[Anesthesia for cardioversion. A comparison of propofol and etomidate].
Anaesthesia for elective direct current cardioversion (DCC) was induced with propofol (Diprivan) 1.2 mg/kg in 28 patients and with 0.2 mg/kg etomidate (Hypnomidate) in 20 patients. These mostly high risk patients (NYHA class II to III) were successfully treated with defibrillation. Blood pressure and heart rate were recorded before and after induction and at 2 minutes intervals up to 20 minutes after DCC. Both anaesthetic agents caused mild hypotension. Heart rate did not change significantly after induction but fell significantly after DCC from the mean value of 124 +/- 26 bpm and 122 +/- 37 bpm to 94 +/- 19 bpm and to 91 +/- 19 bpm in propofol and etomidate treated patients respectively. Four patients became apnoeic necessitating assisted ventilation for approximately four minutes. All propofol treated patients had rapid recovery times and opened eyes on command within 5.6 +/- 1.9 minutes after induction, and were fully orientated about 4 minutes later also. Complete amnesia was observed in all patients in this group. In contrast etomidate induced anaesthesia did not cause respiratory depression, but the recovery time was longer. Four patients of this group complained of recall of DCC. In 7 patients due to involuntary movements or myoclonus, after induction with etomidate reliable EKG monitoring appeared to be difficult.


Elevated circulating levels and tissue expression of pentraxin 3 in uremia: a reflection of endothelial dysfunction.
Elevated systemic pentraxin 3 (PTX3) levels appear to be a powerful marker of inflammatory status and a superior outcome predictor in patients with chronic kidney disease (CKD). As previous data imply that PTX3 is involved in vascular pathology and that adipose tissue mass may influence circulating PTX3 levels, we aimed to study the importance of adipose tissue expression of PTX3 in the uremic milieu and its relation to endothelial dysfunction parameters. Plasma PTX3 and abdominal subcutaneous adipose tissue (SAT) PTX3 mRNA levels were quantified in 56 stage 5 CKD patients (median age 57 [range 25-75] years, 30 males) and 40 age and gender matched controls (median age 58 [range 20-79] years, 27 males). Associations between PTX3 measures and an extensive panel of clinical parameters, including surrogate markers of endothelial function, were assessed. Functional ex vivo studies on endothelial status and immunohistochemical staining for PTX3 were conducted in resistance subcutaneous arteries isolated from SAT. SAT PTX3 mRNA expression correlated with plasma PTX3 concentrations (rho = 0.54, p = 0.0001) and was increased (3.7 [0.4-70.3] vs. 1.2 [0.2-49.3] RQ, p = 0.02) in CKD patients with cardiovascular disease (CVD), but was not significantly different between patients and controls. The association to CVD was lost after adjustments. SAT PTX3 mRNA levels were independently correlated to asymmetric dimethylarginine and basal resistance artery tone developed after inhibition with nitric oxide synthase and cyclooxygenase (rho = -0.58, p = 0.002). Apparent positive PTX3 immunoreactivity was observed in both patient and control arteries. In conclusion, fat PTX3 mRNA levels are associated with measures of endothelial cell function in patients with CKD. PTX3 may be involved in adipose tissue-orchestrated mechanisms that are restricted to the uremic milieu and modify inflammation and vascular complications in CKD patients.


Trends of nonoccupational postexposure prophylaxis in the United States.
To describe national annual rates of nonoccupational postexposure prophylaxis (nPEP) in the United States. Retrospective cohort study of commercially insured individuals in the Merative MarketScan Database from January 1, 2010 to December 31, 2019. Patients at least 13 years old prescribed nPEP per recommended Centers for Disease Control and Prevention guidelines were identified using pharmacy claims. Rates of use were described overall and stratified by sex, age group, and region. These rates were qualitatively compared to the diagnosis rates of human immunodeficiency virus (HIV) observed in the data. Joinpoint analysis identified inflection points of nPEP use. Eleven thousand, three hundred and ninety-seven nPEP users were identified, with a mean age of 33.7 years. Most were males (64.6%) and lived in the south (33.2%) and northeast (32.4%). The rate of nPEP use increased 515%, from 1.42 nPEP users per 100 000 enrollees in 2010 to 8.71 nPEP users per 10 000 enrollees in 2019. The comparative nPEP use rates among subgroups largely mirrored their HIV diagnosis rates, that is, subgroups with a higher HIV rate had higher nPEP use. In the Joinpoint analysis significant growth was observed from 2012 to 2015 [estimated annual percentage change (EAPC): 45.8%; 95% confidence interval (CI): 29.4 - 64.3] followed by a more moderate increase from 2015 to 2019 (EAPC 16.0%; 95% CI: 12.6-19.6). nPEP use increased from 2010 to 2019, but not equally across all risk groups. Further policy interventions should be developed to reduce barriers and ensure adequate access to this important HIV prevention tool.


Drug rash with eosinophilia and systemic symptoms (DRESS): changing carbamazepine to phenobarbital controlled epilepsy without the recurrence of DRESS.
We report a case of drug rash with eosinophilia and systemic symptoms (DRESS) due to carbamazepine. Anticonvulsants are the most common medicines causing DRESS and once it occurs, it is difficult to find an effective alternative treatment. In our case, switching from carbamazepine to phenobarbital successfully controlled both the DRESS and the convulsions. A positive patch test indicates the major role of delayed type allergy in the pathogenesis of this syndrome. Although reactivation of some viruses has been reported, their pathogenic role was not confirmed in our case.


Identifying Individuals at High Risk for Permanent Disability From Depression and Anxiety.
Mental illnesses, among which depression and anxiety are most common, are the leading cause for permanent disability. It is of interest to know what case characteristics determine if a person returns to the work force in spite of mental illness to tailor specific interventions. So far, there has been little research into this field. In the present study a sample of 202 workers who had permanent disability due to depression/anxiety were followed-up on. 22% started some kind of work during follow-up in a period of 30 to 75 months. Logistic regression analyses showed that quick progression into disability, short period of disability, younger age, adequacy of income replacement through insurance benefits and no previous disability predicted return to work. These findings also allow to identify individuals at high risk for progression into permanent disability that can benefit from supporting interventions.


Developments and challenges in biodiesel production from microalgae: A review.
The imminent depletion of fossil fuels and the surging global demand for renewable energy have led to the search for nonconventional energy sources. After a few decades of trial and error, the world is now testing the sources of the third generation of fossil fuels, which contain for most parts microalgae. With more than 80% oil content, being adaptable in growth parameters and highly versatile, microalgae are highly promising sources of biofuels in the present time. The present article makes a sweeping attempt to highlight the various methods employed for cultivation of microalgae, techniques to harvest and extract biomass from huge algal cultures, as well as their downstream production and processing procedures. The advantages, limitations, and challenges faced by each of them have been described to some extent. Major concerns pertaining to biofuels are supposed to be their environmental sustainability and economic viability along with their cost effectiveness. This would require a great deal of empirical data on existing systems and a great deal of optimization to generate a more robust one. We have concluded our article with a SWOT analysis of using algae for biodiesel production in a tabulated form.


[Echo and Doppler cardiographic findings of isolated quadricuspid aortic valve: a case report and a review of the literature].
The two-dimensional and pulsed Doppler echocardiographic features of a case of isolated quadricuspid aortic valve with aortic regurgitation are described. A 62-year-old woman was hospitalized for exertional palpitation and dyspnea. Her physical examination showed the typical findings of aortic regurgitation. Two-dimensional echocardiograms revealed the aortic valve to have four cusps of nearly equal size. The accessory cusp was situated between the right and left coronary cusps. By pulsed Doppler echocardiography, holodiastolic turbulent flow signals were observed in the left ventricle, and the aortic flow pattern showed holodiastolic reverse flow, indicating severe aortic regurgitation. These findings were confirmed by aortography and by surgery. The coronary arteries and pulmonary valve were normal. We attempted a classification of the anatomical variations of the previously reported 34 cases of isolated quadricuspid aortic valves, including our own. They were classified as one smaller (67%), four equal (18%), three smaller (6%), four unequal (6%) and two smaller (3%) types. Twenty of the 34 patients had aortic regurgitation. Bacterial endocarditis and congestive heart failure were the main causes of death.


Molecular mechanisms employed by enteric bacterial pathogens to antagonise host innate immunity.
Many Gram-negative enteric pathogens, including enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC), Salmonella, Shigella, and Yersinia species have evolved strategies to combat host defence mechanisms. Critical bacterial virulence factors, which often include but are not limited to type III secreted effector proteins, are deployed to cooperatively interfere with key host defence pathways. Recent studies in this area have not only contributed to our knowledge of bacterial pathogenesis, but have also shed light on the host pathways that are critical for controlling bacterial infection. In this review, we summarise recent breakthroughs in our understanding of the mechanisms utilised by enteric bacterial pathogens to rewire critical host innate immune responses, including cell death and inflammatory signaling and cell-intrinsic anti-microbial responses such as xenophagy.


Acute administration of phenylpropanolamine fails to affect resting energy expenditure in men of normal weight.
Studies have consistently found that dieters using over-the-counter weight control products containing phenylpropanolamine (PPA) are more successful at losing weight than those who do not. To explore the possibility that drug-induced metabolic changes contribute to weight loss associated with this compound, this study investigated the effects of PPA on resting metabolic rate in 20 healthy men of normal weight between the ages of 18 and 29. After the arrival of the subjects to the laboratory, blood pressure was taken and resting energy expenditure (REE) and respiratory quotient (RQ) were assessed for 20 minutes (Baseline) via indirect calorimetry. Half of the subjects were then given 75 mg of immediate-release PPA (administered orally via a gelatin capsule), while the other half received placebo. Immediately after drug administration, metabolic rate was measured for an additional 95 minutes (During Drug). After this assessment, blood pressure was again measured. Although significant increases in both systolic and diastolic blood pressure were observed after PPA administration, the drug had no effect on REE or RQ. These results, consistent with that previously reported in mildly overweight women, further establish that it is unlikely that drug-induced metabolic changes contribute to PPA-induced weight loss in humans.


