Testicular ischemia secondary to epididymo-orchitis: A case report.
Testicular infarction is a common urological emergency in clinical practice, it is still underreported when it results from other than spermatic cord torsion. It rarely arises from other pathological processes like vasculitis and infectious disease. We report a case of 18-year-old with epididymo-orchitis complicated by testicular ischemia. This case accentuates the need for a high index of suspicion to rule out concomitant testicular ischemia secondary to epididymo-orchitis that might be salvaged in the future with immediate surgical intervention. Testicular infarction is a devastating complication from epididymo-orchitis that is difficult to predict and distinguish from more common presentations of acute scrotum.


Urothelial carcinoma involving vaginal specimens from patients with neobladder: a potential pitfall in diagnostic cytopathology.
Most vaginal neoplasms represent metastasis from the cervix, endometrium, colon and ovary and distinction from a primary lesion does not pose a diagnostic problem. Recently, it has been recognized that women with urothelial carcinoma (UC) who have undergone radical cystectomy with orthotopic neobladder reconstruction are at risk for recurrence in the lower gynecologic tract. Our objective is to describe the cytologic features of cases with confirmed UC in the vagina in this clinical setting. Four vaginal specimens from patients with prior radical cystectomy and orthotopic neobladder reconstruction with histologically confirmed UC were evaluated. The vaginal specimens consisted of Thinprep® and Papanicolaou-stained slides. Cytomorphologic parameters including cellular arrangement, cell size and shape, cytoplasm, and nuclear features were evaluated and compared with a corresponding surgical biopsy. All four cases were highly cellular with abundant neoplastic cells arranged singly and in loose three-dimensional clusters with overlapping nuclei. The neoplastic cells were large and polygonal with well-defined cell borders, high nuclear to cytoplasmic ratio, and granular basophilic cytoplasm. The chromatin was coarse with small nucleoli. Scattered keratinized single cells with atypical hyperchromatic nuclei were observed in each case. In summary, UC involving the vagina can share many morphologic features with primary squamous cell carcinomas at this site, including focal keratinization. Abundant three dimensional clusters of neoplastic cells and a previous history of orthotopic neobladder reconstruction are helpful cytomorphologic and clinical features supporting a diagnosis of UC involving the vagina and may prevent unnecessary work-up for a new primary lesion.


Author Correction: Historical analysis of national subjective wellbeing using millions of digitized books.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Being an ethnic minority nursing student - A meta synthesis.
Our society is characterized by a general globalization and has become more culturally diverse. This diversity is mirrored in nursing education. The purpose of the meta-synthesis is to identify and synthesize data from primary, qualitative studies of ethnic minority nursing students' experiences in a nursing program. Electronic databases, Medline, Embase, and CINAHL, were searched for studies published in English or Nordic languages from 1980 to February 2020. The search generated 1070 unique citations, of which 19 articles met the inclusion criteria. The included studies had a total sample size of 255 students, age range 19-50 years. The participants originated from Asia (65), Africa (53), South America (45), and Eastern Europe (17). Seventy-five students' origins were unknown. The meta-synthesis revealed that participants' experiences were characterized by four main themes: to understand and be understood; the importance of supportive relations; motivated but emotionally distressed; and conflicting cultural expectations. Ethnic minority nursing students experienced challenges related to language, socialization, cultural awareness, and relations with educators and other students. To meet the students' needs and increase their graduation rates, educational institutions and supervisors should work to promote and facilitate their integration and provide a good learning environment.


Comparison of the results of stop-start technique with stop-start technique and sphincter control training applied in premature ejaculation treatment.
The aim of this study is to compare the results of stop-start technique with stop-start technique together with sphincter control training applied in the treatment of premature ejaculation. This research was conducted as a pre-test post-test quasi-experimental study. The sample of the study consisted of 80 men. The study was conducted on men who applied to the urology outpatient clinic of LIV Hospital, a prıvate hospital, in Gaziantep, Turkey, between 01 October 2021 and 01 March 2022. "Personal Information Form", "Intravaginal Ejaculation Latency Time (IELT)", "Fold Increase Intravaginal Ejaculation Latency Time (F-IELT)" "Premature Ejaculation Diagnostic Tool (PEDT) Questionnaire" and "Arabic Index Premature Ejaculation (AIPE)" were used as the data collection tools. Behavioral therapy, consisting of a total of 6 sessions, was applied once every two weeks, with each session lasting for 45 minutes. After 3rd and 6th months from the beginning of the application, the data collection tools were applied again. "Stop-Start Technique (Group A)" and "Stop-Start Technique and Sphincter Control Training (Group B)" were used in the treatment. In both groups, the IELT and AIPE values after 3rd and 6th months from the beginning of the application were statistically higher than those obtained before (p<0.05). IELT and AIPE values increased more in Group B than Group A (p<0.05). F-IELT values after 6th months from the beginning of the application were found to be statistically significant with a low level of effect size than those obtained before (p<0.05, Cohen's d = 0.027). In both groups, the PEDT values in the 3rd and 6th months after the application were statistically lower than those seen before (p<0.05). PEDT value decreased more in Group B than Group A (p<0.05). The differences between the two groups' IELT (Cohen's d = 0.011), AIPE (Cohen's d = 0.044), and PEDT (Cohen's d = 0.066) values in the 3rd month after the application and IELT (Cohen's d = 0.025), AIPE (Cohen's d = 0.048), and PEDT (Cohen's d = 0.024) values in the 6th month after the application were found to be clinically weak. It was determined that the stop-start technique given to men with premature ejaculation increased the time spent in the vagina and eliminated the problem of premature ejaculation. It was determined that the stop-start technique in combination with sphincter control training were more effective than the stop-start technique alone.


Behavioral symptoms in mild cognitive impairment as compared with Alzheimer's disease and healthy older adults.
Mild cognitive impairment (MCI) is a clinical concept that categorizes subjects who are in an intermediate cognitive state between normal aging and dementia. The aim of this study is to characterize behavior in MCI compared with Alzheimer's disease (AD) and healthy older patients. A cross-sectional analysis of baseline data from a prospective, longitudinal study on behavioral symptoms of dementia and MCI was performed. The study population consisted of 270 MCI, 402 AD patients, and 108 healthy controls. Behavioral assessment was performed by means of Middelheim Frontality Score, Behavioral Pathology in Alzheimer's Disease Rating Scale, Cohen-Mansfield Agitation Inventory, and Cornell Scale for Depression in Dementia. Moderate-to-severe behavioral symptoms were present in 13% of MCI patients, as compared with 39% in AD patients and 3% in controls (p < 0.001). The general severity of behavioral symptoms was intermediate between controls and AD patients. The three most frequent symptoms in MCI patients were aggressiveness (49%), affective disturbance (45%), and anxiety (38%); in AD patients, the most frequent symptoms were aggressiveness (60%), activity disturbances (54%), and psychosis (40%). The prevalence and severity of frontal lobe symptoms, aggressiveness, activity disturbances, and delusions was intermediate between normal aging and AD. In addition, the severity of physically non-aggressive and verbally agitated behavior and the severity of depressive symptoms were also intermediate. The behavioral profile of MCI patients is characterized as an intermediate state between normal aging and AD for the prevalence and severity of certain behavioral symptoms. Follow-up is ongoing to test the hypothesis that behavioral disturbances in MCI predict progression to dementia.


Brain tumor image generation using an aggregation of GAN models with style transfer.
In the recent past, deep learning-based models have achieved tremendous success in computer vision-related tasks with the help of large-scale annotated datasets. An interesting application of deep learning is synthetic data generation, especially in the domain of medical image analysis. The need for such a task arises due to the scarcity of original data. Class imbalance is another reason for applying data augmentation techniques. Generative Adversarial Networks (GANs) are beneficial for synthetic image generation in various fields. However, stand-alone GANs may only fetch the localized features in the latent representation of an image, whereas combining different GANs might understand the distributed features. To this end, we have proposed AGGrGAN, an aggregation of three base GAN models-two variants of Deep Convolutional Generative Adversarial Network (DCGAN) and a Wasserstein GAN (WGAN) to generate synthetic MRI scans of brain tumors. Further, we have applied the style transfer technique to enhance the image resemblance. Our proposed model efficiently overcomes the limitation of data unavailability and can understand the information variance in multiple representations of the raw images. We have conducted all the experiments on the two publicly available datasets - the brain tumor dataset and the Multimodal Brain Tumor Segmentation Challenge (BraTS) 2020 dataset. Results show that the proposed model can generate fine-quality images with maximum Structural Similarity Index Measure (SSIM) scores of 0.57 and 0.83 on the said two datasets.


Business of radiology 101: the state of radiology business practice and health care policy curricula at US radiology residency programs.
The aim of this study was to assess the prevalence, content, and perceptions of curricula focused on radiology business practice and health care policy at US radiology residency training programs. The desired survey population was trainees and faculty members of radiology residency programs in the United States. Three anonymous survey instruments were distributed, including an e-mail survey to the membership of the ACR RFS, a paper survey to ACR RFS delegates attending the 2010 AMCLC, and an e-mail survey to the membership of the Association of Program Directors in Radiology (APDR). Response rates for the surveys were 12%, 25%, and 21%, respectively. Members of the APDR and RFS agreed that understanding and competency in business practice and health care policy topics are important to the future careers of residents (total favorable sentiment >86% for APDR members and >96% for RFS members). Most survey respondents' home institutions offer some form of a noninterpretive curriculum (91% of APDR respondents, 74% of RFS respondents), but the breadth of topics addressed and educational time devoted to these curricula were quite variable. Subjective effectiveness of curricula was infrequently rated as very effective by 12% of APDR respondents and 6% of RFS respondents. Despite the perceived importance of radiology business practice and health care policy education, and residency training requirements in competencies related to these subjects that have been in place for more than a decade, curricula addressing these items still seem to be in a stage of acceptance and development. Further commitment to and innovation within these curricula are requisite in educating our future radiologists.


