Hyperthermia in combination with radiotherapy: a review of five years experience in the treatment of superficial tumors.
Facilities for regional tumor hyperthermia has been in use at RPMI since 1976, and have been routinely used to treat patients according to protocol since 1977. Hyperthermia delivery has been exclusively by microwave using 434 MHz, 915 MHz and 2450 MHz. Greatest success at reaching tumor temperatures of 43-44 degrees C with minimal skin heating was obtained using 915 MHz. The majority of the patients were treated with this frequency. Approximately 125 patients have been treated and 70 have achieved completion of therapy and follow-up. Follow-up has been at least one month and several patients have been followed for one to two years. Initially, for entry into the hyperthermia protocol, patients were required to have three or more lesions. One lesion on each patient was treated with 800 rad fractions repeated three times on a 72 hour schedule. The second lesion was treated with 700 rad fractions and the third with 500 rad plus hyperthermia on the same schedule. Twelve patients with multiple melanoma lesions completed this study. One of 12 patients showed no response to the combination of hyperthermia plus radiotherapy, while four showed no response to radiotherapy alone. Of eight patients who survived three months, all lesions treated by hyperthermia plus radiotherapy responded completely, while only five lesions treated by radiotherapy alone so responded. In a second study, 58 patients with superficial tumors were treated by a protocol where hyperthermia was added to optimal conventional radiotherapy. Of the total, 43 patients had complete tumor response at follow-up varying from one month to 18 months. A subgroup of 24 of these patients had two lesions, one of which was treated with hyperthermia in addition to radiotherapy while the other served as control, receiving radiotherapy only. Nineteen lesions demonstrated complete response to hyperthermia plus radiotherapy, while only 14 of the controls had complete response. None of the lesions treated with hyperthermia responded less well than those treated by radiotherapy alone. Morbidity, as measured by skin reaction, was rarely increased in the heated field.


[Indications to the formation of arteriovenous fistulas in performing reconstructive operations in patients with atherosclerotic lesions of the main arteries of the femur and shin at the stage of critical ischemia].
Causes of early shunt thromboses were studied retrospectively in 35 patients with occlusion of the femoro-popliteal segment and critical ischemia, in whom the operation of distal femoro-tibial shunt with the autovein had been performed by the method in situ without an application of the arteio-venous fistula (AVF). Early thromboses of the shunts took place in 8 patients (22.9%). The main cause of the early thromboses of the femorotibial shunts was shown to be a critical occlusive-stenotic lesion of the main arteries of the shin and foot with dysfunction of the plantar arch as well as decompensation of the microcirculation system. Objective criteria of the formation of AVF were worked out. The application of the criteria in operative treatment of 25 patients allowed the number of early thromboses to be reduced to 4%.


The s phase is discrete and is controlled by the circadian clock in the marine dinoflagellate Gonyaulax polyedra.
Cloned cultures of the dinoflagellate Gonyaulax polyedra grown in a 12-h light-12-h dark cycle (LD 12:12) were synchronized to the beginning of G1 by a two sequential filtration technique. After the second filtration, with the cultures growing in LD 12:12, not many cells had divided after 1 day, but approximately half underwent cell division after 2 days. Flow cytometric measurements of the cells revealed that there is one unique S phase starting about 12 h prior to cell division and lasting for less than 4 h. A majority of cells in cultures synchronized in the same way but maintained in continuous light (LL) after filtration also divided synchronously after 2 days. Just as for the cultures in LD 12:12, those in LL have a similar discrete DNA synthesis phase prior to division. It is concluded that the circadian control of cell division acts before the S phase, giving rise to a discontinuous DNA synthesis phased by the circadian clock.


Clinical features and characteristics of blood flow of uterine vascular abnormalities.
The purpose of this study was to assess the clinical features and characteristics of the blood flow in uterine vascular abnormalities using ultrasound and magnetic resonance imaging (MRI). A total of 17 women were diagnosed with uterine vascular abnormalities by ultrasound. The clinical characteristics of the patients and the distribution and waveform of the intrauterine vessels were examined using transvaginal gray-scale and Doppler ultrasonography, spin-echo MRI, and MR angiography. The average age of the 17 subjects was 44.3 years, and 5 were postmenopausal women. The number of pregnancies and deliveries was 2.0 and 1.7, respectively. Of the 17 subjects, 7 had a moderate or severe grade of dysmenorrhea and 7 had a history of vascular disease. In all subjects, vaginal ultrasound demonstrated tubular or numerous tortuous anechoic areas in the uterine wall, and Doppler ultrasound showed that the tubular or numerous dilated tortuous vessels had an atypical wave flow, unlike that of an artery or a vein. The distribution of displayed flow varied, and the waveforms of the Doppler ultrasound displayed three patterns. The averages of the pulse Doppler flow indices showed low impedance in the abnormal uterine vessel and the uterine artery, especially in cases of true arteriovenous malformations. MR angiography demonstrated distinct, tortuous, and coiled vascular channels in the pelvis during and just after the arterial phase. Characterization of the clinical features of uterine vascular abnormalities is considered to be valuable for obstetricians and gynecologists.


Improvement of the accuracy of liver lesion DCEUS quantification with the use of automatic respiratory gating.
To evaluate the efficiency of automatic respiratory gating (ARG) in reducing respiratory motion-induced artefacts from dynamic contrast-enhanced ultrasound (DCEUS) acquisitions and to assess the impact of ARG on DCEUS quantification parameters in patients with liver malignancies. Twenty-five patients with liver metastasis were imaged with DCEUS. The lognormal indicator dilution model was fitted on time-intensity curves extracted from hepatic lesions with and without the use of ARG and DCEUS quantification parameters were extracted. The goodness of fit was assessed using the coefficient of determination (R (2) LN ). The effect respiration had on the data was assessed using the respiration amplitude (RA) metric. Pearson's correlation coefficient (r) was used to assess the correlation between R (2) LN and RA with and without the use of ARG. The RA parameter was strongly correlated with R (2) LN (r = -0.96, P = 7.412 × 10(-15)) and this correlation became weaker with ARG (r = -0.64, P = 5.449 × 10(-4)). ARG significantly influenced the values of the quantification parameters extracted (P ≤ 0.05). The RA was significantly decreased when ARG was used (P = 1.172 × 10(-6)). ARG has a significant impact on the quantification parameters extracted and it has been shown to improve the accuracy of liver lesion DCEUS. • ARG has a significant impact on DCEUS quantification parameters. • ARG can improve the modelling of liver lesion haemodynamics using DCEUS quantification. • ARG significantly reduces the respiration amplitude of DCEUS lesion time-intensity curves.


Using support vector machines to identify literacy skills: Evidence from eye movements.
Is inferring readers' literacy skills possible by analyzing their eye movements during text reading? This study used Support Vector Machines (SVM) to analyze eye movement data from 61 undergraduate students who read a multiple-paragraph, multiple-topic expository text. Forward fixation time, first-pass rereading time, second-pass fixation time, and regression path reading time on different regions of the text were provided as features. The SVM classification algorithm assisted in distinguishing high-literacy-skilled readers from low-literacy-skilled readers with 80.3 % accuracy. Results demonstrate the effectiveness of combining eye tracking and machine learning techniques to detect readers with low literacy skills, and suggest that such approaches can be potentially used in predicting other cognitive abilities.


Examining the Impact of Breast Augmentation vs Hormone Therapy on Chest Femininity of Transgender Women.
For transgender women, there is often the innate assumption that surgical breast augmentation will increase perceived chest femininity beyond hormone therapy alone. This study aimed to evaluate whether lay individuals found surgically augmented breasts more feminine than breast development from hormone replacement therapy alone in transgender patients. We obtained preoperative (maximal breast growth on hormone therapy) and postoperative chest (after primary augmentation) images of 22 transgender patients, and age- and BMI-matched cisgender male (n = 17) and female (n = 21) control patients. Survey respondents (n = 271) rated each image on a scale of 1 (very feminine) to 5 (very masculine). Results were compared by survey respondent gender identity and sexual orientation. There was a significant difference in mean femininity score between all image types. Mean score for transgender patients fell by 0.478 points after surgery (P < .0001). Subgroup analysis looking at transgender participants revealed the same significance trend postoperatively. Transgender respondents also found no difference in femininity between female controls and postoperative transgender patients (P = .132). We also compared mean femininity scores across 4 self-identified respondent subgroups: cisgender and heterosexual, cisgender and lesbian, gay, or bisexual (LGB), transgender and heterosexual, and transgender and LGB. The cisgender and heterosexual subgroup rated the postoperative transgender patients more feminine than any of the other respondent subgroups (LGB P < .001, transgender and LGB P < .001, transgender only P = .018). This study shows that breast augmentation significantly increased the perception of femininity. Furthermore, gender identity and sexual orientation are important in how lay persons perceive transgender patients.


Genetic diversity and structure of Oncomelania hupensis hupensis in two eco-epidemiological settings as revealed by the mitochondrial COX1 gene sequences.
Oncomelania hupensis hupensis is the only intermediate host of Schistosoma japonicum, the causative agent of schistosomiasis in China and is therefore of significant medical and veterinary health importance. Although tremendous progress has been achieved, there remains an understudied area of approximately 2.06 billion m2 of potential snail habitats. This area could be further increased by annual flooding. Therefore, an understanding of population genetics of snails in these areas may be useful for future monitoring and control activities. We sampled snails from Hexian (HX), Zongyang (ZY) and Shitai (ST) in Anhui (schistosomiasis transmission control), and from Hengtang (HT), Taicang (TC), Dongsan (DS) and Xisan (XS) in Jiangsu (schistosomiasis transmission interrupted), downstream of Anhui. ST, DS and XS are classified as hilly and mountainous areas, and HX, ZY, TC and HT as lake and marshland areas. The mitochondrial cytochrome c oxidase subunit I gene were sequenced. Out of 115 snails analyzed, 29 haplotypes were identified. We observed 56 (8.72%) polymorphic sites consisting of 51 transitions, four transversions and one multiple mutational change. The overall haplotype and nucleotide diversity were 0.899 and 0.01569, respectively. Snail populations in Anhui had higher genetic diversity than in Jiangsu. 73.32% of total variation was distributed among sites and 26.68% within sites. Snails were significantly separated according to eco-epidemiological settings in both network and phylogenetic analyses. Our results could provide important guidance towards assessing coevolutionary interactions of snails with S. japonicum, as well as for future molluscan host monitoring and control activities.