Digit ratio (2D:4D) and performance in male surfers.
The relative length of the second and fourth digits (2D:4D) is thought to be negatively related to prenatal testosterone and positively related to prenatal estrogen. Low 2D:4D has been linked to various measures of performance in a range of sports (e.g., soccer, rugby). In this study, we consider the relationship between 2D:4D and performance among male surfers. Our sample comprised 46 competitors in the Men's 5-star Professional World Qualifying Series surfing competition in Newquay, United Kingdom, in 2009. Three experienced surfing coaches rated the participants for overall surfing ability. The coach's ratings were significantly correlated with one another and an overall measure of surfing performance was obtained by calculating the mean of the 3 ratings. In addition, the final placing of the Newquay competition was used as an additional performance measure. Mean 2D:4D (SD) was as follows: right 0.994 (0.023) and left 0.976 (0.028). We found that right 2D:4D (but not left 2D:4D or right-left 2D:4D) was significantly negatively correlated with coaches' ratings (r(s) = 0.58) and the competition result (r(s) = 0.30). It appears that in line with other sports that low right 2D:4D (high prenatal testosterone and low prenatal estrogen) correlates to high surfing ability in men.


Analysis of molecular markers associated with powdery mildew resistance genes in peach (Prunus persica (L.) Batsch)xPrunus davidiana hybrids.
A progeny of 77 hybrids issued from a cross between two heterozygous Prunus, peach [P. persica (L.) Batsch] (variety 'Summergrand') and a related species, P. davidiana (clone 1908), was analysed for powdery mildew resistance in five independent experiments. This population was also analysed for its genotype with isoenzyme and RAPD markers in order to map the genes responsible for resistance. A genetic linkage map was generated for each parent. The 'Summergrand' linkage map is composed of only four linkage groups including 15 RAPD markers and covering 83.1 centiMorgans (cM) of the peach nuclear genome, whereas the P. davidiana linkage map contains 84 RAPD markers and one isoenzyme assigned to ten linkage groups and covering 536 cM. Significant associations between molecular markers and powdery mildew resistance were found in each parent. For P. davidiana, one major QTL with a very strong effect and five other QTLs with minor effects were located in different linkage groups. For 'Summergrand', three QTLs for powdery mildew resistance, with minor effects, were also detected. Consequently, evidence is given here that the powdery mildew resistance of P. davidiana clone 1908 and P. persica variety 'Summergrand' is not a monogenic character but is controlled by at least one major gene and several minor genes.


Positive and negative mood states mediated the effects of psychological resilience on emotional stability among high school students during the COVID-19 pandemic.
This study investigated the parallel mediating effects of positive and negative mood states on the relationship between psychological resilience and emotional stability among first- through third-year senior high school students in China during the challenges of the COVID-19 pandemic. Of 408 questionnaires distributed from April 11 to April 22, 2022, to students at a high school located in Changzhou, Jiangsu, China, 360 were completed correctly and analyzed using a cross-sectional study design. The questionnaire included items from the modified Chinese version of the Psychological Resilience Scale, the Profile of Mood States scale, and the Eysenck Personality Questionnaire Short Scale in Chinese, the latter to assess emotional stability. The mediating effects of mood states on the relationship between psychological resilience and emotional stability were explored by using structural equation modeling and bootstrapping methods. The results indicated that psychological resilience directly affected emotional stability but also indirectly affected emotional stability through the mediating effects of positive and negative mood states. The mediating effect of negative mood states was greater than that of positive mood states. This result differs from that of research conducted prior to the pandemic, which found that compared with the damage caused by negative moods to emotional stability, positive moods more strongly promoted emotional stability. Our findings indicate that high school officials in China should consider strengthening mental health support for students who are taking courses online during home quarantine.


Drosophila melanogaster auxilin regulates the internalization of Delta to control activity of the Notch signaling pathway.
We have isolated mutations in the Drosophila melanogaster homologue of auxilin, a J-domain-containing protein known to cooperate with Hsc70 in the disassembly of clathrin coats from clathrin-coated vesicles in vitro. Consistent with this biochemical role, animals with reduced auxilin function exhibit genetic interactions with Hsc70 and clathrin. Interestingly, the auxilin mutations interact specifically with Notch and disrupt several Notch-mediated processes. Genetic evidence places auxilin function in the signal-sending cells, upstream of Notch receptor activation, suggesting that the relevant cargo for this auxilin-mediated endocytosis is the Notch ligand Delta. Indeed, the localization of Delta protein is disrupted in auxilin mutant tissues. Thus, our data suggest that auxilin is an integral component of the Notch signaling pathway, participating in the ubiquitin-dependent endocytosis of Delta. Furthermore, the fact that auxilin is required for Notch signaling suggests that ligand endocytosis in the signal-sending cells needs to proceed past coat disassembly to activate Notch.


Effects of Nanoceria on Human Platelet Functions and Blood Coagulation.
Cerium oxide nanoparticles (nanoceria) exist in either 3+ or 4+ oxidation state with interesting redox properties and exhibit both oxidant and antioxidant attributes based on concentration, environment and pH. Thanks to their wide spread use in fuel, cosmetics and other industries as well as in biomedical field, nanoceria particles get released into environment with risk of significant human exposure, and thus necessitate careful examination and optimization of their biomedical applications. This research was planned to explore effects of nanoceria on human platelet functions and whole blood coagulation. Platelets and whole blood from volunteer healthy donors were treated with different doses of nanoceria and various platelet functions, fibrin polymerization and blood coagulation were tested. Nanoceria particles were found to reduce platelet aggregation and secretion of granule contents in a dose-dependent manner, impaired fibrin polymerization and retraction of fibrin-rich thrombi, associated with reduced cytosolic filamentous actin. Remarkably, nanoceria instigated early clot formation in whole blood attributable to putative activation of coagulation cascade. Above observations provide cautionary framework to critically re-evaluate and accordingly plan biomedical applications of nanoceria.


Mechanism of Action of the Diphenyl Ether Herbicide Acifluorfen-Methyl in Excised Cucumber (Cucumis sativus L.) Cotyledons : LIGHT ACTIVATION AND THE SUBSEQUENT FORMATION OF LIPOPHILIC FREE RADICALS.
Cucumber (Cucumis sativus L.) cotyledons were sensitive to the diphenyl ether herbicide acifluorfen-methyl (AFM); methyl 5-[2-chloro-4-(trifluoro-methyl)phenoxyl-2-nitrobenzoate. Injury was detected by monitoring the efflux of (86)Rb(+) from treated tissues after exposure to light (600 micro einsteins per meter(2) per second; photosynthetically active radiation).AFM exhibited activity in green and etiolated tissues in the presence of both 1 micromolar 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) and 1 micromolar 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB), inhibitors of photosynthetic electron transport. Protection against injury could be obtained by pretreating the seedlings with a carotenoid biosynthesis inhibitor, 10 micromolar fluridone {1-methyl-3-phenyl-5-[3-(trifluoromethyl)phenyl]-4 (H)-pyridinone}.After a 4-hour dark pretreatment with 1 and 10 micromolar AFM, cotyledons were exposed to light (600 micro einsteins per meter(2) per second; photosynthetically active radiation). Within 1 to 2 hours after light treatment, significant increases in the level of thiobarbituric acid-reacting materials could be detected. Electron microscopic observations of treated tissues revealed significant structural damage to the chloroplast envelope, tonoplast, and plasma membrane. Etiolated cucumber cotyledons treated with 1 micromolar AFM and exposed to light were less susceptible to injury when maintained in an O(2)-deficient atmosphere. Protection against injury could be obtained with 50 micromolar alpha-tocopherol.These results suggest AFM is activated in light by yellow plant pigments and then is involved in the initiation of a free radical chain reaction with polyunsaturated fatty acid moieties of phospholipid molecules making up cellular membranes. The perturbations that follow result in a loss of the membrane's selective permeability characteristics, thereby leading to cellular death.


Detector-induced backaction on the counting statistics of a double quantum dot.
Full counting statistics of electron transport is of fundamental importance for a deeper understanding of the underlying physical processes in quantum transport in nanoscale devices. The backaction effect from a detector on the nanoscale devices is also essential due to its inevitable presence in experiments. Here we investigate the backaction of a charge detector in the form of a quantum point contact (QPC) on the counting statistics of a biased double quantum dot (DQD). We show that this inevitable QPC-induced backaction can have profound effects on the counting statistics under certain conditions, e.g., changing the shot noise from being sub-Poissonian to super-Poissonian, and changing the skewness from being positive to negative. Also, we show that both Fano factor and skewness can be either enhanced or suppressed by increasing the energy difference between two single-dot levels of the DQD under the detector-induced backaction.


Thoracoscopic Lobectomy Versus Sublobar Resection for pStage I Geriatric Non-Small Cell Lung Cancer.
The choice of resection method for geriatric patients with early-stage non-small cell lung cancer (NSCLC) remains contentious. This study aimed to evaluate survival and perioperative outcomes after thoracoscopic lobectomy resection (LR) or sublobar resection (SR) in patients aged ≥75 years with pathologic stage (pStage) I NSCLC. We retrospectively examined 258 consecutive patients aged ≥75 years with pStage I NSCLC who underwent thoracoscopic tumor resection at our institute from 2011 to 2018. Propensity score matching (PSM) analysis identified 60 patients in each group for comparison of survival-related parameters, including disease-free survival (DFS), lung cancer-specific overall survival (OS), and non-lung cancer-specific OS, using the Kaplan-Meier analysis. LR and SR were performed in 84 (32.6%) and 174 (67.4%) patients aged ≥75 years, respectively. The LR group had younger patients, better performance status, larger tumor sizes, and deeper tumor location than the SR group. Multivariate studies showed that the resection method was not a prognostic factor for OS. The two PSM-matched groups were not significantly different with respect to lung cancer-specific OS (p = 0.116), non-lung cancer-specific OS (p = 0.408), and DFS (p = 0.597). SR helped achieve better perioperative outcomes than LR, including fewer postoperative complications (10.0% vs. 28.3%, p = 0.011), shorter operative times (p < 0.001), decreased blood loss (p = 0.026), and shorter chest tube duration (p = 0.010) and hospital stays (p = 0.035). Thoracoscopic SR may provide similar oncological outcomes to LR, but may be a safer and more feasible surgical method for geriatric patients with pStage I NSCLC.


