the patients displayed positive expressions of CREPT, Ki-67 and PCNA via immunohistochemical analysis. The expression of CREPT correlated with histological grade (P = 0.044), and the PCNA expression level correlated with the differentiation of tumor cells and histological grade (P < 0.001 and P = 0.009, respectively). Multivariate analysis showed that survival was associated with histological grade and the expression level of CREPT (P = 0.011 and P = 0.012, respectively). Kaplan-Meier analysis showed that the patients lacking CREPT expression exhibited significantly longer overall postoperative survival (median, 60.0 months) than the patients displaying CREPT expression (median, 33.0 months), and CREPT expression correlated with distant recurrence within 5 years after surgery (P = 0.004). Western blot analyses showed that CREPT was more strongly expressed in the retroperitoneal LMS tumor tissue than in paired control tissue. Based on the above data, we concluded that CREPT displays unique immunostaining for retroperitoneal LMS tissue and can be used to supplement other currently available retroperitoneal LMS markers.


Immunogenic landscape and risk score prediction based on unfolded protein response (UPR)-related molecular subtypes in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is the most common type of cancer and causes a significant number of cancer-related deaths worldwide. The molecular mechanisms underlying the development of HCC are complex, and the heterogeneity of HCC has led to a lack of effective prognostic indicators and drug targets for clinical treatment of HCC. Previous studies have indicated that the unfolded protein response (UPR), a fundamental pathway for maintaining endoplasmic reticulum homeostasis, is involved in the formation of malignant characteristics such as tumor cell invasiveness and treatment resistance. The aims of our study are to identify new prognostic indicators and provide drug treatment targets for HCC in clinical treatment based on UPR-related genes (URGs). Gene expression profiles and clinical information were downloaded from the TCGA, ICGC and GEO databases. Consensus cluster analysis was performed to classify the molecular subtypes of URGs in HCC patients. Univariate Cox regression and machine learning LASSO algorithm were used to establish a risk prognosis model. Kaplan-Meier and ROC analyses were used to evaluate the clinical prognosis of URGs. TIMER and XCell algorithms were applied to analyze the relationships between URGs and immune cell infiltration. Real time-PCR was performed to analyze the effect of sorafenib on the expression levels of four URGs. Most URGs were upregulated in HCC samples. According to the expression pattern of URGs, HCC patients were divided into two independent clusters. Cluster 1 had a higher expression level, worse prognosis, and higher expression of immunosuppressive factors than cluster 2. Patients in cluster 1 were more prone to immune escape during immunotherapy, and were more sensitive to chemotherapeutic drugs. Four key UPR genes (ATF4, GOSR2, PDIA6 and SRPRB) were established in the prognostic model and HCC patients with high risk score had a worse clinical prognosis. Additionally, patients with high expression of four URGs are more sensitive to sorafenib. Moreover, ATF4 was upregulated, while GOSR2, PDIA6 and SRPRB were downregulated in sorafenib-treated HCC cells. The UPR-related prognostic signature containing four URGs exhibits high potential application value and performs well in the evaluation of effects of chemotherapy/immunotherapy and clinical prognosis.


Biocompatibility of Optibond and XR-Bond adhesive systems in nonhuman primate teeth.
This study evaluated the histologic responses of two different adhesive systems on the teeth of seven healthy adult monkeys. Class V cavities in 128 teeth were observed at 7,21 to 27, and 90 to 97 days. Statistical data showed no significant differences in pulp inflammation between the Optibond (Kerr), XR-Bond (Kerr), and IRM (Caulk) groups in pulps at the three time intervals. Some odontoblastic disruption and inflammation was seen in pulps restored with XR-Primer at the three time intervals. Pulp healing was similar in teeth treated with both direct-capped Optibond and calcium hydroxide, and there was no significant increase in pulpal inflammation with time. No abscesses or necrotic pulps were seen in any teeth. Optibond and XR-Bond adhesive systems are biologically acceptable in nonhuman primate pulp tissues.


Investigating the efficacy of topical application of Ipomoea carnea herbal cream in preventing skin damage induced by UVB radiation in a rat model.
Ultraviolet-B irradiation is a common environmental stressor that has detrimental effects on human skin. Natural sunscreens are well-known for their ability to benefit inflamed sunburn and dry skin. This study examined the effect of formulated Ipomoea carnea herbal cream on UVB-induced skin damage. We screened the bioactive compounds of I. carnea crude extract, showing significant antioxidant activity. Additionally, we evaluated the cytotoxicity, revealing that I. carnea extract has less toxicity to vero cells (IC50 98.45 μg/mL) than to A375 cells (IC50 48.95 μg/mL). Based on this, we formulated the I. carnea herbal cream (FIHC) at 50, 100 and 200 mg concentrations and evaluated its organoleptic characteristics. Then, the rats were exposed to UVB radiation (32,800 J/m2) four times/week (on alternate days) before the cream was applied topically to the dorsal skin surface. Under UVB stress without treatment, rats showed deep dermal damage. In contrast, rats treated with the FIHC exhibited significantly reduced sunburn. Moreover, the histopathological and biochemical assays were confirmed by the topical application of FIHC, which had potentially reduced the skin elasticity and maintained the imbalanced enzyme and non-enzymatic antioxidant activity. Our findings amply demonstrate that the FIHC significantly accelerated the recovery of UVB-induced lesions through antioxidant and down-regulation of skin photodamage.