The effect of high cholesterol, high fat diet on rabbit plasma beta-VLDL and its interaction with macrophage.
Rabbits were fed on 1% cholesterol and 10% rape seed oil (group A) or lard (group B). Plasma cholesterol and triglyceride level of group A was strikingly lower than that of group B. No difference was found in the lipid composition of beta-VLDLs between both groups. However, apo E content of beta-VLDL from group A was higher and apo B (higher molecular weight) was lower than that of group B respectively. beta-VLDL of group A caused greater accumulation of cholesterol in mouse peritoneal macrophage than that of group B. Therefore, we assume that the good effect of poly-unsaturated fatty acid on atherosclerosis results not from decreasing accumulation of cholesterol in macrophages but from enhancing elimination of beta-VLDL by the liver.


Bioaccessibility of essential and non-essential metals in commercial shellfish from Western Europe and Asia.
Maximum acceptable concentrations of metals in food - based on total concentrations - have been established in many countries. To improve risk assessment, it would be better to take into account bioaccessible concentrations. A total of seven species of molluscs from France, UK and Hong Kong was examined in this study including clams, mussels, oysters, scallops and gastropods. The species which have total metal concentrations higher than the most severe food security limits are mainly oysters (all of the three studied species), the gastropod Buccinum undatum for cadmium and zinc, and scallops for cadmium. The lowest bioaccessibility (in % extractability with gut juices) was observed for silver (median for all of the species: 14%), it was moderate for lead (median: 33%) and higher for cadmium, zinc and copper (medians were respectively 54%, 65%, and 70%). In most cases, bioaccessible concentrations remained higher than the safety limits, except for cadmium in scallops and zinc in B. undatum. The influence of feeding habit (masticated or swallowed, addition of vinegar or lemon) on metal bioaccessibility in oysters is limited. On the contrary, cooking the gastropods decreased the bioaccessibility of metals, except silver.


Advantages of an electronic recording system for medicolegal autopsies in resource-constrained contexts.
In Africa, the efficiency of death investigation systems is impacted by a shortage of forensic pathologists. The continued use of paper-based documentation is an additional obstacle to accurate and up-to-date statistics and reporting. A sustainable, portable, and low-maintenance data collection system was designed to improve autopsy and statistics reporting and support an environment conducive to research. Accordingly, a mobile data application was created to store pertinent autopsy information in real-time and generate statistics and trend reports for various purposes. This user-friendly application was created for in-training, and practising pathologists use and requires minimal training. Implementation will provide an efficient and reliable system that will positively impact judicial processes and research in forensic pathology. The autopsy data application is currently undergoing user testing and will be piloted. The use of technology and digitisation alleviate multiple challenges, including deteriorating infrastructure, staff shortages, and unavailability of funding. The mobile application which conforms to legal and ethical requirements can significantly improve efficiency and offers a sustainable solution to forensic pathology practice in resource-constrained contexts.


Ambulatory monitoring and physical health report in Vietnam veterans with and without chronic posttraumatic stress disorder.
This study investigated the associations among PTSD, ambulatory cardiovascular monitoring, and physical health self-reports in 117 male Vietnam combat veterans (61 with PTSD and 56 without PTSD). PTSD was associated with health symptoms and number of current health conditions beyond the influence of several covariates. PTSD was associated with greater systolic blood pressure variability, and an elevated percentage of heart rate and systolic blood pressure readings above baseline. Higher mean heart rate and an elevated percentage of heart rate above baseline were associated with physical health symptoms. None of the ambulatory monitoring variables mediated the association between PTSD and physical health outcomes. Findings suggest that the interrelationships among ambulatory autonomic responses, PTSD, and physical health deserve more research attention.


Quantification of six-degree-of-freedom motion during beam delivery in spine stereotactic body radiotherapy using intra-irradiation cone-beam computed tomography imaging technique.
Quantifying intra-fractional six-degree-of-freedom (6DoF) residual errors or motion from approved patient setups is necessary for accurate beam delivery in spine stereotactic body radiotherapy. However, previously reported errors were not acquired during beam delivery. Therefore, we aimed to quantify the 6DoF residual errors and motions during arc beam delivery using a concurrent cone-beam computed tomography (CBCT) imaging technique, intra-irradiation CBCT. Consecutive 15 patients, 19 plans for various treatment sites, and 199 CBCT images were analyzed. Pre-irradiation CBCT was performed to verify shifts from the initial patient setup using the ExacTrac system. During beam delivery by two or three co-planar full-arc rotations, CBCT imaging was performed concurrently. Subsequently, an intra-irradiation CBCT image was reconstructed. Pre- and intra-irradiation CBCT images were rigidly registered to a planning CT image based on the bone to quantify 6DoF residual errors. 6DoF residual errors quantified using pre- and intra-irradiation CBCTs were within 2.0 mm/2.0°, except for one measurement. The mean elapsed time (mean ± standard deviation [min:sec]) after pre-irradiation CBCT to the end of the last arc beam delivery was 6:08 ± 1:25 and 7:54 ± 2:14 for the 2- and 3-arc plans, respectively. Root mean squares of residual errors for several directions showed significant differences; however, they were within 1.0 mm/1.0°. Time-dependent analysis revealed that the residual errors tended to increase with elapsed time. The errors represent the optimal intra-fractional error compared with those acquired using the pre-, inter-beam, and post-6DoF image guidance and can be acquired within a standard treatment timeslot.


Type I and type II insulin-like growth factor receptors and their function in human Ewing's sarcoma cells.
Binding studies using recombinant human 125I-labelled insulin-like growth factor I ([125I]IGF-I) revealed IGF-I receptors in three Ewing's sarcoma cell lines with Kd ranging from 74 x 10(-12) M to 100 x 10(-12) M and Bmax = 36-63 fmol/mg cell protein. [125I]IGF-I binding was displaced by IGF-I, IGF-II and insulin with IC50 values of 1.5 nM, 6.3 nM and 0.7 microM respectively. Recombinant human [125I]IGF-II radioligand-binding assays in the cell lines disclosed specific binding sites for IGF-II with Kd = (110-175) x 10(-12) M and Bmax varying from 21 fmol/mg to 72 fmol/mg cell protein. Neither IGF-I nor insulin displaced [125I]IGF-II binding. IGF-I was found to increase basal glucose transport by maximally 1.5 times with EC50 = 0.9 nM IGF-I. The efficacy and potency of IGF-II on glucose uptake were comparable to those of IGF-I whereas insulin was ineffective. IGF-I and IGF-II also provoked stimulation of glycogen synthesis in Ewing's sarcoma cells. The maximal glycogenic response was reached at 0.01 microM IGF-I and 0.1 microM IGF-II, the EC50 value being approximately 1 nM IGF-I and 2 nM IGF-II. Insulin did not significantly influence glycogen formation. IGF-I and IGF-II but not insulin increased DNA synthesis in Ewing's sarcoma cells. The maximal mitogenic response was obtained with 10 nM IGF-I or IGF-II with an EC50 value of about 0.7 nM for both peptides. alpha-IR-3, a monoclonal antibody specific for the IGF type I receptor, effectively blocked IGF-I- and IGF-II-mediated metabolic responses. In conclusion, the data show that IGF-I and IGF-II induce rapid and long-term biological responses in Ewing's sarcoma cells exclusively through interaction with IGF type I receptors.


Atherosclerotic vascular disease in middle-aged, insulin-treated, diabetic patients. Association with endogenous insulin secretion capacity.
The prevalence of atherosclerotic vascular disease (ASVD) and its risk factors were investigated in 263 insulin-treated diabetic patients, ages 45 to 64 years, who were older than 30 years when their diabetes was diagnosed. The patients were divided into two groups based on the degree of endogenous insulin secretion capacity: Group A: glucagon-stimulated plasma C-peptide less than 0.20 nmol/l and Group B: C-peptide greater than or equal to 0.20 nmol/l. The age-adjusted prevalence of definite myocardial infarction was significantly higher in Group B than in Group A (16.8% vs. 5.2%, p less than 0.01). A similar difference between Groups A and B was found for definite or possible coronary heart disease (54.6% vs. 32.9%, p less than 0.001) and stroke (9.3% vs. 2.0%, p less than 0.05). In multivariate analysis, high glucagon-stimulated plasma C-peptide level (greater than or equal to 0.20 nmol/l) was positively associated with definite or possible coronary heart disease independently of other cardiovascular risk factors. Our results indicate that among insulin-treated patients with a late onset of diabetes, the prevalence of ASVD is markedly higher in those with persistent endogenous insulin secretion (noninsulin-dependent diabetes) than in those with low or no insulin secretion (insulin-dependent diabetes).


Microbiological findings in bile cultures of patients with acute cholangitis undergoing endoscopic retrograde cholangiography.
Acute cholangitis (AC) is potentially fatal. Microbiological identification and susceptibility to antibiotics is essential in every hospital to direct treatment (1). Our hospital is a third-level cancer center. A retrospective, analytical study of 30 patients undergoing endoscopic retrograde cholangiography with AC and positive biliary culture (BC) was performed over a period of six months.


Application of healthcare failure mode and effect analysis in controlling surgical instrument packaging defects.
Surgical instrument packaging defects may affect the safety of medical care and patients and waste the hospital workforce, material resources, and financial resources. This study explored the application of healthcare failure mode and effect analysis in controlling surgical instrument packaging defects. We retrospectively evaluated the packaging process of 183,642 surgical instruments packaged in our hospital during January-June 2020 using the healthcare failure mode and effect analysis. Besides, we used a decision tree model to determine the steps requiring improvement and formulate the improvement measures. We applied the improvement measures to 190,231 surgical instrument packs packaged in our hospital during July-December 2020. Based on the healthcare failure mode and effect analysis, we compared the packaging defect rates before and after adopting the improvement measures. Of the 183,642 packs selected before adopting the improvement measures, 98 defects occurred, with a defect rate of 0.053%. However, of the 190,231 packs selected after adopting the improvement measures, 22 defects occurred, with a defect rate of 0.012%. The defect rate of surgical instrument packaging handled by the central sterile supply department staff was significantly reduced (χ2 = 50.822, P = 0.001) after adopting the improvement measures. Using the medical failure mode and effect analysis method to control the defects in surgical instrument packaging can effectively reduce the packaging defect rate, ensuring patient safety.


Cytotoxicity of denture base acrylic resins: a literature review.
Acrylic resins are widely used in the fabrication of denture bases and have been shown to be cytotoxic as a result of substances that leach from the resin. The primary eluate is residual monomer. Numerous reports suggest that residual monomer may be responsible for mucosal irritation and sensitization of tissues. This information is important, not only to assess the biologic effects of such materials, but also to enable a comparison among the different polymerization methods, thus assisting the clinician in selecting a material with minimal cytotoxicity. This article reviews the literature published from 1973 to 2000, selected by use of a Medline search, associated with cytotoxic effects usually ascribed to acrylic denture base materials.