Proteasome inhibitors and knockdown of SMG1 cause accumulation of Upf1 and Upf2 in human cells.
The ubiquitin-proteasome system (UPS) is one of the most promising anticancer drug targets of the century. However, the involved molecular mechanisms are still unclear. The nonsense-mediated mRNA decay (NMD) pathway is a highly conserved pathway which degrades nonsense mutation‑containing mRNA selectively and efficiently. In this pathway, the SMG1-Upf1-eRF (SURF) complex binds to Upf2 on the exon junction complex and finally causes degradation of nonsense-containing mRNA. To reveal the relationship between the UPS and NMD pathways, we analyzed the effects of proteasome inhibitors on Upf1 and Upf2. The data showed that treatment with proteasome inhibitors caused the accumulation of the Upf1 and Upf2 proteins in A549 cells. In addition, we found that knockdown of SMG1 also caused the upregulation of Upf1 and Upf2 proteins, which was confirmed by different target sequences of siRNA. SMG1 and UPS appear to participate in different pathways of the degradation of Upf1 and Upf2, since simultaneous treatment with both of them caused additive effects. This study demonstrated the quantitative regulation of Upf1 and Upf2 proteins by UPS and SMG1.


Reactions and Interventions for Delusions in Nursing Home Residents with Dementia.
This is a qualitative and quantitative study examining institutional staff members' reactions to delusions experienced by nursing home residents. Participants were 38 nursing home residents aged 65 and older, diagnosed with dementia. Data were collected from 8 nursing homes in Israel between June 2007 and January 2009. Assessments included Behavioral Pathology in Alzheimer's Disease Rating Scale, Neuropsychiatric Inventory: Nursing Home version, Etiological Assessment of Psychotic Symptoms In Dementia, Activities of Daily Living, and Mini-Mental State Examination. A wide variety of interventions with dementia-related symptoms was found to be effective to varying degrees. This included general approaches for a variety of symptoms as well as symptom-specific interventions. Caregivers do not always seem to be aware that multiple approaches are available to them when dealing with dementia. The most effective approaches may be those tailored to the individual. Combining interventions may increase overall effectiveness. Caregiver's experience and the institutional culture may affect the choice of intervention used, either positively or negatively.


[Establishment and characteristics of a human synovial sarcoma cell line].
A human synovial sarcoma cell line (HSS-84), from a painful mass excised locally near the left sternoclavicular joint, was established and has been continuously propagated in vitro for more than one year through 54 passages till the end of 1985. Doubling time was 65 hr. The index of mitosis was 28.8%. The chromosome number for most of the cells was hypertriploid. The cells, stored in liquid nitrogen, had a good revival. Cytologically, some cells, showing elongated, spindle, stellate or spidery shape with prominent processes, were arranged in loose or bundled pattern, similar to sarcoma cells; some cells showed ovoid and polygonal in mosaic arrangement, similar to epithelioid cells. Both features indicated biphasic differentiation of the cells. By electron microscopy, the cells consisted of light and dark cells with microvilli and obvious abnormality. Histopathologically, the tumor, from which HSS-84 originated, was a biphasic differentiation synovial sarcoma. It was composed of malignant spindle interstitial cells and malignant epithelioid cells lining the clefts or spaces. The latter was similar to cultured cells by electron microscopy. HSS-84 was identical with the donor. HSS-84 establishment will be useful for research on diagnosis, therapy, origin and biphasic differentiation of the synovial sarcoma.


Maintaining Peritoneal Dialysis Adequacy: The Process of Incremental Prescription.
Urea kinetics (weekly Kt/V) greater than 1.7 generally define adequate peritoneal dialysis (PD). Adequacy of PD depends on residual renal function and PD clearance. Preserving residual renal function and peritoneal membrane characteristics helps to maintain PD adequacy.The dose of PD can be augmented by increasing the total dialysate volume. Greater volume can be achieved by increasing either the fill volume per exchange or the number of exchanges. Increased time on dialysis can be achieved by keeping PD fluid in the peritoneal cavity at all times. Increasing the convective force enhances solute removal with ultrafiltration.Incremental PD is used during urgent starts and in patients who are newly starting or who have been on PD. Urgent starts require use of frequent low-volume exchanges to avoid leaks at surgical sites. The dialysate volume can be gradually increased provided that no leakage occurs, up to approximately 2 L per exchange on day 14 for an average-size adult. New-start patients require only 1 - 2 exchanges daily if they still have residual renal function. Incremental PD retains patients on PD as residual renal function wanes and peritoneal membrane characteristics change because of dextrose exposure, infection, and inflammation.Use of a cycler permits patients to achieve adequacy by increasing the volume per cycle and the number of cycles per treatment. Using a non-dextrose-based solution, such as icodextrin, allows patients to achieve adequate ultrafiltration with less dextrose exposure.Adequate dialysis can be achieved by manipulating the dialysate dwell volume and the frequency of exchanges, and by optimizing ultrafiltration.


Primary repair of colon injuries: a prospective randomized study.
Due to the results of a 6-year experience with civilian penetrating colon injuries at Mount Carmel/Grace Hospital, in Detroit, Michigan, which had favored primary repair of colon injuries, a prospective randomized study was performed. Seventy-one patients with penetrating colon injuries were entered in a prospective randomized study. Forty-three patients were treated with primary repair or resection and anastomosis, and 28 patients were treated with diversion. The average Penetrating Abdominal Trauma Index score was 25.5 for the primary repair and 23.4 for the diversion groups. The majority of injuries as assessed by the Colon Injury Score (CIS) for the primary repair group were grades 2 (58%) and 3 (28%). The diversion group predominantly had grades 2 (64%) and 3 (25%). There was no significant difference between the two groups. There were 8 (19%) patients with colon and noncolon-related complications in the primary repair group, and 10 (36%) patients with colon, noncolon, and colostomy-related complications in the diversion group. In addition, there were 2 (7%) patients with complications following colostomy reversal. Independent risk factors for adverse outcomes were compared and used to calculate the probability for adverse outcomes with respect to the mode of treatment. The probability for adverse outcomes was statistically greater in the diversion group. An analysis was also made within the primary repair group comparing the subgroups of primary repair with, and without, resection of colon. It appears that the primary repair with resection of colon may have fewer complications; however, this conclusion is based on a statistically insufficient sample size. The authors contend that primary repair or resection with anastomosis is the method of choice for treatment of all penetrating colon injuries in the civilian population despite any associated risk factors for adverse outcomes.


Self-reported symptoms of gynecological morbidity and their treatment in south India.
This article presents an analysis of self-reported symptoms of gynecological problems among 3,600 recent mothers in Karnataka State, India. Approximately one-third of all women reported at least one current symptom; the most common were a feeling of weakness and tiredness (suggestive of anemia); menstrual disorders; white or colored vaginal discharge (suggestive of lower reproductive tract infection); and lower abdominal pain and discharge with fever (suggestive of acute pelvic inflammatory disease). Obstetric morbidity, associated with the last live birth, was strongly predictive of current gynecological symptoms. Women who delivered their last child in a private institution were significantly less likely to report symptoms than were those who delivered at home or in a government hospital. Nonusers or users of reversible contraceptive methods were also less likely to report symptoms of morbid conditions than were sterilized women. These associations persisted in analyses controlling for potentially confounding economic and demographic characteristics, and have far-reaching policy implications.


Fibroepithelial stromal polyp of bladder-a mimicker of sarcoma or angiomyxoma at uncommon location.
The fibroepithelial stromal polyp is a benign polypoid proliferation of the stroma with overlying epithelium. Because the lesion contains atypical stromal cells, sometimes it can be overdiagnosed as sarcoma or with myxoid stroma, it can be misdiagnosed as angiomyxoma. The reported locations are mainly in the lower female genital tract, urethra, and rarely extragenital sites, such as the breast, and are exceptionally rare in the bladder. We encountered a 65-year-old man who presented with two small velvety, erythematous patches on the posterior bladder wall. The final diagnosis is a fibroepithelial stromal polyp of the bladder. Familiarity with this lesion will prevent overinterpretation of this benign lesion as a malignancy.


Current Omics Trends in Personalised Head and Neck Cancer Chemoradiotherapy.
Chemoradiotherapy remains the most common management of locally advanced head and neck cancer. While both treatment components have greatly developed over the years, the quality of life and long-term survival of patients undergoing treatment for head and neck malignancies are still poor. Research in head and neck oncology is equally focused on the improvement of tumour response to treatment and on the limitation of normal tissue toxicity. In this regard, personalised therapy through a multi-omics approach targeting patient management from diagnosis to treatment shows promising results. The aim of this paper is to discuss the latest results regarding the personalised approach to chemoradiotherapy of head and neck cancer by gathering the findings of the newest omics, involving radiotherapy (dosiomics), chemotherapy (pharmacomics), and medical imaging for treatment monitoring (radiomics). The incorporation of these omics into head and neck cancer management offers multiple viewpoints to treatment that represent the foundation of personalised therapy.


Evaluation of a staging system for infected hip arthroplasty.
A previously reported staging system for prosthetic joint infection was evaluated in 26 consecutive patients with an infected hip arthroplasty. Six patients were treated by a definitive resection arthroplasty whereas the remaining 20 patients received delayed insertion of another hip arthroplasty. Four of the 20 patients (20%) receiving a new prosthesis had reinfection develop. The only variable in common among the patients who had reinfection was the use of a massive femoral structural allograft at reconstruction. Because of the small number of patients in this study, the power of statistical analysis did not allow definitive determination of the effect of the staging system score with respect to recurrent infection. Based on this study, recommendations can be suggested for addition and deletion of certain variables within the existing staging system. Although the concept of a staging system for treatment of an infected hip arthroplasty is promising, the number of patients required to evaluate the use of a staging system will require a multicenter collaborative study.


Trivial Excitation Energy Transfer to Carotenoids Is an Unlikely Mechanism for Non-photochemical Quenching in LHCII.
Higher plants defend themselves from bursts of intense light via the mechanism of Non-Photochemical Quenching (NPQ). It involves the Photosystem II (PSII) antenna protein (LHCII) adopting a conformation that favors excitation quenching. In recent years several structural models have suggested that quenching proceeds via energy transfer to the optically forbidden and short-lived S 1 states of a carotenoid. It was proposed that this pathway was controlled by subtle changes in the relative orientation of a small number of pigments. However, quantum chemical calculations of S 1 properties are not trivial and therefore its energy, oscillator strength and lifetime are treated as rather loose parameters. Moreover, the models were based either on a single LHCII crystal structure or Molecular Dynamics (MD) trajectories about a single minimum. Here we try and address these limitations by parameterizing the vibronic structure and relaxation dynamics of lutein in terms of observable quantities, namely its linear absorption (LA), transient absorption (TA) and two-photon excitation (TPE) spectra. We also analyze a number of minima taken from an exhaustive meta-dynamical search of the LHCII free energy surface. We show that trivial, Coulomb-mediated energy transfer to S 1 is an unlikely quenching mechanism, with pigment movements insufficiently pronounced to switch the system between quenched and unquenched states. Modulation of S 1 energy level as a quenching switch is similarly unlikely. Moreover, the quenching predicted by previous models is possibly an artifact of quantum chemical over-estimation of S 1 oscillator strength and the real mechanism likely involves short-range interaction and/or non-trivial inter-molecular states.