A Smart Sensor for Defending against Clock Glitching Attacks on the I2C Protocol in Robotic Applications.
This paper presents a study about hardware attacking and clock signal vulnerability. It considers a particular type of attack on the clock signal in the I2C protocol, and proposes the design of a new sensor for detecting and defending against this type of perturbation. The analysis of the attack and the defense is validated by means of a configurable experimental platform that emulates a differential drive robot. A set of experimental results confirm the interest of the studied vulnerabilities and the efficiency of the proposed sensor in defending against this type of situation.


Impact of COVID-19 Related Lockdown on the Frequency of Acute and Oncological Surgeries-Lessons Learned From an Austrian University Hospital.
Innsbruck Medical University Hospital, Austria, provides the highest level of care for a region of approximately 1.8 million people. During the early COVID-19 outbreak in spring 2020 surgical activity was drastically reduced with the prime goal of preserving hospital capacities, especially intensive care beds. We conducted a retrospective analysis of surgical activities performed at Innsbruck Medical University Hospital during the lockdown period from March 15 to April 14, 2020 and compared these activities to the same period during the previous 5 years. Total surgical activity was reduced by 65.4% compared to the same period during the previous 5 years (p < 0.001); elective surgeries were reduced by 88.7%, acute surgeries by 35.3% and oncological surgeries by 47.8% compared to the previous 5 years (all p < 0.001). This dramatic decrease in acute and oncological surgeries can most likely be ascribed to the fact that many patients avoided health care facilities because of the strict stay-at-home policy and/or the fear of contracting SARS-CoV-2 in the hospital. In view of future waves, the population should be encouraged to seek medical help for acute symptoms and to attend cancer screening programs.


Once upon a dish: engineering multicellular systems.
In February 2020, the European Molecular Biology Laboratory (EMBL) and the Institute for Bioengineering of Catalonia (IBEC) joined forces to unite researchers from all over the globe to discuss emerging topics in 'Engineering Multicellular Systems'. As we review here, key themes that arose throughout the meeting included the ethics of organoids in developmental biology, bottom-up versus top-down models, tissue organizing principles, and the future of improving these systems to better mimic the natural world.


Stress during puberty boosts metabolic activation associated with fear-extinction learning in hippocampus, basal amygdala and cingulate cortex.
Adolescence is characterized by major developmental changes that may render the individual vulnerable to stress and the development of psychopathologies in a sex-specific manner. Earlier we reported lower anxiety-like behavior and higher risk-taking and novelty seeking in rats previously exposed to peri-pubertal stress. Here we studied whether peri-pubertal stress affected the acquisition and extinction of fear memories and/or the associated functional engagement of various brain regions, as assessed with 2-deoxyglucose. We showed that while peri-pubertal stress reduced freezing during the acquisition of fear memories (training) in both sexes, it had a sex-specific effect on extinction of these memories. Moreover hippocampus, basal amygdala and cingulate and motor cortices showed higher metabolic rates during extinction in rats exposed to peri-pubertal stress. Interestingly, activation of the infralimbic cortex was negatively correlated with freezing during extinction only in control males, while only males stressed during puberty showed a significant correlation between behavior during extinction and metabolic activation of hippocampus, amygdala and paraventricular nucleus. No correlations between brain activation and behavior during extinction were observed in females (control or stress). These results indicate that exposure to peri-pubertal stress affects behavior and brain metabolism when the individual is exposed to an additional stressful challenge. Some of these effects are sex-specific.


[A clinical study on cefoperazone in serious infections associated with hematological malignancy].
Clinical and bacteriological efficiencies of cefoperazone (CPZ) in 19 serious infections associated with hematological malignancy were studied. CPZ was clinically effective in 13 cases (68.4%). Excellent effects were obtained in 3 cases (15.8%), good effects in 7 cases (36.8%) and fairly good effects in 3 cases (15.8%). The rate of clinical effectiveness by CPZ was not dependent on neutrophils number in peripheral blood. Bacteriological effectiveness to isolated organisms in 15 cases was obtained in 9 cases (60%). Clinically significant serum concentrations of CPZ persisted over 6 hours after injection (1 g/l hour, d.i.v.). In comparative study of MIC against clinically isolated P. aeruginosa, CPZ was superior to other cephalosporins. Adverse reactions were not significant except for 3 cases with abnormalities of hepatic function.


Use of a Super-hydrophobic Microbioreactor to Generate and Boost Pancreatic Mini-organoids.
Cell remarkable ability to self-organize and rearrange in functional organoids has been greatly boosted by the recent advances in 3-D culture technologies and materials. This approach can be presently applied to model human organ development and function "in a dish" and to predict drug response in a patient specific fashion.Here we describe a protocol that allows for the derivation of functional pancreatic mini-organoids from skin biopsies. Cells are suspended in a drop of medium and encapsulated with hydrophobic polytetrafluoroethylene (PTFE) powder particles, to form microbioreactors defined as "Liquid Marbles," that stimulate cell coalescence and 3-D aggregation. The PTFE shell ensures an optimal gas exchange between the interior liquid and the surrounding environment. It also makes it possible to scale down experiments and work in smaller volumes and is therefore amenable for higher throughput applications.