Design, synthesis and evaluation of novel bis-substituted aromatic amide dithiocarbamate derivatives as colchicine site tubulin polymerization inhibitors with potent anticancer activities.
As the continuation of our work on the development of tubulin inhibitors with potential anticancer activities, novel bis-substituted aromatic amide dithiocarbamate derivatives were designed by contacting bis-substituted aryl scaffolds (potential anti-tubulin fragments) with N-containing heterocycles (potential anti-tubulin fragments) in one hybrid using the anticancer dithioformate unit as the linker. The antiproliferative activity against three digestive tract tumor cells was evaluated and preliminary structure activity relationships were summarized. Among these compounds, compound 20q exhibited most potent antiproliferative activity against MGC-803, HCT-116, Kyse30 and Kyse450 cells with IC50 values of 0.084, 0.227, 0.069 and 0.078 μM, respectively. In further studies, compound 20q was identified as a novel tubulin inhibitor targeting the colchicine binding site. Compound 20q could inhibit the microtubule assembly and disrupt cytoskeleton in Kyse30 and Kyse450 cells. The results of molecular docking suggested that compound 20q could tightly bind into the colchicine binding site of tubulin by hydrogen bonds and hydrophobic interactions. Compound 20q dose-dependently inhibited the cell growth and colony formation, effectively arrested cells at the G2/M phase and induce mitochondrial apoptosis in Kyse30 and Kyse450 cells. In addition, Compound 20q could regulate the expression of G2/M phase and mitochondrial apoptosis related proteins. Collectively, compound 20q was here reported as a novel tubulin inhibitor with potential anticancer activities.


Effect of betamethasone on the dual reaction to anti-human IgE in man: influence of time interval between administration of drug and anti-IgE.
The influence of the time interval between administration of a glucocorticoid, betamethasone, and anti-IgE on the effect of the drug on the early and late phase response (LPR) to anti-IgE was examined in 38 volunteers in a randomized controlled study. The immediate flare and wheal responses to intradermally (i.d.) injected anti-IgE were inhibited by approximately 20 and 30% respectively by a 10 day i.d. pretreatment period with repeated 50 micrograms doses (total 300 micrograms) of betamethasone (P less than 0.01), whereas responses to histamine were not influenced. A single i.d. injection of 50 micrograms betamethasone 24 h prior to anti-IgE challenge attenuated the wheal response (P less than 0.05), whereas injection of the drug 2 h prior to and together with anti-IgE had no influence on the early response. Corresponding LPRs were reduced approximately 30% throughout the observation period of 1-24 h (P less than 0.01). Injecting the drug i.d. 30 min following anti-IgE challenge had no significant influence on the total observation period (1-24 h) of the LPR but antagonized the LPR by 35% at 6-24 h (P less than 0.01). It is concluded that glucocorticoids inhibit IgE-dependent LPRs. When extending the topical pretreatment period with the compounds also the early part of the allergic reaction is attenuated.


Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials.
To compare beta lactam monotherapy with beta lactam-aminoglycoside combination therapy for severe infections. Medline, Embase, Lilacs, Cochrane Library, and conference proceedings, to 2003; references of included studies; contact with all authors. No restrictions, such as language, year of publication, or publication status. All randomised trials of beta lactam monotherapy compared with beta lactam-aminoglycoside combination therapy for patients without neutropenia who fulfilled criteria for sepsis. Two reviewers independently applied selection criteria, performed quality assessment, and extracted the data. The primary outcome assessed was all cause fatality by intention to treat. Relative risks were pooled with the random effect model (relative risk < 1 favours monotherapy). 64 trials with 7586 patients were included. There was no difference in all cause fatality (relative risk 0.90, 95% confidence interval 0.77 to 1.06). 12 studies compared the same beta lactam (1.02, 0.76 to 1.38), and 31 studies compared different beta lactams (0.85, 0.69 to 1.05). Clinical failure was more common with combination treatment overall (0.87, 0.78 to 0.97) and among studies comparing different beta lactams (0.76, 0.68 to 0.86). There was no advantage to combination therapy among patients with Gram negative infections (1835 patients) or Pseudomonas aeruginosa infections (426 patients). There was no difference in the rate of development of resistance. Nephrotoxicity was significantly more common with combination therapy (0.36, 0.28 to 0.47). Heterogeneity was not significant for these comparisons. In the treatment of sepsis the addition of an aminoglycoside to beta lactams should be discouraged. Fatality remains unchanged, while the risk for adverse events is increased.


Sonographic ventriculography: a new potential use for sonographic contrast agents in neonatal hydrocephalus.
Sonographic identification of communicating and noncommunicating forms of posthemorrhagic hydrocephalus can be difficult. This study evaluates the feasibility of using sonographic contrast agents to determine ventricular patency in a newborn animal model. A craniotomy was performed and a catheter was placed under sonographic guidance into the lateral ventricle in five anesthetized newborn piglets. Sonograms were obtained before and after intraventricular injection of 0.01 mL of a sonographic contrast agent (Imagent, formulation AF0150; Alliance Pharmaceutical Corp, San Diego, CA) diluted in 1 mL normal saline, and images were assessed for presence and location of echogenic contrast material. Flow of contrast material was identifiable from the ipsilateral lateral ventricle into the contralateral lateral ventricle, and through the third and fourth ventricles into the basal cisterns during real-time sonography in every animal. Ventricular and cistern echogenicity remained increased for approximately 4 minutes after injection. Contrast-enhanced sonographic ventriculography has the potential to identify patency of CSF pathways in newborns with hydrocephalus and an indwelling ventricular catheter.


Acetone, methyl ethyl ketone, ethyl acetate, acetonitrile and other polar aprotic solvents are strong inducers of aneuploidy in Saccharomyces cerevisiae.
A diploid yeast strain D61.M was used to study induction of mitotic chromosomal malsegregation, mitotic recombination and point mutation. Several ketones (including acetone and methyl ethyl ketone) and some organic acid esters (including the methyl, ethyl and 2-methoxyethyl esters of acetic acid) and acetonitrile strongly induced aneuploidy but not recombination or point mutation. Only diethyl ketone induced low levels of recombination and point mutation in addition to aneuploidy. Related compounds were weak inducers of aneuploidy: methyl n-propyl ketone, the methyl esters of propionic and butyric acid, acetic acid esters of n- and iso-propanol and ethyl propionate. No mutagenicity was found with n-butyl and isoamyl acetate, ethyl formate, acetyl acetone (2,5-dipentanone) and dioxane. Methyl isopropyl ketone induced only some recombination and point mutation but no aneuploidy. Efficient induction was only observed with a treatment protocol in which growing cells were exposed to the chemicals during a growth period of 4 h at 28 degrees C followed by incubation in ice for more than 90 min, usually overnight for 16-17 h. Aneuploid cells could be detected in such cultures during a subsequent incubation at growth temperature if the chemical was still present. Detailed analysis showed that there was a high incidence of multiple events of chromosomal malsegregation. It is proposed that the mutagenic agents act directly on tubulin during growth so that labile microtubules are formed which dissociate in the cold. When cells are brought back to temperatures above the level critical for reassembly of tubulin and allowed to grow, faulty microtubules are formed.


Impact of Spinal Instrumentation on Neurological Outcome in Patients with Intermediate Spinal Instability Neoplastic Score (SINS).
Background: Adequate assessment of spinal instability using the spinal instability neoplastic score (SINS) frequently guides surgical therapy in spinal epidural osseous metastases and subsequently influences neurological outcome. However, how to surgically manage 'impending instability' at SINS 7−12 most appropriately remains uncertain. This study aimed to evaluate the necessity of spinal instrumentation in patients with SINS 7−12 with regards to neurological outcome. Methods: We screened 683 patients with spinal epidural metastases treated at our interdisciplinary spine center. The preoperative SINS was assessed to determine spinal instability and neurological status was defined using the Frankel score. Patients were dichotomized according to being treated by instrumentation surgery and neurological outcomes were compared. Additionally, a subgroup analysis of groups with SINS of 7−9 and 10−12 was performed. Results: Of 331 patients with a SINS of 7−12, 76.1% underwent spinal instrumentation. Neurological outcome did not differ significantly between instrumented and non-instrumented patients (p = 0.612). Spinal instrumentation was performed more frequently in SINS 10−12 than in SINS 7−9 (p < 0.001). The subgroup analysis showed no significant differences in neurological outcome between instrumented and non-instrumented patients in either SINS 7−9 (p = 0.278) or SINS 10−12 (p = 0.577). Complications occurred more frequently in instrumented than in non-instrumented patients (p = 0.016). Conclusions: Our data suggest that a SINS of 7−12 alone might not warrant the increased surgical risks of additional spinal instrumentation.


Effects of Commercial Sunscreens on Survival, Reproduction and Embryonic Development of the Aquatic Snail Biomphalaria glabrata (SAY, 1818).
Over the past few years, there has been a significant increase in the use of sunscreens. Consequently, the occurrence in aquatic environments of ultraviolet filters has also increased. The present study aims to evaluate the toxicity of two commercial sunscreens to the aquatic snail Biomphalaria glabrata. Acute assays were performed with adult snails exposed to solutions of the two products in synthetic soft water. Reproduction and development assays were carried out, involving individual adult and egg masses exposure to assess fertility and embryonic development. Sunscreen A showed a LC50-96 h of 6.8 g/L and reduction in number of eggs and egg masses per individual in the concentration of 0.3 g/L. Sunscreen B presented higher malformation rates in 0.4 g/L with 63% of malformed embryos. Results indicate that the formulation used in sunscreens is an important factor in aquatic toxicity and needs to be evaluated before the final product is commercialized.


Alterations in the corticomotor evoked potential following spinal cord ischemia.
A simple yet reliable model of spinal cord ischemia has been previously developed by inserting a Swan-Ganz catheter into the abdominal aorta of rabbits and inflating the balloon just inferior to the renal arteries. Recent investigations have shown that paraplegia is consistently reproduced if the balloon remains inflated for 20 min after loss of the N3 component of the somatosensory evoked potential. Because of its high reliability, this model has been frequently and successfully used to determine the efficacy of pharmacological agents thought to provide protection against spinal cord ischemia. Results from the present report demonstrate that a similar degree of reliability can be achieved in this model for testing motor activity. A simple method of evoking highly reproducible motor potentials, that can be percutaneously recorded from the spinal cord in response to cortical stimulation, was developed. Predictable and repeatable changes in the configuration of the corticomotor evoked potential were found during spinal cord ischemia and reperfusion. With this added dimension of functional assessment, future application of the current spinal cord ischemia model have been greatly expanded.


Morphometric comparison of the human corpus callosum in deaf and hearing subjects: an MRI study.
Auditory cortices are interconnected to each other by fibers passing through the corpus callosum (CC). In totally deaf persons no auditory impulses are conveyed to the auditory cortices, hence the auditory pathways become nonfunctional. It was reported that there has been cross-modal plasticity between auditory, visual, and somatosensory cortices. In this study, our aim was to make a comparison in the CC morphometry in hearing subjects and in a selected group in which the auditory system was deprived before the age of 2. 18 deaf and 18 hearing male, handedness matched volunteers, ages varying between 28 and 56 years old were examined. Audiometrical tests were applied to both groups and then T1-weighted midsagittal MR images were obtained. Certain dimensions and areas were measured on these images. There were no statistically significant difference between deaf and hearing subjects, either when dimensions and areas were analyzed by multivariate analysis of variance or when areas were analyzed by univariate analysis of variance. Absence of any significant morphometric difference in the CC of deaf subjects could be thought as an evidence of reflection of functional cortical plasticity.