The role of alternative splicing in lung cancer.
Aberrant alternative splicing (AS) events are frequently observed in lung cancer, which can be attributed to aberrant gene AS, alterations in splicing regulatory factors, or changes in splicing regulatory mechanisms. Consequently, the dysregulation of alternative RNA splicing is the fundamental cause of lung cancer. In this review, we have summarized the pivotal role of AS in the development, progression, invasion, metastasis, angiogenesis, and drug resistance of lung cancer. Ultimately, this review emphasizes the potential of AS as biomarkers in lung cancer prognosis and diagnosis, and introduces some applications of AS isoform in the treatment of lung cancer. The comprehension of the AS may provide a glimmer of hope for the eradication of lung cancer.


Determination of apoptosis, uracil incorporation, DNA strand breaks, and sister chromatid exchanges under conditions of thymidylate deprivation in a model of BER deficiency.
Thymidylate synthase (TS) is an important target of several chemotherapeutic agents. During TS inhibition, dTTP levels decrease with a subsequent increase in dUTP. Uracil incorporated into the genome is removed by base excision repair (BER). BER has been hypothesized to play a role in the response to thymidylate deprivation, despite a lack of direct evidence. We previously found that beta-pol null murine fibroblasts were approximately six-fold more resistant than wild-type cells to raltitrexed, a folate-based inhibitor specific for TS. In this study, a number of endpoints were determined to understand the influence of BER and beta-pol during raltitrexed treatment. Raltitrexed induced apoptosis in wild-type cells to a greater extent than in beta-pol null cells. A PARP inhibitor decreased the sensitivity to raltitrexed, although the extent was not different between wild-type and beta-pol null cells. No evidence was seen for extensive strand break formation that preceded apoptosis, although raltitrexed induced more sister chromatid exchanges in wild-type cells. Increased levels of uracil in DNA were detected following treatment in wild-type and beta-pol null cells. However, uracil levels were only approximately two-fold higher in DNA from treated cells compared to untreated. Uracil DNA glycosylase activity was slightly higher in beta-pol null cells, although not sufficiently different to explain the difference in sensitivity to raltitrexed. Taken together, the data suggest that the sensitivity of the wild-type cells to raltitrexed is not associated with activation of PARP-1 dependent BER, extensive uracil incorporation into DNA and persistent strand breaks, but rather with changes suggestive of DNA recombination.


Bad splits in bilateral sagittal split osteotomy: systematic review of fracture patterns.
An unfavourable and unanticipated pattern of the mandibular sagittal split osteotomy is generally referred to as a 'bad split'. Few restorative techniques to manage the situation have been described. In this article, a classification of reported bad split pattern types is proposed and appropriate salvage procedures to manage the different types of undesired fracture are presented. A systematic review was undertaken, yielding a total of 33 studies published between 1971 and 2015. These reported a total of 458 cases of bad splits among 19,527 sagittal ramus osteotomies in 10,271 patients. The total reported incidence of bad split was 2.3% of sagittal splits. The most frequently encountered were buccal plate fractures of the proximal segment (types 1A-F) and lingual fractures of the distal segment (types 2A and 2B). Coronoid fractures (type 3) and condylar neck fractures (type 4) have seldom been reported. The various types of bad split may require different salvage approaches.


Some biochemical characteristics and cell membrane actions of a toxic phospholipase A2 isolated from the venom of the pit viper Agkistrodon halys (Pallas).
A toxic component (AgTx) from the venom of Agkistrodon halys (Pallas) was isolated using DEAE-cellulose DE11 and CM-Sephadex C50 column chromatography and finally purified to homogeneity by FPLC on a MonoQ column. The toxin is a neutral (pI 6.9) single chain polypeptide with a mol. wt of 14,000 and an amino acid composition (123 residues) roughly similar to that of notexin. AgTx was found to have phospholipase A2 activity which was dependent on calcium and stimulated by sodium deoxycholate. The toxin caused efflux of 2-deoxy-(1-3H)-glucose-6-phosphate (a cell membrane integrity probe) as well as of [3H]acetylcholine from rat brain synaptosomes. No cell membrane damage was induced by AgTx on cultured N1E 115 neuroblastoma cells and chick myotube cultures. The LD50 ws 150 micrograms/kg (i.p.) in mice. The main symptom observed was respiratory paralysis. The results obtained show that AgTx can be classified as a toxic phospholipase A2 with a presynaptic site of action.


What is the "weight" of body mass index on sexual functioning in women? A mediation model.
It is well known that body mass index (BMI) affects how individuals perceive their well-being and that obese individuals tend to report poorer levels of subjective health status. The aim of this study was to compare subjects with and without FSD and to examine the direct and indirect impact of BMI on female sexual dysfunction (FSD) in overweight/obese and normal-weight women. A cross-sectional study was conducted on 186 overweight/obese and 233 normal-weight women. FSD assessed with the Female Sexual Function Index (FSFI) was investigated in relation to body satisfaction assessed with the Body Uneasiness Test (BUT-A) and self-esteem assessed with the Rosenberg Self-Esteem scale (RSE). No difference in the prevalence of FSD was found between overweight/obese (44.4%) and normal-weight women (55.6%), even though significant between-group differences in body image were found. Structural Equation Modelling (SEM) showed that BMI contribute to FSD only through the mediating role of body dissatisfaction and self-esteem. The present results support the notion that sexual functioning is not related directly to BMI in women but to a more complex interactions of body weight, satisfaction with one's own body image, and levels of self-esteem. Clinicians should take into account that for women having a good sexual life seems not related to body weight but to the way their body weight is perceived within the context of self-image. Level III, case-control analytic study.


Reweighting Signal Spectra to Improve Spatial Sensitivity for an Electrostatic Sensor.
The ring-shaped electrostatic sensor is a gas-solid flow measurement system, which has a problem of flow profile dependency. To deal with this problem, a method was introduced in this paper, which was to repeatedly use the successive "tails" of the sensor's overall output power spectrum to identify elementary frequency components corresponding to the equivalent roping flow streams. From the radial locations of these equivalent flow streams, the decomposed power frequency spectral components were then reweighted accordingly. Through such signal processing, an improved electrostatic sensor spatial sensitivity was achieved without modifying the sensor's structure. The method of interpolation was presented and discussed, and the effect of velocity profile on the proposed method was evaluated under different velocity profiles.


Evidence for nitric oxide mediated effects on islet hormone secretory phospholipase C signal transduction mechanisms.
We have investigated the putative role of nitric oxide (NO) as a modular of islet hormone release, when stimulated by the muscarinic receptor agonist phospholipase C activator, carbachol, with special regard to whether the IP3-Ca2+ or the diacylglycerol-protein kinase C messenger systems might be involved. It was observed that the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methylester (L-NAME) markedly potentiated insulin release and modestly inhibited glucagon release induced by carbachol. Similarly, insulin release induced by the phorbol ester TPA (protein kinase C activator) was markedly potentiated. Glucagon release, however, was unaffected. Dynamic perifusion experiments with 45C2+ -loaded islets revealed that the inhibitory action of L-NAME on carbachol-stimulated NO-production was reflected in a rapid and sustained increase in insulin secretion above carbachol controls, whereas the 45Ca2+ -efflux pattern was similar in both groups with the exception of a slight elevation of 45C2+ in the L-NAME-carbachol group during the latter part of the perifusion. No difference in either insulin release or 45Ca2+ -efflux pattern between the carbachol group and L-NAME-carbachol group was seen in another series of experiments with identical design but performed in the absence of extracellular Ca2+. However, it should be noted that in the absence of extracellular Ca2+ both 45Ca2+ -efflux and, especially, insulin release were greatly reduced in comparison with experiments in normal Ca2+. Further, in the presence of diazoxide, a potent K+ ATP-channel opener, plus a depolarizing concentration of K+ the NOS-inhibitor L-NAME still markedly potentiated carbachol-induced insulin release and inhibited glucagon release. The enantiomer D-NAME, which is devoid of NOS-inhibitory properties, did not affect carbachol-induced hormone release. TPA-induced hormone release in depolarized islets was not affected by either L-NAME or D-NAME. The pharmacological intracellular NO donor hydroxylamine dose-dependently inhibited insulin release stimulated by TPA. Furthermore, a series of perifusion experiments revealed that hydroxylamine greatly inhibited carbachol-induced insulin release without affecting the 45Ca2+ -efflux pattern. In summary, our results suggest that the inhibitory effect of NO on carbachol-induced insulin release is not to any significant extent exerted on the IP3-Ca2+ messenger system but rather through S-nitrosylation of critical thiol-residues in protein kinase C and/or other secretion-regulatory thiol groups. In contrast, the stimulating action of NO on carbachol-induced glucagon release was, at least partially, connected to the IP3-Ca2+ messenger system. The main effects of NO on both insulin and glucagon release induced by carbachol were apparently exerted independently of membrane depolarization events.


Treatment effects after maxillary expansion using invisalign first system vs. acrylic splint expander in mixed dentition: a prospective cohort study.
Invisalign First System (First) is a new type of orthodontic appliance for maxillary arch expansion in mixed dentition children. Till now, few studies have evaluated the expansion effects of First versus other appliances. What's more, most studies of arch expansion did not include a natural group to rule out growth effects. This prospective cohort study aimed to evaluate the dental and dentoalveolar effects using First or acrylic splint rapid maxillary expander (RME) in adolescents excluding growth factors. After screening by strict inclusion criteria and propensity score matching (PSM), fifty-one patients were included: First group (n = 17), RME group (n = 17), and natural growth (NG) group (n = 17). Nine indicators including dental arch width, dentoalveolar arch width, and inclination of the molars were measured on digital dental casts at baseline (T0) and six-month follow-up (T1). Paired t-tests were used for intra-group results, and two-sample independent t-tests were used for inter-group comparisons. There was no significant increase in all indicators within six months in the NG group (p > 0.05). In the First group and RME group, all width indicators were significantly increased after treatment (p < 0.05). The RME group exhibited greater expansion than the First group in intercanine width, first interpremolar width, second interdeciduous molar width, first intermolar width, arch perimeter, intercanine dentoalveolar width, intermolar dentoalveolar width, and inclination of the molars (p < 0.05). Whereas, there was no significant difference in arch depth between the two treated groups. Both First and RME can expand the maxillary arch in mixed dentition. In case of mild to moderate maxillary transverse deficiency (MTD), Invisalign First System could be a reasonable option. RME shows significant better efficiency of dental arch expansion than First, recommended for patients with severe MTD. This prospective study was registered on ClinicalTrials.gov (01/02/2022, registration number: ChiCTR2200056220). The trial was approved by the Ethical Committee of the Hunan Xiangya Stomatological Hospital Central South University (20,200,088), and informed consent was obtained from all subjects and their legal guardian(s).