Platelet markers of thromboembolic disease.
Platelets may be useful as markers of thromboembolic disease. When labeled with indium 111 they allow external imaging of localized clots. Indium 111 is much superior to chromium 51 for this procedure. Detection of circulating platelet aggregates also appears to be a simple means of determining the presence of thromboembolic disorders. In response to injury or involvement in clotting, platelets release several unique proteins not normally found in the plasma. Therefore, elevated levels of these proteins suggest the presence of such damage. Platelet factor 4 and beta-thromboglobulin are the most widely studied of these proteins, and both can be quantitated by radioimmunoassay. Such assays are now commercially available. Elevated levels have been demonstrated in such diverse disorders as deep venous thrombosis, atherosclerosis and diabetes. However, blood must be drawn with great care to avoid in vitro damage to platelets and false elevation of these markers. All of these procedures are promising at present, but their precise role and value await further study.


[Pathogenesis of glomerulonephritis following streptococcal infection].
Group A streptococci are responsible for the induction of serious pyoderma and pharyngitis in humans. The nonsuppurative sequelae "acute rheumatic fever" (ARF) and "acute poststreptococcal glomerulonephritis" (APGN) do very often occur with variable attack rates in epidemics with these microorganisms. At present, immune complex formation in the blood circulation system, in situ complex formation within the glomeruli, antibody cross-reactions between beta-hemolytic group A streptococci and human kidney tissue as well as tissue damage independent of specific antibodies are intensively discussed to explain the pathogenesis of acute poststreptococcal glomerulonephritis. However, the pathophysiological course of APGN has not yet been precisely identified.


Endoscopic management of gastrointestinal motility disorders - part 1: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.
ESGE recommends the use of a graded pneumatic dilation protocol in achalasia, starting with a 30-mm dilation and followed by a 35-mm dilation at a planned interval of 2 - 4 weeks, with a subsequent 40-mm dilation when there is insufficient relief, over both a single balloon dilation procedure or the use of a larger balloon from the outset.Strong recommendation, high quality of evidence, level of agreement 100 %.ESGE recommends being cautious in treating spastic motility disorders other than achalasia with peroral endoscopic myotomy (POEM).Strong recommendation, very low quality of evidence, level of agreement 87.5 %.ESGE recommends against the routine use of botulinum toxin injections to treat patients with non-achalasia hypercontractile esophageal motility disorders (Jackhammer esophagus, distal esophageal spasm). However, if, in individual patients, endoscopic injection of botulinum toxin is chosen, ESGE recommends performing injections into four quadrants of the lower esophageal sphincter and in the lower third of the esophagus.Strong recommendation, low quality of evidence, level of agreement 78.6 %.ESGE recommends that endoscopic pylorus-directed therapy should be considered only in patients with symptoms suggestive of gastroparesis in combination with objective proof of delayed gastric emptying using a validated test, and only when medical therapy has failed.Strong recommendation, very low quality of evidence, level of agreement 100 %.ESGE recommends against the use of botulinum toxin injection in the treatment of unselected patients with gastroparesis. Strong recommendation, high quality of evidence, level of agreement 92.9 %.ESGE recommends consideration of gastric peroral endoscopic myotomy (G-POEM) in carefully selected patients only, because it is an emerging procedure with limited data on effectiveness, safety, and durability. G-POEM should be performed in expert centers only, preferably in the context of a clinical trial.Strong recommendation, low quality of evidence, level of agreement 100 %.


Two Pyroptosis-Related Subtypes with Distinct Immune Microenvironment Characteristics and a Novel Signature for Predicting Immunotherapy Response and Prognosis in Uveal Melanoma.
Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults with poor prognosis. Pyroptosis is a well-known form of programmed cell death. However, pyroptosis has not been sufficiently discussed in UM. This study aims to explore the expression patterns of pyroptosis-related genes (PRGs) and their relationship with tumor microenvironment (TME) characteristics and prognosis in UM. In this study, unsupervised clustering analysis was performed based on the expression of 10 PRGs to identify pyroptotic subtypes. TME characteristics were evaluated by using the ssGSEA, ESTIMATE and CIBERSORT algorithms. In addition, a related scoring model (PRscore) was established to quantify pyroptotic patterns of individual UM patients via principal component analysis. The correlation between PRscore and TME characteristics was assessed by Spearman analysis. Furthermore, univariate and multivariate Cox regression analysis were performed to identify whether the PRscore can be an independent factor for predicting the overall survival (OS) of UM patients. The results revealed that there were two distinct pyroptotic patterns with different TME characteristics in UM. PRscore was found to be associated with TME characteristics and patient prognosis. In addition, combined with the clinical characteristics, the PRscore was found to be an independent factor for predicting the OS of UM patients. Furthermore, PRscore might be a useful tool for predicting the response to immunotherapy in UM patients. The status of pyroptosis was associated with TME characteristics in UM. In addition, evaluating the pyroptotic pattern (Prscore) would help us to predict the prognosis and immunotherapy response of individual UM patient. Furthermore, our results may offer novel insights into the development of a promising strategy for treating UM, i.e. the combination of chemodrugs targetting the induction of pyroptosis and immune checkpoint inhibitors (ICIs).