Patient Education on Scarring Following Mohs Micrographic Surgery: Patient Preference for Information Delivery.
There are multiple modalities for patient education ranging from written to audiovisual formats. However, little is known regarding which modality is optimal. To assess patient preference for educational materials about scar care following surgery for facial skin cancer using the FACE-Q Skin Cancer patient reported outcome measure. On the day of Mohs surgery, patients were given a written handout or viewed a 3-minute animation video regarding best practices in scar improvement. Afterward, patients received the FACE-Q Skin Cancer-Satisfaction with Information: Appearance scale. Three months later, patients were called and given the same scale and additional questions regarding scar care. A total of 75 patients were enrolled. There was no difference between the 2 groups' preoperative information scores (p = .85) and the three-month postoperative scores (p = .37). The change in preoperative and postoperative score showed no significant difference between the 2 groups (p = .21); but there was a trend of higher satisfaction in the video group on the day of Mohs surgery. After the 3-month timepoint, there was a higher satisfaction trend observed with the written handout group. Patient preferences in information delivery and accessibility will contribute to greater information retention and satisfaction.


Estrogen-binding proteins in the human postmenopausal uterus.
Two intracellular high-affinity, low-capacity estrogen-binding proteins, which have the characteristics of receptors, with equilibrium dissociation constants of 10(-10)M and 10(-9)M, have been observed in the human uterus. The higher-affinity protein (10(-10)M) appears to play the main role in activating end-organ response to estrogen stimulation. The role of the lower-affinity protein (10(-9)M) is uncertain. In a human postmenopausal uterine system without estrogen stimulation, Scatchard analysis of uterine cytosol partially purified by ammonium sulfate fractionation and incubated at 4 degrees C for 18 hours revealed only the higher-affinity receptor component (10(-10)M). In a post menopausal uterine system with estrogen priming (and in the premenopausal uterus) both the high- and low-affinity components were observed. Competition studies indicated that the receptors were specific for estradiol. The clinical significance of these findings is discussed.


Perforated hemorrhagic cholecystitis in a patient with Bernard-Soulier syndrome.
Bernard-Soulier syndrome is an inherited coagulopathy, with an incidence of one per million. Hemorrhagic cholecystitis is a rare and life-threatening complication of acute cholecystitis. Less than 50 patients have been reported in the previous literature. Bleeding diathesis and anticoagulant treatment are well-known predisposing factors for hemorrhagic cholecystitis. We present a 57-year-old male patient who was referred to our department with a complaint of right upper quadrant abdominal pain. Contrast-enhanced computed tomography revealed a high-density mass associated with the gallbladder lumen, and blood clot in the gallbladder lumen and hemoperitoneum which were compatible for hemorrhagic cholecystitis and gallbladder perforation. The patient underwent urgent cholecystectomy. Hemorrhagic cholecystitis often manifests as typical acute cholecystitis presentation; but several clinical findings such as fever, lower gastrointestinal bleeding or severe intraabdominal bleeding-related hypovolemic shock may also occur. Most of the described cases in prior literature have been reported to use anticoagulant medications. This report describes the second hemorrhagic cholecystitis patient with inherited bleeding diathesis and the first case with Bernard-Soulier syndrome.


Some features of hydrogen (ion) secretion by the frog skin.
We have studied the movements of H+ from the in vitro frog skin into the outside solution because it has been suggested that the movement of sodium from the outside solution into the skin may result from the forced exchange of Na+ by H+. Our main observations can be summarized as follows: (a) Hydrogen moves from the skin into the outside solution at a rate of 0.04 muequiv-cm-2-h-1 while Na+ influx had a value of 0.49 muequiv-cm-2-h-1. (b) The rate of H+ secretion is not significantly affected by substituting the Na+ in the outside solution by K+ nor by inhibiting Na+ influx with amiloride (5-10(-5) M). (c) Acetazolamide (5-10(-3) M) blocked H+ secretion without altering the potential difference across the skin. (d) The rate of H+ production is not underestimated because it may have been neutralized by HCO3- secreted into the outside solution in exchange for Cl-. Substituting all the Cl- by SO4(2-) in the outside solutions does not result in an increase in the rate of H+ production. (e) The steady-state rate of H+ secretion is not affected by large changes in electrochemical potential gradients for H+. Neither abolishing the potential difference across the skin nor a 10-fold change in H+ concentration in the outside solution affected significantly the steady-state rate of H+ secretion. (f) The H+ secretion was abolished by the metabolic inhibitors dinitrophenol (1-10(-4) M) and Antimycin A (1.5-10(-6) M) which also markedly reduced the potential difference across the skin. Observations (a), (b), and (c) suggest that H+ and Na+ movements across the outer border of the isolated frog skin are not coupled. The ratio of Na+ to H+ movements is very different from unity and Na+ movements can be abolished without any effects on H+ secretion and conversely H+ movements can be abolished without interruption of Na+ uptake. A second conclusion suggested by these results is that the H+ secretion does not result from movement of H+ following its electrochemical potential gradient since that rate of secretion is not affected by marked changes in either potential or [H+]. Furthermore, the effects of metabolic inhibitors suggest that H+ secretion requires the expenditure of energy by the cell.


Investigating the functional role of a buried interchain aromatic cluster in Escherichia coli GrpE dimer.
Aromatic clusters in the core of proteins are often involved in imparting structural stability to proteins. However, their functional importance is not always clear. In this study, we investigate the thermosensing role of a phenylalanine cluster present in the GrpE homodimer. GrpE, which acts as a nucleotide exchange factor for the molecular chaperone DnaK, is well known for its thermosensing activity resulting from temperature-dependent structural changes that allow control of chaperone function. Using mutational analysis, we show that an interchain phenylalanine cluster in a four-helix bundle of the GrpE homodimer assists in the thermosensing ability of the co-chaperone. Substitution of aromatic residues with hydrophobic ones in the core of the four-helix bundle reduces the thermal stability of the bundle and that of a connected coiled-coil domain, which impacts thermosensing. Cell growth assays and SEM images of the mutants show filamentous growth of Escherichia coli cells at 42°C, which corroborates with the defect in thermosensing. Our work suggests that the interchain edge-to-face aromatic cluster is important for the propagation of the structural signal from the coiled-coil domain to the four-helical bundle of GrpE, thus facilitating GrpE-mediated thermosensing in bacteria.


Validated spectrofluorimetric assay of two co-administered drug mixtures containing hydroxychloroquine with either moxifloxacin or ofloxacin as a drug regimen for hospital-acquired pneumonia in patients with COVID-19.
Moxifloxacin and ofloxacin are two broad-spectrum quinolone antibiotics. They are among the most widely used antibiotics, at this time, applied to control the COVID-19 pandemic. Hydroxychloroquine is an FDA-approved drug for the treatment of COVID-19. This work describes a simple, green, selective, and sensitive spectrofluorimetric method for the assay of moxifloxacin and ofloxacin in the presence of hydroxychloroquine, two co-administered mixtures used in the treatment of hospital-acquired pneumonia in patients with COVID-19. Simultaneous assay of hydroxychloroquine and moxifloxacin was carried out in methanol using a direct spectrofluorimetric method (method I) at 375 and 550 nm, respectively, after excitation at 300 nm. The direct spectrofluorimetric assay was rectilinear over concentration ranges 50.0-400.0 and 300.0-2500.0 ng/ml for hydroxychloroquine and moxifloxacin, respectively, with limits of detection (LOD) of 6.4 and 33.64 ng/ml and limits of quantitation (LOQ) of 19.4 and 102.6 ng/ml, respectively, for the two drugs. The assay for hydroxychloroquine and ofloxacin was carried out by measuring the first derivative synchronous amplitude for hydroxychloroquine at the zero crossing point of ofloxacin and vice versa at Δλ = 140 nm (method II). Hydroxychloroquine was measured at 266 nm, while ofloxacin was measured at 340 nm over the concentration range 4-40 ng/ml for hydroxychloroquine and 200-2000 ng/ml for ofloxacin with LOD of 0.467 and 25.3 ng/ml and LOQ of 1.42 and 76.6 ng/ml, respectively, for the two drugs. The two methods were validated following International Conference on Harmonization guidelines and were applied to the analysis of the two drugs in plasma with good percentage recoveries (109.73-93.17%).


A geographic regression model for medical statistics.
A method for modeling geographic processes using census-type data is introduced in an analysis of male and female lung cancer mortality rates. The study area comprises the counties in those states which abut the Gulf of Mexico and the southeast Atlantic Coast of the United States. A spatially autoregressive model is used to estimate the strength of the univariate relationship between both the male and female lung cancer mortality rates in a country and in the respective lung cancer rates in the first to fifth order adjacent counties. The results show that male lung cancer exhibits spatial autocorrelation while female lung cancer does not, and that the female data exhibit a spatial trend while the male data do not. These findings suggest that factors which vary at the regional scale play a greater role in the etiology of female lung cancer and that factors that vary at the neighborhood scale play a greater role in the etiology of male lung cancer.


MXene-Based Composites as Nanozymes in Biomedicine: A Perspective.
MXene-based nanozymes have garnered considerable attention because of their potential environmental and biomedical applications. These materials encompass alluring and manageable catalytic performances and physicochemical features, which make them suitable as (bio)sensors with high selectivity/sensitivity and efficiency. MXene-based structures with suitable electrical conductivity, biocompatibility, large surface area, optical/magnetic properties, and thermal/mechanical features can be applied in designing innovative nanozymes with area-dependent electrocatalytic performances. Despite the advances made, there is still a long way to deploy MXene-based nanozymes, especially in medical and healthcare applications; limitations pertaining the peroxidase-like activity and sensitivity/selectivity may restrict further practical applications of pristine MXenes. Thus, developing an efficient surface engineering tactic is still required to fabricate multifunctional MXene-based nanozymes with excellent activity. To obtain MXene-based nanozymes with unique physicochemical features and high stability, some crucial steps such as hybridization and modification ought to be performed. Notably, (nano)toxicological and long-term biosafety analyses along with clinical translation studies still need to be comprehensively addressed. Although very limited reports exist pertaining to the biomedical potentials of MXene-based nanozymes, the future explorations should transition toward the extensive research and detailed analyses to realize additional potentials of these structures in biomedicine with a focus on clinical and industrial aspects. In this perspective, therapeutic, diagnostic, and theranostic applications of MXene-based nanozymes are deliberated with a focus on future perspectives toward more successful clinical translational studies. The current state-of-the-art biomedical advances in the use of MXene-based nanozymes, as well as their developmental challenges and future prospects are also highlighted. In view of the fascinating properties of MXene-based nanozymes, these materials can open significant new opportunities in the future of bio- and nanomedicine.