Relationship between Trypanosoma brucei rhodesiense genetic diversity and clinical spectrum among sleeping sickness patients in Uganda.
Human African trypanosomiasis (HAT) due to Trypanosoma brucei rhodesiense in East and southern Africa is reported to be clinically diverse. We tested the hypothesis that this clinical diversity is associated with a variation in trypanosome genotypes. Trypanosome DNA isolated from HAT patients was genotyped using 7 microsatellite markers directly from blood spotted FTA cards following a whole genome amplification. All markers were polymorphic and identified 17 multi-locus genotypes with 56% of the isolates having replicate genotypes. We did not observe any significant clustering between isolates and bootstrap values across major tree nodes were insignificant. When genotypes were compared among patients with varying clinical presentation or outcome, replicate genotypes were observed at both extremes showing no significant association between genetic diversity and clinical outcome. Our study shows that T. b. rhodesiense isolates are homogeneous within a focus and that observed clinical diversity may not be associated with parasite genetic diversity. Other factors like host genetics and environmental factors might be involved in determining clinical diversity. Our study may be important in designing appropriate control measures that target the parasite.


Diverse signaling pathways in the cellular actions of insulin.
Insulin is one of the most important regulators of glucose and lipid homeostasis. Many of its cellular actions are mediated by changes in protein phosphorylation. The consequences of these phosphorylation events extend from a series of different short-term metabolic actions to longer-term effects of the hormone on cellular growth and differentiation. Although the insulin receptor itself is a tyrosine kinase that is activated upon hormone binding, the ensuing changes in phosphorylation occur predominantly on serine and threonine residues. Moreover, insulin can simultaneously stimulate the phosphorylation of some proteins and the dephosphorylation of others. These paradoxical effects of insulin suggest that separate signal transduction pathways may emanate from the receptor itself to produce the pleiotropic actions of the hormone.


Trypanosoma cruzi: monoclonal antibodies to the surface glycoprotein superfamily differentiate subsets of the 85-kDa surface glycoproteins and confirm simultaneous expression of variant 85-kDa surface glycoproteins.
Most surface glycoproteins expressed by mammalian-stage forms of Trypanosoma cruzi are homologous to the parasite's trans-sialidase and therefore are members of the parasite's trans-sialidase superfamily. Few members of this superfamily have trans-sialidase activity. The SA85-1 family is a subfamily of the trans-sialidase superfamily whose members lack trans-sialidase activity. The function of these non-trans-sialidase members remains unknown. In this report a series of monoclonal and polyclonal antibodies to the SA85-1 glycoproteins is presented. The mAbs define distinct subgroups of SA85-1 glycoproteins, and these distinct subgroups are simultaneously expressed by individual trypomastigotes, supporting previous studies indicating that multiple SA85-1 glycoproteins and trans-sialidase superfamily glycoproteins are simultaneously expressed by each trypomastigote. In addition, the antibodies define two major subsets of the SA85-1 family (subset 1 and subset 2) based on differences in migration in SDS-PAGE; the subsets do not appear to be created by differences in glycosylation. Subset 1 migrates slower and is spontaneously released or shed preferentially from the parasite surface compared to subset 2. In addition, subset 1 is attached to the trypomastigote surface by a GPI linkage. Since these glycoprotein subsets are differentially expressed, they may have different functions.


Gut Biofactory-Neurocompetent Metabolites within the Gastrointestinal Tract. A Scoping Review.
The gut microbiota have gained much scientific attention recently. Apart from unravelling the taxonomic data, we should understand how the altered microbiota structure corresponds to functions of this complex ecosystem. The metabolites of intestinal microorganisms, especially bacteria, exert pleiotropic effects on the human organism and contribute to the host systemic balance. These molecules play key roles in regulating immune and metabolic processes. A subset of them affect the gut brain axis signaling and balance the mental wellbeing. Neurotransmitters, short chain fatty acids, tryptophan catabolites, bile acids and phosphatidylcholine, choline, serotonin, and L-carnitine metabolites possess high neuroactive potential. A scoping literature search in PubMed/Embase was conducted up until 20 June 2020, using three major search terms "microbiota metabolites" AND "gut brain axis" AND "mental health". This review aimed to enhance our knowledge regarding the gut microbiota functional capacity, and support current and future attempts to create new compounds for future clinical interventions.


Prospective detection of mutations in cerebrospinal fluid, pleural effusion, and ascites of advanced cancer patients to guide treatment decisions.
Many advanced cases of cancer show central nervous system, pleural, or peritoneal involvement. In this study, we prospectively analyzed if cerebrospinal fluid (CSF), pleural effusion (PE), and/or ascites (ASC) can be used to detect driver mutations and guide treatment decisions. We collected 42 CSF, PE, and ASC samples from advanced non-small-cell lung cancer and melanoma patients. Cell-free DNA (cfDNA) was purified and driver mutations analyzed and quantified by PNA-Q-PCR or next-generation sequencing. All 42 fluid samples were evaluable; clinically relevant mutations were detected in 41 (97.6%). Twenty-three fluids had paired blood samples, 22 were mutation positive in fluid but only 14 in blood, and the abundance of the mutant alleles was significantly higher in fluids. Of the 34 fluids obtained at progression to different therapies, EGFR resistance mutations were detected in nine and ALK acquired mutations in two. The results of testing of CSF, PE, and ASC were used to guide treatment decisions, such as initiation of osimertinib treatment or selection of specific ALK tyrosine-kinase inhibitors. In conclusion, fluids close to metastatic sites are superior to blood for the detection of relevant mutations and can offer valuable clinical information, particularly in patients progressing to targeted therapies.


Hydrogen peroxide is critical for UV-induced apoptosis inhibition.
Apoptosis is an important cell death system that deletes damaged and mutated cells, preventing the induction of cancer. We previously have reported that UV irradiation inhibited the apoptosis induced by serum starvation and cell detachment. This phenomenon is suitable for clarifying the relationship between cancer and the dysregulation of apoptosis by UV irradiation. Here, we have studied the factors responsible for this inhibition of apoptosis, focusing on reactive oxygen species (ROS) and DNA damage. Treatment with xanthine oxidase in the presence of hypoxanthine, which is known to produce superoxide anion (O2*-) and hydrogen peroxide (H2O2), inhibited the induction of apoptosis. The xanthine oxidase-induced anti-apoptotic effect was suppressed in the presence of an H2O2-eliminating enzyme, catalase, but not in the presence of an O2*--eliminating enzyme, superoxide dismutase. Treatment with H2O2 itself significantly inhibited the induction of apoptosis. Furthermore, the effect of the inhibition of cell death by UVB irradiation and by H2O2 treatment decreased in H2O2-resistant cells. Although both UVB and H2O2 are known to induce DNA damage, other DNA damaging agents, like gamma-irradiation and treatment with cisplatin and bleomycin, showed no inhibition of apoptosis. These findings suggested that H2O2 was essential to the inhibition of apoptosis, in which DNA damage had no role.


Automatic diagnosis of melanoma using linear and nonlinear features from digital image.
Melanoma is the most serious type of skin cancer and causes more deaths than other forms of skin cancer. It is a tiny small malignant mole that is usually black or brown but also appears in other color patterns. Early detection of melanoma is key as this is the time period when it is most likely to be cured. Due to the advancement of smartphone technology, automatic and efficient detection of melanoma mole using a smartphone is an active area of research. In this study, we developed an automatic melanoma diagnosis system using images captured from the digital camera. Our work differs from other studies in the area of segmentation of melanoma region and consideration of non-linear features for classification of malignant and benign melanoma. In this paper, a combination of Otsu and k-means clustering segmentation methods are applied to automatically segment and extract the borders of affected region with satisfactory accuracy. Also, we explored and extracted different non-linear features along with color and texture features existed in literature from the lesion mole. The effectiveness of these features was predicted with a machine learning model consisting of five different classifiers. Our model predicted the diagnosis of mole with an accuracy of 89.7%, i.e., around 10% more than reported results by others (to the best of our knowledge) with the same database.


Design of a Targeted Sequencing Assay to Detect Rare Mutations in Circulating Tumor DNA.
Qualitative and quantitative detection of circulating tumor DNA (ctDNA) is a liquid biopsy technology used for early cancer diagnosis. However, the plasma ctDNA content is extremely low, so it is difficult to detect somatic mutations of tumors using conventional sequencing methods. Target region sequencing (TRS) technology, through enrichment of the target genomic region followed by next generation sequencing, overcomes this challenge and has been widely used in ctDNA sequencing. We designed a ctDNA sequencing panel to capture 128 tumor genes, and tested the performance of the panel by running TRS for ctDNA of a clear cell renal cell carcinoma (ccRCC) patient and 12 breast cancer patients. TRS using the new ctDNA panel at more than 500 × coverage depth achieved almost the same accuracy as traditional whole-exome sequencing (WES). PBRM1 p.L641V was detected in the plasma sample of the ccRCC patient with an allele frequency of 0.2%. The ctDNA of 12 breast cancer patients was sequenced at a depth of 500-fold, achieving 99.89% coverage; 34 genes were detected with mutations, including the drug target genes BRCA2, PTEN, TP53, APC, KDR, and NOTCH2. This TRS new ctDNA panel can be used to detect mutations in cell-free DNA from multiple types of cancer.


[Expression and significance of caudal type transcription factor-2 in gastric mucosa at different stages of gastric carcinogenesis].
To investigate the expression and significance of caudal type transcription factor-2 (Cdx2) in gastric mucosa at different stages of carcinogenesis. By using ABC immunohistochemistry, the expression of Cdx2 was detected in the biopsy specimens of 104 cases of chronic superficial gastritis, 98 cases of chronic atrophic gastritis, 112 cases of intestinal metaplasia, 106 cases of dysplasia and 97 cases of intestinal-type gastric carcinoma. Cdx2 was expressed in the specimens of intestinal metaplasia with an expression rate of 86.6% (97/112), significantly higher than those in dysplasia (58.5%, 62/106) and intestinal-type gastric carcinoma (56.9%, 53/93) (both P < 0.01), while was not expressed in the specimens of chronic superficial gastritis and chronic atrophic gastritis. No significant difference was found between the expression rate of Cdx2 was between the specimens of dysplasia and those of intestinal-type gastric carcinoma (P > 0.05). Cdx2 may be a novel marker of intestinal metaplasia and may play an important role in the carcinogenesis of the intestinal-type gastric carcinoma.


