Pluripotency Stemness and Cancer: More Questions than Answers.
Embryonic stem cells and induced pluripotent stem cells provided us with fascinating new knowledge in recent years. Mechanistic insight into intricate regulatory circuitry governing pluripotency stemness and disclosing parallels between pluripotency stemness and cancer instigated numerous studies focusing on roles of pluripotency transcription factors, including Oct4, Sox2, Klf4, Nanog, Sall4 and Tfcp2L1, in cancer. Although generally well substantiated as tumour-promoting factors, oncogenic roles of pluripotency transcription factors and their clinical impacts are revealing themselves as increasingly complex. In certain tumours, both Oct4 and Sox2 behave as genuine oncogenes, and reporter genes driven by composite regulatory elements jointly recognized by both the factors can identify stem-like cells in a proportion of tumours. On the other hand, cancer stem cells seem to be biologically very heterogeneous both among different tumour types and among and even within individual tumours. Pluripotency transcription factors are certainly implicated in cancer stemness, but do not seem to encompass its entire spectrum. Certain cancer stem cells maintain their stemness by biological mechanisms completely different from pluripotency stemness, sometimes even by engaging signalling pathways that promote differentiation of pluripotent stem cells. Moreover, while these signalling pathways may well be antithetical to stemness in pluripotent stem cells, they may cooperate with pluripotency factors in cancer stem cells - a paradigmatic example is provided by the MAPK-AP-1 pathway. Unexpectedly, forced expression of pluripotency transcription factors in cancer cells frequently results in loss of their tumour-initiating ability, their phenotypic reversion and partial epigenetic normalization. Besides the very different signalling contexts operating in pluripotent and cancer stem cells, respectively, the pronounced dose dependency of reprogramming pluripotency factors may also contribute to the frequent loss of tumorigenicity observed in induced pluripotent cancer cells. Finally, contradictory cell-autonomous and non-cell-autonomous effects of various signalling molecules operate during pluripotency (cancer) reprogramming. The effects of pluripotency transcription factors in cancer are thus best explained within the concept of cancer stem cell heterogeneity.


Cranial ultrasonographic screening findings among healthy neonates and their association with neurodevelopmental outcomes.
To analyze the findings of cranial ultrasonographic screening in asymptomatic neonates and to assess the association between abnormal results and neurodevelopment. We retrospectively reviewed the cranial ultrasonographic screening results of healthy neonates born between 35 and 42 weeks gestation at our hospital from October 2011 to October 2018. In total, 11,681 neonates underwent cranial ultrasonographic screening during the study period, and 9666 (82.7%) had normal results. Of 2015 neonates with abnormal findings, 294 had more than two abnormalities. The most common minor findings were subependymal cysts (8.99%), choroid plexus cysts (2.43%), lenticulostriate vasculopathy (2.34%), frontal horn cysts (1.80%), and enlarged cisterna magna (1.04%). Then, 33 (0.28%) neonates had major abnormalities, including cerebral hemorrhage, periventricular heterotopia, focal cortical dysplasia, anomalies of the corpus callosum, and vascular malformation. Of 1334 neonates who underwent serial clinical evaluations, 76 (5.69%) had neurodevelopmental disorders, including developmental delay, attention-deficit/hyperactivity disorder, and autistic spectrum disorder. The incidence rate of intracranial anomalies in healthy neonates was 17.3%, and about 5.69% had neurodevelopmental disorders. Cranial ultrasonographic screening has its own value in helping early detection of intracranial anomalies in healthy neonates, some of which have prognostic implications.


Effect of resveratrol on superovulation in mice.
Oocyte quality is one of the key factors affecting the outcome of ART. Therefore, how to improve oocyte quality has become an urgent problem in the field of ART. In this study we evaluated the effect of resveratrol (RSV), added during the process of superovulation, on embryonic development in mice. The results showed that the blastocyst rate was significantly higher in the RSV treated group than in the control group when oocytes were parthenogenetically activated in vitro (61.67 vs 41.51%, P = 0.032). In the naturally fertilized oocytes group, the rates of cleavage and blastocyst were significantly higher in the RSV treatment group than in the control group (74.47% vs 60.98%, P = 0.035; 96.19% vs 70.00%, P = 0.000, respectively). For the aged mice, the average number of oocytes, the rates of cleavage and blastocyst were also significantly higher in RSV treated groups than in the control group (19.47 ± 5.98 vs 10.30 ± 4.82, P = 0.028; 69.03 vs 50.75%, P = 0.014; 64.10% vs 44.12%, P = 0.049, respectively). Mitochondrial membrane potential and mtDNA copy number in oocytes were significantly increased after RSV treatment in both the young and aged populations. The expression of mitochondrial biogenesis related genes was significantly upregulated in cumulus cells of young and aged mice following RSV treatment. Our data suggest that supplementation of RSV during superovulation improves oocytes quality in young and aged mice, increases the number of oocytes retrieved from aged mice, and improves oocytes mitochondrial function.


Alternate pathways for removal of the class II actin initiator methionine.
Class II actin genes usually specify a polypeptide with a Met-Cys-Asp NH2 terminus, whereas the actin itself begins with an acetyl (Ac)-Asp(Glu). Previous studies with Drosophila actin showed that the first detectable intermediate is one with an Ac-Cys NH2 terminus which is subsequently cleaved in a novel reaction to expose the Asp. The initiator Met was probably removed early in translation as a free amino acid. To determine whether the class II actin initiating Met could also be removed in an acetylation-dependent manner, we translated Drosophila mRNA in a rabbit reticulocyte lysate in which protein acetylation was inhibited. After 60 min, three actin intermediates were detected, NH2-Met-Cys-Asp-actin, Ac-Met-Cys-Asp-actin, and NH2-Cys-Asp-actin. During processing in the presence of acetyl-CoA, three additional species were observed with NH2-terminal Ac-Cys-Asp, NH2-Asp, and Ac-Asp segments. In a time- and acetyl-CoA-dependent fashion, Met-Cys-Asp-actin was processed to the mature actin, presumably through an Ac-Met-Cys-Asp intermediate. Thus, two different pathways for removal of the initiator Met of class II actins, acetylation-dependent and independent, are possible. Since no class II actin intermediate containing the initiator Met is seen in vivo, although in class I actins this intermediate is observed, the most probable pathway for class II actins in vivo is the cotranslational removal of the initiator Met as a free amino acid.


Improving assessment of alcohol treatment barriers among Latino and White adults with an alcohol use disorder: Development of the barriers to specialty alcohol treatment scale.
The present study's aims were two-fold. First, we sought to validate a novel measure to assess barriers to specialty alcohol treatment among White and Latino individuals with an alcohol use disorder (AUD): The Barriers to Specialty Alcohol Treatment (BSAT) scale. Second, we sought to demonstrate that the BSAT scale could be used to explain Latino-White disparities in barriers to alcohol treatment. In 2021, we recruited an online national sample of 1200 White and Latino adults with a recent AUD. Participants completed an online questionnaire that included the BSAT items. Confirmatory and exploratory factor analyses were conducted to validate the BSAT. Multiple group analyses across race/ethnicity and language were also performed using the final model. The final model consisted of 36 items across 7 factors that reflect barriers related to low problem recognition, recovery goals, low perceived treatment efficacy, cultural factors, immigration-related concerns, low perceived social support, and logistical barriers. The final model's factor structure and factor loadings held up across race/ethnicity and language. The top endorsed barriers were low problem recognition, recovery goals, low perceived social support, logistical issues, and low perceived treatment efficacy. Compared to Whites, Latinos were more likely to report perceived lack of social support, logistical barriers, low perceived treatment efficacy, cultural barriers, and immigration-related concerns as barriers. Findings provide empirical support for the validity of the BSAT scale, which offers improved measurement of specialty alcohol treatment barriers and can be used to explore Latino-White disparities in a future study.


Dual modification based on electrostatic repulsion of bentonite and SPR effect of Bi facilitate charge transfer of Bi2WO6 for antibiotics degradation.
Development of efficient photocatalysts is vital for light-driven removal of refractory antibiotics. Herein, Bi2WO6 microspheres were successfully anchored on the surface of bentonite, and metallic Bi was reduced in-situ by a one-step solvothermal method. Notably, the Bi/Bi2WO6/BT with a mass ratio of 0.15:1:0.1 exhibited the best photocatalytic activity toward degradation of tetracycline (TC) and ciprofloxacin (CIP) after 120 min of visible light irradiation, and their reaction rate constants were 8.0 and 5.5 folds higher than that of pristine Bi2WO6, respectively. The boosted photocatalytic activity over Bi/Bi2WO6/BT was ascribed to the establishment of electrostatic repulsion and SPR effect, which synergistically promoted charges transfer, thus achieving more h+ and ·O2- radical generation. Moreover, possible TC and CIP degradation pathways over Bi/Bi2WO6/BT were proposed based on the identified intermediates, and most of the intermediates were less toxic than TC and CIP. The study provides options to develop high-efficiency photocatalytic composites for contaminants elimination using semiconductors and readily available bentonite.


[FUNCTIONAL INTERACTION BETWEEN THE DOPAMINE AND MELANOCORTIN SYSTEMS IN THE BRAIN].
The brain melanocortin system plays a key role in the regulation of energy metabolism and feeding behavior and is involved in memory formation, and its abnormalities lead to metabolic disorders and cognitive deficit. The brain dopamine system controls the motor activity, the functions of the nervous, endocrine and cardiovascular systems, and is also involved in the regulation of peripheral metabolism and feeding behavior and in the formation of effect of reward and reinforcement. The fact that a large number of the important physiological functions are controlled by the melanocortin and dopamine systems indicates a close functional relationship between them in different areas of the brain. The basis of this relationship is colocalization of the components of melanocortin and dopamine signaling systems in neurons and interaction between them, which ensures a cross-talk between melanocortin and dopamine pathways in the CNS. The review includes a comprehensive analysis of the current state of the problem concerning the interaction between the melanocortin and dopamine systems of the brain at both the structural and functional levels.