[Methods for evaluation of the therapeutic properties of elastic stockings and compression bandages].
The advisability of examination of compressive bandages is discussed. The manner of the therapeutic action in changed leg venous system is given. The methods for examination of the elastic stockings and elastic bandages are presented.


Leader region of the gene encoding DNA polymerase III of Bacillus subtilis.
Previously we cloned and sequenced the polC gene of Bacillus subtilis and identified regions corresponding to various catalytic domains of DNA polymerase III, the enzyme it encodes. In the present study, by using primer extension, we have identified the transcription start site and a 139 nucleotide leader region upstream of the first codon. This region contains a DnaA box in the non-transcribed DNA strand. An RNA transcript of the leader would contain a sequence that could form a 29 bp stem-loop secondary structure followed by a strong terminator sequence, rich in uracil, before the ribosome binding site. Plasmids were constructed containing either the intact leader region or deletion mutations of the leader, fused to the Escherichia coli lacZ gene in an expression vector. Single copies of the fusions were then integrated into the B. subtilis genome by transformation. Studies of the expression of beta-galactosidase by the transformed cells supported the idea that the leader region is important in regulating polC gene expression.


Cold-induced ginsenosides accumulation is associated with the alteration in DNA methylation and relative gene expression in perennial American ginseng (Panax quinquefolius L.) along with its plant growth and development process.
Ginsenosides accumulation responses to temperature are critical to quality formation in cold-dependent American ginseng. However, the studies on cold requirement mechanism relevant to ginsenosides have been limited in this species. Two experiments were carried out: one was a multivariate linear regression analysis between the ginsenosides accumulation and the environmental conditions of American ginseng from different sites of China and the other was a synchronous determination of ginsenosides accumulation, overall DNA methylation, and relative gene expression in different tissues during different developmental stages of American ginseng after experiencing different cold exposure duration treatments. Results showed that the variation of the contents as well as the yields of total and individual ginsenosides Rg1, Re, and Rb1 in the roots were closely associated with environmental temperature conditions which implied that the cold environment plays a decisive role in the ginsenoside accumulation of American ginseng. Further results showed that there is a cyclically reversible dynamism between methylation and demethylation of DNA in the perennial American ginseng in response to temperature seasonality. And sufficient cold exposure duration in winter caused sufficient DNA demethylation in tender leaves in early spring and then accompanied the high expression of flowering gene PqFT in flowering stages and ginsenosides biosynthesis gene PqDDS in green berry stages successively, and finally, maximum ginsenosides accumulation occurred in the roots of American ginseng. We, therefore, hypothesized that cold-induced DNA methylation changes might regulate relative gene expression involving both plant development and plant secondary metabolites in such cold-dependent perennial plant species.


Widely divergent transcriptional patterns between SLE patients of different ancestral backgrounds in sorted immune cell populations.
Systemic lupus erythematosus (SLE) is a complex autoimmune disease of uncertain etiology. Patients from different ancestral backgrounds demonstrate differences in clinical manifestations and autoantibody profiles. We examined genome-wide transcriptional patterns in major immune cell subsets across different ancestral backgrounds. Peripheral blood was collected from African-American (AA) and European-American (EA) SLE patients and controls. CD4 T-cells, CD8 T-cells, monocytes, and B cells were purified by flow sorting, and each cell subset from each subject was run on a genome-wide expression array. Cases were compared to controls of the same ancestral background. The overlap in differentially expressed gene (DEG) lists between different cell types from the same ancestral background was modest (<10%), and only 5-8% overlap in DEG lists was observed when comparing the same cell type between different ancestral backgrounds. IFN-stimulated gene (ISG) expression was not up-regulated synchronously in all cell types from a given patient, for example a given subject could have high ISG expression in T and B cells, but not in monocytes. AA subjects demonstrated more concordance in ISG expression between cell types from the same individual, and AA patients demonstrated significant down-regulation of metabolic gene expression which was not observed in EA patients. ISG expression was significantly decreased in B cells in patients taking immunosuppressants, while ISGs in other cell types did not differ with medication use. In conclusion, gene expression was strikingly different between immune cell subsets and between ancestral backgrounds in SLE patients. These findings emphasize the critical importance of studying multiple ancestral backgrounds and multiple cell types in gene expression studies. Ancestral backgrounds which are not studied will not benefit from personalized medicine strategies in SLE.


Using simulation to design a central sterilization department.
A simulation project was performed to assist with redesign of the surgery department of a large tertiary hospital and to help administrators make the best decisions about relocating, staffing, and equipping the central sterilization department. A simulation model was created to analyze department configurations, staff schedules, equipment capacities, and cart-washing requirements. Performance measures examined include tray turnaround time, surgery-delay rate, and work-in-process levels. The analysis provides significant insight into how the proposed system will perform, allowing planning for expected patient volume increases. This work illustrates how simulation can facilitate the design of a central sterilization department and improve surgical sterilization operations.


Pressure-temperature control of activity of RNA polymerase ribozyme.
A representative role of nucleic acids (DNA and RNA) is in the storage of genetic information. In contrast, RNAs act as ribozymes that catalyze various biochemical reactions. The "RNA world" hypothesis suggests that the origin of life was RNA because a ribozyme that shows RNA replication activity has been identified. However, prebiotic conditions in the RNA world remain unknown. In this study, we investigated the effect of high pressure and temperature on RNA replication using an RNA polymerase ribozyme tC9Y. We found that pressure accelerated the RNA replication activity of tC9Y ribozyme at higher temperatures than physiological conditions. Furthermore, molecular crowding by concentrated polyethylene glycol 200 (average molecular weight 200) synergistically enhanced the replication activity at higher pressure and temperature because the negative effect of a volumetric contribution of hydration on the tC9Y ribozyme activity decreased under crowding conditions. As a comparison, proteinaceous RNA polymerase that exists in the modern era did not show accelerated activity under high pressure and temperature. Thus, these results imply that the prebiotic conditions for the RNA world were at high pressure and temperatures under crowding conditions.


Herbs for lochia discharge used among postpartum women in Taiwan.
In the traditional Taiwanese culture of "postpartum confinement", the term "lochia discharge" is a synonym for assisting postpartum uterine involution. Postpartum women in Taiwan consult traditional Chinese medicine (TCM) pharmacies to obtain various TCM formulations that facilitate lochia discharge. As an ethnopharmacy study, we aimed to conduct field investigations to explore the herbal composition of TCM formulations for lochia discharge provided by TCM pharmacies in Taiwan and to identify the pharmaceutical implications of these TCM formulations. Through stratified sampling, we collected 98 formulations for postpartum lochia discharge from TCM pharmacies, which used a total of 60 medicinal materials. The most common plant families of the medicinal materials found in Taiwanese lochia discharge formulations were Fabaceae and Lauraceae. Abiding by the TCM theory of nature and flavor, most drugs were warm in nature and sweet in flavor, and predominantly focused on the traditional functions of qi tonifying and blood activating. Correlation and network analyses of the medicinal components of lochia discharge formulations identified 11 core herbs, which, in the order of most to least frequently used, include Angelica sinensis, Ligusticum striatum, Glycyrrhiza uralensis, Zingiber officinale, Prunus persica, Eucommia ulmoides, Leonurus japonicus, Lycium chinense, Hedysarum polybotrys, Rehmannia glutinosa, and Paeonia lactiflora. These 11 herbs formed a total of 136 drug combinations in the 98 formulations, with 2-7 herbs in each combination. In addition, in the center of the network were A. sinensis and L. striatum, which jointly appeared in 92.8% of the formulations analyzed. To our knowledge, this is the first study to systematically review lochia discharge formulations in Taiwan. The results of this study could provide an important basis for subsequent research in the clinical efficacy of Taiwanese lochia discharge formulations and the pharmacological mechanisms of their herbal components.


Cigarette smoking damages women's reproductive life.
Female smokers experienced menopause significantly (P <or= 0.000001) earlier than non-smokers (47.1 +/- 3.3 versus 49.4 +/- 3.6 years, mean age at menopause +/- SD) and the prevalence of cigarette smoking is more frequent in females with ovarian failure before 46 years of age. These data are consistent with a possible detrimental effect of cigarette smoking on ovarian function and suggest new investigations are needed in this field. Detailed information about this important negative effect is strongly recommended, particularly for female smokers of reproductive age.


Role of PYK2 in the development of obesity and insulin resistance.
Non-receptor proline-rich tyrosine kinase-2 (PYK2), which is activated by phosphorylation of one or more of its tyrosine residues, has been implicated in the regulation of GLUT4 glucose transporter translocation and glucose transport. Some data favor a positive role of PYK2 in stimulating glucose transport, whereas other studies suggest that PYK2 may participate in the induction of insulin resistance. To ascertain the importance of PYK2 in the setting of obesity and insulin resistance, we (1) evaluated the regulation of PYK2 in mice fed a high-fat diet and (2) characterized body and glucose homeostasis in wild type (WT) and PYK2(-/-) mice on different diets. We found that both PYK2 expression and phosphorylation were significantly increased in liver and adipose tissues harvested from high-fat diet fed mice. Wild type and PYK2(-/-) mice were fed a high-fat diet for 8 weeks to induce insulin resistance/obesity. Surprisingly, in response to this diet PYK2(-/-) mice gained significantly more weight than WT mice (18.7+/-1.2g vs. 9.5+/-0.6g). Fasting serum leptin and insulin and blood glucose levels were significantly increased in high-fat diet fed mice irrespective of the presence of PYK2 protein. There was a close correlation between serum leptin and body weight. Intraperitoneal glucose tolerance tests revealed that as expected, the high-fat diet resulted in increased blood glucose levels following glucose administration in wild type mice compared to those fed normal chow. An even greater increase in blood glucose levels was observed in PYK2(-/-) mice compared to wild type mice. These results demonstrate that a lack of PYK2 exacerbates weight gain and development of glucose intolerance/insulin resistance induced by a high-fat diet, suggesting that PYK2 may play a role in slowing the development of obesity, insulin resistance, and/or frank diabetes.