Apomorphine-stimulated growth hormone release.
Apomorphine, a dopaminergic receptor stimulant, was tested and compared in subemetic doses (0.76 mg subcutaneously) to levodopa (500 mg orally) as a stimulant of growth hormone release in 10 normal volunteer subjects (five male, five female). The administration of levodopa failed to cause a normal increment in serum growth hormone levels (greater than 5 ng/ml from base line) in four patients, produced a borderline normal response in two patients with a normal response in four patients. Apomorphine stimulation produced a borderline normal response in one patient and a normal response in the remaining nine patients. The peak response to apomorphine administration was 26.94 +/- 6.60 ng/ml and to levodopa 9.76 +/- 2.67 ng/ml (p less than 0.025). There was no statistical difference between men and women in whom apomorphine testing was utilized. Side effects (nausea, vomiting) were seen in three patients tested with levodopa and in four patients tested with apomorphine. Such symptoms began within 20 minutes of apomorphine administration, persisted from 30 to 40 minutes and disappeared abruptly. All patients treated with apomorphine noted transient drowsiness.


Efficient hydrolysis of starch by α-amylase immobilized on cloisite 30B and modified forms of cloisite 30B by adsorption and covalent methods.
In this paper, α-amylase from Bacillus subtilis was successfully immobilized on three supports. First, α-amylase was immobilized on cloisite 30B via the adsorption method. Then cloisite 30B was activated with tosyl chloride and epichlorohydrin. These activated supports were used for covalent immobilization of α-amylase, and their enzymatic activities were effectively tested in the starch hydrolysis. The results demonstrated that the specific activity of α-amylase immobilized on cloisite 30B was 2.39 ± 0.03, for α-amylase immobilized on activated cloisite 30B with epichlorohydrin was 1.96 ± 0.05 and for α-amylase immobilized on activated cloisite 30B with tosyl chloride was 2.17 ± 0.05 U mg-1. The optimum pH for the activity of free α-amylase was 7, but for α-amylase immobilized on cloisite 30B was 8, and for α-amylase immobilized on activated supports was 7.5. The immobilized enzymes had better thermal resistance and storage stability than free α-amylase, and they also showed excellent reusability.


Metastatic bone cancer pain: etiology and treatment options.
Painful metastatic bone disease remains a challenge for physicians. The treatment choices available are wide and varied, with each having its appropriate place in the management of painful bone metastases. Radiotherapy remains the mainstay of treatment with or without surgery. Advances in understanding the intricate pathway responsible for pain generation and the addition of agents such as bisphosphonates to the physician's armamentarium further assist in the management of painful bone metastases.


First case report of Moraxella osloensis diarrhea in a hemolytic uremic syndrome/acute renal failure child from rural coastal India-Manipal, Karnataka.
The authors report a rare case of diarrhea caused by Moraxella osloensis in a pediatric child with Hemolytic Uremic Syndrome/Acute Renal Failure (HUS/ARF). A 6-y-old boy was referred to the Pediatric Unit with a 3 d history of bloody diarrhea with mucus and fever and decreased urine output for 6 d. Microbiological investigations were done as per CLSI guidelines. His diarrhea, and the subsequent renal failure resolved with appropriate treatment. To the best of authors' knowledge and pubmed search, this is the first case of M. osloensis causing diarrhea in a HUS/ARF pediatric patient reported from India-Manipal.


Critical Access Hospital Use of TeamSTEPPS to Implement Shift-Change Handoff Communication.
Implementation of handoff as part of TeamSTEPPS initiatives for improving shift-change communication is examined via qualitative analysis of on-site interviews and process observations in 8 critical access hospitals. Comparing implementation attributes and handoff performance across hospitals shows that the purpose of implementation did not differentiate between high and low performance, but facilitators and barriers did. Staff involvement and being part of the "big picture" were important facilitators to change management and buy-in.


Home video telemetry in children: A comparison to inpatient video telemetry.
Home Video Telemetry (HVT) combines ambulatory EEG with simultaneous video recording. No previous reports have compared HVT and inpatient video telemetry (IVT) in a purely paediatric population. This study compares HVT and IVT in this group in terms of diagnostic efficacy, recording quality and acceptability to parents/carers. 33 HVT and 29 IVT patients aged 1-17 years were included. Information regarding patient demographics, ictal capture, diagnostic utility, recording quality (e.g. video clarity, EEG artefacts) and parent/carer preferences was documented. Difficulties using HVT equipment were recorded. 62% of IVT patients and 64% of HVT patients had typical attacks during the recording. 59% of IVT and 70% of HVT recordings were considered to have answered the referral question. Study quality was similar in both groups. In HVT studies the rate of equipment difficulties was 52%; problems included camera positioning and failure to turn on the infrared button at night. Diagnostic information was lost in 15% of patients. 76% of parents/carers of HVT patients would choose this investigation again. The diagnostic efficacy and study quality of HVT and IVT are similar in paediatric patients. HVT is acceptable to most parents/carers. User error may compromise the investigation in a minority of cases but did not impact on diagnostic utility. Adoption of HVT investigation could provide an accessible and economic alternative to IVT.


Astragaloside IV ameliorates experimental autoimmune myasthenia gravis by regulating CD4 + T cells and altering gut microbiota.
Myasthenia gravis (MG) is an antibody-mediated autoimmune disease and its pathogenesis is closely related to CD4 + T cells. In recent years, gut microbiota is considered to play an important role in the pathogenesis of MG. Astragaloside IV (AS-IV) is one of the main active components extracted from Astragalus membranaceus and has immunomodulatory effects. To study the immunomodulatory effect of AS-IV and the changes of gut microbiota on experimental autoimmune myasthenia gravis (EAMG) mice, we explore the possible mechanism of AS-IV in improving MG. In this study, network pharmacology was utilized to screen the crucial targets of AS-IV in the treatment of MG. Subsequently, a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to identify potential pathways through which AS-IV acts against MG. Furthermore, experimental investigations were conducted to validate the underlying mechanism of AS-IV in MG treatment. Before modeling, 5 mice were randomly selected as the control group (CFA group), and the other 10 were induced to EAMG model. These mice were randomly divided into EAMG group and EAMG + AS-IV group, n = 5/group. In EAMG + AS-IV group, AS-IV was administered by gavage. CFA and EAMG groups were given the same volume of PBS. Body weight, grip strength and clinical symptoms were assessed and recorded weekly. At the last administration, the feces were collected for 16S RNA microbiota analysis. The levels of Treg, Th1 and Th17 cells in spleen and Th1 and Th17 cells in thymus were detected by flow cytometry. The levels of IFN-γ, IL-17 and TGF-β in serum were measured by ELISA. Furthermore, fecal microbial transplantation (FMT) experiments were performed for exploring the influence of changed intestinal flora on EAMG. After EAMG model was induced, the mice were treated with antibiotics daily for 4 weeks to germ-free. Then germ-free EAMG mice were randomly divided into two groups: FMT EAMG group, FMT AS-IV group, n = 3/group. Fecal extractions from EAMG and EAMG + AS-IV groups as gathered above were used to administered daily to the respective groups for 4 weeks. Body weight, grip strength and clinical symptoms were assessed and recorded weekly. The levels of Treg, Th1 and Th17 cells in spleen and Th1 and Th17 cells in thymus were detected at the last administration. The levels of IFN-γ, IL-17 and TGF-β in serum were measured by ELISA. The network pharmacology and KEGG pathway analysis revealed that AS-IV regulates T cell pathways, including T cell receptor signaling pathway and Th17 cell differentiation, suggesting its potential in improving MG. Further experimental verification demonstrated that AS-IV administration improved muscle strength and body weight, reduced the level of Th1 and Th17 cells, enhanced the level of Treg cells, and resulted in alterations of the gut microbiota, including changes in beta diversity, the Firmicutes/Bacteroidetes (F/B) ratio, and the abundance of Clostridia in EAMG mice. We further conducted FMT tests and demonstrated that the EAMG Abx-treated mice which were transplanted the feces of mice treated with AS-IV significantly alleviated myasthenia symptoms, reduced Th1 and Th17 cells levels, and increased Treg cell levels. This study speculated that AS-IV ameliorates EAMG by regulating CD4 + T cells and altering the structure and species of gut microbiota of EAMG.


Neutral lipid storage disease with myopathy: a whole-body nuclear MRI and metabolic study.
Neutral lipid storage disease with myopathy (NLSDM) is caused by a mutation in the gene encoding adipose triglyceride lipase (ATGL), and is characterized by the presence of numerous triglyceride-containing cytoplasmic droplets in type I muscle fibers. Major clinical manifestations concern the heart and skeletal muscle, and some patients also present diabetes mellitus. We report the clinical, metabolic, and whole-body nuclear magnetic resonance imaging findings of three patients with NLSDM. Muscle MRI study was consistent with previous descriptions, and allowed to show a common pattern of fatty replacement. Muscle changes predominated in the paravertebral muscles, both compartments of legs, and posterior compartment of the thighs. A more variable distribution of muscle involvement was observed on upper limbs, with marked asymmetry in one patient, and alterations predominating on supra and infra spinatus, biceps brachialis and anterior compartment of arms. Cardiac NMR studies revealed anomalies despite normal echocardiography in two patients. Endocrine studies showed low leptin and adiponectine levels, a moderate increase in insulin levels at fasting state, and even greater increase after oral glucose tolerance test in one patient. Two patients had elevated triglycerides and low cholesterol-HDL. Based on these analyses, regular control of cardiometabolic risks appear mandatory in the clinical follow-up of these subjects.