Survival Outcomes in Patients With Hormone Receptor-Positive Metastatic Breast Cancer With Low or No ERBB2 Expression Treated With Targeted Therapies Plus Endocrine Therapy.
Approximately 45% to 60% of hormone receptor (HR)-positive metastatic breast cancer (mBC) shows a low-level expression of ERBB2. Low ERBB2 expression is defined as ERBB2 immunohistochemical expression of 1+ or 2+ with a negative ERBB2 amplification by in situ hybridization. The efficacy of the antibody-drug conjugate trastuzumab deruxtecan in low-ERBB2, HR-positive mBC has been practice changing. However, there are conflicting data on the prognostic value of low ERBB2 expression in HR-positive mBC and whether low ERBB2 expression is a separate entity. To examine whether outcomes differ by immunohistochemical analysis for patients with HR-positive mBC with low ERBB2 expression vs those without ERBB2 expression when treated with targeted therapy (TT) plus endocrine therapy (ET). This single-institution cohort study used prospectively collected electronic data from the MD Anderson Cancer Center for patients with a diagnosis of HR-positive mBC treated with ET in combination with a TT (cyclin-dependent kinase 4/6 inhibitors [CDK4/6is], everolimus, or alpelisib) between January 1, 2010, and December 31, 2021. HR-positive mBC with either low or no ERBB2 expression. The main outcomes were median progression-free survival and overall survival. Data on demographic characteristics, estrogen and progesterone receptor status, ERBB2 status, histologic subtype, menopausal status, treatment duration, and survival status were collected. A total of 1585 women (median [range] age, 51 [24-92] years) were included in the study. Of these women, 1013 (63.9%) had mBC with low ERBB2 expression and 572 (36.1%) had mBC with no ERBB2 expression. A total of 1084 (68.4%) were treated with a CDK4/6i (912 patients were treated in the first line and 172 were treated in the second line); 475 (30.0%) received everolimus and 26 (1.6%) received alpelisib. In the patients who received a first-line CDK4/6i, 618 (67.8%) received an aromatase inhibitor as their ET backbone and 265 (29.1%) received fulvestrant. With a median follow-up time of 17.9 months (range, 1-111 months), progression-free survival and overall survival were not statistically different between the patients with low and no ERBB2 expression treated with TT plus ET. In this cohort study of patients with HR-positive mBC treated with TT plus ET, low ERBB2 expression did not have a significant association with prognosis.


[A multicenter clinical study of nafate for treatment of hepatic fibrosis in patients with chronic liver diseases].
To investigate the effect of nafate (compound fetal cow liver extract tablets) in hepatic fibrosis patients with chronic liver diseases. One hundred fifteen hepatic fibrosis patients with chronic liver diseases from 3 medical centers were included in this study. All patients were given nafate orally for twenty-four weeks. Before treatment and 12, 24 and 36 weeks after the treatment, serum levels of hyaluronic acid (HA), laminin (LN) and type IV collagen (IV-C) of the patients were measured by radioimmunoassay and their liver biopsy specimens were also assessed. Before treatment and 24 and 36 weeks after the nafate treatment, serum levels of HA were (279.2+/-81.4) ng/ml, (136.8+/-56.7) ng/ml and (86.9+/-40.7) ng/ml respectively, serum levels of LN were (170.8+/-73.0) ng/ml, (112.5+/-39.5) ng/ml, and (60.8+/-31.8) ng/ml respectively, and IV-C levels were (153.7+/-60.1) ng/ml, (112.4+/-43.1) ng/ml, and (96.3+/-44.1) ng/ml respectively. There was a significant reduction in these serum values after the treatments. Histopathological examinations of the liver biopsies showed that the degree of hepatic fibrosis obviously declined by one or two degrees after the treatments. nafate has positive effects in treating hepatic fibrosis.


The probability of HIV infection in a new host and its reduction with microbicides.
We use a simple mathematical model to estimate the probability and its time dependence that one or more HIV virions successfully infect target cells. For the transfer of a given number of virions to target cells we derive expressions for the probability P(inf), of infection. Thus, in the case of needlestick transfer we determine P(inf) and an approximate time window for post-exposure prophylaxis (PEP). For heterosexual transmission, where the transfer process is more complicated, a parameter gamma is employed which measures the strength of the infection process. For the smaller value of gamma, P(inf) is from 6 x 10(-5) to 0.93 or from 7.82 x 10(-6) to 0.29, where the lower figures are for the transfer of 100 virions and the upper figures are for the transfer of 4.4 million virions. We estimate the reductions in P(inf) which occur with a microbicide of a given efficacy. It is found that reductions may be approximately as stated when the number of virions transferred is less than about 10(5), but declines to zero for viral loads above that number. It is concluded that PEP should always be applied immediately after a needlestick incident. Further, manufacturers of microbicides should be encouraged to investigate and report their effectiveness at various transferred viral burdens.


A comprehensive insight into autophagy and its potential signaling pathways as a therapeutic target in podocyte injury.
As part of the glomerular filtration membrane, podocyte is terminally differentiated, structurally unique, and highly specialized in maintaining kidney function. Proteinuria caused by podocyte injury (foot process effacement) is the clinical symptom of various kidney diseases (CKD), including nephrotic syndrome. Podocyte autophagy has become a powerful therapeutic strategy target in ameliorating podocyte injury. Autophagy is known to be associated significantly with sirtuin-1, proteinuria, and podocyte injury. Various key findings in podocyte autophagy were reported in the past ten years, such as the role of endoplasmic reticulum (ER) stress in podocyte autophagy impairment, podocyte autophagy-related gene, essential roles of the signaling pathways: Mammalian Target of Rapamycin (mTOR)/ Phosphoinositide 3-kinase (PI3k)/ serine/threonine kinase 1 (Akt) in podocyte autophagy. These significant factors caused podocyte injury associated with autophagy impairment. Sirtuin-1 was reported to have a vital key role in mTOR signaling, 5'AMP-activated protein kinase (AMPK) regulation, autophagy activation, and various critical pathways associated with podocyte's function and health; it has potential value to podocyte injury pathogenesis investigation. From these findings, podocyte autophagy has become an attractive therapeutic strategy to ameliorate podocyte injury, and this review will provide an in-depth review on therapeutic targets he podocyte autophagy.


Anisotropic mechanical properties in the healthy human brain estimated with multi-excitation transversely isotropic MR elastography.
Magnetic resonance elastography (MRE) is an MRI technique for imaging the mechanical properties of brain in vivo, and has shown differences in properties between neuroanatomical regions and sensitivity to aging, neurological disorders, and normal brain function. Past MRE studies investigating these properties have typically assumed the brain is mechanically isotropic, though the aligned fibers of white matter suggest an anisotropic material model should be considered for more accurate parameter estimation. Here we used a transversely isotropic, nonlinear inversion algorithm (TI-NLI) and multiexcitation MRE to estimate the anisotropic material parameters of individual white matter tracts in healthy young adults. We found significant differences between individual tracts for three recovered anisotropic parameters: substrate shear stiffness, μ (range: 2.57 - 3.02 kPa), shear anisotropy, ϕ (range: -0.026 - 0.164), and tensile anisotropy, ζ (range: 0.559 - 1.049). Additionally, we demonstrated the repeatability of these parameter estimates in terms of lower variability of repeated measures in a single subject relative to variability in our sample population. Further, we observed significant differences in anisotropic mechanical properties between segments of the corpus callosum (genu, body, and splenium), which is expected based on differences in axonal microstructure. This study shows the ability of MRE with TI-NLI to estimate anisotropic mechanical properties of white matter and presents reference properties for tracts throughout the healthy brain.


Dihydropyrimidine dehydrogenase deficiency. Neurological aspects.
A family with dihydropyrimidine dehydrogenase (DPD) deficiency is presented. In 3 persons a complete deficiency, and in 3 others a partial deficiency was detected in cultured fibroblasts. Two homozygote subjects and 1 heterozygote subject suffered from epileptic manifestations, in one of these homozygote subjects also microcephaly was found. DPD deficiency might be an etiological factor in the clinical picture of these patients. An autosomal recessive mode of inheritance of this deficiency was found.


Snakebites and ethnobotany in the northwest region of Colombia: Part II: neutralization of lethal and enzymatic effects of Bothrops atrox venom.
Twelve of 74 ethanolic extracts of plants used by traditional healers for snakebites in the northwest region of Colombia, were active against lethal effect of Bothrops atrox venom when they were i.p. injected into mice (18-20 g). After preincubation of sublethal doses of every extract (0.5-4.0 mg/mouse) with 1.5 i.p. lethal dose 50% (LD50) (99.3 microg) of venom, seven of them demonstrated 100% neutralizing capacity within 48 h. These were the stem barks of Brownea rosademonte (Caesalpiniaceae) and Tabebuia rosea (Bignoniaceae); rhizomes of Renealmia alpinia (Zingiberaceae) and Heliconia curtispatha (Heliconiaceae); the whole plants of Pleopeltis percussa (Polypodiaceae) and Trichomanes elegans (Hymenophyllaceae); and the ripe fruits of Citrus limon (Rutaceae). The other five extracts showing partial neutralization (45-80%; 10-30% survival rate in the control group receiving the venom alone; P<0.05) were: leaves, branches and stem of Costus lasius (Costaceae); the whole plant of Sida acuta (Malvaceae); rhizomes of Dracontium croatii (Araceae); leaves and branches of Bixa orellana (Bixaceae) and Struthanthus orbicularis (Loranthaceae). When the extracts were independently administered per oral or i.p. route 60 min before an i.m. venom injection (204 microg=1.5 i.m. LD50), C. limon, T. elegans, B. orellana and T. rosea extracts had partial and significant neutralizing capacity against B. atrox venom lethal effect. C. limon extract was also partially effective when it was administered either i.v. 15 min before or i.p. 5 min after an i.m. venom injection. Three of the 12 extracts with anti-lethal effect (C. limon, D. croatii and S. acuta) were devoid of antiphospholipase A2 activity, when they were tested against one minimum indirect hemolytic dose of B. atrox venom (2 microg) in agarose-erythrocyte-egg yolk gels.