Advances in chiral nanozymes: a review.
Nanomaterials with intrinsic enzymatic activity are often referred to as nanozymes. They exhibit many advantages over natural enzymes such as temporal and thermal stability, recyclability, controllable activity, and ease of large-scale preparation. Many efforts have been made in the past 5 years in order to improve their specificity for chiral substrates. This review (with 74 refs.) summarizes the state of the art in the design of nanozymes with chiral selectivity. Following an introduction into nanozymes and chiral selectivity in general, a first large section covers nanozymes based on the use of chiral chemicals. The next two sections describe nanozymes using amino acids and DNA as chiral ligands. A table summarizes the kinetic and selectivity parameters of the currently known chiral enzyme mimics. A concluding section addresses current challenges, and gives perspectives and an outlook on trends. Graphical abstract Chiral nanozymes exhibit the ability of asymmetric catalysis and enantioselective discrimination by modifying with chiral ligands.


A role of fas-associated death domain (FADD) in increased apoptosis in aged humans.
Fas-associated death domain (FADD) is an adapter protein that is recruited to the death-inducing signaling complex (DISC) during signaling via death receptors. FADD is a common conduit in both CD95-mediated and TNF-R-mediated apoptosis. In aging, T cells show increased susceptibility to death receptor-induced apoptosis. Therefore, in this investigation, we have examined the role of FADD in increased TNF-alpha-induced apoptosis of lymphocytes from aged humans. Our study shows that FADD expression is increased in lymphocytes from aged humans as compared to those from young subjects. Furthermore, transfection of aged lymphocytes with FADD dominant negative (FADD dn) plasmid resulted in the reduction of TNF-induced apoptosis in aged lymphocytes to a level comparable to that of young subjects. In addition, overexpression of FADD by transfection of lymphocytes from young subjects with wild-type FADD (FADD wt) resulted in increased apoptosis of young lymphocytes to a level comparable to that of young subjects. These data suggest that FADD plays an important role in increased apoptosis in aged lymphocytes signaled via TNF-R.


Melatonin protects against diazinon-induced neurobehavioral changes in rats.
Diazinon is an organophosphorous pesticide with a prominent toxicity on many body organs. Multiple mechanisms contribute to diazinon-induced deleterious effects. Inhibition of acetyl-cholinesterase, cholinergic hyperstimulation, and formation of reactive oxygen species may play a role. On the other hand, melatonin is a pineal hormone with a well-known potent antioxidant activity and a remarkable modulatory effect on many behavioral processes. The present study revealed that oral diazinon administration (25 mg/kg) increased anxiety behavior in rats subjected to elevated plus maze and open-field tests possibly via the induction of changes in brain monoamines levels (dopamine, norepinephrine, and serotonin). Additionally, brain lipid peroxides measured as malondialdehyde (MDA) and tumor necrosis factor alpha (TNF-α) levels were elevated, while the activity of brain glutathione peroxidase enzyme was reduced by diazinon. Co-administration of oral melatonin (10 mg/kg) significantly attenuated the anxiogenic activity of diazinon, rebalanced brain monoamines levels, decreased brain MDA and TNF-α levels, and increased the activity of brain glutathione peroxidase enzyme.


Determinants of stunting in children under five years old in South Sulawesi and West Sulawesi Province: 2013 and 2018 Indonesian Basic Health Survey.
The prevalence of stunting in South Sulawesi and West Sulawesi Province is relatively high. Studies reveal various household, parental, and child factors are associated with stunting. This paper aimed to determine the determinants of stunting among children under five in South and West Sulawesi Province using the 2013 and 2018 Indonesia Basic Health Survey. This study was a secondary data analysis using the 2013 and 2018 Indonesian Basic Health Surveys. The unit of analysis was children under five years, and the study obtained 3641 and 4423 children in South Sulawesi Province from the 2013 and 2018 Indonesia Basic Health Survey, respectively, and 804 and 1059 children from the 2013 and 2018 Indonesia Basic Health Survey in West Sulawesi Province, respectively. The multivariable poisson regression model was conducted to determine the determinants of stunting. The results showed that the mean age of children in South Sulawesi and West Sulawesi Province was 31.1 months and 30.8 months, respectively, on 2013 survey compare to 29.6 months and 29.1 months on the 2018 survey. The determinants of stunting in children under five in South Sulawesi Province in 2013 survey were household with two children under five (APR:1.24; 95% CI: 1.1-1.3; p-value = 0.006), maternal BMI (APR: 1.1; 95% CI: 1.03-1.1; p-value = <0.001), maternal weight (APR: 0.9; 95% CI: 0.94-0.97; p-value = <0.001), children aged 12-23 months (APR: 2.2; 95% CI: 1.7-2.7; p-value = <0.001), children aged 24-59 months (APR: 2.2; 95% CI: 1.8-2.7; p-value = <0.001), birthweight (APR: 1.9; 95% CI: 1.5-2.5; p-value = <0.001). In the 2018 survey, the determinants were maternal weight (APR: 0.9; 95% CI: 0.98-0.99; p-value = 0.005), mothers with no education or with education in primary school (APR: 1.5; 95% CI: 1.3-1.9; p-value = <0.001), mothers with education in middle school (APR: 1.3; 95% CI: 1.1-1.6; p-value = 0.014), mothers with a height less than 151 cm (APR: 1.3; 95% CI: 1.5-3.1; p-value = <0.001), mothers with a height of 151-160 cm (APR: 1.3; 95% CI: 1.1-1.6; p-value = 0.014), children aged 12-23 months (APR: 2.2; 95% CI: 1.7-2.8; p-value = <0.001), children aged 24-59 months (APR: 2.5; 95% CI: 2.0-3.2; p-value = <0.001)., birthweight (APR: 1.5; 95% CI: 1.2-1.9; p-value = <0.001). The determinants of stunting in children under five in West Sulawesi Province in 2013 survey were children under five years living in poor households (APR: 1.9; 95% CI: 1.1-3.3; p-value = 0.021), children under five who lived in a household with three or more children under five (APR:1.8; 95% CI: 1.2-2.7; p-value = 0.002), children aged 12-23 months (APR: 1.8; 95% CI: 1.2-2.6; p-value = 0.006), children aged 24-59 months (APR: 1.9; 95% CI: 1.3-2.7; p-value = 0.001). On the 2018 survey, the determinants were maternal BMI (APR: 1.02; 95% CI: 1.01-1.03; p-value = 0.004), maternal weight (APR: 0.9; 95% CI: 0.95-0.98; p-value = <0.001), mothers with no education or with education in primary school (APR: 1.9; 95% CI: 1.3-2.7; p-value = 0.001), mothers with education in middle school (APR: 1.9; 95% CI: 1.3-2.7; p-value = 0.001), mothers with education in high school (APR: 1.8; 95% CI: 1.2-2.6; p-value = 0.004), children aged 12-23 months (APR: 2.1; 95% CI: 1.4-3.0; p-value = <0.001), children aged 24-59 months (APR: 2.6; 95% CI: 1.9-3.6; p-value = <0.001), male (APR: 1.2; 95% CI: 1.01-1.4; p-value = 0.035), and acute respiratory infection (ARI) (APR: 1.6; 95% CI: 1.04-2.5; p-value = 0.030). The determinants of stunting in children under five in South Sulawesi Province are number of children under five in the household, maternal education, maternal weight, maternal height, maternal BMI, child's age, and birthweight. Meanwhile, the determinants of stunting in children under five in West Sulawesi were wealth, maternal education, maternal weight, maternal BMI,, child's age, child's sex, and history of acute respiratory infection. Hence, intervention on household and child levels as well as maternal sociodemographic factors need to be addressed.


Systematic review of qualitative literature on occupational health and safety legislation and regulatory enforcement planning and implementation.
The ability of occupational health and safety (OHS) legislation and regulatory enforcement to prevent workplace injuries and illnesses is contingent on political, economic, and organizational conditions. This systematic review of qualitative research articles considers how OHS legislation and regulatory enforcement are planned and implemented. A comprehensive search of peer-reviewed, English-language articles published between 1990 and 2013 yielded 11 947 articles. We identified 34 qualitative articles as relevant, 18 of which passed our quality assessment and proceeded to meta-ethnographic synthesis. The synthesis yielded four main themes: OHS regulation formation, regulation challenges, inspector organization, and worker representation in OHS. It illuminates how OHS legislation can be based on normative suppositions about worker and employer behavior and shaped by economic and political resources of parties. It also shows how implementation of OHS legislation is affected by "general duty" law, agency coordination, resourcing of inspectorates, and ability of workers to participate in the system. The review identifies methodological gaps and identifies promising areas for further research in "grey" zones of legislation implementation.


Short term use of intracavernous vasoactive drugs in the treatment of persistent psychogenic erectile dysfunction.
The objective of this retrospective study is to evaluate the effectiveness of short term intracavernous pharmacotherapy in the treatment of persistent psychogenic impotence. The study included 153 patients evaluated within an Andrology clinic in a general hospital working in close relation to three psychiatry clinics in three hospitals. Patients underwent an average of two office sessions of intracavernous injections for the selection of the appropriate intracavernous agent and dose, and for self injection training. Of the 153 patients included in our study 98 (64%) needed the injection for less than three months, only 18 (12%) patients needed the injections up to one year. We concluded that intracavernous self injection of vasoactive drugs is an effective alternative in the treatment of men with persistent psychogenic impotence when sex therapy is unsuccessful.


Phosphorylation of hydroxyproline in a synthetic peptide catalyzed by cyclic AMP-dependent protein kinase.
The cyclic AMP-dependent protein kinase catalyzes the phosphorylation of hydroxyproline present in the heptapeptide, Leu-Arg-Arg-Ala-Hyp-Leu-Gly. The Km value for the reaction with this substrate was high (approximately 18 mM) compared to the Km values reported for the analogous threonine and serine-containing peptides, which were 0.59 mM and 0.016 mM, respectively (Kemp, B.E., Graves, D.J., Benjamini, E., and Krebs, E.G. (1977) J. Biol. Chem. 252, 4888-4894). The Vmax value with the hydroxyproline-containing peptide was 1 mumol . min-1 mg-1 in contrast to Vmax values of 6 mumol . min-1 mg-1 and 20 mumol . min-1 mg-1 for the threonine- and serine-containing peptides, respectively. Phosphate esterified to hydroxyproline present in the peptide was relatively stable in hot alkali, only 10% being released as Pi within 30 min in 0.1 N NaOH at 100 degrees C, whereas all of the phosphate was released from the phosphoserine peptide analogue under these conditions. Phosphohydroxyproline in the peptide was also more stable to acid (5.7 N HCl, 110 degrees C) than phosphoserine, the time for 50% release as Pi being 15 h in contrast to 6 h for the latter.