Inhibition of chemically induced mammary carcinogenesis in rats by long-term exposure to butylated hydroxytoluene (BHT): interrelations among BHT concentration, carcinogen dose, and diet.
In outbred female Sprague-Dawley rats long-term exposure to dietary butylated hydroxytoluene [3,5-di-tert-butyl-4-hydroxytoluene (BHT); CAS: 128-37-0] 1 week before carcinogen administration to termination resulted in a dose-related inhibition of mammary tumorigenesis and adrenocortical nodulogenesis. In animals fed the cereal-based NIH-07 diet and receiving a low dose (5 mg/rat) of 7,12-dimethylbenz [a] anthracene [(DBMA) CAS: 57-97-6], there was a significant overall inhibitory trend in tumor incidence observed among those receiving 300, 1,000, 3,000, and 6,000 ppm BHT. Maximal inhibition was approximately 50% at the highest concentration of BHT (6,000 ppm). The inhibitory effect of BHT on mammary tumor incidence was less pronounced when BHT was administered to rats initiated with a high carcinogen dose: At 15 mg DMBA/rat maximal inhibition was only 20% at the highest concentration of BHT (6,000 ppm). In contrast, when tumor yield was assessed in terms of latency or tumor multiplicity, the inhibitory effect of BHT was more pronounced in the groups given a high dose of DMBA than in the groups given a low dose. In animals given a low dose of DMBA (5 mg) and fed 6,000 ppm BHT in the casein-based AIN-76A diet, tumor incidence was inhibited by 50% of that of the controls; in contrast, when initiation was with a high dose of DMBA (15 mg), tumor incidence was decreased by only 28% of that of the controls. In animals fed the NIH-07 diet, DMBA-induced adrenocortical nodule formation was also inhibited in a dose-dependent fashion by BHT. At 5 mg DMBA maximal inhibition was 86% of control levels (6,000 ppm BHT); at 15 mg DMBA maximal inhibition was 66% of control levels (6,000 ppm BHT). However, when BHT was incorporated into the AIN-76A diet, its inhibitory effects on adrenocortical nodulogenesis were unexpectedly feeble and unrelated to carcinogen dose: In animals initiated with 5 mg DMBA and administered 6,000 ppm BHT, nodule incidence was decreased by only 25%, whereas in animals initiated with 15 mg DMBA, nodule incidence was decreased by 30% of that of the controls. These results indicate that while chronic exposure to dietary BHT suppressed the development of DMBA-induced mammary tumors and adrenocortical nodules, the degree of suppression depended on the dose of carcinogen administered, the level of BHT in the diet, and the parameter being measured. Diet-dependent differences in BHT action were observed with regard to DMBA-induced adrenocortical nodulogenesis but not with regard to mammary tumorigenesis.


Relative Expression of OCT4, SOX2 and NANOG in Oral Squamous Cell Carcinoma Versus Adjacent Non- Tumor Tissue.
Objective: Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral neoplasms. Finding molecular markers for predicting prognosis is a high priority. The core transcription factors, OCT4, SOX2, and NANOG that regulate embryonic stem cell pluripotency have been implicated in progression of various malignancies. The predictive value of these markers and their role in the development of OSCC is still controversial. In this study, we therefore evaluated their expression in OSCCs and adjacent non-tumor tissue. Methods: A total of 60 frozen tumor and adjacent non-tumor tissue samples from 30 patients with OSCC were examined using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Clinical and pathological data of patients including tumor stage, lymph node metastasis and tumor grade were also recorded. Results: Expression of SOX2 was significantly higher in adjacent non-tumor as compared to tumor tissue (P=0.04). No statistically significant differences were found for expression of OCT4 (P=0.50) and NANOG (P=0.68). Also, there was no significant association between expression of OCT4, SOX2, and NANOG and clinical or pathological data (P>0.05), although slightly higher values were noted in patients without lymph node metastasis. Conclusion: Based on the present data, decreased expression of SOX2 is correlated with carcinogenesis in the oral cavity and development of OSCC.


Patient-Reported Quality of Life Before and After Total Knee Arthroplasty: A Multicenter Observational Study.
To compare patients' self-reported health-related quality of life (HRQoL) before and after total knee arthroplasty (TKA) and determine factors contributing to any heterogeneity in HRQoL. This prospective multicenter observational study included 404 patients with knee osteoarthritis who underwent TKA between April 1, 2019 and December 30, 2019 and whose HRQoL was assessed preoperatively and 7 days and 1, 3, and 6 months postoperatively. Sociodemographic characteristics were assessed using a General Information Questionnaire, disability using the Knee Injury and Osteoarthritis Outcome Score (KOOS-PS), resting pain using the visual analogue scale (Pain-VAS), and HRQoL using the European Quality of Life Five Dimension Five Level (EQ-5D-5L) scale. The growth mixture model was used to identify group heterogeneity in the developmental trajectories of KOOS-PS, Pain-VAS, and EQ5D5L. Logistic regression was used to explore the factors influencing the developmental trajectories of factors affecting the developmental trajectory of HRQoL. The mean EQ-5D-5L score improved from 0.69 preoperatively to 0.90 at 6 months postoperatively. Longitudinal heterogeneity in HRQoL was observed in patients during recovery: 1) patients with a small and slow improvement in HRQoL and 2) patients who showed marked and rapid improvement in HRQoL. The main characteristics of the latter group were decreasing VAS pain scores, a monthly family income >2000 CNY (100 CNY equals approximately 14.9 USD), exercising for <30 min daily, and better knee function at baseline. Baseline knee function and change in knee function were significantly associated with the percentage change in HRQoL. HRQoL improved considerably after TKA. However, there was heterogeneity in the changes in HRQoL depending on patients' socioeconomic status, exercise, and baseline knee function. Dynamic tracking of the HRQoL of TKA patients and timely provision of rehabilitation guidance will promote continuous improvement of the HRQoL of TKA patients.