Additional in-series compliance reduces muscle force summation and alters the time course of force relaxation during fixed-end contractions.
There are high mechanical demands placed on skeletal muscles in movements requiring rapid acceleration of the body or its limbs. Tendons are responsible for transmitting muscle forces, but, because of their elasticity, can manipulate the mechanics of the internal contractile apparatus. Shortening of the contractile apparatus against the stretch of tendon affects force generation according to known mechanical properties; however, the extent to which differences in tendon compliance alter force development in response to a burst of electrical impulses is unclear. To establish the influence of series compliance on force summation, we studied electrically evoked doublet contractions in the cane toad peroneus muscle in the presence and absence of a compliant artificial tendon. Additional series compliance reduced tetanic force by two-thirds, a finding predicted based on the force-length property of skeletal muscle. Doublet force and force-time integral expressed relative to the twitch were also reduced by additional series compliance. Active shortening over a larger range of the ascending limb of the force-length curve and at a higher velocity, leading to a progressive reduction in force-generating potential, could be responsible. Muscle-tendon interaction may also explain the accelerated time course of force relaxation in the presence of additional compliance. Our findings suggest that a compliant tendon limits force summation under constant-length conditions. However, high series compliance can be mechanically advantageous when a muscle-tendon unit is actively stretched, permitting muscle fibres to generate force almost isometrically, as shown during stretch-shorten cycles in locomotor activities. Restricting active shortening would likely favour rapid force development.


Laparoscopic lymph node dissection around the inferior mesenteric artery with preservation of the left colic artery.
Curative resection of sigmoid and rectal cancer includes "high tie" of the inferior mesenteric artery (IMA). However, IMA ligation compromises blood flow to the anastomosis, which may increase the leakage rate. Accordingly, some surgeons employ a technique of lymph node (LN) dissection around the IMA, preserving the IMA and left colic artery (LCA). The same technique was reported to need longer time in laparoscopic surgery due to technical difficulties. We present herein a simple and secure method of laparoscopic LN dissection around the IMA that allows preservation of the IMA and LCA, and report the operative results. Our method involves peeling off the vascular sheath from the IMA and dissection of the LN around the IMA together with the sheath. The feasibility of the technique was evaluated in 72 consecutive cases of laparoscopic resection of sigmoid and rectal cancer. The IMA was ligated at its root in 27 cases (high tie, group A). Lymph nodes around the IMA were dissected with preservation of the IMA and LCA in 21 cases (group B). The root of the superior rectal artery was ligated in 24 cases of Tis and T1N0 ("low tie," group C). Mean operative time was 207.6, 221.2, and 198.5 min for group A, B, and C, respectively. Respective blood loss was 47.8, 44.0, and 58.5 g, and mean numbers of harvested LN were 17.3, 16.3, and 10.7. None of the operative results of groups A and B were different statistically. LN dissection was not associated with any morbidity. Our method allows equivalent laparoscopic lymph node dissection to the high tie technique without excessive operative time or bleeding.


A history of the treatment of appendicitis in children: lessons learned.
During the latter half of the 19th century, surgeons increasingly reported performing appendicectomies. Fitz from Harvard, Groves from Canada and Tait from Britain all recorded successful removal of the appendix. McBurney described the point of maximal tenderness in classic appendicitis and also the muscle-splitting incision centred on this point. Priority is given to McArthur in describing the lateral muscle-splitting incision. The direction of the cutaneous incision was later modified by Elliott and Lanz. Incisions that healed well were essential to recovery. Appendicectomy became a 'fashionable' operation after the London surgeon, Treves, removed the appendix of King Edward VII. Through the 20th century, the mortality from appendicitis fell notably with the advent of sulphonamide and penicillin, improvements in fluid therapy and safer anaesthesia. By 1990, diagnostic delay was the main cause of death. Semm performed the first laparoscopic appendicectomy in 1990, roundly criticized at the time for what is now a routine procedure. We view contemporary debates on the indications for appendicectomy, the best approach and how to optimize recovery in the light of the history of this intriguing disease.


Effect of estrogen on pressor responses to alpha1-adrenoreceptor agonist in conscious female rats.
We examined the effect of estrogen on pressor responses to an alpha1-adrenoreceptor agonist (phenylephrine) in conscious female Wistar-Kyoto rats. At the age of 11 weeks, rats underwent ovariectomy or a sham procedure. At the age of 15 weeks, ovariectomized (OVX) rats received intramuscular injection of estradiol valerate (EV) 5 microg (OVX+EV 5 microg group; n = 6), EV 25 microg (OVX+EV 25 microg group; n=7), or placebo (OVX group; n = 8), and sham-operated rats received placebo (sham group; n = 8). After 4 days, dose-pressor response curves to phenylephrine were examined under the condition where the renin-angiotensin, vasopressin and autonomic nervous systems were pharmacologically blocked. Ovariectomy shifted the dose-pressor response curve to phenylephrine leftward with a significantly decreased log ED50 (microg/kg) (the dose needed to reach 50% of the maximal response) (sham: 0.81 +/- 0.04; OVX: 0.57 +/- 0.05; p < 0.05). Supplementation with EV 25 mircog, but not EV 5 microg, reversed the dose-pressor response curve to phenylephrine in OVX rats to the level of the curve in sham-operated rats with a significantly increased log ED50 (microg/kg) (OVX+xEV 5 microg: 0.47 +/- 0.05; OVX+EV 25 microg: 0.75 +/- 0.08). These results suggest that the physiological level of estrogen seen in intact female rats attenuates pressor responses to alpha1-adrenoreceptor agonist, while supplementation with a moderate dose of estrogen is needed to restore such effects of physiological-level estrogen within a short-term period after chronic estrogen withdrawal.


Diazepam alters cocaine self-administration, but not cocaine-stimulated locomotion or nucleus accumbens dopamine.
Cocaine is known to enhance nucleus accumbens dopamine (NAcc DA), to serve as a positive reinforcer and to produce negative effects, such as anxiety. The influence of diazepam on cocaine intake, cocaine-stimulated behavioral activity and NAcc DA was investigated using self-administration and experimenter-administered intravenous (i.v.) cocaine. In Experiment 1, rats were pretreated with diazepam (0.25 mg/kg) or saline (0.1 ml) 30 min prior to 20 daily 1-hour cocaine (0.75 mg/kg/injection) self-administration sessions. Cocaine intake increased for all animals across sessions, but was highest in diazepam-pretreated animals. Diazepam rats also self-administered their first cocaine injection of each session faster than controls. Experiment 2 utilized in vivo microdialysis to assess NAcc DA levels before and after experimenter-administered i.v. cocaine injections (0.75 mg/kg/injection x 2; 10-min interval) in diazepam- and saline-pretreated rats. Group differences were not revealed across basal and cocaine-stimulated NAcc DA assessments, indicating that diazepam did not decrease NAcc DA during cocaine self-administration. Findings that diazepam enhances cocaine self-administration and decreases cocaine response latency support the notion that cocaine-induced anxiety limits voluntary cocaine intake. It is further suggested that individual variations in cocaine-induced aversive effects may determine whether cocaine use is avoided or repeated.


Chemoradiation in female patients with anal cancer: Patient-reported outcome of acute and chronic side effects.
We evaluated acute and chronic side effects of 3D conformal radiotherapy (3D-CRT) and intensity-modulated radiation therapy (IMRT) in female patients with anal carcinoma and accessed correlations between dosimetric parameters and the considered toxicities. For 70 women with anal cancer treated at our department, acute and chronic side effects and quality of life (QoL) were evaluated with questionnaires using the Common Terminology Criteria for Adverse Events (CTCAE v. 4.0.) and Late Effects in Normal Tissue, Subjective, Objective Management and Analytic Scales (LentSoma) before, during, and after the treatment. Forty-seven out of 70 (67%) patients completed the questionnaire and were enrolled in the study. Only poor urinary stream, loss of pubic hair during chemoradiation, and chronic vaginal dryness were observed more frequently in the 3D-CRT group compared to the IMRT group (univariable logistic regression p = .032, p = .04, p = .049, respectively). After the treatment, 43% in the 3D-CRT group and 29% in the IMRT group reported a severe loss of QoL. A higher proportion among the patients receiving a genital V20 ⩾35% showed grade 1-3 side effects such as chronic dyspareunia ( p = .035; Fisher exact test). Our results suggest that the use of IMRT decreases acute and chronic adverse effects although reduced QoL also occurred in the IMRT group. These effects are likely to be underreported in retrospective studies using physician-reported outcome measures.


Associations of wrong surgery with other critical healthcare quality and patient safety challenges: a cross-sectional nationwide study of 100 general hospitals in Spain.
Wrong surgery (wrong-site, wrong-procedure, or wrong-patient surgery) is among the most feared patient safety problems in hospitals. We aimed to evaluate associations between numeric assessment of risk assigned to wrong surgery with that of other healthcare quality and patient safety challenges. This nationwide study collected information from healthcare quality experts in charge of a clinical quality and/or patient safety department in general hospitals of ≥ 150 beds in Spain. Out of the 100 included hospitals, the highest strength of associations were observed with risk priority number (RPN) for hospital-acquired pressure ulcers, RPN for venous thromboembolism in hospitalized patients, RPN for incorrect patient identification, RPN for lack of informed consent for diagnostic or therapeutic procedures, RPN for catheter-related bacteremia, and RPN for adverse events and injuries due to medical devices related to use and/or design. These results are of potential interest for designing combined and coordinated strategies to improve patient safety in hospitals.


Intranasal Oncolytic Virotherapy with CXCR4-Enhanced Stem Cells Extends Survival in Mouse Model of Glioma.
The challenges to effective drug delivery to brain tumors are twofold: (1) there is a lack of non-invasive methods of local delivery and (2) the blood-brain barrier limits systemic delivery. Intranasal delivery of therapeutics to the brain overcomes both challenges. In mouse model of malignant glioma, we observed that a small fraction of intranasally delivered neural stem cells (NSCs) can migrate to the brain tumor site. Here, we demonstrate that hypoxic preconditioning or overexpression of CXCR4 significantly enhances the tumor-targeting ability of NSCs, but without altering their phenotype only in genetically modified NSCs. Modified NSCs deliver oncolytic virus to glioma more efficiently and extend survival of experimental animals in the context of radiotherapy. Our findings indicate that intranasal delivery of stem cell-based therapeutics could be optimized for future clinical applications, and allow for safe and repeated administration of biological therapies to brain tumors and other CNS disorders.