Do women who consult with naturopaths or herbalists have a healthy lifestyle?: a secondary analysis of the Australian longitudinal study on women's health.
Australians report consulting with a naturopaths or herbalists to improve their wellbeing, yet little is known about the associations between these consultations and the patients' health behaviours. This cross-sectional study aimed to examine the relationship between health behaviour and consultations with naturopaths or herbalists in three age cohorts of Australian women. Women aged 19-25 years, 31-36 years, and 62-67 years from the Australian Longitudinal Study on Women's Health (ALSWH) were surveyed regarding smoking, alcohol or drug use, physical activity and dietary behaviour; and whether they consulted with naturopath/herbalists in the last 12 months. Associations were analysed using multivariable logistic regression. A total of 9151 (19-25 years), 8200 (31-36 years) and 11,344 (62-67 years) women were included in the analysis. Between 7.3 and 11.9% of women reported to have consulted with naturopaths/herbalists in the last 12 months. Women of all cohorts consulting with naturopath/herbalist were less likely to smoke (19-25 yrs.: Odds Ratio [OR] 0.61; 31-36 years: OR 0.58; 62-67 years: OR 0.29), more likely to report at least moderate levels of physical activity (19-25 yrs.: OR 1.41; 31-36 years: OR 1.34; 62-67 years: OR 1.34), and the use of vegetarian diets(19-25 yrs.: OR 1.40; 31-36 years: OR 1.77; 62-67 years: OR 2.28), compared to women not consulting with naturopaths/herbalists. Women consulting with naturopaths/herbalists however were also more likely to have used marijuana (19-25 yrs.: OR 1.18; 31-36 years: OR 1.42), or illicit drugs in the last 12 months (19-25 yrs.: OR 1.24; 31-36 years: OR 1.40). Consultations with a naturopath or herbalist are associated with positive health behaviours that are protective of internationally important non-communicable diseases. Psychoactive drug use is also reported among women visiting a naturopath or herbalist. Further research is needed to understand the role naturopaths play in advising patients with regards to health and non-healthy behaviours.


Long-term analysis of telescopic crown retained removable partial dentures: survival and need for maintenance.
The aim of this retrospective longitudinal study was to evaluate the clinical long-term survival of telescopic crown retained removable partial dentures (TRPDs), the influencing factors on survival as well as the type and number of necessary treatments during the observation time. The study is based on the data of 463 patients who had received a total of 554 TRPDs with a total of 1758 telescopic crowns between 1995 and 2004 in our Dental School. The influence of the patient's gender, location of the denture, number of abutment teeth per telescopic denture, their distribution (Kennedy-class) and the impact of a routinely follow-up programme on the survival probability were analysed. During the observation period (mean 5.3+/-2.9 years) 4.7% of the TRPDs ceased functioning and 3.8% of the abutment teeth were extracted. The survival probability after 5 years was 95.1% for the TRPDs and 95.3% for the abutment teeth. No denture with more than four abutments required replacement. Only the covariates number of abutment teeth and patient in-follow-up showed a significant (p<0.01) influence on the survival probability. 26.9% of the TRPDs needed facing repairs, 34.8% relines, 20.6% loss of cementation of a primary crown and 1% abutment tooth treatment. Within the limits of a retrospective study it can be concluded that the number of attachments and thorough aftercare have a considerable impact on the long-term success of TRPDs. Though loss of cementation and defects of the facings were significant in number, they did not endanger the long-term success of a TRPD at all.


The war of tools: how can NMR spectroscopists detect errors in their structures?
Protein structure determination by NMR methods has started in the mid-eighties and has been growing steadily since then. Ca. 14% of the protein structures deposited in the PDB have been solved by NMR. The evaluation of the quality of NMR structures however is still lacking a well-established practice. In this work, we examined various tools for the assessment of structural quality to ascertain the extent to which these tools could be applied to detect flaws in NMR structures. In particular, we investigated the variation in the scores assigned by these programs as a function of the deviation of the structures induced by errors in assignments or in the upper distance limits used. These perturbations did not distort radically the protein fold, but resulted in backbone RMS deviations up to 3 A, which is in line with errors highlighted in the available literature. We found that it is quite difficult to discriminate the structures perturbed because of misassignments from the original ones, also because the spread in score over the conformers of the original bundle is relatively large. varphi-psi distributions and normality scores related to the backbone conformation and to the distribution of side-chain dihedral angles are the most sensitive indicators of flaws.


American Society of Tropical Medicine and Hygiene--49th annual meeting.
This broad-based meeting covered all areas of tropical medicine, from basic science to clinical aspects, and focused on the perspectives from both Western travelers and public health strategies in developing countries. There was considerable interest in the development, assessment and implementation of antimalarial drug treatments, ranging from the most effective way to use existing compounds, to the strategic arguments associated with the desirability, feasibility and implementation of combination chemotherapy. Finally, attention was focused on the use of molecular markers to track and predict the emergence of antimicrobial drug resistance. Abstracts can be viewed on the ASTMH website, www.astmh.org, or obtained as a supplement to the American Journal of Tropical Medicine and Hygiene.


Use of the CHA2DS2-VASc score to predict subsequent myocardial infarction in atrial fibrillation.
The risk of subsequent myocardial infarction (MI) varies widely in patients with atrial fibrillation (AF). No convenient scoring system currently exists to identify MI in AF. While each element of the CHA2DS2-VASc (congestive heart failure; hypertension; age ≥75 years [doubled]; type 2 diabetes; previous stroke or thromboembolism [doubled]; vascular disease; age 65-75 years; and sex category) score can increase the likelihood of MI, this retrospective longitudinal study aimed to determine the accuracy of the CHA2DS2-VASc score in predicting subsequent MI risk in AF. A total of 29,341 patients with AF were enrolled and followed up from January 2010 until the first occurrence of MI or until December 2020. The primary endpoint was the occurrence of subsequent MI. The average age of the study population was 71 years, and 43.2% were male. The mean CHA2DS2-VASc score was found to be higher in patients with AF who had experienced an MI than in those who had not (3.56 ± 1.92 vs. 3.32 ± 1.81, p < 0.001). During the long-term follow-up, the risk of subsequent MI increased by 22% with every one-point increase in the CHA2DS2-VASc score (hazard ratio 1.22, 95% confidence interval 1.19-1.25; p < 0.001). Kaplan-Meier analysis revealed that high CHA2DS2-VASc scores were more likely to experience an MI than those with low CHA2DS2-VASc scores (log-rank p < 0.001). Furthermore, the CHA2DS2-VASc score was a significant predictor of MI in multivariate regression analysis. The CHA2DS2-VASc score is a valuable predictor of subsequent MI risk in patients with AF.


Dopamine, serotonin and impulsivity.
Impulsive people have a strong urge to act without thinking. It is sometimes regarded as a positive trait but rash impulsiveness is also widely present in clinical disorders such as attention deficit hyperactivity disorder (ADHD), drug dependence, mania, and antisocial behaviour. Contemporary research has begun to make major inroads into unravelling the brain mechanisms underlying impulsive behaviour with a prominent focus on the limbic cortico-striatal systems. With this progress has come the understanding that impulsivity is a multi-faceted behavioural trait involving neurally and psychologically diverse elements. We discuss the significance of this heterogeneity for clinical disorders expressing impulsive behaviour and the pivotal contribution made by the brain dopamine and serotonin systems in the aetiology and treatment of behavioural syndromes expressing impulsive symptoms.


Early Childhood Caries.
Early childhood caries (ECC) is a common childhood disease with highest prevalence found in poor, socially disadvantaged, and minority groups. The main risk factors for ECC are frequent sugar consumption, lack of tooth brushing, and enamel hypoplasia. Contributory factors include environmental and psychosocial stresses that modify caregiver behaviors. Strategies for prevention include preventing mutans streptococci transmission, restricting dietary sugars, tooth brushing, topical fluoride applications, and early dental examinations. This article provides an overview of ECC based on current understanding of its cause, prevention, and management.


Diversity of acetic acid bacteria present in healthy grapes from the Canary Islands.
The identification of acetic acid bacteria (AAB) from sound grapes from the Canary Islands is reported in the present study. No direct recovery of bacteria was possible in the most commonly used medium, so microvinifications were performed on grapes from Tenerife, La Palma and Lanzarote islands. Up to 396 AAB were isolated from those microvinifications and identified by 16S rRNA gene sequencing and phylogenetic analysis. With this method, Acetobacter pasteurianus, Acetobacter tropicalis, Gluconobacter japonicus and Gluconacetobacter saccharivorans were identified. However, no discrimination between the closely related species Acetobacter malorum and Acetobacter cerevisiae was possible. As previously described, 16S-23S rRNA gene internal transcribed spacer (ITS) region phylogenetic analysis was required to classify isolates as one of those species. These two species were the most frequently occurring, accounting for more than 60% of the isolates. For typing the AAB isolates, both the Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR and (GTG)5-PCR techniques gave similar resolution. A total of 60 profiles were identified. Thirteen of these profiles were found in more than one vineyard, and only one profile was found on two different islands (Tenerife and La Palma).


Salt-inducible kinase inhibition promotes the adipocyte thermogenic program and adipose tissue browning.
Norepinephrine stimulates the adipose tissue thermogenic program through a β-adrenergic receptor (βAR)-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling cascade. We discovered that a noncanonical activation of the mechanistic target of rapamycin complex 1 (mTORC1) by PKA is required for the βAR-stimulation of adipose tissue browning. However, the downstream events triggered by PKA-phosphorylated mTORC1 activation that drive this thermogenic response are not well understood. We used a proteomic approach of Stable Isotope Labeling by/with Amino acids in Cell culture (SILAC) to characterize the global protein phosphorylation profile in brown adipocytes treated with the βAR agonist. We identified salt-inducible kinase 3 (SIK3) as a candidate mTORC1 substrate and further tested the effect of SIK3 deficiency or SIK inhibition on the thermogenic gene expression program in brown adipocytes and in mouse adipose tissue. SIK3 interacts with RAPTOR, the defining component of the mTORC1 complex, and is phosphorylated at Ser884 in a rapamycin-sensitive manner. Pharmacological SIK inhibition by a pan-SIK inhibitor (HG-9-91-01) in brown adipocytes increases basal Ucp1 gene expression and restores its expression upon blockade of either mTORC1 or PKA. Short-hairpin RNA (shRNA) knockdown of Sik3 augments, while overexpression of SIK3 suppresses, Ucp1 gene expression in brown adipocytes. The regulatory PKA phosphorylation domain of SIK3 is essential for its inhibition. CRISPR-mediated Sik3 deletion in brown adipocytes increases type IIa histone deacetylase (HDAC) activity and enhances the expression of genes involved in thermogenesis such as Ucp1, Pgc1α, and mitochondrial OXPHOS complex protein. We further show that HDAC4 interacts with PGC1α after βAR stimulation and reduces lysine acetylation in PGC1α. Finally, a SIK inhibitor well-tolerated in vivo (YKL-05-099) can stimulate the expression of thermogenesis-related genes and browning of mouse subcutaneous adipose tissue. Taken together, our data reveal that SIK3, with the possible contribution of other SIKs, functions as a phosphorylation switch for β-adrenergic activation to drive the adipose tissue thermogenic program and indicates that more work to understand the role of the SIKs is warranted. Our findings also suggest that maneuvers targeting SIKs could be beneficial for obesity and related cardiometabolic disease.