Ignored and distressed: a cross-sectional study of the impact of COVID-19 on last responders.
Last responders constitute an occupational category that includes all those that are involved in the postmortem care of deceased persons and their families. Last responders are exposed to several categories of work-related stressors that affect their health and well-being. COVID-19 exacerbated these stressors. Research to understand the consequences of COVID-19 on the health and wellbeing of last responders is nascent. This study aimed to assess COVID-19 related stress, coping and wellbeing among last responders in the United States. We conducted a national cross-sectional survey of last responders in July through September of 2020. The survey measured wellbeing, stress, coping, and stigma; COVID-19 experiences, and socio-demographics. A ridge regression model was fit for the outcome variables. Analysis was conducted on 366 respondents from 43 states. Respondents were male (55.4%), age 50 + (57.4%), and White non-Hispanic (90.3%); 54% reported moderate-high stress and 41% endorsed mild-severe anxiety. Seventy-seven percent had experienced at least one form of stigma related to their occupation. Variables associated with higher perceived stress and anxiety included gender (female), shorter length of employment, perceiving a higher impact from COVID-19 on everyday life, and increased perceived stigma. Last responders are a critical part of the health care system. Throughout this pandemic, last responders have been frequently ignored and not prioritized for protection and support. Interventions to support last responders cope with stress, and to decrease anxiety are urgently needed. There is also a critical need to challenge community stigma towards last responders.


Visualizing Statistical Mix Effects and Simpson's Paradox.
We discuss how "mix effects" can surprise users of visualizations and potentially lead them to incorrect conclusions. This statistical issue (also known as "omitted variable bias" or, in extreme cases, as "Simpson's paradox") is widespread and can affect any visualization in which the quantity of interest is an aggregated value such as a weighted sum or average. Our first contribution is to document how mix effects can be a serious issue for visualizations, and we analyze how mix effects can cause problems in a variety of popular visualization techniques, from bar charts to treemaps. Our second contribution is a new technique, the "comet chart," that is meant to ameliorate some of these issues.


Validating and norming of the Greek SF-36 Health Survey.
The main objective of this study was to validate the Greek SF-36 Health Survey and to provide general population normative data. The survey was administered to a stratified representative sample (n = 1426) of the general population residing in the broader Athens area and the response rate was 70.6%. Statistical analysis, according to documented procedures developed within the IQOLA Project, was performed. The missing value rate was very low, ranging from 0.1 to 1.3% at the item level. Multitrait scaling analysis confirmed the hypothesized scale structure of the SF-36. Cronbach's alpha coefficient met the criterion (>0.70) for group analysis in all eight scales. Known group comparisons yielded consistent support of construct validity of the SF-36. Significant statistical differences in mean scores were observed in relation to demographic and social characteristics such as gender, age, education and marital status.


On the consistency of a class of R-symmetry gauged 6D N = (1,0) supergravities.
R-symmetry gauged 6D (1, 0) supergravities free from all local anomalies, with gauge groups G × G R where G R is the R-symmetry group and G is semisimple with rank greater than one, and which have no hypermultiplet singlets, are extremely rare. There are three such models known in which the gauge symmetry group is G 1 × G 2 × U(1) R , where the first two factors are ( E 6 / Z 3 ) × E 7 , G 2 × E 7 and F 4 × Sp(9). These are models with single tensor multiplet, and hyperfermions in the (1, 912), (14, 56) and (52, 18) dimensional representations of G 1 × G 2, respectively. So far, it is not known if these models follow from string theory. We highlight key properties of these theories, and examine constraints which arise from the consistency of the quantization of anomaly coefficients formulated in their strongest form by Monnier and Moore. Assuming that the gauged models accommodate dyonic string excitations, we find that these constraints are satisfied only by the model with the F 4 × Sp(9) × U(1) R symmetry. We also discuss aspects of dyonic strings and potential caveats they may pose in applying the stated consistency conditions to the R-symmetry gauged models.


Omics technologies towards sesame improvement: a review.
Genetic improvement of sesame (Sesamum indicum L.), one of the most important oilseed crops providing edible oil, proteins, minerals, and vitamins, is important to ensure a balanced diet for the growing world population. Increasing yield, seed protein, oil, minerals, and vitamins is urgently needed to meet the global demand. The production and productivity of sesame is very low due to various biotic and abiotic stresses. Therefore, various efforts have been made to combat these constraints and increase the production and productivity of sesame through conventional breeding. However, less attention has been paid to the genetic improvement of the crop through modern biotechnological methods, leaving it lagging behind other oilseed crops. Recently, however, the scenario has changed as sesame research has entered the era of "omics" and has made significant progress. Therefore, the purpose of this paper is to provide an overview of the progress made by omics research in improving sesame. This review presents a number of efforts that have been made over past decade using omics technologies to improve various traits of sesame, including seed composition, yield, and biotic and abiotic resistant varieties. It summarizes the advances in genetic improvement of sesame using omics technologies, such as germplasm development (web-based functional databases and germplasm resources), gene discovery (molecular markers and genetic linkage map construction), proteomics, transcriptomics, and metabolomics that have been carried out in the last decade. In conclusion, this review highlights future directions that may be important for omics-assisted breeding in sesame genetic improvement.


Factors affecting research utilisation of nurses and midwives working in North Gondar and West Gojjam Zone public hospitals, Ethiopia: a cross-sectional study.
Research utilisation in clinical decision-making is crucial to enhance quality healthcare, professional development and cost-effective health service. Nurses and midwives have a vital role in research utilisation. However, many factors influence research utilisation of nurses and midwives. To determine research utilisation and identify factors that affect research utilisation among nurses and midwives. An institutional-based, cross-sectional study was conducted from 23 May to 30 June 2019. A total of 631 nurses and midwives participated in the study. Categorical variables were coded with dummy variables and multiple linear regression model was carried out. The level of significance was set at p value less than or equal to 0.05 with 95% CI. Participants' total mean score in the research utilisation scale was 2.27 (SD±0.77) and their mean age was 28.41 (SD±4.71) years. The study revealed that 70.4% (444) of participants had poor research utilisation. Self-efficacy in research utilisation skills (B=0.86, 95% CI 0.75 to 0.97), support for research utilisation (B=0.4, 95% CI 0.25 to 0.55), attitude (B=0.23, 95% CI 0.07 to 0.38), barriers to research utilisation (B=-0.63, 95% CI -0.72 to -0.54), nursing/midwifery work index (B=0.07, 95% CI 0.04 to 0.11) and hospital's level of healthcare (B=4.5, 95% CI 2.13 to 6.9) were statistically significantly associated factors of research utilisation. This study revealed poor research utilisation among nurses and midwives. Barriers to research utilisation, supporting factors for research utilisation, attitude, self-efficacy in research utilisation skills, hospital's level of healthcare and nursing/midwifery work index were found to be statistically significant predictors of research utilisation. The most common barriers to research utilisation were insufficient time and inability to understand statistical terms used in research articles.


Vertical locking of the metacarpophalangeal joint of the little finger: A case report.
Locking of the metacarpophalangeal (MCP) joint is commonly caused by hyperextension of the thumb or moderate flexion of the index or middle finger. We report a rare case of vertical locking of the MCP joint of the little finger in a 16-year old female after blunt trauma to the little finger. The MCP joint was locked when positioned at approximately 90-degree-flexion and could not extend actively or passively. A manual reduction was easily achieved and no immobilization was applied. Vertical locking of the MCP joint can be easily reduced, and immobilization is unnecessary after reduction. Correct diagnosis prior to reduction and differentiation from other types of locking are essential to prevent overtreatment.


Prevalence and role of serum IgE antibodies to the Staphylococcus aureus-derived superantigens SEA and SEB in children with atopic dermatitis.
The skin of patients with atopic dermatitis exhibits a striking susceptibility to colonization and infection with Staphylococcus aureus. In this context it has been previously shown that S aureus-derived superantigens could function as classic allergens, inducing production of functionally relevant specific IgE antibodies. The aim of this study was to determine the prevalence and the role of circulating staphylococcal enterotoxin A (SEA)- and staphylococcal enterotoxin B (SEB)-specific IgE antibodies in children with atopic dermatitis. In a cross-sectional study of 58 children with atopic dermatitis, the presence of IgE antibodies to SEA and SEB was correlated with the severity of the disease and the total and other unrelated allergen-specific IgE titers and density of colonization with S aureus strains on atopic skin and episodes of superficial S aureus skin infections. Twenty of 58 children (34%) were sensitized to superantigens (45% to SEB, 10% to SEA, 45% to SEA and SEB). In this group, severity of atopic dermatitis and levels of specific IgE to food and air allergens were significantly higher. The degree of disease severity correlated to a higher extent with the presence of SEA/SEB-specific antibodies than with total serum IgE levels. Density of colonization with superantigen-secreting S aureus strains was higher in the superantigen IgE-positive group. Sixty-three percent of these children experienced repeated episodes of superficialS aureus skin infections. Sensitization to S aureus-derived superantigens may be involved in disease exacerbation. The presence of SEA/SEB-specific antibodies had additional explanatory value for disease severity and therefore may be helpful in the characterization of children with severe atopic dermatitis.


Emotional and cognitive empathy in patients with non-epileptic seizures.
Evidence suggests that impairments in social cognition are associated with the occurrence of NES. Our aim was to investigate impairments in social cognition in the form of emotional and cognitive empathy in patients with NES compared to healthy controls. For this purpose, we recruited 41 patients with video-EEG secured NES and compared them to 41 healthy controls matched by age, gender and educational level. Emotional and cognitive empathy were assessed using the Multifaceted Empathy Task (MET) and the Read the Mind in the Eye Test (RMET). Self-assessment questionnaires were used to record psychopathology in both groups. Patients with NES showed no differences in cognitive empathy compared to the healthy controls. Additionall, they seem to have less emotional empathy specifically towards positive emotions, compared to healthy controls. Our results are an indication of possible emotional empathy abnormalities in patients with NES. Those deviations, if replicated in large sample sizes, could implicate, that interventions for patients with NES should focus on improving empathy skills.