Complex multilocus effects of catechol-O-methyltransferase haplotypes predict pain and pain interference 6 weeks after motor vehicle collision.
Catechol-O-methyltransferase, encoded by COMT gene, is the primary enzyme that metabolizes catecholamines. COMT haplotypes have been associated with vulnerability to persistent non-traumatic pain. In this prospective observational study, we investigated the influence of COMT on persistent pain and pain interference with life functions after motor vehicle collision (MVC) in 859 European American adults for whom overall pain (0-10 numeric rating scale) and pain interference (Brief Pain Inventory) were assessed at week 6 after MVC. Ten single nucleotide polymorphisms spanning the COMT gene were successfully genotyped, and nine were present in three haploblocks: block 1 (rs2020917, rs737865, rs1544325), block 2 (rs4633, rs4818, rs4680, rs165774), and block 3 (rs174697, rs165599). After adjustment for multiple comparisons, haplotype TCG from block 1 predicted decreased pain interference (p = 0.004). The pain-protective effect of the low pain sensitivity (CGGG) haplotype from block 2 was only observed if at least one TCG haplotype was present in block 1 (haplotype × haplotype interaction p = 0.002 and <0.0001 for pain and pain interference, respectively). Haplotype AG from block 3 was associated with pain and interference in males only (sex × haplotype interaction p = 0.005 and 0.0005, respectively). These results suggest that genetic variants in the distal promoter are important contributors to the development of persistent pain after MVC, directly and via the interaction with haplotypes in the coding region of the gene.


MGlu5 antagonism impairs exploration and memory of spatial and non-spatial stimuli in rats.
Metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in memory processing in some but not all learning tasks. The reason why this receptor is involved in some tasks but not in others remains to be determined. The present experiments using rats examined effects of the mGlu5-antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP)--applied systemically i.p. (1-10mg/kg) or bilaterally into the prelimbic cortex (1-10 microg)---on the ability of rats to explore and remember new stimuli. A cross-maze, open field, and object recognition task were used to evaluate exploration and memory and it was found that: (1) locomotion during exploration of spatial environments and exploration time at novel objects were reduced by i.p. but not by prelimbic administration of MPEP, (2) spatial short-term memory was impaired in cross-maze and object discrimination was reduced after both types of administration, (3) long-term retention of spatial conditioning in the cross-maze was inhibited after i.p. applications which (4) also inhibited spontaneous alternation performance during maze-exploration. Reduced exploratory locomotion and exploration time after i.p. injections may have contributed to the observed retention impairments. However, the fact that prelimbic administration of MPEP inhibited retention without reducing exploration shows that memory formation was also impacted directly by prelimbic mGlu5 in both spatial and non-spatial learning.


Impact of an alcohol withdrawal syndrome practice guideline on surgical patient outcomes.
To standardize treatment of alcohol withdrawal syndrome (AWS) in surgical patients using an AWS practice guideline with a symptom-triggered approach. Prospective interventional (pilot group) and retrospective (comparison group). University teaching hospital. Thirty-eight trauma, orthopedic, and general surgery patients identified at risk for AWS in the pilot group, and 34 patients who were managed using nonstandardized approaches. At-risk patients in the pilot group were assessed using the AWS Type Indicator. They received lorazepam, clonidine, or haloperidol, based on AWS Type Indicator assessment and AWS practice guideline criteria. A standardized symptom-triggered approach to managing AWS was expected to decrease the use of benzodiazepines, avoid undertreatment of adrenergic hyperactivity and delirium, decrease the need for sitters and physical restraints, and reduce hospital length of stay. Pilot patients received a mean of 23 mg less benzodiazepine (p=0.01), 0.1 mg more clonidine (p=0.01), and 20 mg less haloperidol (p=0.06) than comparison patients. Pilot patients also required significantly fewer sitter hours (p=0.04) and hours of restraint use (p=0.09) than comparison patients. No significant differences were found between groups for length of stay (p=0.77). This pilot project suggests that trauma, orthopedic, and general surgery patients at risk for AWS can be safely and effectively managed with a standardized, symptom-triggered approach. Moreover, this approach decreased the amounts of benzodiazepines and haloperidol administered to patients at risk for AWS.


Psychological factors in exceptional, extreme and torturous environments.
Our cognitive system has adapted to support goal-directed behaviour within a normal environment. An abnormal environment is one to which we are not optimally adapted but can accommodate through the development of coping strategies. These abnormal environments can be 'exceptional', e.g., polar base, space station, submarine, prison, intensive care unit, isolation ward etc.; 'extreme', marked by more intense environmental stimuli and a real or perceived lack of control over the situation, e.g., surviving at sea in a life-raft, harsh prison camp etc.; or 'tortuous', when specific environmental stimuli are used deliberately against a person in an attempt to undermine his will or resistance. The main factors in an abnormal environment are: psychological (isolation, sensory deprivation, sensory overload, sleep deprivation, temporal disorientation); psychophysiological (thermal, stress positions), and psychosocial (cultural humiliation, sexual degradation). Each single factor may not be considered tortuous, however, if deliberately structured into a systemic cluster may constitute torture under legal definition. The individual experience of extremis can be pathogenic or salutogenic and attempts are being made to capitalise on these positive experiences whilst ameliorating the more negative aspects of living in an abnormal environment.


Physiologic and behavioral responses to companion animals.
There is a set of behavioral and physiologic responses to companion animals that can be reliably observed under both experimental and natural conditions. These responses indicate that contact with companion animals can be an effective means of reducing stress.


Complex rhythmicity of growth hormone secretion in humans.
To better characterize the 24 hr GH secretion pattern in humans, we studied frequently sampled 24 hr GH profiles in 93 young (18-45 years of age) healthy, fed volunteers: men (n=67) and women (n=26) with BMI<26 kg/m(2). Analysis of the composite GH series in men revealed 3 significant GH "waves" with peaks occurring at midnight (p<0.0001), at noon (p<0.02) and at 1800 h (p<0.0001). In women, similar pattern was seen, with three GH "waves" peaking at midnight (p<0.0001), 1100 h (p<0.02) and at 1600 h (p<0.002). We conclude that the 24 hr rhythmicity of GH secretion is far more complex than currently appreciated. The attribution of the two daytime GH "waves" to food consumption is unlikely but cannot be excluded at the present time. The complex temporal pattern of pulsatile GH secretion may have important effects on regulation of target cell function.


Fifty years since the first European synchrotron-radiation-derived XAFS spectrum (Frascati, 1963).
The first absorption spectra recorded in Europe using synchrotron radiation as the X-ray source were the K-edge of Al and the LIII-edge of Cu taken at Frascati electron synchrotron in May 1963 by the French-Italian group comprised of Y. Cauchois, C. Bonnelle and G. Missoni.


Artefacts and Family Resemblance.
I develop in this paper a conception of artefacts based on L. Wittgenstein's idea of family resemblance. My approach peruses the notion of frame, which was invented in cognitive psychology as an operationisable extension of this philosophical idea. Following the metaphor of life-cycle I show how this schematic notion of frame may be filled with the content relevant for artefacts if we consider them from the point of view of their histories. The resulting conception of artefacts provides a new insight into the current debate on artefact categorisation.


Esterase and lipase in camel tick Hyalomma dromedarii (Acari: Ixodidae) during embryogenesis.
Esterase and lipase activity showed significant changes during embryogenesis of camel tick Hyalomma dromedarii. From the elution profile of chromatography on DEAE-cellulose, six forms of H. dromedarii esterase (El to EVI) can be distinguished. Esterase EIII was purified to homogeneity after chromatography on Sepharose 6B. The molecular mass of esterase EIII was 45 kDa for the native enzyme and represented a monomer of 45 kDa by SDS-PAGE. Esterase EIII had an acidic pI at 5.3. Lipase activity was detected in the same DEAE-cellulose peaks (LI to LVI) of H. dromedarii esterases. The highest lipase activity was exhibited by lipase LIII. Esterase EIII and lipase LIII were compared with respect to Michaelis constant, substrate specificity, temperature optimum, heat stability, pH optimum, effect of metal ions and inhibitors. This study suggests that H. dromedarii lipolytic enzymes may play a central role in the interconversion of lipovitellins during embryogenesis.


Electroneurography in the acute stage of facial palsy as a predictive factor for the development of facial synkinesis sequela.
We investigated whether the value of ENoG is a predictive factor for the development of facial synkinesis in patients with facial palsy. The degree of oral-ocular synkinesis was evaluated quantitatively by an asymmetry of the interpalpebral space width during the mouth movement (% eye opening). Twenty healthy volunteers without a history of facial palsy (12 men and 8 women; 25-65 years old; mean age: 42.3±9.7years) were included in the study to examine the normal range of % eye opening. Fifty-one patients with facial palsy including 38 with Bell palsy and 15 with herpes zoster oticus (28 men and 25 women; 11-86 years old; mean age: 54±19years) were enrolled to examine the relationship between the ENoG value 10-14days after the onset of facial palsy, and the % eye opening 12 months later. Receiver operating characteristic (ROC) curve for the ENoG value was then used to decide the optimum cut-off value as a predictor of the development of oral-ocular synkinesis. We defined a % eye opening inferior to 85% as an index of the development of oral-ocular synkinesis. There was a significant correlation between the values of ENoG 10-14days after the onset of facial palsy and those of % eye opening 12 months later (ρ=0.81, p<0.001). The area under the ROC curve for the ENoG value was the predictor for the development of oral-ocular synkinesis at 0.913 (95%CI: 0.831-0.996, p<0.001). The optimum cut-off value of ENoG 10-14days after the onset of facial palsy was 46.5% to predict the development of oral-ocular synkinesis 12 months after the onset of facial palsy (sensitivity 97.1% and specificity 77.5%). The value of ENoG 10-14days after the onset of facial palsy is a predictive factor for the development of facial synkinesis 12 months later. Since facial palsy patients with a ENoG value inferior to 46.5% have a high risk of developing synkinesis, they should receive the facial biofeedback rehabilitation with a mirror as a preventive therapy.


The Association Between Alcohol Consumption and Condom Use: Considering Correlates of HIV Risk Among Black Men Who Have Sex with Men.
Epidemiological data indicate Black men who have sex with men (MSM) are the most at-risk group for HIV infection. However, the factors driving this disparity are not fully understood. Condom use remains a significant point of intervention in mitigating sexually transmitted infections. Alcohol consumption is highly prevalent among Black MSM, has a significant role in the culture of sex, and may significantly interfere with condom use. This review will examine the relationship between alcohol consumption and condom use among Black MSM. In this review we, (a) discuss the prevalence of alcohol use among MSM and its association with condom use; (b) consider the role of alcohol in the culture of MSM; (c) review the literature on the relationship between alcohol and condom use; and (d) discuss the role of several empirically-supported moderating variables in strengthening the relationship between alcohol use and noncondom use. This review places the finding and implications for HIV risk among Black MSM in the context of the broader literature on MSM.