Quantitative assessment of parkinsonian patients by continuous wrist activity monitoring.
The aim of this study was to examine the quantitative relationship between activity monitor measures and clinical scores of patients with Parkinson disease (PD). Motor activity was recorded continuously for 5 to 6 days at home with a wrist-worn activity monitor in 69 PD patients and 59 healthy controls. Clinical scores of the patients, age, and sex were submitted to multiple regression analysis to examine the quantitative relationship with measures reflecting the activity level and the proportion of activity and immobility over time. The patients' age, sex, and scores representing hypokinesia and rigidity and resting tremor explained approximately 50% of the variance of the motor activity measures. All motor activity measures declined with age; the rate of decline was similar for the patients and controls. Sex emerged as a predictor of the motor activity measures in the patients only. Male patients with PD showed significantly lower values for all motor activity measures than female patients and controls. Our results show that activity monitoring can be used as an objective quantitative assessment in PD.


Protein kinase C activation after cellular adhesion on fibronectin: partial suppression after inhibition of protein isoprenylation.
The cellular events following interaction between matrix proteins and cells are important requisites for physiological mechanisms as well as the progress of a number of diseases. Cellular adhesion to fibronectin, an important component of the extracellular matrix has been demonstrated to be associated with translocation of protein kinase C (PKC) by an integrin-dependent pathway. For this process G-proteins may play an important role as coupling proteins. Membrane association and activity of G-proteins has been shown to be regulated by isoprenylation. We therefore studied whether fibronectin mediated adhesion resulted in PKC translocation and if isoprenylation of cellular proteins may play a role for this integrin-dependent pathway of PKC activation. Chinese hamster ovary (CHO) cells were pretreated with either the Hydroxy-methylglutaryl(HMG)-CoA reductase inhibitor lovastatin or prenylation inhibitor limonene. For the stimulation by extracellular matrices, CHO cells were plated on tissue culture dishes coated with fibronectin or bovine serum albumin and PKC activity was determined. To investigate direct effects of inhibition of isoprenylation on cytoskeletal organization, phalloidin-stained stress fibers were characterized after adhesion on different matrices. CHO cells seeded on fibronectin displayed over twice the PKC translocation to the particulate fraction in comparison to that measured in cells on albumin. Pretreatment of CHO cells with lovastatin or limonene resulted in partial suppression of PKC activation after cell-seeding on the specific matrix fibronectin. Changed PKC distribution was not due to a disorganization of the actin skeleton. These data show that inhibition of isoprenylation of cellular proteins, possibly small Guanosine triphosphate(GTP)-binding proteins, alters only the integrin-mediated PKC distribution but does not greatly influence constitutive PKC distribution.


Ca(2+)-induced Ca2+ oscillations in parathyroid cells.
Parathyroid cells from patients with hyperparathyroidism were first cultured in a growth cocktail supplemented version of Dulbecco's MEM/F12 medium and then used for measurements of the cytoplasmic Ca2+ concentration ([Ca2+]i). Elevation of extracellular Ca2+ from 0.5 to 1.5-3 mM often triggered rhythmic oscillations of [Ca2+]i. Whereas the amplitude of the oscillations remained constant their frequency (0.4-2.6 /min) increased with the Ca2+ concentration and there was sometimes transformation into sustained increase of [Ca2+]i at the highest extracellular Ca2+ concentration. The oscillations were abolished by the inorganic Ca2+ channel blocker Ce3+ and by K+ depolarisation, which lowered [Ca2+]i, as well as by thapsigargin, an inhibitor of the intracellular Ca(2+)-pumping ATPase. The data indicate that extracellular Ca2+ can trigger [Ca2+]i oscillations in parathyroid cells, dependent on mobilisation of the ion from intracellular Ca2+ stores and on influx through non-voltage dependent channels.


Adaptation, psychometric properties, and implementation of the Mini-CEX in dental clerkship.
Workplace-based assessment is a key component of dental-student clerkships, allowing students to demonstrate clinical proficiency. This study adapts the Mini-Clinical Evaluation Exercise (Mini-CEX) to a dentistry-program clerkship, analyzing the results and examining the psychometric properties of Mini-CEX. First, Delphi panel methodology was used to ensure content validity. Mini-CEX was then piloted in the dental-clerkship program, with each student assessed by at least 2 supervisors and a peer student. Subsequently, psychometric properties, acceptability, and observation time were analyzed. The study was conducted between July and November 2019. Overall, 140 Mini-CEX evaluation exercises were carried out on 30 students by 84 supervisors and 56 peers. The adapted instrument was found to be unidimensional, obtaining an acceptable internal consistency (α = 0.74). As the assessor type changed, there were differences in observation time; the medians (Q1-Q3) were 10 minutes (5-15) for supervisors and 30 minutes (20-45) for peer students (P < 0.001). This difference was also observed in assessor perceptions (P < 0.001), with supervisors scoring a median of 6 (6-6.75) and peer students scoring a median of 7 (6-7). No differences were found between supervisor and peer scores. The adapted version of Mini-CEX can objectively assess the clinical performance of dental students, achieving validity and reliability values similar to those obtained in the original instrument.


Enzyme replacement therapy in Fabry's disease: recent advances and clinical applications.
Fabry's disease is a rare X-linked recessive disorder resulting from deficient lysosomal enzyme, alpha-galactosidase A (alpha-Gal A) activity. The deficiency leads to progressive glycosphingolipid globotriaosylceramide (Gb3) accumulation in fluids and tissues, including vascular endothelium, connective tissue, kidney, heart, brain and peripheral nerves. Classic Fabry's disease in hemizygous males has high morbidity and mortality due to end-stage renal disease (ESRD) requiring hemodialysis (HD) or kidney transplantation, myocardial involvement and central nervous system (CNS) complications. Most heterozygous females can also suffer from this severe disease deterioration. Until recently, Fabry's disease management consisted of symptomatic and palliative treatment, but this has changed with the availability of the recombinant human alpha-Gal A enzyme, agalsidase. Two different agalsidase formulations have been obtained: one from human fibroblast (agalsidase alpha), and one from Chinese hamster ovary (CHO) cells (agalsidase beta). Both preparations underwent clinical trials that documented the feasibility, efficacy and safety of the treatment. In addition, several clinical observations have proved that agalsidase reduces the storage of the substrate from several organs and tissues and, consequently, improves signs and symptoms of Fabry's disease. Additional clinical experiences have confirmed the initial clinical trial results, but further studies are needed to evaluate the long-term outcome of enzyme replacement therapy (ERT). We reviewed the clinical trial observations, as well as subsequent clinical experiences with ERT in patients with Fabry's disease.


Fat Ful'fill'ment: A Review of Autologous Fat Grafting.
For more than a century, clinicians have attempted to utilise fat for the treatment of tissue deficiencies and contour abnormalities. Autologous fat transplantation for soft-tissue augmentation has become increasingly popular in recent years. The popularity of tumescent liposuction has brought renewed interest and accessibility of fat for transplantation. Newer techniques and approaches to augmentation have provided more predictable and reproducible results. Fat augmentation has become an effective, safe and reliable method for restoring volume and correcting the atrophy that accompanies senescence. In this review, the authors have described their approach to fat transplantation.


Ethanol production from xylose by a recombinant Candida utilis strain expressing protein-engineered xylose reductase and xylitol dehydrogenase.
The industrial yeast Candida utilis can grow on media containing xylose as sole carbon source, but cannot ferment it to ethanol. The deficiency might be due to the low activity of NADPH-preferring xylose reductase (XR) and NAD(+)-dependent xylitol dehydogenase (XDH), which convert xylose to xylulose, because C. utilis can ferment xylulose. We introduced multiple site-directed mutations in the coenzyme binding sites of XR and XDH derived from the xylose-fermenting yeast Candida shehatae to alter their coenzyme specificities. Several combinations of recombinant and native XRs and XDHs were tested. Highest productivity was observed in a strain expressing CsheXR K275R/N277D (NADH-preferring) and native CsheXDH (NAD(+)-dependent), which produced 17.4 g/L of ethanol from 50 g/L of xylose in 20 h. Analysis of the genes responsible for ethanol production from the xylose capacity of C. utilis indicated that the introduction of CsheXDH was essential, while overexpression of CsheXR K275R/N277D improved efficiency of ethanol production.


Neural network modelling of dose distribution and dose uniformity in the Tunisian Gamma Irradiator.
In this paper an approach to model dose distributions, isodose curves and dose uniformity in the Tunisian Gamma Irradiation Facility using artificial neural networks (ANNs) are described. For this purpose, measurements were carried out at different points in the irradiation cell using polymethyl methacrylate dosemeters. The calculated and experimental results are compared and good agreement is observed showing that ANNs can be used as an efficient tool for modelling dose distribution in the gamma irradiation facility. Monte Carlo (MC) photon-transport simulation techniques have been used to evaluate the spatial dose distribution for extensive benchmarking. ANN approach appears to be a significant advance over the time-consuming MC or the less accurate regression methods for dose mapping. As a second application, a detailed dose mapping using two different product densities was carried out. The minimum and maximum dose locations and dose uniformity as a function of the irradiated volume for each product density were determined. Good agreement between ANN modelling and experimental results was achieved.


A rare complication of a common disease: Bouveret syndrome, a case report.
This is a case report of an 85-year old patient who presented with abdominal pain, nausea and vomiting associated with altered liver function test. The plain X-rays and CT scan showed pneumobilia with an ectopic gallstone. The patient was diagnosed with Bouveret syndrome and managed surgically. The report is followed by a discussion about Bouveret syndrome.


The role of sampling in mycotoxin contamination: an holistic view.
The need to obtain a representative sample deserves particular consideration since a wrong sampling plan can greatly affect the reliability of the measured levels of mycotoxins. This can even result in legal disputes and barriers to trade. Reported here is an holistic view for an ideal sampling plan, which is based on two consecutive steps: (i) To establish 'why, where and when' sampling has to be performed by assessing the purpose, the appropriate time and the site for collecting the samples; (ii) To establish 'how' to draw samples by assessing practical ad hoc guidelines, considering that, for bulk goods in particular, mycotoxins are not at all homogeneously distributed in a lot. So far, step 1 is not yet covered by specific guidelines while for step 2, European regulations establish the procedures for the sampling of bulk and retail products potentially contaminated by mycotoxins.