Effects of novel synthesized retinobenzoic acid (Am-80) on adenylate cyclase and arachidonic acid release in pig epidermis.
It has been well established that the psoriatic hyperproliferative epidermis is characterized by a defective beta-adrenergic adenylate cyclase response and an increased arachidonic acid metabolism. Effects of a newly synthesized retinoid, Am-80 (4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)amino) carbamoyl]benzoic acid), on the beta-adrenergic adenylate cyclase response and on the arachidonic acid metabolism of pig epidermis were investigated. Am-80 augmented the beta-adrenergic adenylate cyclase response of the epidermis. The effect was observed at the concentrations of more than 1 microM. The maximum beta-adrenergic augmentation effect induced by Am-80 was similar to those of all-trans-retinoic acid and of hydrocortisone. Am-80 inhibited the basal arachidonic acid release as well as 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated arachidonic acid release from epidermal keratinocytes. The effect was observed at the concentrations of 50-100 microM. The inhibitory effect of Am-80 was similar to those of all-trans-retinoic acid and of hydrocortisone. Our results indicate that Am-80, a newly synthesized retinoid, reveals the beta-adrenergic adenylate cyclase response augmentation effect and the inhibitory effect on the arachidonic acid metabolism of the epidermis. These effects are consistent with a view that Am-80 is another retinoid which has significant pharmacological effects on keratinocytes.


Dendroaspis natriuretic peptide and its functions in pig ovarian granulosa cells.
Dendroaspis natriuretic peptide (DNP), a 38-amino acid peptide, was isolated from the venom of green mamba. It has structural and functional similarities to the other members of the natriuretic peptide family. The purpose of this study was to determine whether DNP is present in pig ovarian granulosa cells and to define its biological functions. The serial dilution curves of extracts of granulosa cells and follicular fluid were parallel to the standard curve of DNP, and a major peak of molecular profile of both extracts by HPLC was synthetic DNP. The concentration of DNP was 7.51+/-1.46 pg/10(7) cells and 24.81+/-2.38 pg/ml in granulosa cells and follicular fluid, respectively. Natriuretic peptides increased cGMP production in the purified membrane of granulosa cells with a rank order of potency of C-type natriuretic peptide (CNP)>atrial natriuretic peptide (ANP)=DNP. mRNAs for natriuretic peptide receptor-A (NPR-A), NPR-B and NPR-C were detected by RT-PCR. The binding site of (125)I-DNP was also observed in granulosa cell layer by in vitro autoradiography. Synthetic DNP inhibited the secretion of ANP from granulosa cells in a concentration-dependent manner and the potency was similar to CNP. The concentration of DNP and CNP, which inhibited the secretion of ANP by 50%, was about 1 nM. Increases in production of cGMP in granulosa cells were observed by DNP or CNP. Therefore, these results show the existence of DNP system and the cross-talk between natriuretic peptides in pig ovarian granulosa cells.


Validity of quantitative ultrasound and bioelectrical impedance analysis for measuring bone density and body composition in children.
Using dual X-ray absorptiometry (DXA) to assess body composition in children has limitations including expense, lack of portability, and exposure to radiation. The aims of this study were to examine: (1) validity of quantitative ultrasound (QUS) against DXA for measuring bone density and (2) the validity of in-built algorithm of bioelectrical impedance analysis (BIA) for measuring body composition in children (8-13 years) living in New Zealand. Total body less head (TBLH), bone mineral content (BMC), bone mineral density (BMD), and body composition were measured with DXA (QDR Discovery A, Hologic, USA); calcaneal BMD and stiffness index (SI) with QUS (Sahara QUS, Hologic, USA), and BIA on the InBody 230 (Biospace Ltd., Seoul, Korea). Relative validity was assessed using Pearson's and Lin's concordance correlation coefficients (CCC), and Bland-Altman plots. In 124 healthy children, positive correlations between QUS SI and DXA (BMC and BMD) were observed (range = 0.30-0.45, P < 0.01). Results from Lin's CCC test showed almost perfect correlations between BIA and DXA fat free mass (0.96), fat mass (0.92), and substantial correlation for percentage of fat mass (0.75) (P < 0.05). Although BIA results were not as accurate as DXA and DXA remains the gold standard method for clinical assessment, BIA can be an alternative method for investigating body composition among children in large cohort field studies. Calcaneal QUS and DXA are not interchangeable methods for measuring bone density in children similar to our study population.


Epidemiology and outcome of patients admitted to intensive care after anaphylaxis in France: a retrospective multicentre study.
Few data are available on patients who have experienced anaphylaxis and were admitted to ICUs. The purpose of this observational study was to describe the epidemiology and management of these patients. This was a multicentre retrospective study carried out in 23 French ICUs between 2012 and 2017. All patients who suffered anaphylaxis and were transferred to an ICU were included. Data were collected using an electronic database after approval by an ethics committee. A total of 339 patients were included, and 17 (5%) died secondary to anaphylaxis. The main triggers were drugs (77%), contrast media (11%), and food (7%). Epinephrine was administered before ICU admission in 88% of patients with Grade III anaphylaxis and 100% of patients with Grade IV anaphylaxis. Most patients with Grades III and IV anaphylaxes did not receive the recommended dose of i.v. fluid of 30 ml kg-1 within the first 4 h of ICU admission. The time to epinephrine administration was not statistically different between survivors and non-survivors, but non-survivors received a higher dose of epinephrine (median: 5 [3-10] vs 3 [2-7] mg; P<0.0001), which suggests that some forms of anaphylactic shock may be resistant to epinephrine. In multivariate analysis, only lactate concentration at ICU admission was a predictor of death (odds ratio: 1.47 [1.15-1.88]; P=0.002). Lactate concentration at ICU admission appeared to be the most reliable criterion for assessing prognosis. Epinephrine is widely used during anaphylaxis, but the volume of fluid resuscitation was consistently lower than recommended. NCT04290507.


[Ultrasound role in assessment of vesicoureteral reflux endoscopic treatment results].
Since the beginning of the application of the RVU treatment, the use of the ultrasound was used taking into account two main indications/symptoms: a) identification of the complications; b) assessment of the result (visualization of the implanted material and the presence of the "uretheral jet" by means or through/of ecodoppler-color). To determine the value of the ultrasound in the assessment of the result of the endoscopic treatment of the RVU and in the detection of its complications. From 2001-2002 we have carried out the endoscopic treatment to an overall of 261 ureteral units of all degree and etiology. 246 were assessed post-operation with an ultrasound per month and all of them were evaluated with a cistography after 3 months. In a random sample of 92 units, the result of the isotopic cistography has been compared with the visualization of the implanted material in the bladder; and in a random sample of 56 units, the result of the isotopic cistography has been compared with the presence of ureteral jet in the study with ecodoppler-color after moisturizing of the patient. In order to do, we have done two corresponding comparative charts 2 x 2 and we have calculated the Sensibility and Specificity of the tests, as well as their predictive positive and negative values, the degree of similarity of both tests with the Kappa index, and the degree of statistical relevance with Chi squared. The ultrasound did not show significant changes if compared to previous studies in 213 units (86,58 %) although in 5 patients an ectasia has been identified as attributed to the treatment. 3 of this patients have developed renoureteral pain, and in 2 pain has spontaneously disappeared as shown in later tests. The S and the E of the presence of implanted material is 94% and 10%respectively and its VPP and VPN of 80% and 10% and estadistical. The S and E of the jet visualization is 82% and 30%, with a VPP of 84% and a VPN of 27%, a level of statistical relevance of 0.836 and a degree of correlation of 0.121. Ultrasound is not a useful technique in the assessment of the result of the endoscopic treatment of the RVU. The role it plays in the assessment of complications is a small one and its use is only indicated to confirm the suspicion of ectasia in those patients that present renoureteral pain.


Long-term survival data of patients with limited disease small cell lung cancer: a retrospective analysis.
In patients with limited disease small cell lung cancer (LD-SCLC) treated with concurrent chemoradiotherapy (CCRT), long-term survival data have not been fully evaluated. Moreover, the association between long-term prognosis and prognostic factors has not been sufficiently investigated. In this retrospective study, we evaluated the efficacy of CCRT in 120 patients with LD-SCLC with a plan for curative CRT using concurrent accelerated hyperfractionated radiotherapy. The patients had a median age of 65.5 years, predominantly male (73%), and had clinical stage III disease (80%). The median follow-up time for overall survival (OS) was 72.2 months, median OS was 42.5 months, and the 3-year and 5-year survival rates were 52.4% and 41.8%, respectively. The median progression-free survival (PFS) was 12.5 months, and the 3-year and 5-year PFS rates were 37.6% and 33.6%, respectively. The 5-year OS rates of patients who achieved PFS at each time point were 70.9%, 83.6%, and 91.9% at 12, 24, and 36 months, respectively. The gradual increase in the 5-year OS rate following PFS extension and initial depression of the Kaplan-Meier curve showed disease progression frequently occurred in the first 2 years after initiation of CCRT. The Cox proportional hazards model showed no significant factors correlated with long-term survival through univariate and multivariate analyses. Although the prognostic factors associated with long-term prognosis in LD-SCLC were not identified, the 5-year survival rate was 41.8%, and among patients without disease progression at 2 years, the 5-year survival rate was 83.6%. These data suggested that the prognosis of patients with LD-SCLC was improving.


Synthesis and characterization of a sulfated pentasaccharide containing the Lewisx motif.
We report the synthesis of a sulfated pentasaccharide containing the Lewis(x) motif used for an NMR study described in Carbohydr. Res. 2003, 338, this issue, see following communication: doi:10.1016/S0008-6215(03)00243-X, using the dibutylstannylene acetal methodology.


Creating COVID-19 alternate care site trainings for interprofessional teams.
To describe the planning and development of alternate care site (ACS) trainings for community COVID care delivery. A timeline of activities by the core training team is presented from the lens of the State of Colorado Emergency Operations, leading to the pilot test of a templated training that was completed during the first week of June 2020. Lessons learned and training topics are described. This case study of the Colorado experience developing training for community-based COVID care delivery sites can inform other public health planners creating the same in their locales. And, public access materials from this project may supplement training for both public health and community health nurse educators.


High complication rate in locking plate fixation of lower periprosthetic distal femur fractures in patients with total knee arthroplasties.
Fixation of the distal portion of the femur in patients with total knee arthroplasties can be challenging. Locking plates have emerged as a promising treatment. Twenty-seven patients with periprosthetic distal femur fractures after total knee arthroplasties were treated using a contralateral reverse distal femoral locking plate. The average time for union and weight-bearing was 4.5 ± 2.7 months. The union rate was 89%. Thirty-seven percent experienced complications, with 2 delayed unions (7.4%), 1 nonunion (3.7%), and 7 fixation failures (26%). Alteration in blood supply and biomechanics as well as poor existing bone quality and minimal distal femur bone stock may contribute to treatment difficulties.