Frozen section in laparoscopic management of macroscopically suspicious ovarian masses.
To study the usefulness of and applications for frozen section in the laparoscopic management of adnexal masses. Historical prospective study (Canadian Task Force classification II-3). Large tertiary care hospital with university affiliation. One hundred forty-one women undergoing laparoscopy for a suspicious adnexal mass. Adnexal masses suspicious on ultrasound were managed by laparoscopy. After laparoscopic diagnosis, frozen sections were used to confirm a diagnosis of malignancy. Treatment was performed by laparoscopy whenever feasible. The results of frozen section were compared with the results of permanent sections, and the consequences of the intraoperative diagnosis on the surgical management were evaluated. The frozen section diagnosis was correct in 125 of the 141 patients (88.7%). In one patient, the result was false negative. Specifically, frozen section diagnosis was correct in 96.8% of cases when a cyst or biopsy was sent for pathologic examination and in 86.4% when the whole adnexa was sent. It was correct in 93% of the cases involving tumors smaller than 100 mm and in 74% of larger tumors. It was correct in 92.3% of the women younger than 50 years and in 81.6% of women older than age 50. Intraoperative pathologic diagnosis was correct in 95.5% of benign tumors, 77.8% of low-malignancy tumors, and 75% of cancer cases. Frozen section is a useful examination for surgical management decision making; however, the limitations and the difficulties should be taken into account.


BMI Is a Risk Factor for Colorectal Cancer Mortality.
The relationship between dietary and lifestyle risk factors and long-term mortality from colorectal cancer is poorly understood. Several factors, such as obesity, intakes of red meat, and use of aspirin, have been reported to be associated with risk of colorectal cancer mortality, though these findings have not been replicated in all studies to date. In the Minnesota Colon Cancer Control Study, 46,551 participants 50-80 years old were randomly assigned to usual care (control) or annual or biennial screening by fecal occult blood testing. Colon cancer mortality was assessed after 30 years of follow-up. Dietary intake and lifestyle risk factors were assessed by questionnaire at baseline. Age [hazard ratio (HR) 1.09; 95% CI 1.07, -1.11], male sex (HR 1.25; 95% CI 1.01, 1.57), and higher body mass index (BMI) (HR 1.03; 95% CI 1.00-1.05) increased the risk of CRC mortality, while undergoing screening for CRC was associated with a reduced risk of colorectal cancer mortality (HR 0.76; 95% CI 0.61-0.94 and 0.67; 95% CI 0.53-0.83 for biennial and annual screening, respectively). Intakes of grains, meats, proteins, coffee, alcohol, aspirin, fiber, fruits, and vegetables were not associated with colorectal cancer mortality. Our study confirms the relationship between BMI and long-term colorectal cancer mortality. Modulation of BMI may reduce risk of CRC mortality.


Correlation between Imaging Morphological Findings and Laboratory Biomarkers in Patients with Diabetic Macular Edema.
To investigate the potential association between peripheral blood biomarkers and morphological characteristics of retinal imaging in patients with diabetic macular edema (DME). Participants in this cross-sectional study were 36 consecutive patients (36 eyes) with treatment-naïve DME, who underwent spectral domain-optical coherence tomography (SD-OCT), fundus photography, and fundus fluorescein angiography (FFA). In addition, peripheral blood samples were taken to evaluate full blood count and biochemical parameters. Correlation between imaging characteristics and laboratory parameters was examined. Eyes with central subfield thickness greater than 405 μm presented significantly higher neutrophils/lymphocytes (p = 0.043) and higher lipoprotein (a) compared to eyes with CST < 405 μm (p = 0.003). Presence of hyperreflective foci on SD-OCT was associated with significantly higher white blood cell count (p = 0.028). Ellipsoid zone disruption was associated with significantly lower hematocrit (p = 0.012), hemoglobin (p = 0.009), and red blood cell count (p = 0.026), as well as with higher lipoprotein (a) (p = 0.015). Macular ischemia on FFA was associated with significantly higher monocytes (p = 0.027) and monocytes/HDL (p = 0.019). No significant associations were found between laboratory parameters and subretinal fluid, intraretinal fluid, exudates, cysts, disorganization of inner retinal layers, epiretinal membrane, and external limiting membrane condition. Specific imaging morphological characteristics were found to be associated with laboratory parameters in patients with DME. These findings may shed light on the pathophysiology of DME and its correlation with the development of specific clinical signs.