Acquired long QT syndrome in hospitalized patients.
Acquired long QT syndrome (ALQTS) has long been overlooked in clinical practice. Recent studies reported that severe ALQTS (QTc ≥500 ms) in hospitalized patients is associated with increased all-cause mortality. The purpose of this study was to determine the role of ALQTS in the clinical outcomes of hospitalized patients. Electronic medical records were reviewed to identify severe ALQTS in hospitalized patients in a single study center from September 1, 2013, to February 28, 2014. Up to 1-year follow-up was conducted in the ALQTS subjects and compared with age-, gender-, and admitting diagnosis-matched hospitalized patients with a normal QT interval. Severe ALQTS (QTc 529 ± 38 ms) was seen in 0.7% (293/41,649) of hospitalized patients, of whom 86% were treated in noncardiology departments. All-cause mortality was 32% in the ALQTS group vs 14% in the control group (P <.001) during follow-up of 255 ± 63 days. Syncope and life-threatening ventricular arrhythmia were more frequent in patients with severe ALQTS (6% vs 0.6%, P <.0001). Cerebral hemorrhage (odds ratio [OR] 6.405, 95% confidence interval [CI] 2.341-17.525), cancer (OR 5.937, 95% CI 2.658-13.260), infection (OR 2.207, 95% CI 1.124-4.333), and end-stage disease (OR 2.092, 95% CI 1.045-4.191) are the major contributors to all-cause mortality in ALQTS. Severe ALQTS is not uncommon in hospitalized patients. It can be easily overlooked because the majority of patients with severe ALQTS are treated in noncardiology departments. The clinical outcome of severe ALQTS is poor. Removing QT-prolonging factors may reduce the risks of fatal arrhythmia and sudden death in patients with ALQTS.


The structure of Bacillus subtilis RecU Holliday junction resolvase and its role in substrate selection and sequence-specific cleavage.
We have determined the structure of the enzyme RecU from Bacillus subtilis, that is the general Holliday junction resolving enzyme in Gram-positive bacteria. The enzyme fold reveals a striking similarity to a class of resolvase enzymes found in archaeal sources and members of the type II restriction endonuclease family to which they are related. The structure confirms the presence of active sites formed around clusters of acidic residues that we have also shown to bind divalent cations. Mutagenesis data presented here support the key role of certain residues. The RecU structure suggests a basis for Holliday junction selectivity and suggests how sequence-specific cleavage might be achieved. Models for a resolvase-DNA complex address how the enzyme might organize junctions into an approximately 4-fold symmetric form.


Engineering receptors and antibodies for biosensors.
Biosensor sensitivity and selectivity depend essentially on the properties of the biorecognition elements to be used for analyte binding. Two principally different applications are considered, (1) effects monitoring with biological components as targets for bioeffective substances, among them endocrine disruptors; and (2) immunochemical analysis employing antibodies as binding proteins for a wide variety of analytes such as pesticides. Genetic engineering provides an elegant way not only for providing unlimited amounts of biorecognition molecules but also for the alteration of existing properties and the supplementation with additional functions. Instrumental applications were carried out with the optical sensor BIAcore. The first example deals with the characterization of receptors. For this purpose, the human estrogen receptor alpha was used. Binding studies were carried out with natural as well as xenoestrogens. An equilibrium dissociation constant K(d) of 2.3x10(-10) (M) was derived for 17beta-estradiol. A competition assay was performed with a bovine serum albumin (BSA)-17beta-estradiol conjugate, immobilized at the optical sensor surface, and the free estrogen. The signals obtained represent estradiol equivalents. This format was transferred to a microplate-based enzyme-linked receptor assay. It reached a detection limit of 0.02 microg l(-1) 17beta-estradiol and proved suitable for the detection of natural and synthetic estrogens as well as xenoestrogens in field studies. The second example is targeted at kinetic and affinity measurements of recombinant antibody fragments derived from antibody libraries with s-triazine selectivities. Different strategies for the synthesis of antibody fragment libraries, followed by the selection of specific antibody variants, were examined. An antibody library was derived from a set of B cells. Chain shuffling of the heavy and light chains provided the best binders. An enzyme linked immunosorbent assay (ELISA) was achieved for atrazine with an IC(50) of 0.9 microg l(-1) and a detection limit of 0.2 microg l(-1). The close relations between the optimization of recombinant antibodies by evolutionary strategies and genetic algorithms are considered.


Antimalarial drugs inhibit the replication of SARS-CoV-2: An in vitro evaluation.
In December 2019, a new severe acute respiratory syndrome coronavirus (SARS-CoV-2) causing coronavirus diseases 2019 (COVID-19) emerged in Wuhan, China. African countries see slower dynamic of COVID-19 cases and deaths. One of the assumptions that may explain this later emergence in Africa, and more particularly in malaria endemic areas, would be the use of antimalarial drugs. We investigated the in vitro antiviral activity against SARS-CoV-2 of several antimalarial drugs. Chloroquine (EC50 = 2.1 μM and EC90 = 3.8 μM), hydroxychloroquine (EC50 = 1.5 μM and EC90 = 3.0 μM), ferroquine (EC50 = 1.5 μM and EC90 = 2.4 μM), desethylamodiaquine (EC50 = 0.52 μM and EC90 = 1.9 μM), mefloquine (EC50 = 1.8 μM and EC90 = 8.1 μM), pyronaridine (EC50 = 0.72 μM and EC90 = 0.75 μM) and quinine (EC50 = 10.7 μM and EC90 = 38.8 μM) showed in vitro antiviral effective activity with IC50 and IC90 compatible with drug oral uptake at doses commonly administered in malaria treatment. The ratio Clung/EC90 ranged from 5 to 59. Lumefantrine, piperaquine and dihydroartemisinin had IC50 and IC90 too high to be compatible with expected plasma concentrations (ratio Cmax/EC90 < 0.05). Based on our results, we would expect that countries which commonly use artesunate-amodiaquine or artesunate-mefloquine report fewer cases and deaths than those using artemether-lumefantrine or dihydroartemisinin-piperaquine. It could be necessary now to compare the antimalarial use and the dynamics of COVID-19 country by country to confirm this hypothesis.


Massively parallel manipulation of single cells and microparticles using optical images.
The ability to manipulate biological cells and micrometre-scale particles plays an important role in many biological and colloidal science applications. However, conventional manipulation techniques--including optical tweezers, electrokinetic forces (electrophoresis, dielectrophoresis, travelling-wave dielectrophoresis), magnetic tweezers, acoustic traps and hydrodynamic flows--cannot achieve high resolution and high throughput at the same time. Optical tweezers offer high resolution for trapping single particles, but have a limited manipulation area owing to tight focusing requirements; on the other hand, electrokinetic forces and other mechanisms provide high throughput, but lack the flexibility or the spatial resolution necessary for controlling individual cells. Here we present an optical image-driven dielectrophoresis technique that permits high-resolution patterning of electric fields on a photoconductive surface for manipulating single particles. It requires 100,000 times less optical intensity than optical tweezers. Using an incoherent light source (a light-emitting diode or a halogen lamp) and a digital micromirror spatial light modulator, we have demonstrated parallel manipulation of 15,000 particle traps on a 1.3 x 1.0 mm2 area. With direct optical imaging control, multiple manipulation functions are combined to achieve complex, multi-step manipulation protocols.


Viral IL-10 promotes cell proliferation and cell cycle progression via JAK2/STAT3 signaling pathway in nasopharyngeal carcinoma cells.
Epstein-Barr virus (EBV) is positively related to the morbidity of nasopharyngeal carcinoma (NPC) in Asia. After infection, EBV can produce several proteins, including viral interleukin-10 (vIL-10). But the mechanism by which vIL-10 contributes to NPC cell proliferation and cell cycle progression is not well understood. In this study, EBV negative and positive cell lines, and the JAK2/STAT3 signal pathway inhibitor AG490 were used to illustrate the role of vIL-10 in NPC. Cell proliferation and cell cycle were measured by CCK-8 and flow cytometry. The expression levels of related protein were measured by Western blotting. High concentrations of vIL-10 and IL-6 were found in the EBV positive patients. The expression level of IL-6 was positively related to the presence of concentration of vIL-10. vIL-10 can promote cancer cell proliferation and G1 to S phase transmission via upregulating the IL-6 protein level by activating the JAK2/STAT3 signal pathway. Furthermore, EBV can induce the formation of cytotoxic T cells, whereas vIL-10 can block the function of cytotoxic T cells. Taken together, these results suggest that vIL-10 promotes cell proliferation and cell cycle progression via JAK2/STAT3 signaling pathway in NPC.


Determination of a common genetic variant of luteinizing hormone using DNA hybridization and immunoassays.
An immunologically anomalous form of LH, due to two point mutations in codons 8 and 15 of the LH beta gene, has previously been described. LH status, i.e. the discrimination between wild-type (WT) and variant (V) LH, is usually determined by immunoassays, which can be unreliable at low serum concentrations of LH. A DNA hybridization assay was therefore developed to score the LH genotype in all subjects, independent of their serum LH concentrations. To evaluate the performance of the hybridization method, and to expand our observations of the worldwide occurrence of the V-LH, we determined its frequency in additional populations. To confirm the connection between the anomalous immunoreactivity and the V-LH beta gene, we also sequenced the LH beta subunit gene of a homozygous person. According to the ratio of two immunoassays, one detecting only WT-LH and the other detecting equally WT and V-LH, individuals can be classified as homozygotes for the V-LH beta allele, heterozygotes or WT. DNA samples from persons with known LH status, according to the immunoassays, were used for the development and evaluation of a new allele-specific DNA hybridization assay. This assay, and PCR and restriction fragment length polymorphism analysis, were used to determine the frequency of the V-LH beta allele in DNA samples obtained from eight populations. Ambulatory adult men and women, apparently healthy and with no endocrine disorders. The LH genotyping by immunoassays and by the new hybridization method gave identical results with all samples analysed (n = 25). The V-LH beta subunit was observed to always have the two point mutations, and to be identical with the ones previously reported. The V-LH beta carrier frequency in the DNA samples collected from various populations varied between 0 and 53.5%. The immunoassay technique and the hybridization assay can be used as alternatives to determine the LH status. A great variation in carrier frequency of the V-LH beta allele is observed in different populations.