Bleaching in endodontics: an online study guide.
The Editorial Board of the Journal of Endodontics has developed a literature-based study guide of topical areas related to endodontics. This study guide is intended to give the reader a focused review of the essential endodontic literature and does not cite all possible articles related to each topic. Although citing all articles would be comprehensive, it would defeat the idea of a study guide. This section presents bleaching of endodontically treated teeth, bleaching of teeth with vital pulps, and cervical resorption associated with bleaching.


Bending elastic modulus of red blood cell membrane derived from buckling instability in micropipet aspiration tests.
Observation of cell membrane buckling and cell folding in micropipette aspiration experiments was used to evaluate the bending rigidity of the red blood cell membrane. The suction pressure required to buckle the membrane surface initially was found to be about one-half to two-thirds of the pressure that caused the cell to fold and move up the pipet. A simple analytical model for buckling of a membrane disk supported at inner and outer radii correlates well with the observed buckling pressures vs. pipet radii. The buckling pressure is predicted to increase in inverse proportion to the cube of the pipet radius; also, the buckling pressure depends inversely on the radial distance to the toroidal rim of the cell, normalized by the pipet radius. As such, the pressure required to buckle the membrane with 1 X 10(-4) cm diam pipet would be about four times greater than with a 2 X 10(-4) cm pipet. This is the behavior observed experimentally. Based on analysis of the observed buckling data, the membrane bending or curvature elastic modulus is calculated to be 1.8 X 10(-12) dyn-cm.


Calcium homeostasis and exercise.
Calcium homeostasis is altered by strenuous physical exercise. The mechanism is unclear. Our study was designed to investigate this relationship, particularly any associated changes in the calcium regulating hormones. Six subjects carried out a strenuous exercise programme for 10 min on a bicycle ergometer. Blood samples were analysed for ionized calcium, total calcium, calcitonin and pH. Plasma parathormone was assayed using a new and very sensitive N-terminal assay. Serum ionized calcium was significantly elevated by exercise at 50% of maximum aerobic capacity (VO2 max). The rise persisted until the late recovery phase, when it fell significantly below resting levels. Plasma parathormone levels were initially depressed by moderate exercise (50% VO2 max.) but were significantly elevated during and immediately after severe exercise. Our results suggest that exercise stimulates the hormonal, osteolytic influences acting on the skeleton, with increases in plasma parathormone and mobilisation of calcium stores. These changes may provide a supply of raw material allowing the osteogenic mechanical forces initiated by exercise to produce a positive skeletal balance. In view of the possible relevance of these findings to the understanding and management of osteoporosis we feel that this area merits further study.


Larval feeding stimulants for a rutaceae-feeding swallowtail butterfly, Papilio xuthus L. in Citrus unshiu leaves.
Larvae of a swallowtail butterfly, Papilio xuthus L., feed exclusively on plants of the family Rutaceae, including various Citrus crops. Larvae were strongly stimulated to feed on paper strips impregnated with ethanolic extracts of host-plant leaves. Stimulation of feeding on extracts of Citrus unshiu leaves required a mixture of chemicals including sugars (D: -glucose, D: -fructose, and D: -sucrose), a betaine [(-)-stachydrine], a cyclic peptide (citrusin I), a polymethoxyflavone (isosinensetin), and the lipids 1-linolenoylglycerol, 1-linoleoylglycerol, 1-octadecenoylglycerol, 1-stearoylglycerol, and 1,2-dilinolenoyl-3-galactosyl-sn-glycerol. When these compounds were assayed individually, few larvae consumed test strips. However, larvae readily chewed the test strips treated with a mixture of all compounds, indicating that host recognition by P. xuthus larvae is mediated by a specific combination of both primary and secondary substances. Comparison of 11 stimulant components with 10 compounds from C. unshiu leaves previously reported as stimulant components for oviposition by P. xuthus adult females revealed only one compound, stachydrine, as an ingredient in common. While the larval feeding-stimulant mixture is dominated by nutrients and other compounds of general significance for primary metabolism, the component oviposition stimulants are mostly secondary substances, including flavonoid glycosides, protoalkaloids, a cyclitol, and a betaine, that have restricted distributions in plants. Reliance by adult females on unique profiles of secondary compounds presumably reflects the need to locate and recognize specific host-plant species within a diverse flora. Since the initial host choice for the larvae is made typically by the ovipositing female, however, unique secondary compounds may be less important for larval feeding than are compounds useful for indicating food and microhabitat quality once on the host plant.


Cytogenetics, conserved synteny and evolution of chicken fucosyltransferase genes compared to human.
Fucosyltransferases appeared early in evolution, since they are present from bacteria to primates and the genes are well conserved. The aim of this work was to study these genes in the bird group, which is particularly attractive for the comprehension of the evolution of the vertebrate genome. Twelve fucosyltransferase genes have been identified in man. The orthologues of theses genes were looked for in the chicken genome and cytogenetically localized by FISH. Three families of fucosyltransferases: alpha6-fucosyltransferases, alpha3/4-fucosyltransferases, and protein-O-fucosyltransferases, were identified in the chicken with their associated genes. The alpha2-fucosyltransferase family, although present in some invertebrates and amphibians was not found in birds. This absence, also observed in Drosophila, may correspond to a loss of these genes by negative selection. Of the eight chicken genes assigned, six fell on chromosome segments where conservation of synteny between human and chicken was already described. For the two remaining loci, FUT9 and FUT3/5/6, the location may correspond to a new small syntenic area or to an insertion. FUT4 and FUT3/5/6 were found on the same chicken chromosome. These results suggest a duplication of an ancestral gene, initially present on the same chromosome before separation during evolution. By extension, the results are in favour of a common ancestor for the alpha3-fucosyltransferase and the alpha4-fucosyltransferase activities. These observations suggest a general mechanism for the evolution of fucosyltransferase genes in vertebrates by duplication followed by divergent evolution.


[Age-related indicators of the rheorectography in healthy persons].
Using the method of rheography the authors studied the rectal circulation in 77 healthy individuals. The electrodes of different length (30, 70, 100, 130 and 160 mm) designed expressly for the recording of the rheorectography findings were used. On the grounds of the analysis of 369 RRG the authors have drawn the conclusion about reliability and prospects of this electrophysiological study and set forth the normal indices of RRG as related to the age.


[Current concept for the microbiological safety of cell-based medicinal products].
Ensuring microbiological safety in advanced-therapy medicinal products is still a big challenge for manufacturers. There are fundamental problems, especially in cell-based medicinal products, regarding sterility of source materials, short shelf-life of final products, and the selection of suitable microbiological methods. Different from classical medicinal products, there is the need to evaluate a large number of possible risks and to calculate the risk-benefit balance. Depending on the source material, the presence of micro-organisms with specific growth requirements has to be considered. They cannot be detected by conventional testing methods, but may replicate after the application of the preparation in the recipient. Mycoplasmas are the primary representatives of these contaminants and specific testing procedures are required. Additionally, depending on the source and processing of the biological material, specific testing methods for mycobacteria and other contaminants should be included. Alternative microbiological methods (e.g. NAT, flow cytometry) should be applied in order to reduce the time to detection and to provide reliable results before application of a preparation, but should be also assessed for their possible use for the detection of conventionally undetectable micro-organisms.


Clinical and biological significance of an isozyme tumor marker--PLAP.
In 1930 the determination of serum alkaline phosphatase in patients with bone or liver disease ushered in the era of clinical enzymology. The association of elevated (bone) alkaline phosphatase in serum of patients with osteogenic sarcoma was the first evidence that tumor cells themselves produced the enzyme. It became clear, however, in the 1960s that the serum alkaline phosphatase was not a single enzyme but consisted of a family of isozymes originating from liver, bone, intestine, and placenta. This was a consequence of the introduction of a combination of electrophoretic separations, heat inactivation, and organ-specific amino acid inhibitors. This combination of measurements made possible the demonstration of a serum alkaline phosphatase of lung cancer origin, as confirmed by the histochemical visualization in lung cancer of the Regan Isozyme (placental alkaline phosphatase-PLAP). At present, the measurement of PLAP has its greatest utility as a tumor marker in seminoma and ovarian cancer. A PLAP-like isozyme in normal testis and ovary is expressed in these and other neoplasias and appears to be related to rare alleles of placental alkaline phosphatase. Current studies have utilized a panel of monoclonal antibodies to detect useful epitopes that suggest that PLAP and PLAP-like isozymes are coded by different genes. The PLAP gene has now been cloned and sequenced by Millan and others. This fundamental new information is providing a base line that will make it possible to explain the overlapping specificities of intestinal and placental isozymes, the degree of uniqueness of the PLAP-like isozyme, the precise mechanism of uncompetitive inhibition by L-phenylalanine and the evolutionary history of the alkaline phosphatases.(ABSTRACT TRUNCATED AT 250 WORDS)


Fractionated Stereotactic Radiation Therapy for Pituitary Adenomas: An alternative escalating protocol of hypofractionated stereotactic radiotherapy delivering 35Gy in 5 fractions.
Evaluate efficacy and toxicity of hypofractionated stereotactic radiotherapy (HSRT) for patients treated for pituitary adenoma (PA) with an alternative HSRT escalating protocol delivering 35Gy in 5 fractions. From June 2007 to March 2017, 29 patients with pituitary adenoma were treated in Antoine Lacassagne Cancer Centre with an alternative HSRT protocol. Prescribed dose was 35Gy in 5 fractions of 7Gy. Radiographic responses were assessed by annual MRI. Hormone blood samples were evaluated each year after HSRT. A total of 29 patients aged between 23 and 86 years (median 54 years) were included. Twelve patients received HSRT for recurrent cases and 12 received postoperative adjuvant HSRT, 5 patients did not have surgery. After a median follow-up period of 47 months local control rate was 96%. One patient presented an out-field tumor regrowth 73 months after HSRT. The majority of PA were endocrine-active (18 patients, 62%). After HSRT, 8 patients (44%) presented complete response on initial secretion, 4 patients (23%) presented partial response on initial secretion. Four patients (14%) presented grade 2 or more acute radiation toxicities. One grade 4 visual disorder was observed for one patient. HSRT delivering 35Gy in 5 fractions represents a feasible treatment and shows promising results to reduce hormonal overproduction and to improve local control in PA.