Unusually Situated Binding Sites for Bacterial Transcription Factors Can Have Hidden Functionality.
A commonly accepted paradigm of molecular biology is that transcription factors control gene expression by binding sites at the 5' end of a gene. However, there is growing evidence that transcription factor targets can occur within genes or between convergent genes. In this work, we have investigated one such target for the cyclic AMP receptor protein (CRP) of enterotoxigenic Escherichia coli. We show that CRP binds between two convergent genes. When bound, CRP regulates transcription of a small open reading frame, which we term aatS, embedded within one of the adjacent genes. Our work demonstrates that non-canonical sites of transcription factor binding can have hidden functionality.


Quantum Chemical Calculations of Monomer-Dimer Equilibria of Aromatic C-Nitroso Compounds.
Monomer-dimer equilibria of nitrosobenzene and 2-nitrosopyridine in gas phase and solution were studied by range of quantum chemical methods in an attempt to find the level of theory suitable for modeling dimerization reactions of aromatic C-nitroso compounds in general. The best agreement with the experimental standard reaction Gibbs energies was obtained with a combination of double-hybrid density functionals B2PLYP-D3, PBE0DH, and DSD-PBEB86, and basis sets of triple-ζ quality. Of all other tested functionals, global hybrid PBE0 behaved equally well, and proved to be more than adequate for at least preliminary work. Other tested methods either produced inferior results (MP2, MP4(SDQ), CCSD, G4(MP2), CBS-QBS, CBS-APNO), or were too demanding for practical use (CCSD(T)). Analysis of computationally obtained thermodynamic data reveal intricate details of these reactions. Both E- and Z-dimers have several different conformers, which all have different solvation energies. While in the gas phase the nitrosobenzene E-dimer is more stable that its Z-form, in chloroform, the Z-form is more stable. Gas-phase dimerization entropies are large and negative, so these reactions are strongly temperature dependent. In some cases, like with 2-nitrosopyridines, entropy and enthalpy terms essentially cancel each other out, allowing structural and media effects to significantly influence dimerization equilibria.


[Update on the 2016 WHO classification of tumors of the central nervous system - Part 1: Diffusely infiltrating gliomas].
Revised WHO 2016 classification of tumors of the central nervous system (CNS) incorporates for the first time genetic information in addition to morphology for classification of many tumor entities. One of the most important changes is restructuring the chapter of diffuse gliomas. Based on shared genetic driver mutations, diffusely infiltrating astrocytomas and oligodendrogliomas are now classified together, separately from "other" glial tumors with a more circumscribed growth pattern, different pathogenesis and clinical outcome. Diffuse gliomas can now be more objectively diagnosed and further prognostically stratified by use of a relatively small number of markers (ATRX and IDH1/2 mutations and del 1p/19q). Another newly genetically-defined and clinically relevant entity is diffuse midline glioma, H3 K27M-mutant. Some glioma entities, variants and growth patterns were deleted and new variants, such as epithelioid glioblastoma and glioblastoma with a primitive neural component were added. In the article, the most important changes of diffuse gliomas classification are summarized and a practical diagnostic approach is illustrated.


Neonatal testosterone voids sexually differentiated microglia morphology and behavior.
The involvement of immunity in psychiatric disorders, such as anxiety, is typified by the morphologic adaptation of microglia, immune cells of the brain, to anxiogenic stimuli. We previously reported sexually differentiated microglia morphology in adult rodents, in brain locations implicated in anxiety, including the pre-frontal cortex. These physiologic differences likely drive sex-dependent patterns of microglia morphologic remodeling in response to varied stress conditions in different periods of life, that correlate with sex-dependent behavioral adaptation to anxiogenic stimuli. The time-window of appearance of sex differences in microglia, correlating with sex-specific behavioral performance in anxiogenic conditions are still unknown. In rodents, a postnatal peak of the sexual hormone testosterone is determinant for the so-called brain masculinization and sex-determined behavioral traits. In the present work we aim to clarify if differences in microglia morphology are present at birth or can be driven by postnatal testosterone and impacts on the ability to deal with an anxiogenic context. Differences in microglia morphology are not present at birth, but are observable at adolescence (increased complexity of male microglia, particularly in branches more proximal to the soma), when differences in behavior are also observed. Our data also show that adolescent females neonatally treated with testosterone exhibit masculinized microglia and behavior. Importantly, between adolescence and adulthood, a sex-determined shift in the pattern of complexity takes place and microglia from females become more complex. When testosterone is administered, this morphological effect is partially abolished, approximating microglia and behavior to the male phenotype.


Primary corneal myxoma.
Primary corneal myxoma is extremely rare. It has only been reported on 2 previous occasions. Secondary corneal myxomas are more common, arising from corneal diseases such as infective keratitis, keratoconus, and bullous keratopathy. Myxomas occur commonly in other soft tissues such as the heart, paranasal sinuses, and muscles but can rarely present in periocular structures including the conjunctiva, orbit, and eyelid. Ours is only the third case of primary corneal myxoma reported in the literature and illustrates several unusual features. These include an inferonasal location between the corneal epithelium and Bowman layer and with no relationship to the corneal stroma, rapid tumor growth over a 3-month period, and no previous ocular trauma or conjunctival pathology. The histology of this lesion has an important part to play in the management of this condition as it determines the cellular origin, establishes a benign or malignant state, and helps with treatment and prognosis. One reported case of primary corneal myxoma recurred within 2 months after local resection. This was treated with bandage soft contact lens, and no recurrence had been reported since. Our case is now 12 months post op and has had no recurrence.