Sampling challenges in end-of-life research: case-finding for family informants.
Research on end-of-life care is hampered by challenges in accessing appropriate subjects for data collection. Although families of decedents are rich sources of research data, they are underutilized, most likely due to the access difficulties they present to investigators. To describe case-finding strategies that can achieve a large and representative sample of family informants for research studies about end-of-life care. Case-finding strategies were developed and honed over the course o fthree epidemiological studies on end-of-life care. Family location information was culled from death certificates and a combination of public and commercial sources. The researchers generated large random samples of study-eligible decedents and, using the case-finding strategies described, recruited family members of decedents as informants. By the third study, two-thirds of family members were located and interviewed within the narrow time frame of 2-5 months following the death of their loved one. Epidemiological studies on end-of-life, using large random samples of decedents and their family members, are feasible when armed with an array of effective case finding strategies.


Concomitant cisplatin and radiotherapy in locally advanced cervical carcinoma.
Patients with locally advanced cervical cancer have a poor prognosis. The efficacy of radiotherapy is limited by the presence of large tumor volume and nodal disease. As cisplatin is a documented radiosensitizer and has activity in squamous cell carcinomas, a prospective study was designed to evaluate the toxicity and potential synergism of concurrent cisplatin (20 mg/m2 x 5 d every 21 days) and radiotherapy in locally advanced cervical cancer. Forty-three patients were studied, of which 14 were stage IB/IIA (bulky disease) and 29 were stage IIB/IIIB/IVA. Of the 32 evaluable patients, there were 29 complete responders. Of these 29 patients, 27 remain without evidence of disease, with a median follow-up of 12 months. There were no treatment-related deaths. Cisplatin and radiotherapy appear to be a well-tolerated and highly effective regimen for locally advanced cervical cancer.


Tumor suppressor in lung cancer-1 (TSLC1) mediated by dual-regulated oncolytic adenovirus exerts specific antitumor actions in a mouse model.
The tumor suppressor in lung cancer-1 (TSLC1) is a candidate tumor suppressor of lung cancer, and frequently inactivated in primary non-small cell lung cancer (NSCLC). In this study, we investigated the effects of TSLC1 mediated by a dual-regulated oncolytic adenovirus on lung cancer, and the mechanisms underlying the antitumor actions. The recombinant virus Ad·sp-E1A(Δ24)-TSLC1 was constructed by inserting the TSLC1 gene into the dual-regulated Ad·sp-E1A(Δ24) vector, which contained the survivin promoter and a 24 bp deletion within E1A. The antitumor effects of Ad·sp-E1A(Δ24)-TSLC1 were evaluated in NCI-H460, A549, and H1299 lung cancer cell lines and the normal fibroblast cell line MRC-5, as well as in A549 xenograft model in nude mice. Cell viability was assessed using MTT assay. The expression of TSLC1 and activation of the caspase signaling pathway were detected by Western blot analyses. The tumor tissues from the xenograft models were examined using H&E staining, IHC, TUNEL, and TEM analyses. Infection of A549 lung cancer cells with Ad·sp-E1A(Δ24)-TSLC1 induced high level expression of TSLC1. Furthermore, the Ad·sp-E1A(Δ24)-TSLC1 virus dose-dependently suppressed the viability of NCI-H460, A549, and H1299 lung cancer cells, and did not affect MRC-5 normal fibroblast cells. Infection of NCI-H460, A549, and H1299 lung cancer cells with Ad·sp-E1A(Δ24)-TSLC1 induced apoptosis, and increased activation of caspase-8, caspase-3 and PARP. In A549 xenograft model in nude mice, intratumoral injection of Ad·sp-E1A(Δ24)-TSLC1 significantly suppressed the tumor volume, and increased the survival rate (from less than 15% to 87.5% at d 60). Histological studies showed that injection of Ad·sp-E1A(Δ24)-TSLC1 caused tumor cell apoptosis and virus particle propagation in tumor tissues. The oncolytic adenovirus Ad·sp-E1A(Δ24)-TSLC1 exhibits specific antitumor effects, and is a promising agent for the treatment of lung cancer.


HIV/AIDS-associated stigma among Afro-Caribbean people living in the United States.
Estimates of AFRO-CARIBBEAN people living with HIV/AIDS are questionable because this population is unwilling to be tested or disclose their status, fearing stigmatization. The purpose of this study was to explore attitudes about HIV/ AIDS-associated stigma for churchgoing Afro- Caribbean people in the United States. Two focus groups of mothers and daughters were convened. The research question was How do young people your age feel about having a friend who is HIV-positive? and How do mothers feel about their daughters having a friend who is HIV-positive? Information from mothers and daughters was evaluated separately through content analysis. Results are discussed.


Flunarizine in the treatment of headache with or without neurological symptoms.
Flunarizine was given in daily doses of 10 mg for periods of two to four months to 176 patients suffering from various types of headache. The symptoms were improved in 82% of the cases treated. No differences emerged among the various types of headache reported by the patients or in relation to the presence or absence of neurological involvement or its type.


Prevalence of asthma, allergic rhinoconjunctivitis and allergic sensitization in Mongolia.
Studies in countries, such as Mongolia, which are in transition from farming to industrial society permit evaluation of the impact of environmental change on atopic diseases. In the screening study, questionnaire data were obtained from 9453 subjects aged 10-60 years. In the clinical study, a subsample of 869 subjects (participation rate 50.0%) was examined. A questionnaire-based interview, clinical examination, skin prick tests, spirometry and bronchodilation test or methacholine challenge test were used to define the clinical diagnoses. The prevalences of atopic diseases were evaluated at the population level using two-phase data and sampling weights. The prevalences of asthma, allergic rhinoconjunctivitis and allergic sensitization with 95% confidence intervals were 1.1% (0.3-2.0%), 9.3% (4.0-14.6%) and 13.6% (7.4-19.9%) in Mongolian villages, 2.4% (1.4-3.5%), 12.9% (8.2-17.7%) and 25.3% (17.1-33.6%) in rural towns and 2.1% (1.3-3.0%), 18.4% (13.3-23.4%) and 31.0% (24.5-37.5%) in Ulaanbaatar city, respectively. The prevalence of allergic rhinoconjunctivitis (P = 0.02) and allergic sensitization (P = 0.003) increased significantly with increasing urbanization. The prevalences of atopic diseases were low in rural Mongolia and increased with increasing urbanization suggesting that rural living environment protects against atopy.


Deciphering metformin action in obese mice: A critical re-evaluation of established protocols.
Despite extensive efforts and a plethora of suggested targets and pathways, the mechanism via which metformin lowers blood glucose remains obscure. Obstacles that hamper progress in understanding metformin action include unexplained discrepancies between preclinical models and patients. We treated obese male C57BL/6J mice fed high fat diet with metformin provided in the form of a single dose, daily intraperitoneal injections, admixture to drinking water, or continuous infusion via intraperitoneal minipumps. The results suggest several superimposed components, via which metformin acts on blood glucose. These include (i) marked glucose lowering shortly after dosing, which fades rapidly with the decrease in metformin concentrations in plasma and liver, but could, at least to a major extent, rely on the mechanism also accounting for metformin's therapeutic action in humans; (ii) indirect action via reduced weight gain, which might be responsible for glucose lowering observed in many previous rodent studies; and (iii) deterioration of glucose homeostasis by prolonged treatment that can be unmasked by avoidance of dosing shortly before measuring blood glucose in combination with exclusion of weight-related actions via restricted feeding of the control mice. Our work raises the question whether elucidation of metformin's anti-diabetic mechanism(s) in rodent experiments may in the past have been hampered by failure to mimic clinical circumstances, as caused by insufficient consideration of pharmacokinetics and multiplicity of involved actions.


[Retroperitoneal lipoblastoma in an infant. A case report].
Lipoblastoma is a benign neoplasia of the adipose tissue. It is a rare conditionand almost exclusively presents in children under 3 years old. It usually occurs in extremities as a painless volume increase of progressive growth, with the definitive diagnosis being established by pathological and cytogenetic analysis. The treatment of choice is complete resection, and follow-up period of up to five years is recommended due to a recurrence of up to 25%. To present an unusual location of this uncommon condition in an infant, and review the related literature. A sixteen-month child with an increase in abdominal growth of six-months progression, associated with a decreased food intake, and with no other symptoms. The imaging study revealed a lipoid-like image compromising almost the entire abdominal cavity, very suggestive of lipoblastoma. A resection was performed on an 18cm diameter retroperitoneal tumour that rejected the adjacent organs. Histological analysis was enough to confirm diagnosis without the need for cytogenetic analysis. The follow-up showed no recurrence of the disease. Given the rarity of this disease and its unusual presentation, we communicate this clinical case, in order to be considered in the differential diagnosis of abdominal mass in chilhood.


Prevalence of obesity and clinical and metabolic correlates in first-episode schizophrenia relative to healthy controls.
People with schizophrenia exhibit a high obesity rate. However, little is known about the prevalence of obesity and its relationship with clinical symptoms and metabolic indicators in first-episode drug-naïve (FEDN) schizophrenia. Demographic and lipid parameters were gathered from 297 FEDN schizophrenia and 325 healthy controls. The patients' symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS). The obesity rate of FEDN patients was 10.77%, similar to that of controls (10.5%). The prevalence of overweight plus obesity of patients was 44.8%, significantly higher than that of controls (36.6%). Compared with non-obese patients, obese patients had higher levels of cholesterol (4.81 ± 0.93 vs 4.22 ± 1.00 mmol/L), triglyceride (0.27 ± 0.21 vs 0.14 ± 0.24 mg/dL), low-density lipoprotein (0.48 ± 0.12 vs 0.40 ± 0.12 mg/dL), greater ratio of triglyceride/high-density lipoprotein (2.01 ± 1.23 vs 1.44 ± 1.26), and higher PANSS positive symptom subscale score (29.81 ± 6.29 vs 27.05 ± 6.15), general psychopathology subscale score (70.75 ± 11.74 vs 66.87 ± 11.37), and total score (149.81 ± 21.08 vs 140.64 ± 21.58), but lower high-density lipoprotein level (1.09 ± 0.21 vs 1.27 ± 0.34 mg/dL) (all p < 0.05). Correlation analysis revealed that body mass index (BMI) was positively correlated with triglyceride, cholesterol, high-density lipoprotein, low-density lipoprotein, triglyceride/high-density lipoprotein ratio, PANSS positive symptoms, general psychopathology, and total scores (all p < 0.05, r = 0.124 ~ 0.335). Multiple regression analysis confirmed that PANSS positive symptoms, total score, and cholesterol level were significantly associated with BMI (all p < 0.05, β: 0.126-0.162). There was no significant difference in the prevalence of obesity between FEDN patients and the control group. Moreover, BMI was positively associated with positive symptom severity in FEDN patients.