[Sensitivity of the splenic cells of different mouse strains to the antiproliferative action of alkylating compounds].
A method of quantitative evaluation of lymphocytes' sensitivity to the antiproliferative effect of the alkylating drugs has been developed. Chlorbutin, mafosfamide (Asta Z 7654) and "active" metabolites of cyclophosphamide were studied. This research allowed to distinguish more sensitive strains (DBA/2 and C57BL/6) and those with low sensitivity (BALB/c and CC57BR). These differences do not depend on proliferation reaction, neither on the type of alkylating drugs nor haplotypes H-2.


mRNA for interphotoreceptor retinoid-binding protein (IRBP): distribution and size diversity in vertebrate species.
Northern blots of total retinal RNA from a number of different vertebrate species were probed with a cDNA fragment corresponding to translated portions of bovine IRBP mRNA. A hybridizing band was detected in normal human retina (4.6 kb), Y-79 human retinoblastoma cells (4.4 kb), and in retinas of monkey (4.6 kb), guinea-pig (4.9 kb), mouse (6.1 kb), rat (two bands at 5.4 kb and 6.6 kb), rabbit (6.3 kb), cow (6.5 kb), and hamster (7.6 kb). Thus, the IRBP gene is expressed in the retinas of a wide variety of mammalian species. The mRNAs could be readily detected in about 20 micrograms of total RNA, suggesting that, in these species, IRBP message is relatively abundant. In contrast, only very weak hybridization was detected on northern blots of the three bird species examined (chicken, duck, quail). IRBP mRNA is thus relatively well expressed in mammals, but not in birds.


On-target versus off-target effects of drugs inhibiting the replication of SARS-CoV-2.
The current epidemic of coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) calls for the development of inhibitors of viral replication. Here, we performed a bioinformatic analysis of published and purported SARS-CoV-2 antivirals including imatinib mesylate that we found to suppress SARS-CoV-2 replication on Vero E6 cells and that, according to the published literature on other coronaviruses is likely to act on-target, as a tyrosine kinase inhibitor. We identified a cluster of SARS-CoV-2 antivirals with characteristics of lysosomotropic agents, meaning that they are lipophilic weak bases capable of penetrating into cells. These agents include cepharentine, chloroquine, chlorpromazine, clemastine, cloperastine, emetine, hydroxychloroquine, haloperidol, ML240, PB28, ponatinib, siramesine, and zotatifin (eFT226) all of which are likely to inhibit SARS-CoV-2 replication by non-specific (off-target) effects, meaning that they probably do not act on their 'official' pharmacological targets, but rather interfere with viral replication through non-specific effects on acidophilic organelles including autophagosomes, endosomes, and lysosomes. Imatinib mesylate did not fall into this cluster. In conclusion, we propose a tentative classification of SARS-CoV-2 antivirals into specific (on-target) versus non-specific (off-target) agents based on their physicochemical characteristics.


Detection and Measurement of Chimeric RNAs by RT-PCR.
Reverse-transcription polymerase chain reaction (RT-PCR) is a powerful combination of assays useful in detection and measurement of expressed RNA transcripts. RT-PCR consists of RNA isolation and reverse transcription into complementary DNA (cDNA), which can then be used as input to a variety of PCR-based procedures such as standard PCR, real-time or quantitative PCR (qPCR or qRT-PCR), or TaqMan PCR procedures. These assays are useful in detection of chimeric transcripts, especially when careful consideration is applied to experimental design. In this chapter, we provide guidelines and procedures for use of RT-PCR in detection and measurement of chimeric RNA expression.


Inhibition of excessive kallikrein-8 improves neuroplasticity in Alzheimer's disease mouse model.
We recently identified excessive cerebral kallikrein-8 (KLK8) mRNA and protein levels at incipient stages of Alzheimer's disease (AD) in AD patients and TgCRND8 mice. Additionally, we showed that antibody-mediated KLK8 inhibition exerts therapeutic effects on AD along with enhancing neuroplasticity, resulting in improved spatial memory in mice. Mounting evidence further substantiates an important role of the protease KLK8 in neuroplasticity. In the present study we sought to gain new mechanistic insights in the interplay between KLK8, neuroplasticity and tau phosphorylation in the context of AD. We here demonstrate that KLK8 inhibition increased the number of hippocampal Ki-67 and doublecortin positive, proliferative neuronal progenitor cells in transgenic mice, whereas the same action in wildtypes had no effect. In line with these results, KLK8 inhibition reduced the levels of its pro-proliferative interaction partners KLK6 and protease-activated receptor 2 only in wildtypes, while the levels of its proliferation-supporting substrate neuregulin-1 and the non-complexed form of its complexing-partner phosphatidylethanolamine binding protein 1 were enhanced in both genotypes. Concomitant incubation of beta-amyloid (Aβ)-producing primary neurons with KLK8 and its inhibitory antibody increased neurite complexity and soma size. KLK8 inhibition in SH-SY5Y cells or in primary neurons increased levels of the neuroplasticity-supporting KLK8 substrate ephrin receptor B2 (EPHB2) and total tau while decreasing the relative amount of phospho-tau in relation to total tau. KLK8 blockade further enhanced cell proliferation in SH-SY5Y cells. Additional co-incubation with an inhibitory anti-EPHB2 antibody decreased total tau levels and neurite complexity and increased the ratio of phospho-tau/total tau, underlining the key role of EPHB2 on this plastic change. In a reverse in vitro approach, KLK8 induction reduced EPHB2 and total tau and increased the ratio of phospho-tau/total tau, leading to impaired proliferation and neuronal differentiation. These results underline the therapeutic potential of KLK8 inhibition by counteracting plasticity deficits in AD-affected brain.


Gene Expression of Human Beta-Defensin-3 and Cathelicidin in the Skin of Leprosy Patients, Household Contacts, and Healthy Individuals from Indonesia.
Leprosy, a chronic infectious peripheral neuropathy, is caused by Mycobacterium leprae. This bacterium produces triacylated lipopeptides that can induce the immune system via the Toll-like receptor 2/1 (TLR 2/1) complex. Activation of TLR 2/1 produces proinflammatory cytokines and antimicrobial peptides (AMPs), including human beta-defensin-3 (HBD-3) and cathelicidin. To analyze differences in gene expression of HBD-3 and cathelicidin in the skin of leprosy patients, household contacts, and healthy individuals. An analytic observational study was conducted at the Outpatient Clinic of Dermatology and Venereology of Dr Mohammad Hoesin General Hospital, Palembang, Indonesia, from January 2021 to June 2022. In each group of 18 subjects, 72 samples were collected, including skin lesion in leprosy patients, normal skin in leprosy patients, household contacts, and healthy individuals. A comparison of HBD-3 and cathelicidin gene expression between the four groups was analyzed using Pearson Chi Square, Kruskal-Wallis, and Mann-Whitney Test. The median value of HBD-3 gene expression on skin lesion in leprosy patients was 260.61 (0.19-3734.10); normal skin in leprosy patients was 1.91 (0.01-151.17); household contacts skin was 7.93 (0.27-121.10); and healthy individuals' skin was 1.00 (1.00-1.00) is highly significant difference (p < 0.0001). The median value of cathelicidin gene expression on skin lesion in leprosy patients was 38.72 (0.28-1852.17); normal skin in leprosy patients was 0.48 (0.01-15.83); household contacts skin was 9.8 (0.04-128.0); and healthy individual skin was 1.00 (1.00-1.00), also highly significant difference (p < 0.0001). Gene expression of HBD-3 and cathelicidin increased in skin lesions of leprosy patients and household contacts.


No morphine sparing effect of ketamine added to morphine for patient-controlled intravenous analgesia after uterine artery embolization.
Pain following embolization of the uterine arteries (UAEs) is variable and may be very severe requiring large doses of parenteral opioids for relief. The present study tested the hypothesis that the addition of ketamine to i.v. patient-controlled morphine reduces the amount of morphine required for pain-control during the first 24 h after UAE embolization. Fifty-six patients undergoing UAE embolization for treatment of symptomatic uterine leiomyomata were randomized to receive either 2 mg/ml of morphine (Control group, n=30) or 2 mg/ml of both morphine and ketamine (Ketamine group, n=26) by i.v. patient-controlled analgesia (IV-PCA). Pump settings were bolus dose 1 ml, lockout 10 min, no background infusion. In addition, all patients received diclofenac and acetaminophen for pain relief. Pain scores, morphine consumption and adverse events like nausea, vomiting, itching, visual disturbances, anxiety, dreaming and hallucinations, if any, were recorded for 24 h after embolization. The mean +/- SD 24-h consumption of patient-controlled morphine was 38.3 +/- 21.0 mg in the Ketamine group vs. 33.3 +/- 18.3 mg in the Control group (NS). The difference between the means was 5.0 mg (95% confidence interval: -5.7; 15.6). One patient in the Ketamine group vs. none in the Control group experienced auditory hallucinations. Studying an unselected group of patients undergoing embolization of the UAEs for treatment of symptomatic uterine leiomyomata under conditions of basal analgesia with acetaminophen and diclofenac, we failed to demonstrate any morphine-sparing effect of IV-PCA ketamine and morphine compared with IV-PCA morphine alone.


Imaging of a synchronous neuronal assembly in the human visual brain.
Perception, motion, and cognition involve the formation of cooperative neuronal assemblies distributed over the cerebral cortex. It remains to explore what characterizes the assemblies, their location, and the structural substrate of assembly formation. In this EEG/fMRI study, we describe the response of the visual areas of the two hemispheres in subjects who viewed bilateral iso-oriented (IG) or orthogonally-oriented (OG) moving gratings projected in the two hemifields. The IG stimulus synchronized activity across the hemispheres, as shown by an increased EEG coherence. The increase was restricted to the occipital electrodes and to the beta band. Compared with OG, IG increased the BOLD signal in a restricted territory corresponding to area VP/V4. Within this territory, a linear relation was found between the increased interhemispheric EEG coherence and BOLD. Thus, the increased BOLD localized a trans-hemispheric, synchronous neuronal assembly probably achieved by a callosal cortico-cortical connection. This assembly might reflect an early stage of perceptual grouping since the IG stimulus conforms to Gestalt psychology principles of collinearity and common fate.