Techniques of facial lesion excision and closure.
The goals of facial lesion excision and closure are to minimize scar formation and to camouflage the unavoidable. The extent and quality of the scar depend upon the patient's age and heredity, the exact location of the lesion, and the degree of inflammation. Of these, only the inflammatory response can be controlled. Scarring may be reduced by keeping inflammation to a minimum through atraumatic tissue handling, absolute hemostasis, suture placement to avoid strangulation, and early removal of skin sutures. When these plastic surgical maxims are followed, and if the incision is placed correctly, the final scar will be nearly invisible.


[Leukocyte depletion of blood products and transfusion tolerance].
Leukodepletion of red blood cell or platelet concentrates decreases significantly the number of febrile non hemolytic transfusion reactions. Filtration appears to be very efficient on red blood cell transfusion reactions while its effect with platelet concentrates remains variable.


Stability of Aqueous Suspensions of COOH-Decorated Carbon Nanotubes to Organic Solvents, Esterification, and Decarboxylation.
Carbon nanotubes are among the most widely used nanosystems, and stability of carbon nanotube suspensions is critical for nanotechnology and environmental science. Remaining in aqueous environment alone misses important factors that regulate colloidal stability in the presence of electrolytes. Indeed, introduction of (80-95) vol % organic solvents leads to sharp changes in suspension properties depending on the solvent. For example, the critical coagulation concentrations for a given inorganic or organic coagulating ion can change by 2 orders of magnitude when going from dimethyl sulfoxide to acetonitrile. We establish and explain these trends by Lewis acid-base interactions and show that a strong interaction extending beyond the standard theory of aggregation plays an important role.


[Non-alcoholic fatty liver disease and hepatocellular carcinoma - 2016].
In the past decade non-alcoholic liver disease became the most frequently diagnosed liver disease in developed countries. At the same time, the dramatic rise in the incidence of hepatocellular carcinoma is attributed to this common metabolic disorder, and mainly to its severe form, non-alcoholic steatohepatitis. The risk factors of these associated diseases are genetic predisposition, obesity and diabetes as well as chronic low grade necro-infammation, which often leads to liver fibrosis. Free fatty acids, cytokines, lipotoxicity, insulin resistance, microRNS dysregulation and alteration in intestinal microbiota play a pivotal role in the pathogenesis. Treatment of non-alcoholic fatty liver disease - weight reduction and physical exercise in obesity, metformin in diabetes, statins in dyslipidemia and, as a new option, obeticholic acid - may diminish the risk of the hepatocellular carcinoma related to this metabolic disease.


Non-invasive imaging of diabetic vascular disease.
A high proportion of diabetic subjects are referred with atherosclerotic disease and higher risk for cardiovascular events. Rapid expansion of the use of non-invasive coronary and peripheral arteries imaging, facilitated by technological advances, have found diagnostic and prognostic roles in this population. This review, which includes important and actual works, guidelines, and algorithms on cardiovascular disease in the diabetic population, indicates mandatory screening for arterial disease in these patients in light of their appropriate management.


Effect of Self-Management Program on Health Status and Dyspnea in Patients with Chronic Obstructive Pulmonary Disease.
Self-management is becoming increasingly important in patients with chronic obstructive pulmonary disease (COPD) as it is associated with improved clinical outcomes. The aim of this study was to determine the effect of a self-management program on health status and dyspnea severity in patients with COPD. This semi-experimental study was done on patients with COPD who were hospitalized at Ayatollah Kashani and Hajar hospitals from July 2017 to November 2019 in Shahrekord, Iran. Sixty patients with COPD were selected and completed three questionnaires, including a demographic questionnaire, COPD Assessment Test (CAT), and Dyspnea Scale (mMRC). The researcher educated the self-management skills to the intervention group, and the control group received routine care only. Three months after the intervention, the questionnaires were completed again by the control and intervention groups. Data were analyzed using descriptive and analytical statistics by SPSS version 24. The results of this study showed that there was no significant difference in health status between the two groups before the intervention (p=0.827). Three months after the intervention, the health status score in the control and intervention groups were 20.93±5.00 and 18.00±5.18, respectively, which this difference was statistically significant (p=0.030). Also, at the beginning of the study, the difference in dyspnea score between the two groups was not statistically significant (p=0.593). However, three months after the intervention, the score of dyspnea in the control and intervention groups was 2.1±0.995 and 1.53±1.074, respectively, which this difference was significant (p= 0.038). This study showed that self-management intervention could improve the health status and reduce the dyspnea of patients with COPD.


Longitudinal associations between television in the bedroom and body fatness in a UK cohort study.
To assess longitudinal associations between screen-based media use (television (TV) and computer hours, having a TV in the bedroom) and body fatness among UK children. Participants were 12 556 children from the UK Millennium Cohort Study who were followed from age 7 to age 11 years. Associations were assessed between screen-based media use and the following outcomes: body mass index (BMI), fat mass index (FMI), and overweight. In fully adjusted models, having a bedroom TV at age 7 years was associated with significantly higher BMI and FMI (excess BMI for boys=0.29, 95% confidence interval (CI) 0.06-0.52; excess BMI for girls=0.57, 95% CI 0.31-0.84; excess FMI for boys=0.20, 95% CI 0.04-0.37; excess FMI for girls=0.39, 95% CI 0.21-0.57) and increased risk of being overweight (relative risk (RR) for boys=1.21, 95% CI 1.07-1.36; RR for girls=1.31, 95% CI 1.15-1.48) at age 11 years, compared with having no bedroom TV. Hours spent watching TV or digital versatile disks were associated with increased risk of overweight among girls only. Computer use at age 7 years was not related to later body fatness for either gender. Having a TV in the child's bedroom was an independent risk factor for overweight and increased body fatness in this nationally representative sample of UK children. Childhood obesity prevention strategies should consider TVs in children's bedrooms as a risk factor for obesity.