Subchronic exposure to leachate activates key markers linked with neurological disorder in Wistar male rat.
The linking of various environmental chemicals exposure to neurodegenerative disorders is current. This study was undertaken to elucidate the toxic effects and the underlying biochemical mechanism of leachate obtained from Elewi Odo municipal battery recycling site (EOMABRL) using key markers of neuronal damage in rat via an oral route. Analysis of the concentrations of heavy metals showed that lead, cadmium, nickel, chromium, manganese, and iron were higher than the acceptable limits set by the regulatory authority-the World Health Organization. Whereas, copper, zinc, and cobalt were lower than permissible limits. EOMABRL was administered at 0, 20, 40, 60, 80, and 100% concentrations to adult male rats for 60 days. An in vitro study was also carried out in the cerebellum to assess cholinesterase biochemistry assays. Following exposure, brain was collected to determine the antioxidant status. EOMABRL administration significantly increased superoxide dismutase (SOD) and catalase (CAT) activities, and a sequential decrease in reduced glutathione (GSH) level with a concomitant increase in the accumulation of hydrogen peroxide (H2O2) and malondialdehyde (MDA) level was observed, when compared with the control. The treated rat had a significant (P < 0.05) increase in the activities of acetycholinesterase (AChE) and butyrylcholinesterase (BuChE). Taken together, these findings conclude that some possible mechanisms by which EOMABRL elicits neuronal disorder in male rat could be through the activation of AChE and BuChE and induction of oxidative stress with necrosis of neuronal cells.


Voxel-wise analysis of dynamic 18F-FET PET: a novel approach for non-invasive glioma characterisation.
Glioma grading with dynamic 18F-FET PET (0-40 min p.i.) is typically performed by analysing the mean time-activity curve of the entire tumour or a suspicious area within a heterogeneous tumour. This work aimed to ensure a reader-independent glioma characterisation and identification of aggressive sub-volumes by performing a voxel-based analysis with diagnostically relevant kinetic and static 18F-FET PET parameters. One hundred sixty-two patients with a newly diagnosed glioma classified according to histologic and molecular genetic properties were evaluated. The biological tumour volume (BTV) was segmented in static 20-40 min p.i. 18F-FET PET images using the established threshold of 1.6 × background activity. For each enclosed voxel, the time-to-peak (TTP), the late slope (Slope15-40), and the tumour-to-background ratios (TBR5-15, TBR20-40) obtained from 5 to 15 min p.i. and 20 to 40 min p.i. images were determined. The percentage portion of these values within the BTV was evaluated with percentage volume fractions (PVFs) and cumulated percentage volume histograms (PVHs). The ability to differentiate histologic and molecular genetic classes was assessed and compared to volume-of-interest (VOI)-based parameters. Aggressive WHO grades III and IV and IDH-wildtype gliomas were dominated by a high proportion of voxels with an early peak, negative slope, and high TBR, whereby the PVHs with TTP < 20 min p.i., Slope15-40 < 0 SUV/h, and TBR5-15 and TBR20-40 > 2 yielded the most significant differences between glioma grades. We found significant differences of the parameters between WHO grades and IDH mutation status, where the effect size was predominantly higher for voxel-based PVHs compared to the corresponding VOI-based parameters. A low overlap of BTV sub-volumes defined by TTP < 20 min p.i. and negative Slope15-40 with TBR5-15 > 2- and TBR20-40 > 2-defined hotspots was observed. The presented approach applying voxel-wise analysis of dynamic 18F-FET PET enables an enhanced characterisation of gliomas and might potentially provide a fast identification of aggressive sub-volumes within the BTV. Parametric 3D 18F-FET PET information as investigated in this study has the potential to guide individual therapy instrumentation and may be included in future biopsy studies.


Livestock-associated Staphylococcus aureus: origin, evolution and public health threat.
Staphylococcus aureus is a major pathogen responsible for severe nosocomial and community-associated infections of humans and infections of economically important livestock species. In recent years, studies into livestock-associated S. aureus including methicillin-resistant (MRSA) strains have provided new information regarding their origin and host adaptation, and their capacity to cause zoonotic infections of humans. Furthermore, a potential role for human activities such as domestication and industrialisation in the emergence of S. aureus clones affecting livestock has been highlighted. Here, I summarise recent developments in this emerging field and suggest questions of importance for future research efforts.


Alcohol consumption and cardiovascular risk factors.
This chapter reviews epidemiologic evidence relating alcohol consumption to the cardiovascular risk factors of high-density lipoprotein (HDL)-cholesterol and blood pressure. Alcohol consumption shows a linear dose-response relationship with HDL-cholesterol that is independent of other known determinants of HDL-cholesterol. The effect of alcohol on HDL-cholesterol appears to be reversible. The relationship of alcohol consumption to HDL-cholesterol subfractions and to the HDL apoproteins is not clear. Alcohol consumption also shows a linear dose-response relationship with blood pressure. Although the association is consistent, the estimated effect of alcohol consumption on blood pressure is small. This effect of alcohol may also be reversible. No biological mechanisms have been established for these associations. Some of the effect of alcohol on the risk of coronary heart disease may be explained by the effects of alcohol on these risk factors. It remains to be determined if alcohol also exerts an effect that is independent of these risk factors.


Orbital atherectomy of calcified coronary ostial lesions.
To evaluate the feasibility and safety of coronary orbital atherectomy (OA) for the treatment of calcified ostial lesions. Percutaneous coronary intervention (PCI) is increasingly being completed in complex patients and lesions. OA is effective for severely calcified coronary lesions; however, there is a dearth of evidence on the use of OA in ostial lesions, especially with long-term outcome data. Data were obtained from a retrospective analysis of patients who underwent OA of heavily calcified ostial lesions followed by stent implantation from December 2010 to June 2019 at two high-volume PCI centers. Kaplan-Meier analysis was utilized to assess the primary endpoints of 30-day, 1-year, and 2-year freedom-from (FF) major adverse cardiac events (MACE: death, myocardial infarction, or target vessel revascularization), stroke, and stent thrombosis (ST). A total of 56 patients underwent OA to treat heavily calcified ostial coronary lesions. The mean age was 72 years with a high prevalence of diabetes (55%) and heart failure (36%), requiring hemodynamic support (14%). There was high FF angiographic complications (93%), and at 30-day, 1-year, and 2-year, a high FF-MACE (96%, 91%, and 88%), stroke (98%, 96%, and 96%), and ST (100%), respectively. This study represents the largest real-world experience of coronary OA use in heavily calcified ostial lesions with long-term outcomes over 2 years. The main finding in this retrospective analysis is that, despite the complex patients and lesions included in this analysis, OA appears to be a feasible and safe treatment option for calcified coronary ostial lesions.


Effects of gelatinization degree and boiling water kneading on the rheology characteristics of gluten-free oat dough.
The effects of gelatinization degree of oat flour and boiling water on the rheological characteristics of oat dough were investigated. Gelatinized oat flour had higher water absorption (2.25-3.83 g/g) and swelling (2.40-4.19), but lower solubility (6.20-8.60 %) at 25 °C. Oat dough gradually developed a honeycomb-like structure with the increase of gelatinization degree. Gelatinization treatment and boiling water kneading increased bound water content (9.39-12.89 %) and enhanced the elastic behavior of oat dough, with moderate G', lower tan δ, and higher relative elastic portion (77.40 %) and stress relaxation percentage (34.55 %) in the dough prepared by 50 % or 65 % gelatinized oat flour. Chemical interactions showed hydrogen bond and covalent bond were the main interactions in oat dough made from moderately gelatinized oat flour. Moderately gelatinization and boiling water kneading could modify the rheological characteristics and improve the texture and processing adaptability (lower adhesiveness) of oat dough.


[The cutaneous neurosensory axis and the neuro-immuno-cutaneous system].
Since a few years the concept of a neuro-immuno-cutaneous system complementary to the neuro-sensorial cutaneous axis is emerging. It opens new ways to interpret the physiopathologic response of skin to a nociceptive stress, particularly the modulation of inflammation and immunity.


Current conditions and significance of outpatient cardiac rehabilitation and home nursing-care services in heart failure patients with mid-range or preserved ejection fraction: post-hoc analysis of the REAL-HF registry.
The effects of outpatient cardiac rehabilitation (OCR) implementation and home nursing-care services (HNS) use are not well defined in patients with heart failure (HF) with mid-range or preserved left-ventricular ejection fraction (EF) (HFmrEF or HFpEF). Through a post-hoc analysis of the HF registry in Hiroshima Prefecture of Japan (REAL-HF), we investigated the current conditions and significance of OCR and HNS in HFmrEF or HFpEF patients. The REAL-HF enrolled adult patients hospitalized with HF in eight regional core hospitals. Patients discharged home were followed for conditions of OCR and HNS and the primary endpoints (all-cause death or unscheduled readmission) for 1 year. The patients were classified into HF with reduced EF (< 40%) (HFrEF) or HFmrEF (40% ≤ EF < 50%) or HFpEF (EF ≥ 50%) group. We followed 195 HFrEF and 381 HFmrEF or HFpEF patients. OCR was generally underutilized, especially in HFmrEF or HFpEF patients (rate of completion [5-month program], 3.2%), whereas HFmrEF or HFpEF patients were more likely to use HNS after discharge home than HFrEF patients (44.1% vs. 27.2%, P < 0.0001). Patients with the use of HNS generally had lower scores of Mini-Mental State Examination and EuroQol 5 dimensions than those without. Multivariate analysis adjusted for medical and social factors showed that the completion of OCR was a strong negative predictor of the primary endpoints both in HFrEF (hazard ratio [HR] 0.10; 95% confidence interval [CI] 0.01-0.75; P = 0.025) and HFmrEF or HFpEF (HR 0.11; 95% CI 0.01-0.78; P = 0.028) patients, whereas the use of HNS was a positive predictor only in HFmrEF or HFpEF patients (HR 1.41; 95% CI 1.00-1.97; P = 0.047). In conclusion, continuous OCR, despite its inadequate implementation, was associated with favorable overall outcomes, while the necessity for HNS related to impaired cognitive function and quality of life was associated with poorer overall outcomes in HFmrEF or HFpEF patients discharged home. Further study is warranted to fully consider the factors related to OCR implementation and HNS use.