Post-recurrence survival analysis of stage I non-small-cell lung cancer.
Background The aim of this retrospective study was to review recurrence patterns of stage I non-small-cell lung cancer and identify prognostic factors for post-recurrence survival. Methods Among 940 patients with pathological stage I non-small-cell lung cancer who underwent curative resection, 261 experienced a recurrence; of these, 188 had adenocarcinoma and 62 had squamous cell carcinoma. Oligo-recurrence was defined as 1-3 recurrent lesions restricted to a single organ. Potentially curative local treatment included surgery, stereotactic radiotherapy, and photodynamic therapy. Results The median follow-up duration was 65 months (range 4-186 months). The most common site of recurrence was the lung in 145 patients, followed by mediastinal lymph nodes in 49, pleura in 30, and brain in 27. Local treatment for recurrent tumors included surgery in 59 patients, stereotactic radiotherapy in 46, photodynamic therapy in 2, and other radiotherapy in 41. Seventy-eight patients received chemotherapy only, and 35 received conservative treatment. Among 125 patients who were evaluated for an epidermal growth factor receptor gene mutation, 31 were treated with epidermal growth factor receptor-tyrosine kinase inhibitor. The 3- and 5-year post-recurrence survival rates were 49.1% and 33.8%, respectively. Age at recurrence, adenocarcinoma cell type, disease-free interval, epidermal growth factor receptor-tyrosine kinase inhibitor treatment, and potentially curative local treatment were independent prognostic factors for survival in multivariate analysis. Conclusions Local treatment for recurrence should be considered in selected candidates, and use of epidermal growth factor receptor-tyrosine kinase inhibitor I is reasonable if an epidermal growth factor receptor mutation is detected.


Apparent idiopathic hyponatremia in an ambulatory geriatric population.
The purpose of this descriptive analysis is to demonstrate that among older patients with hyponatremia, there is a subset with apparent hyponatremia of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) type, which appears associated with the aging process. A retrospective chart review was done to identify patients with hyponatremia and to classify them into non-SIADH, SIADH, and idiopathic categories. The participants were the ambulatory population of The Mount Sinai Hospital's outpatient geriatric clinic. Pertinent data generated during the antecedent 24 months were collected from outpatient charts and included sets of laboratory values (consisting of one sodium, glucose, BUN and creatinine level), age, sex, race, clinical history, present diagnosis, medications, and prescribed diets for each patient in the total population. Patients demonstrating hyponatremia with serum sodium levels of less than 135 mEq/L were identified from the total population and were further divided into SIADH and non-SIADH etiologies. The SIADH patients were then subdivided into known etiology SIADH and apparent idiopathic SIADH. In an ambulatory geriatric population of 405 subjects, 46 had hyponatremia, with SIADH the apparent cause in 27. Of the SIADH population, seven patients were considered to have idiopathic SIADH. An apparent predilection for development of this syndrome was observed among non-black patients and the old old. The results support the hypothesis that aging is a risk factor for the development of SIADH-like hyponatremia in a subset of older patients who do not have an apparent underlying etiology. Thus, aging may be an independent etiology for the development of hyponatremia.


Quantitative and rapid Plasmodium falciparum malaria diagnosis and artemisinin-resistance detection using a CMOS Lab-on-Chip platform.
Early and accurate diagnosis of malaria and drug-resistance is essential to effective disease management. Available rapid malaria diagnostic tests present limitations in analytical sensitivity, drug-resistance testing and/or quantification. Conversely, diagnostic methods based on nucleic acid amplification stepped forwards owing to their high sensitivity, specificity and robustness. Nevertheless, these methods commonly rely on optical measurements and complex instrumentation which limit their applicability in resource-poor, point-of-care settings. This paper reports the specific, quantitative and fully-electronic detection of Plasmodium falciparum, the predominant malaria-causing parasite worldwide, using a Lab-on-Chip platform developed in-house. Furthermore, we demonstrate on-chip detection of C580Y, the most prevalent single-nucleotide polymorphism associated to artemisinin-resistant malaria. Real-time non-optical DNA sensing is facilitated using Ion-Sensitive Field-Effect Transistors, fabricated in unmodified complementary metal-oxide-semiconductor (CMOS) technology, coupled with loop-mediated isothermal amplification. This work holds significant potential for the development of a fully portable and quantitative malaria diagnostic that can be used as a rapid point-of-care test.


Decreased plasma prorenin levels in primary aldosteronism: potential diagnostic implications.
Primary aldosteronism could exert a negative feedback on prorenin secretion, of possibly different magnitude, whether it is related to an aldosterone-producing adenoma (APA) or an idiopathic hyperaldosteronism (IHA). The objectives of this study were to evaluate the level of prorenin in three subgroups: APA, IHA, and essential hypertension; and the performance of the aldosterone-to-prorenin ratio (APR) for the diagnosis of an APA. Seven hundred and forty-six hypertensive patients with a standardized work-up, including a prorenin measurement, were considered. Ninety-six patients without neutral treatment and 38 patients with other forms of secondary hypertension were excluded. APA and IHA were categorized according to computed tomography scan, adrenal venous sampling, pathological analysis and improvement of hypertension after surgery. Thirty-five patients had a diagnosis of APA, 57 of IHA and 504 of essential hypertension. Prorenin was lower in APA and IHA than in essential hypertension (32.9, 40.4 and 50.3 pg/ml, respectively; P < 0.001). APR was higher in patients with APA and IHA than in those with essential hypertension (24.0, 11.8, and 4.0 pmol/l per pg/ml, respectively; P < 0.001). The APR was more discriminant than the aldosterone-to-renin ratio to identify APA compared to IHA (area under the receiver operating curve at 0.750 and 0.639, respectively; P = 0.04). The optimal cut-off values were 22 pmol/l per pg/ml for APR (sensitivity 57.0%, specificity 93.0%) and 440 pmol/l per pg/ml for aldosterone-to-renin ratio (sensitivity 54.3%, specificity 82.5%). Primary aldosteronism and particularly its most caricatural form, that is APA, seems associated with a lower level of prorenin than essential hypertension. The APR could be included in the diagnostic strategy of APA.


Characterization and partial purification of endothelin-converting enzyme in rat lung.
Endothelin-1 (ET-1) was originally identified in the culture supernatant of porcine aortic endothelial cells. From the deduced amino acid sequence, a biosynthetic pathway has been proposed that a prepro- form of porcine ET-1 is initially processed by dibasic pair proteolysis to a 39-amino acid intermediate form (big ET), which is then converted to ET-1 by specific proteolytic cleavage between Trp21 and Val22. We have identified an enzyme activity that converts human big endothelin[1-38] to endothelin[1-21] and a C-terminal fragment (CTF, 22-38) in a homogenate fraction from rat lung. The conversion activity was enriched threefold in a plasma membrane fraction. Metal ions activated the activity by about 1.5- to 2.5-fold, in the order of Mn2+ greater than Zn2+ = Ca2+ greater than Mg2+ greater than Ba2+. The conversion activity was optimal at pH 4.0, was inhibited by pepstatin-A (IC50 = 20 nmol), but not affected by TLCK, aprotinin, PMSF, E-64, bestatin, phosphoramidon, or thiorphan at 40 microM. The converting enzyme was partially purified from rat lung plasma membranes by sequential HPLC on Mono Q, Superose 12, and Mono P. The enzyme has an apparent molecular mass of 90 kDa as estimated by SDS-PAGE or gel filtration and appears to be a single peptide protein. The enzyme may exist as isozymes with isoelectric point (pI) values at 6.2 and 6.3.


Evaluation of the Effectiveness and Safety of Alirocumab Use in Statin-Intolerant Veterans.
Since 1987, statin therapy has been the mainstay of treatment for hypercholesterolemia, and current practice guidelines recommend statins as first-line therapy given demonstrated reductions in elevated low-density lipoprotein cholesterol (LDL-C) and cardiovascular (CV) mortality reduction in robust clinical trials. The primary objective of this case series was to assess LDL-C reduction associated with alirocumab use in statin-intolerant veterans at a single US Department of Veterans Affairs medical center. The secondary objective was to assess the incidence of CV events. A retrospective chart review was conducted to identify statin-intolerant veterans who were initiated on treatment with alirocumab for LDL-C and/or CV risk reduction between June 2017 and May 2019. Electronic health records of all eligible patients who received alirocumab were reviewed, and basic demographics (patient age, sex, and race/ethnicity) as well as medical characteristics at baseline were collected. Baseline LDL-C was compared with levels at 4 and 24 weeks. Although a majority of patients saw a significant and clinically meaningful reduction in LDL-C, the group of patients with an increase in LDL-C may have benefitted from targeted intervention to improve medication and dietary adherence. Alirocumab use in 24 statin-intolerant veterans resulted in a significant reduction in LDL-C at 4 and 24 weeks after initiation. Large long-term studies would better evaluate CV benefit associated with alirocumab therapy in a veteran population.


FLIP: molecular switch between apoptosis and necroptosis.
Cancerous growth is one of the most difficult diseases to target as there is no one clear cause, and targeting only one pathway does not generally produce quantifiable improvement. For a truly effective cancer therapy, multiple pathways must be targeted at the same time. One way to do this is to find a gene that is associated with several pathways; this approach expands the possibilities for disease targeting and enables multiple points of attack rather than one fixed point, which does not allow treatment to evolve over time as cancer does. Inducing programmed cell death (PCD) is a promising method to prevent or inhibit the progression of tumor cells. Intricate cross talk among various programmed cell death pathways including cell death by apoptosis, necroptosis or autophagy plays a critical role in the regulation of PCD. In addition, the complex and overlapping patterns of signaling and lack of understanding of such networks between these pathways generate hurdles for developing effective therapeutic approaches. This review article focuses on targeting FLIP (Fas-associated death domain-like interleukin-1-converting enzyme-like inhibitory protein) signaling as a bridge between various PCD processes as an effective approach for cancer management.


Effective pain management of older adult hospice patients with cancer.
Pain is subjective and a unique and individual experience. For those involved in the care of hospice patients, pain management can be challenging and is not always effectively managed. This case study explores an older adult cancer patient's pain experience at the end of her life with implementation of pain management strategies from hospice.