Synopsis of the shore bugs of China (Hemiptera: Heteroptera: Leptopodomorpha: Saldidae).
In China, most research on shore bugs (Hemiptera: Leptopodomorpha: Saldidae) has been conducted intermittently during the second half of the 19th century. Records from the literature supplemented by our collections were used to construct an annotated list of 50 species in 13 genera and 2 subfamilies (Chiloxanthinae and Saldinae) of Saldidae now known from China. This paper also presents new distributional records and color plates depicting 26 species. Further, a list of 12 species of Saldidae known in neighboring territories that might occur in China is presented.


Turning EGFR mutation-positive non-small-cell lung cancer into a chronic disease: optimal sequential therapy with EGFR tyrosine kinase inhibitors.
Four epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), erlotinib, gefitinib, afatinib and osimertinib, are currently available for the management of EGFR mutation-positive non-small-cell lung cancer (NSCLC), with others in development. Although tumors are exquisitely sensitive to these agents, acquired resistance is inevitable. Furthermore, emerging data indicate that first- (erlotinib and gefitinib), second- (afatinib) and third-generation (osimertinib) EGFR TKIs differ in terms of efficacy and tolerability profiles. Therefore, there is a strong imperative to optimize the sequence of TKIs in order to maximize their clinical benefit. Osimertinib has demonstrated striking efficacy as a second-line treatment option in patients with T790M-positive tumors, and also confers efficacy and tolerability advantages over first-generation TKIs in the first-line setting. However, while accrual of T790M is the most predominant mechanism of resistance to erlotinib, gefitinib and afatinib, resistance mechanisms to osimertinib have not been clearly elucidated, meaning that possible therapy options after osimertinib failure are not clear. At present, few data comparing sequential regimens in patients with EGFR mutation-positive NSCLC are available and prospective clinical trials are required. This article reviews the similarities and differences between EGFR TKIs, and discusses key considerations when assessing optimal sequential therapy with these agents for the treatment of EGFR mutation-positive NSCLC.


Extraperitoneal pelvioscopy in staging of bladder carcinoma and detection of pelvic lymph node metastasis.
This study was carried out to examine the efficacy of extraperitoneal pelvioscopy in detecting pelvic metastasis in patients scheduled to undergo radical cystectomy without preoperative chemo- or radiotherapy. The results of pelvioscopy were compared with those obtained by laparotomy. 54 consecutive patients underwent pelvioscopy without complications. Three were technically insufficient. Lymphatic tissue was biopsied in 29 (54%). Pelvioscopy demonstrated tumor dissemination in 5 patients (9.3%): 2 had pT4b tumor, 2 pelvic nodal metastases and 1 both. The remaining 49 patients with benign pelvioscopy were scheduled for laparotomy but 7 patients did not undergo the procedure: 3 had extrapelvic metastasis, 1 bronchial carcinoma, 1 aortic aneurysm, 1 refused surgery and 1 had pulmonary insufficiency. Accordingly, 42 patients underwent open exploration which demonstrated pelvic metastasis in 11: 9 had nodal metastasis, 1 a pT4b tumor and 1 both. Consequently the sensitivity of pelvioscopy in detecting pelvic metastasis was calculated at only 31%. This result indicates that extraperitoneal pelvioscopy should be considered a screening procedure rather than an accurate staging procedure for pelvic metastasis.


[Immunologic reactivity in patients with nonspecific aortoarteritis].
In 48 patients with non-specific aortoarteritis (NAA) and 32 normal subjects, the immunologic investigations were performed. In patients with NAA, the sharp suppression of the factors of non-specific protection, which manifested itself in decrease in the titer of complement and phagocytic activity of neutrophil granulocytes, deep depression of T-links of the immunity, was revealed. Against the background of decrease in the level of B-lymphocytes, the increase in their functional activity, which manifested itself in increase in the IgG and IgA content, was revealed. A study of the immunologic status in patients with NAA is of great importance for determination of activity of the inflammatory process and choice of a method for treatment. With the aim of increasing the effectiveness of surgical treatment, it is expedient at the preoperative period to perform immunologic correction under guidance of the indices of the immunity.


Size of two-body weakly bound objects: short versus long range potentials.
The variation of the size of two-body objects is investigated, as the separation energy approaches zero, with both long range potentials and short range potentials having a repulsive core. It is shown that long range potentials can also give rise to very extended systems. Except for the l = 0 state, the asymptotic laws differ according to the range of the potential. For short range potentials defined by two and three parameters, their sensitivity to the shape and length is studied. These ideas as well as the transition from the short to the long range regime for the l = 0 case are illustrated using the Kratzer potential.