Emotion in health care: the cost of caring.
The purpose of this paper is to understand the centrality of emotion, and how that emotion both created and contributed to meaning, in the communication of health professionals who worked in a regional pilot program for cancer screening. As the third phase of a larger study, thematic analysis of semi-structured interviews was carried out with the 19 members of the professional groups, which comprised the service. Brief comments were included from the questionnaire survey in phases 1 and 2 of the study to demonstrate the overflow effects on those served by the organization. Emotion was found to be a critical component in the communication interface between the groups. The complexity of the way in which emotion was managed with the client group overflowed into the management of the communication process between the professional groups in the organization. However, it was not always recognised, and thus created difficulties for a number of staff. Although the research was limited to one health-care organization, it is possible that other health professions are experiencing similar situations as they cope with the certainty of unending change. Also, although secondary interviews were carried out to ensure that themes were credible to participants, it is possible that carrying out the interviews in the work environment may have constrained some participants. Stresses the importance of the emotional component of communication and how it is recognised to facilitate effective working relationships and support staff coping with change and heavy workloads in health-care organizations.


A repeat region from the Brassica juncea HMA4 gene BjHMA4R is specifically involved in Cd2+ binding in the cytosol under low heavy metal concentrations.
HMA4 transporters are involved in the transport and binding of divalent heavy metals (Cd, Zn, Pb [lead] and Co [cobalt]). In general, as efflux pumps, HMA4 transporters can increase the heavy metal tolerance of yeast and Escherichia coli. Additional research has shown that the C-terminus of HMA4 contains a heavy metal-binding domain and that heterologous expression of a portion of peptides from this C-terminal domain in yeast provides a high level of Cd tolerance and Cd hyperaccumulation. We cloned BjHMA4 from Brassica juncea, and quantitative real-time PCR analysis revealed that BjHMA4 was upregulated by Zn and Cd in the roots, stems and leaves. Overexpression of BjHMA4 dramatically affects Zn/Cd distribution in rice and wheat seedlings. Interestingly, BjHMA4 contains a repeat region named BjHMA4R within the C-terminal region; this repeat region is not far from the last transmembrane domain. We further characterized the detailed function of BjHMA4R via yeast and E. coli experiments. Notably, BjHMA4R greatly and specifically improved Cd tolerance, and BjHMA4R transformants both grew on solid media that contained 500 μM CdCl2 and presented improved Cd accumulation (approximately twice that of wild-type [WT] strains). Additionally, visualization via fluorescence microscopy indicated that BjHMA4R clearly localizes in the cytosol of yeast. Overall, these findings suggest that BjHMA4R specifically improves Cd tolerance and Cd accumulation in yeast by specifically binding Cd2+ in the cytosol under low heavy metal concentrations. Moreover, similar results in E. coli experiments corroborate this postulation. BjHMA4R can specifically bind Cd2+ in the cytosol, thereby substantially and specifically improving Cd tolerance and accumulation under low heavy metal concentrations.


A 3D in vitro model to explore the inter-conversion between epithelial and mesenchymal states during EMT and its reversion.
Epithelial-to-mesenchymal transitions (EMT) are strongly implicated in cancer dissemination. Intermediate states, arising from inter-conversion between epithelial (E) and mesenchymal (M) states, are characterized by phenotypic heterogeneity combining E and M features and increased plasticity. Hybrid EMT states are highly relevant in metastatic contexts, but have been largely neglected, partially due to the lack of physiologically-relevant 3D platforms to study them. Here we propose a new in vitro model, combining mammary E cells with a bioengineered 3D matrix, to explore phenotypic and functional properties of cells in transition between E and M states. Optimized alginate-based 3D matrices provided adequate 3D microenvironments, where normal epithelial morphogenesis was recapitulated, with formation of acini-like structures, similar to those found in native mammary tissue. TGFβ1-driven EMT in 3D could be successfully promoted, generating M-like cells. TGFβ1 removal resulted in phenotypic switching to an intermediate state (RE cells), a hybrid cell population expressing both E and M markers at gene/protein levels. RE cells exhibited increased proliferative/clonogenic activity, as compared to M cells, being able to form large colonies containing cells with front-back polarity, suggesting a more aggressive phenotype. Our 3D model provides a powerful tool to investigate the role of the microenvironment on metastable EMT stages.


Prosthetic posterior teeth with cusps may improve patient satisfaction with complete dentures.
The Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials, Medline, OLDMedline, Embase, Zetoc (Zetoc provides access to the British Library's electronic table of contents of approx. 20,000 current journals and 16,000 conference proceedings published per year. The database covers 1993 to date and is updated daily. It includes an e-mail alert service to enable you to keep up-to-date with relevant new articles and papers), System for Information on Grey Literature in Europe (SIGLE) (SIGLE is a bibliographic database covering European non-conventional (or 'grey') literature in the fields of pure and applied science and technology, economics, social sciences and humanities), and the Science Citation Index were used to source studies. Reference lists of identified, relevant trials and review articles were scanned. Unpublished data were sought through personal contact with experts in the field. There was no language restriction. Randomised controlled trials (RCT) or quasi-RCT were selected that recruited edentulous adults and compared complete dentures with different occlusal schemes, with regard to patient satisfaction and masticatory function. The quality assessment of included trials was undertaken independently and in duplicate by two reviewers. Data were also extracted by two reviewers independently. Disagreements were discussed and a third reviewer consulted as necessary. Authors were contacted for clarification or missing information. Data were excluded until further clarification if agreement could not be reached. Thirteen trials were thought to be potentially relevant. Ten of these studies were subsequently excluded following further analysis. Two trials require further information from the author before being considered eligible for inclusion. Only one crossover trial (n=30), which compared lingualised teeth and zero-degree teeth, fully met the review's inclusion criteria. Twenty patients preferred the lingualised denture, five the zero-degree denture and five patients had no preference. There was a statistically significant difference in favour of the lingualised denture with an odds ratio of 10.00 (95% confidence interval, 2.04-48.96). There is weak evidence that it may be advantageous for dentists who provide a complete denture service to prescribe prosthetic posterior teeth with cusps, rather than cuspless teeth, to improve patient satisfaction. This conclusion may only be made tentatively until further, well-conducted trials are undertaken that compare different occlusal schemes for complete dentures.


Postradiation renovascular hypertension.
Radiation injury to arteries can represent a significant complication of therapeutic irradiation, even when the dosage used has not been excessive as judged by approved protocols. Children in whom therapeutic abdominal irradiation has been used should be monitored indefinitely for the development of hypertension. The presence of hypertension in such children with normal blood urea nitrogen (BUN) and creatinine, and without proteinuria, should prompt investigation for a renovascular lesion. Standard bypass procedures are usually effective, although the long-term success may be compromised by continuing changes in affected vessels.


Volcanic disruption: the impact of Whakaari White Island on the provision of elective surgical care in Counties Manukau.
On 9 December 2019, Whakaari White Island erupted while 47 people were on the island. Thirty-one people were subsequently hospitalized. Fourteen volcanic burn victims were managed at the National Burns Centre at Middlemore Hospital. Between December 2019 and March 2020 these patients required 124 procedures in theatre, using 23 709 operative minutes. Elective surgical lists were cancelled to fulfil this demand for acute operating theatre time and theatre staff. To quantify the elective surgical resource lost in the aftermath of the Whakaari White Island eruption by surgical specialty. A data set listing all surgical procedures undertaken within Counties Manukau District Health Board during the period 1 December 2019-1 March 2020 and the corresponding months from the preceding 3 years was analysed. Sum operating time and procedures post-Whakaari were compared with the average of the prior 3 years to quantify loss in resource. In the 3 months post-Whakaari, 698 fewer elective operations were completed across all surgical specialties than the average of the previous 3 years, a decrease of 26.3%. All major surgical specialties except urology showed an absolute decrease in elective procedures completed. The most significant decrease was the 59.1% (533 procedures) loss in plastic surgery elective procedures, with no sign of recovery by March 2021. The plastic surgery department was the worst affected by the Whakaari disaster. Overall elective surgical delivery within Counties Manukau was substantially impacted, and would not yet recover by the time of the national COVID-19 lockdown in March 2020.


Design of commissioning process for Halcyon™ linac with a new rigid board: A clinical experience.
This study performed the accurate measurements of beam profiles with a new rigid board, which was consistent with the supplied reference beam profiles (RBPs) for clinical Halcyon model. Percentage depth doses (PDDs), lateral and diagonal dose profiles were measured and compared with RBPs. A water tank was set on the rigid board bridged Halcyon bore without sagging and source-to-surface distance was 90.0 cm. Field sizes were from 2.0 to 28.0 cm squares and depths of lateral and diagonal dose profiles were 1.3, 5.0, 10.0, and 20.0 cm. For the PDD, the depth of maximum dose (dmax), PDD value at depth of 10.0 cm (PDD10), and absolute dose difference (DD) between RBP and measured beam profiles (MBP) were evaluated. For lateral and diagonal dose profiles, DDs for the whole and divided areas (central, shoulder, and extended areas) defined by third derivative, and distance-to-agreement (DTA) in the penumbra area were evaluated. For PDDs, the differences of dmax and PDD10 and DD beyond the dmax were within 1.0 mm, 0.3%, and 1.0%, respectively. For lateral and diagonal dose profiles, the DDs reached approximately 5.0% in the whole area because of penumbra area, while the DDs in the central, shoulder, and extended areas were within 1.0%, 2.0%, and 1.0%, respectively. The DTAs in the penumbra area were within 0.8 mm. The supplied RBPs can be used clinically owing to the good agreement with the accurate MBPs with rigid board.


Low power upconverted near-IR light for efficient polymeric nanoparticle degradation and cargo release.
By encapsulating NaYF4 :Tm.Yb upconverting nanocrystals in UV-degradable polymer capsules, it is possible to access efficient polymer photodegradation and remotely controlled release using near-IR laser light at an unprecedentedly low power.


Graphene-based nanomaterials for cancer therapy and anti-infections.
Graphene-based nanomaterials (GBNMs) has been thoroughly investigated and extensively used in many biomedical fields, especially cancer therapy and bacteria-induced infectious diseases treatment, which have attracted more and more attentions due to the improved therapeutic efficacy and reduced reverse effect. GBNMs, as classic two-dimensional (2D) nanomaterials, have unique structure and excellent physicochemical properties, exhibiting tremendous potential in cancer therapy and bacteria-induced infectious diseases treatment. In this review, we first introduced the recent advances in development of GBNMs and GBNMs-based treatment strategies for cancer, including photothermal therapy (PTT), photodynamic therapy (PDT) and multiple combination therapies. Then, we surveyed the research progress of applications of GBNMs in anti-infection such as antimicrobial resistance, wound healing and removal of biofilm. The mechanism of GBNMs was also expounded. Finally, we concluded and discussed the advantages, challenges/limitations and perspective about the development of GBNMs and GBNMs-based therapies. Collectively, we think that GBNMs could be potential in clinic to promote the improvement of cancer therapy and infections treatment.