Effects of perampanel on secondary bilateral synchrony and behavioral problems in adolescents with epilepsy showing insufficient response with levetiracetam.
The purpose of this study was to determine the efficacy of perampanel (PER) on secondary bilateral synchrony (SBS) and behavioral problems in adolescents with epilepsy who showed insufficient response to levetiracetam (LEV). The primary criterion for patient selection was the presence of SBS. The criteria such as age between 12 and 18 years, seizures refractory to antiseizure medications including LEV, at least four seizures a month, neuropsychological impairments, and at least 12 months of follow-up also had to be fulfilled. Patients were given PER at an initial dose of 2 mg/day, followed by increments of +2 mg/day every 2 weeks. Concomitant medications remained unchanged during evaluation period. Responders for electroencephalogram (EEG) and seizures were identified as showing a ≥50 % reduction from the baseline SBS on EEG and seizure frequency, respectively. Neuropsychological impairments as per the Japanese manuals for the Aberrant Behavior Checklist (ABC-J) were evaluated before and after PER administration. Eight of 14 patients were considered responders for seizures. Among these 8 responders, 6 patients were considered responders for EEG and behavioral problems. Mean ABC-J scores in both EEG non-responders and responders were decreased significantly at 12 months (p < 0.05 and p < 0.05, respectively). ABC-J scores were significantly lower in EEG responders than in EEG non-responders at 12 months (p < 0.01). Moreover, among patients with decreased ABC-J scores, the degree of decrease was larger in EEG responders than in EEG non-responders (p < 0.01). PER may be useful in reducing SBS on EEG, seizure frequency, and behavioral problems.


The SIN domain of the histone octamer is essential for intramolecular folding of nucleosomal arrays.
The SIN domain within histones H3 and H4 is defined by a set of single amino acid substitutions that were initially identified as mutations that alleviate the transcriptional defects associated with inactivation of the SWI/SNF chromatin remodeling complex. Here we use recombinant histones to investigate how Sin- versions of H4 alter the structure of nucleosomal arrays. We find that an R45C substitution within the SIN domain of H4 does not disrupt nucleosome positioning nor does this Sin- version alter the accessibility of nucleosomal DNA. In contrast, we find that the R45C substitution eliminates Mg2+-dependent, intramolecular folding of the nucleosomal arrays. Our results suggest that Sin- versions of histones may alleviate the need for SWI/SNF in vivo by disrupting higher-order chromatin folding.


Extrudates of lipophilic tetracycline complexes: A new option for periodontitis therapy.
The objective of this study was to develop an improved drug delivery system for the local antimicrobial treatment of periodontitis, that offers enhanced drug stability, easy application and controlled release over several weeks. Chelate complexes consisting of a tetracycline antibiotic and a fatty acid salt were developed. Minocycline and doxycycline were paired with magnesium- and calcium stearate in different molar ratios. These chelate complexes stabilize the active pharmaceutical ingredient and enable the incorporation into a PLGA (poly(lactic-co-glycolic acid)) polymer matrix via hot melt extrusion. The chelate complexes were characterized via UV/Vis- and IR-spectroscopy. A high antibiotic activity of the complex was observed in a disc diffusion test. The drug complex was mixed with different PLGA-polymers and cryomilled in advance of the extrusion. The hot melt extrusion yielded homogeneous extrudates with a diameter from 600 to 900 µm. They contain 11.5% of minocycline, are adjustable in length and are easy to handle. In vitro release studies revealed a controlled release of the drug over 42 days. In conclusion, the developed extrudates are promising systems to improve the treatment of periodontitis.


Isolation of the homogeneous constituents from non-diffusible sugar-peptide (NSP) fraction originating from bovine plasma. III. The method of isolation and partial characterization of the four peptide constituents.
The purification of four different peptides from the NSP fraction of bovine plasma, using: organic solvents extraction, column Sephadex G-50 filtration, thin-layer Sephadex G-25 electrophoresis in 5 M guanidine hydrochloride and thin-layer Bio-Gel P-6 electrophoresis methods was described. The molecular weights of the isolated peptides and their amino acid composition were determined. The dose-dependent effect two of the four peptides on 3H-thymidine incorporation into BHK-21 and BHK/RSV cells was described. The results support previous observations that the NSP fraction contains a peptide growth prometing factor and a potent peptide growth inhibitor. The possible physiological role of the peptide growth inhibitor was discussed.


The cardiomyocyte cell cycle in hypertrophy, tissue homeostasis, and regeneration.
Mammalian cardiomyocytes withdraw from the cell cycle shortly after birth. Although the adult heart is unable to regenerate, numerous reports have shown that adult cardiomyocytes exhibit a dynamic range of cell cycle activity under various physiological and pathological conditions. Reason and consequence of cardiomyocyte cell cycle activity remain unclear and have led to a number of misconceptions. Understanding the scenarios in which cycling happens may promote new perspectives on the differentiated state of cardiomyocytes, treatments for hypertrophy, heart regeneration and cancer therapy. In this review we discuss the result of cardiomyocyte cell cycle activity in aging and disease and studies manipulating cardiac cell cycle activity to promote cardiac regeneration. In addition, we focus on cardiomyocyte differentiation, cell cycle exit, and the relationship between ploidy and regenerative potential. Finally, we provide observations that may further advance the goal of inducing adult mammalian heart regeneration through cardiomyocyte proliferation.


The Brain of Dexter Morgan: the Science of Psychopathy in Showtime's Season 8 of Dexter.
This article identifies and discusses on the ways in which biological influences to psychopathy are thematically portrayed in the eighth season of Dexter to describe Dexter's psychopathy, particularly focusing on fatalism and the inevitability of succumbing to one's "biological self." This paper, utilizing traditional content analysis, focuses on seven qualitative themes surrounding "biological fatalism" and psychopathy in this final season of Dexter. As lay theories of psychopathy are thought to originate from the media's conceptualization of the disorder, such thematic portrayals serve to potential affect lay understandings of psychopathy and correspondingly, how the disorder is treated and perceived in the criminal justice process as a modern psychopathy-related "CSI Effect." The conclusion focuses on the messages that this final season of Dexter sends to the lay public about the biological influences to psychopathy and how this may create implications for the criminal justice system.


Contemporary Care and Outcomes of Critically-ill Children With Clinically Diagnosed Myocarditis.
To describe contemporary management and outcomes in children with myocarditis who are admitted to a cardiac intensive care unit (CICU) and to identify the characteristics associated with mortality. All patients in the Pediatric Cardiac Critical Care Consortium (PC4) registry between August 2014 and June 2021 who were diagnosed with myocarditis were included. Univariable analyses and multivariable logistic regression evaluated the factors associated with in-hospital mortality. There were 847 CICU admissions for myocarditis in 51 centers. The median age was 12 years (IQR 2.7-16). In-hospital mortality occurred in 53 patients (6.3%), and 60 (7.1%) had cardiac arrest during admission. Mechanical ventilation was required in 339 patients (40%), and mechanical circulatory support (MCS) in 177 (21%); extracorporeal membrane oxygenation (ECMO)-only in 142 (16.7%), ECMO-to-ventricular assist device (VAD) in 20 (2.4%), extracorporeal cardiac resuscitation in 43 (5%), and VAD-only in 15 (1.8%) patients. MCS was associated with in-hospital mortality; 20.3% receiving MCS died compared to 2.5% without MCS (P < 0.001). Mortality rates were similar in ECMO-only, ECMO-to-VAD and VAD-only groups. The median time from CICU admission to ECMO was 2.0 hours (IQR 0-9.4) and to VAD, it was 9.9 days (IQR 6.3-16.8). Time to MCS was not associated with mortality. In multivariable modeling of patients' characteristics, smaller body surface area (BSA) and low eGFR were independently associated with mortality, and after including critical therapies, mechanical ventilation and ECMO were independent predictors of mortality. This contemporary cohort of children admitted to CICUs with myocarditis commonly received high-resource therapies; however, most patients survived to hospital discharge and rarely received VAD. Smaller patient size, acute kidney injury and receipt of mechanical ventilation or ECMO were independently associated with mortality.


Outcomes in primary and revision surgery for pediatric onset stapedial pathology.
To analyze audiometric outcomes of surgery for pediatric onset stapedial pathology (POSP). Retrospective cohort study. Single-institution database. Retrospective analysis of 809 stapes procedures performed at a single high-volume tertiary referral otology practice, 75 of which were POSP cases. Oval window drillout for thick footplate and aborting the procedure were more common in POSP cases compared to the rest of the cohort (28.0% versus 9.8% [p < .001] and 5.3% versus 1.2% [p = .007], respectively). Postoperative complications were rare. Postoperative Air-Bone Gap (pABG) closure to ≤20 dB was significantly lower in the POSP group (80.0% versus 89.0%, p = .021). Rates of sensorineural hearing loss (SNHL) were not different between the two groups. Poor audiometric outcomes in the POSP group were largely driven by revision cases; pABG≤10 dB was 60.3% in primary cases but only 11.8% in revisions (p < .001), and postoperative SNHL was significantly higher in revisions (29.4% versus 0.0%, p < .001). In multivariate analysis, POSP was not a predictor of successful closure of the pABG at either level, nor did it predict significant postoperative SNHL. Surgery for pediatric onset stapedial pathology had significantly worse audiometric outcomes, particularly in revision cases, as compared to the rest of the cohort.