An 8 MeV Electron Beam Modified In:ZnO Thin Films for CO Gas Sensing towards Low Concentration.
In the present investigation, electron beam-influenced modifications on the CO gas sensing properties of indium doped ZnO (IZO) thin films were reported. Dose rates of 5, 10, and 15 kGy were irradiated to the IZO nano films while maintaining the In doping concentration to be 15 wt%. The wurtzite structure of IZO films is observed from XRD studies post electron beam irradiation, confirming structural stability, even in the intense radiation environment. The surface morphological studies by SEM confirms the granular structure with distinct and sharp grain boundaries for 5 kGy and 10 kGy irradiated films whereas the IZO film irradiated at 15 kGy shows the deterioration of defined grains. The presence of defects viz oxygen vacancies, interstitials are recorded from room temperature photoluminescence (RTPL) studies. The CO gas sensing estimations were executed at an optimized operating temperature of 300 °C for 1 ppm, 2 ppm, 3 ppm, 4 ppm, and 5 ppm. The 10 kGy treated IZO film displayed an enhanced sensor response of 2.61 towards low concentrations of 1 ppm and 4.35 towards 5 ppm. The enhancement in sensor response after irradiation is assigned to the growth in oxygen vacancies and well-defined grain boundaries since the former and latter act as vital adsorption locations for the CO gas.


Cardiorespiratory Fitness, Different Measures of Adiposity, and Cardiovascular Disease Mortality Risk in Women.
Background: Associations among cardiorespiratory fitness (CRF), different adiposity exposures, and cardiovascular disease (CVD) mortality in women are not well defined. Materials and Methods: A total of 19,838 women completed a baseline examination between 1971 and 2013. Measures included body mass index (BMI), waist circumference (WC), waist-to-height (W:HT) ratio, skinfold-derived percent body fat (% Fat), and CRF estimated from a maximal treadmill test. CRF categories were low (quintile 1), moderate (quintiles 2-3), and high (quintiles 4-5); standard cut points were used for adiposity exposures. Hazard ratios (HRs) were estimated using Cox regression. Results: During a mean follow-up period of 19.2 ± 10.3 years, 391 cardiovascular deaths occurred. HRs (95% confidence interval) for CVD in moderate and low CRF groups, using high CRF as the referent, were 1.87 (1.46-2.38) and 2.54 (1.93-3.35), respectively (p trend <0.001). HRs of obese women within each adiposity exposure were higher when compared with normal-weight women (p ≤ 0.03). Joint associations of CRF × adiposity showed a positive trend in CVD mortality across decreasing categories of CRF within each category of W:HT and % Fat, as well as within the normal and overweight BMI categories and the normal WC category (p ≤ 0.03 for each). Conclusion: Higher levels of CRF are associated with lower CVD mortality risk in women, and predict lower risk of CVD mortality in normal-weight women and in obese women. Using different measures of adiposity to predict CVD mortality risk in women may be misleading unless CRF is taken into account. These results support the American Heart Association (AHA) recommendation for including CRF as a clinical vital sign.


Diversity of Insect Sesquiterpenoid Regulation.
Insects are arguably the most successful group of animals in the world in terms of both species numbers and diverse habitats. The sesquiterpenoids juvenile hormone, methyl farnesoate, and farnesoic acid are well known to regulate metamorphosis, reproduction, sexual dimorphism, eusociality, and defense in insects. Nevertheless, different insects have evolved with different sesquiterpenoid biosynthetic pathway as well as products. On the other hand, non-coding RNAs such as microRNAs have been implicated in regulation of many important biological processes, and have recently been explored in the regulation of sesquiterpenoid production. In this review, we summarize the latest findings on the diversity of sesquiterpenoids reported in different groups of insects, as well as the recent advancements in the understanding of regulation of sesquiterpenoid production by microRNAs.


Eggshell membrane as a bioactive agent in polymeric nanotopographic scaffolds for enhanced bone regeneration.
A bone regeneration scaffold is typically designed as a platform to effectively heal a bone defect while preventing soft tissue infiltration. Despite the wide variety of scaffold materials currently available, such as collagen, critical problems in achieving bone regeneration remain, including a rapid absorption period and low tensile strength as well as high costs. Inspired by extracellular matrix protein and topographical cues, we developed a polycaprolactone-based scaffold for bone regeneration using a soluble eggshell membrane protein (SEP) coating and a nanotopography structure for enhancing the physical properties and bioactivity. The scaffold exhibited adequate flexibility and mechanical strength as a biomedical platform for bone regeneration. The highly aligned nanostructures and SEP coating were found to regulate and enhance cell morphology, adhesion, proliferation, and differentiation in vitro. In a calvaria bone defect mouse model, the scaffolds coated with SEP applied to the defect site promoted bone regeneration along the direction of the nanotopography in vivo. These findings demonstrate that bone-inspired nanostructures and SEP coatings have high potential to be applicable in the design and manipulation of scaffolds for bone regeneration.


The affinity and activity of the multiple hormone response element in the proximal promoter of the human oxytocin gene.
In vivo there appears to be a marked association between oestrogen levels and the expression of the oxytocin (OT) gene in most tissues. Transfection and DNA-protein binding experiments using high levels of either oestrogen receptor (ER)alpha or ERbeta imply a direct interaction of these transcription factors with the multiple hormone response element (HRE) at approximately -160 from the transcription start site of the OT gene in most species. In an extensive set of experiments, we show, using both transfection and protein-DNA binding, that low to moderate amounts of either oestrogen receptor, while being able to interact directly with a classic oestrogen response element (ERE) fail to interact with the human OT -160 HRE. Instead, this element, similar to its bovine counterpart, has a high affinity for the orphan receptors steroidogenic factor 1 and chicken ovalbumin upstream promoter transcription factor. Second, the human and bovine OT promoter can be made artificially responsive towards oestrogen in a cotransfection system over-expressing ERalpha or ERbeta, but not in cells expressing natural levels of these steroid receptors. Interestingly, nuclear extracts from both ERalpha-positive MCF7 cells and ERalpha-negative MDA-MB231 cells both contain a transcription factor which binds specifically to both the hOT-HRE element and to a classic ERE, and which has orphan receptor-like binding properties rather than those of an oestrogen receptor. Together, these and other results suggest that oestrogen action in vivo on the OT gene in all species is more likely to involve a DNA-independent mechanism than classic direct interactions with dimeric oestrogen receptors.


Vena porta thrombosis in patient with inherited factor VII deficiency.
Most clotting factor VII (FVII)-deficient patients suffer from bleeding episodes and occasionally thromboembolic complications after surgical interventions or replacement therapy. However, thromboses without apparent triggering factors may occur as well. We report a case of a pregnant woman with inherited FVII deficiency and chronic vena porta thrombosis. She presented at 32 weeks of gestation with spontaneously increased international normalized ratio, severe thrombocytopenia and very few unspecific symptoms. The extensive examination of the patient revealed cavernous transformation of the portal vein with well expressed portosystemic collaterals, heterozygosity for three common polymorphisms in FVII gene, associated with reduction in plasma FVII levels, and no other factors predisposing to thrombosis.


Basic Mechanisms in Neurodegenerative Disease: Implications for Behavioral Pathogenesis and Treatment.
Current therapies for neurodegenerative diseases focus primarily on the use of psychotropic drugs to influence their non-cognitive manifestations. In this article, we take a conceptual approach to understanding behavioral syndromes in dementing disorders, with a heuristic emphasis on Alsheimer's disease. We draw upon recent developments in research to explore the fundamental mechanisms implicated in the pathophysiology of neuropsychiatric impairments, and consider endocrine, vascular, genetic, and interpersonal factors that may modulate their expression. Emerging evidence points to dysfunction of particular neural systems within the diseased brain as the basis for neuropsychiatric syndromes, but the specificity of postulated clincal-pathologic correlations remains to be verified by research designed to test critical hypotheses. We highlight advances in clinical and experimental psychopharmacology that extend conventional concepts of the actions of psychotropic drugs, and prompt a broad approach to investigating and treating behavioral pathology in dementia.


Molecular characterization of hepatitis A virus from a large outbreak from Kerala, India.
Hepatitis A is highly prevalent in India and mainly presents as a sporadic disease. This study investigated an outbreak of viral hepatitis at Medical College Hospital area, Kottayam, Kerala state, India during January 2005. Blood (133), faecal (1), sewage (4), and water samples (13) were collected. Sera were tested for IgG- and IgM-anti-HAV and IgM antibodies against hepatitis E (IgM-anti-HEV). Sewage, faeces and water samples were tested for HAV RNA in nested RT-PCR and HAV RNA positive samples were further processed for RNA quantitation using Real Time PCR. Of the 1180 total cases, 540 were reported from Medical college area. Two deaths were reported among doctors. Patients from the community gave a previous history of visit to medical college hospital area. The sewage treatment plant at the campus was non-functional since 1990 and the untreated sewage was constantly overflowing and getting mixed with a canal. At the time of the study, all the water sources were superchlorinated. HAV RNA was present in the faeces of hepatitis A patient (1.36 x 10(7) copies/ml), sewage tank (2.57 x 10(3) copies/ml and the canal (<100 copies/ml). None of the 13 water samples concentrated 10,000-fold and the soil sample showed presence of HAV RNA. Phylogenetic analysis based on 5'-non-coding and P2 regions showed HAV-genotype IIIA in all samples. The aetiological agent of the present outbreak was found to be HAV. Epidemic hepatitis A (genotype-IIIA) is emerging in Indian adults, emphasizing the need for definite policy for control.


Multivariable Analysis of Nutritional and Socio-Economic Profiles Shows Differences in Incident Anemia for Northern and Southern Jiangsu in China.
Anemia is a prevalent public health problem associated with nutritional and socio-economic factors that contribute to iron deficiency. To understand the complex interplay of risk factors, we investigated a prospective population sample from the Jiangsu province in China. At baseline, three-day food intake was measured for 2849 individuals (20 to 87 years of age, mean age 47 ± 14, range 20-87 years, 64% women). At a five-year follow-up, anemia status was re-assessed for 1262 individuals. The dataset was split and age-matched to accommodate cross-sectional (n = 2526), prospective (n = 837), and subgroup designs (n = 1844). We applied a machine learning framework (self-organizing map) to define four subgroups. The first two subgroups were primarily from the less affluent North: the High Fibre subgroup had a higher iron intake (35 vs. 21 mg/day) and lower anemia incidence (10% vs. 25%) compared to the Low Vegetable subgroup. However, the predominantly Southern subgroups were surprising: the Low Fibre subgroup showed a lower anemia incidence (10% vs. 27%), yet also a lower iron intake (20 vs. 28 mg/day) compared to the High Rice subgroup. These results suggest that interventions and iron intake guidelines should be tailored to regional, nutritional, and socio-economic subgroups.