Syringenes M - Q, Eremophilane Sesquiterpenoid Dimers from the Peeled Stems of Syringa pinnatifolia.
As a part of systematic studies on Syringa pinnatifolia, a continued phytochemical investigation guided by 1 H-NMR and LC/MS data on the ethanol extract afforded five new dimeric eremophilane sesquiterpenoids, namely syringenes M-Q (1-5). These structures were elucidated by extensive analysis of spectroscopic data, including infrared (IR), high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), nuclear magnetic resonance (NMR), quantum-mechanics-based computational analysis of NMR chemical shifts, and single-crystal X-ray diffraction. Compounds 4 and 5 showed inhibitory activities against NO production induced by lipopolysaccharide in RAW264.7 macrophage cells, with IC50 values of 5.1 and 9.3 μM, compared to positive control indomethacin (IC50 33.6 μM). These dimeric eremophilane sesquiterpenoids may be potential markers for discriminating this species from the genus Syringa and the Oleaceae family.


An ab initio computational molecular orbital study of the conformers of muconaldehyde, and the possible role of 2-formyl-2H-pyran in bringing about the conversion of a (Z,Z)-muconaldehyde structure into an (E,Z)-muconaldehyde structure.
To determine whether conformers of 2-formyl-2H-pyran (2F2HP) can serve as intermediates in the isomerization (Z,Z)-muconaldehyde-->(E,Z)-muconaldehyde--an essential step in the metabolic oxidation of benzene in which (E,E)-muconic acid is formed--we have carried out ab initio molecular orbital calculations at the MP2/6-31G* (frozen core, valence orbitals active) level with full geometry optimization at the RHF/6-31G* level. Taking account of the configuration about the carbon-carbon single bonds as well as that about the double bonds, the six conformers of (Z,Z)-muconaldehyde have been characterized, as well as the eight conformers of (E,Z)-muconaldehyde. Axial and equatorial conformers of 2F2HP have been identified, which exist in stable syn or anti forms depending on the relative position of the pyran and carbonyl O-atoms. Each step in the metabolic pathway is stereospecific. The initial ring opening in 2,3-epoxyoxepin gives (eZzZz)-muconaldehyde, which then undergoes ring closure to give anti-axial-2F2HP (step a). Inversion of the ring gives anti-equatorial-2F2HP, which upon ring opening gives (zEzZz)-muconaldehyde (step b). An alternative pathway links (zZzZz)-muconaldehyde with syn-axial-2F2HP (step a'), and syn-equatorial with (eEzZz)-muconaldehyde (step b'). Half-reaction times, taking into account the fractional representation of each reacting conformer in rapidly established equilibrium mixtures, suggest that the operative pathway is via step a, with little to choose between steps b and b'.


Mushroom poisoning cases in dogs and cats: diagnosis and treatment of hepatotoxic, neurotoxic, gastroenterotoxic, nephrotoxic, and muscarinic mushrooms.
Of the several thousand species of mushrooms found in North America, less than 100 are toxic. Species in the genus Amanita are responsible for the vast majority of reported mushroom poisonings. In general, the number of reported mushroom poisonings in animals is low, most likely because toxicology testing is available for a limited number of mushroom toxins and thus many cases are not confirmed or reported. Also, only a limited number of mushrooms are submitted for identification purposes. Mushroom intoxications require tremendous efforts from clinicians and toxicologists in terms of making a diagnosis and treatment, and management is challenging.


Subscapularis sparing total shoulder arthroplasty through a superolateral approach: a radiographic study.
Most anatomic total shoulder arthroplasty (ATSA) techniques release and reattach the subscapularis tendon. The risk of failed healing is a widely recognized complication. The purpose of this study was to radiographically compare a traditional deltopectoral (DP) approach and a superolateral subscapularis sparing (SSS) technique through the rotator interval. A single, independent, blinded, reviewer analyzed preoperative and postoperative radiographs of patients undergoing ATSA performed by a single surgeon. The reviewer assessed humeral head height, humeral head medial offset, humeral head diameter, head-neck angle, humeral head centering, and coracohumeral offset, and used the anatomic reconstruction index (ARI) to evaluate overall reconstruction quality. There were 70 SSS and 20 DP patients included. When comparing preoperative with postoperative differences, we found that there was no difference between groups in humeral head height (P = .19), humeral head medial offset (P = .38), and coracohumeral offset (P = .07). The DP group had a mean humeral head diameter oversizing of 1.4 mm, whereas the superolateral group had an undersizing of 2.8 mm (P < .001). The head-neck angle difference of the SSS approach was 2° greater than that found with the DP group (P < .001). The humeral head centering in the DP group was 7% displaced vs. 12% with the SSS group (P = .001) relative to the glenoid size. The ARI was 7.35 for the DP group and 6.93 for the SSS group (P = .50). Radiographic comparison of these 2 ATSA techniques identified no statistical significant difference in 4 of 7 radiographic measurements and ARI. The SSS ATSA is a reasonable approach that yields similar radiographic measurements as a traditional DP total shoulder arthroplasty approach.


Induction of fusion in aggregated and nonaggregated liposomes bearing cationic detergents.
The addition of polyanionic polymers such as poly(aspartic acid) (PASP), DNA or dextran sulfate to liposomes composed of phosphatidylcholine (PC) and cholesterol (CHOL) and bearing the quaternary ammonium detergent [[[(1,1,3,3-tetramethylbutyl)cresoxy]ethoxy]ethyl]dimethy lbe nzylammonium hydroxide (DEBDA[OH]) resulted in liposome aggregation and fusion. Liposome-liposome fusion was studied by using fluorescently labeled liposomes and fluorescence-dequenching (DQ) methods. Addition of monoanions, such as aspartate or acetate, to liposomes bearing DEBDA[OH] caused neither their aggregation nor liposome-liposome fusion. Aggregation of liposomes bearing DEBDA[OH] by the binding pair avidin-biotin did not result in their fusion. Fusion in such aggregated liposomes was observed by the addition of chaotropic anions, such as nitrate or thiocyanate, or by PASP. A variety of other quaternary ammonium detergents behaved similarly to DEBDA[OH] in their ability to confer fusogenic properties upon PC/chol liposomes. The relevance of these findings to the mechanism of liposome-liposome fusion is discussed.


Reflectance confocal microscopy of facial neoplasms: Follicular involvement as a clue to diagnosis.
Facial skin is characterized by high density of follicles. Facial neoplasms may present overlapping clinical and dermoscopic findings. Our goal was to evaluate and compare, via reflectance confocal microscopy (RCM), follicular involvement in facial neoplasms. We retrospectively searched our image database, between January 2008 and December 2020, for all facial lesions with (1) a standardized set of clinical, dermoscopic, and RCM images, and (2) a biopsy-proven diagnosis of lentigo maligna/lentigo maligna melanoma (LM/LMM, n = 39), basal cell carcinoma (BCC, n = 51), squamous cell carcinoma in situ (SCCIS, n = 5), actinic keratosis (AK, n = 11), and lichen-planus-like keratosis (LPLK, n = 18). Two readers jointly evaluated the RCM images for a set of predefined features of follicular involvement. Diffuse obliteration of follicles was frequent in BCC (88%), while follicular infiltration by refractile dendritic cells and/or by bright round nucleated cells was common in melanoma (90% and 44%, respectively). Extension of atypical keratinocytes down follicles was more prominent among SCCIS than AK (80% vs. 45%, p = 0.01). In most LPLK (89%), there was follicular sparing. Evaluation of RCM criteria centering on the follicles can be useful in the differential diagnosis between common facial neoplasms.


Macular thickness and aging in retinitis pigmentosa.
This study was designed to analyze macular tomography in patients of different ages with retinitis pigmentosa (RP) and correlate their visual function with macular thickness, which was measured by optical coherence tomography. In all, 75 RP patients and 75 controls were stratified into three age groups and macular thickness was measured by optical coherence tomography. The tomography was subdivided into three circular zones, four quadrants, and nine areas for analysis. Ophthalmic examinations, which involved ophthalmoscopic examinations, dark adaptation tests, visual acuities, visual field examinations, electrooculography, and color sense discrimination tests, were performed. Macular thickness of the RP patients decreased in the middle age group (45- to 55-year old), whereas the oldest group showed an increased thickness. The thickness of the outer inferior area remained virtually unchanged, whereas the thickness of the inner temporal area showed the most fluctuation with age. In terms of circular sections, the most dramatic changes in macular thickness were observed in the fovea, and the aging effect decreased outward to the outer ring. Furthermore, the thickness of the fovea was more important than the thickness of the inner ring and the outer ring for electrooculography, visual acuity, and color sense discrimination in RP patients. In middle age RP patients, the macular thickness decreased, whereas an increased thickness was observed in patients older than 55 years. In addition, the inner temporal area was the most fragile, and the outer inferior area was the least affected in patients with RP.


Teledermatology in the time of COVID-19.
The enormous spread of the novel Corona virus disease (COVID-19) represents a challenge to dermatological practice. Accumulating evidence has suggested a possible role of teledermatology in facing this challenge. In this article, we aimed to give a general overview of teledermatology in terms of models of practice, modes of delivery, advantages, limitations, ethical considerations and legislative challenges as well as discussing, using examples from literature, how dermatological practice can benefit from teledermatology during the time of the COVID-19 pandemic. Teledermatology could be an accessible, accurate and cost-effective substitute for conventional face-to-face dermatological consultations during the COVID-19 pandemic. However, teledermatology practice needs updated legislation and guidelines. More efforts should be done to encourage dermatologists, especially in underserved communities, to provide teledermatology services. Ethical issues and data security related to teledermatology have to be considered.


Heads, stalks and everything else: how can antibodies eradicate influenza as a human disease?
Current seasonal influenza virus vaccines are effective against infection but they have to be reformulated on a regular basis to counter antigenic variations. The majority of the antibodies induced in response to seasonal vaccination are strain-specific. However, antibodies targeting conserved epitopes on the hemagglutinin protein have been identified and they offer broad protection. Most of these antibodies bind the hemagglutinin stalk domain and are generated from preexisting memory B cells. Broadly protective stalk-biased responses induced by antigenically divergent influenza strains, in concert with prior immunity, are sufficient to eradicate seasonally circulating strains. Future vaccine trials should aim to harness and maintain such a response with the realistic goal of developing a universal influenza vaccine.