The molecular events behind ferulic acid mediated modulation of IL-6 expression in LPS-activated Raw 264.7 cells.
Identification of new antioxidant and anti-inflammatory bioactive molecules is an important tool for selecting effective formulations for the treatment of inflammation. The mouse macrophage cell line RAW 264.7, lipopolysaccharide (LPS)-activated, is associated with an inflammation response. Activated macrophages produce reactive oxygen species (ROS), nitric oxide (NO) and inflammatory cytokines such as IL-6, TNF-α and IL-10. In the present study we have showed that pre-treatment with Ferulic Acid (FA) reduces NO accumulation in the culture medium of LPS-induced macrophage cells. Moreover, real-time experiments have revealed that FA has an inhibitory effect at the transcriptional level on the expression of some inflammatory mediators such as IL-6, TNF-α and iNOS and an activation effect on the expression of some antioxidant molecules such as Metallothioneins (MT-1, MT-2). Importantly, we have found that FA reduced the translocation of NF-E2-related factor 2 (Nrf2) and nuclear transcription factor-κB (NF-κB) into the nuclei through a reduction of the expression of phosphorylated IKK and consequently inhibited IL-6 and NF-κB promoter activity in a luciferase assay. Our data clearly suggest that FA anti-inflammatory effects are mainly mediated through IKK/NF-κB signalling pathway. Therefore, FA could represent a new natural drug extremely useful to improve anti-inflammatory treatment.


Genera-specific immunofluorescence labeling of ammonia oxidizers with polyclonal antibodies recognizing both subunits of the ammonia monooxygenase.
Polyclonal antibodies that recognize the two subunits AmoA and AmoB of the ammonia monooxygenase (AMO) were applied to identify ammonia-oxidizing bacteria by immunofluorescence (IF) labeling in pure, mixed, and enriched cultures. The antibodies against the AmoA were produced using a synthetic peptide of the AmoA of Nitrosomonas eutropha, whereas the antibodies against the AmoB had been developed previously is against the whole B-subunit of the AMO [Pinck et al. (2001) Appl Environ Microbiol 67:118-124]. Using IF labeling, the AmoA antibodies were specific for the detection of all species of the genus Nitrosomonas. In contrast, the antiserum against AmoB labeled all genera of ammonia oxidizers of the beta-subclass of Proteobacteria (Nitrosomonas, Nitrosospira, Nitrosolobus, and Nitrosovibrio). The fluorescence signals of the AmoA antibodies were spread all over the cells, whereas the signals of the AmoB antibodies were associated with the cytoplasmic membranes. The specificity of the reactions of the antisera with ammonia oxidizers were proven in pure and mixed cultures, and the characteristic IF labeling and the morphology of the cells enabled their identification at the genus level. The genus-specific IF labeling could be used to identify ammonia oxidizers enriched from various habitats. In enrichment cultures of natural sandstone, cells of the genera Nitrosomonas, Nitrosovibrio, and Nitrosospira were detected. Members of the genus Nitrosovibrio and Nitrosolobus were most prominent in enriched garden soil samples, whereas members of the genus Nitrosomonas dominated in enriched activated sludge. The antibodies caused only slight background fluorescence on sandstone and soil particles compared to oligonucleotide probes, which could not be used to detect ammonia oxidizers on these materials because of strong nonspecific fluorescence.


[A variant in integrating the activities of therapeutic and tuberculosis control services].
The author finds it appropriate to take advantage of antituberculous sanatoria for secondary prevention of various diseases during annual mass screening of population with account of pathomorphosis of tuberculosis.


Rosiglitazone plus metformin is effective and well tolerated in clinical practice: results from large observational studies in people with type 2 diabetes.
This study investigated the efficacy during daily practice of rosiglitazone (RSG) added to metformin (MET) in poorly controlled type 2 diabetes mellitus. Two post-marketing observational studies were conducted in Germany over 6 months. RSG (4 mg/day titrated to 8 mg/day as required) was added to existing MET in 11,014 subjects. Subjects were maintained on diet and exercise. Addition of RSG to MET significantly reduced median HbA 1c by 1.3% (8.1 vs. 6.8%; p < 0.0001) and median fasting blood glucose (FBG) by 47.0 mg/dl (171.0 vs. 124.0 mg/dl; p < 0.0001) after 6 months. The proportion of subjects achieving HbA(1c) targets of < or = 6.5 and < or = 7.0% increased from 3.5 to 38.8% and from 13.5 to 63.7%, respectively. Mean systolic and diastolic blood pressure decreased by 7 and 3 mmHg, respectively (p < 0.0001). Mean weight decreased by 1.7 kg and was constant or reduced in most (74.1%) subjects. Addition of RSG to MET significantly reduces median HbA 1c and FBG in clinical practice and is generally well tolerated.


Anterior and superior plate positions in diaphyseal clavicle fractures produce similar patient outcomes.
While diaphyseal clavicle fractures can be treated with plate fixation on either the superior or anteroinferior aspect of the clavicle, the optimal plate position remains controversial. The purpose of this study was to determine if anteroinferior vs. superior plating for clavicle fracture fixation leads to better patient outcomes. A retrospective review of patients who sustained clavicle fractures (OTA/AO 15.2) treated with superior or anteroinferior plating at a tertiary Level I trauma center from 2015 to 2021 was performed. The clinical outcomes of clavicle fractures were compared between groups treated with an anterior versus a superior approach via Mann-Whitney U and Chi-squared tests as appropriate to evaluate for differences in outcomes between the two plate positions. A total of 315 diaphyseal clavicle fractures were identified. One hundred and forty patients were excluded due to inadequate follow-up. Of the remaining 175 patients, 25 were treated with an anteroinferior approach (14%) and 150 were treated with a superior approach (86%). There were no differences in age, BMI, tobacco use, or substance use between the two groups (p > 0.05 for all). On univariate analysis, there was no difference in rate of union (p = 0.60), nerve injury (p = 0.60), infection (p = 1.0), implant-related irritation (p = 0.42), implant removal (p = 0.26), or revision (p = 1.0) based on approach. Contoured plates had an association with risk of nerve injury (p = 0.04). There are no differences in union, nerve injury, infection, symptomatic implant, or revision rate between anteroinferior and superior clavicle approaches. Plate positioning during diaphyseal clavicle fracture fixation can reasonably be dictated based on surgeon preference and ideal reduction quality.


One-pot lipase-catalyzed aldol reaction combination of in situ formed acetaldehyde.
A facile tandem route to α,β-unsaturated aldehydes was developed by combining the two catalytic activities of the same enzyme in a one-pot strategy for the aldol reaction and in situ generation of acetaldehyde. Lipase from Mucor miehei was found to have conventional and promiscuous catalytic activities for the hydrolysis of vinyl acetate and aldol condensation with in situ formed acetaldehyde. The first reaction continuously provided material for the second reaction, which effectively reduced the volatilization loss, oxidation, and polymerization of acetaldehyde, as well as avoided a negative effect on the enzyme of excessive amounts of acetaldehyde. After optimizing the process, several substrates participated in the reaction and provided the target products in moderate to high yields using this single lipase-catalyzed one-pot biotransformation.


Motorcyclist fatalities and the repeal of mandatory helmet wearing laws.
Previous studies had estimated that repeal of mandatory helmet wearing laws resulted in increases in the number of fatalities ranging from nearly 40% to essentially zero. This study was performed to determine more definitively the influence on motorcyclist fatalities of these repeals. After repeal, motorcyclist fatalities increased more in the states which repealed their laws than in those which did not in 24 cases out of 26, with the 95% confidence interval for the average effect being 25 +/- 6%. It is therefore concluded that repeals of mandatory helmet wearing laws for motorcyclists were followed by substantial increases in motorcyclist fatalities.


Glued intraocular lens implantation for eyes with defective capsules: A retrospective analysis of anatomical and functional outcome.
To analyze the anatomical and functional outcome of glued intra ocular lens (IOL) implantation technique and its modifications. Retrospective observational case series. This is a retrospective analysis of the patients who underwent glued intra ocular lens implantation from December 2007 to August 2010. Post operative uncorrected vision, best corrected visual acuity (BCVA), intra ocular pressure, IOL position, endothelial cells and anterior chamber reaction at their last follow up are analyzed from their concerned case sheets documentation. Subjective changes are analyzed via individual questionnaire. Immediate and late postoperative complications are also evaluated. Surgical modifications and the difference in the operated eyes are analyzed. Total 210 glued IOL eyes have been reviewed. Out of this 210, there are 152 (PMMA glued IOL), 21 (three piece foldable IOL), 5 (multifocal foldable IOL), 12 (pediatric glued IOL), 5 (20G sutureless vitrectomy), 2 (glued iris prosthesis) and 3 (transposition of posterior chamber IOL into anterior chamber). In combined surgeries there are, 5 (optical penetrating keratoplasty), 2 (descemet's stripping endothelial keratoplasty) and 3 (iridoplasty). The modifications in glued IOL are handshake technique, injectable or foldable glued IOL, Multifocal glued IOL and intraoperative 23/25G trocar cannula infusion. Decentration (1.97%), macular edema (1.97%) and optic capture (2.63%) are the post operative complications encountered in rigid glued IOL. Good patient satisfaction is seen in the eyes with IOL repositioning, IOL exchange and multifocal glued IOL. There is significant improvement in BCVA in PMMA IOL (p = 1.35 × 10(-5)) and foldable IOL (p = 0.000). Glued IOL seems to be a good alternative in IOL implantation in eyes with deficient capsules. The modifications in the existing technique decrease the learning time and risk for complications.


A Game-Theoretic Model of Cholera with Optimal Personal Protection Strategies.
Cholera is an acute gastro-intestinal infection that affects millions of people throughout the world each year, primarily but not exclusively in developing countries. Because of its public health ramifications, considerable mathematical attention has been paid to the disease. Here we consider one neglected aspect of combating cholera: personal participation in anti-cholera interventions. We construct a game-theoretic model of cholera in which individuals choose whether to participate in either vaccination or clean water consumption programs under assumed costs. We find that relying upon individual compliance significantly lowers the incidence of the disease as long as the cost of intervention is sufficiently low, but does not eliminate it. The relative costs of the measures determined whether a population preferentially adopts a single preventative measure or employs the measure with the strongest early adoption.


The effect of taxation and regulation on cigarette smoking: Fresh evidence from Turkey.
Enacting Law No 5247 in May 2008, Turkey has initiated crucial anti-tobacco policies in the last decade. This paper aims to reveal on the effect of anti-tobacco policies such as excise taxes and regulations on cigarette smoking. To this aim, I empirically investigate the long-term dynamics of demand for cigarettes in Turkey through the OLS estimation strategy under various scenarios and models. Using monthly and quarterly data that cover the pre- and post- anti-smoking policy periods, I estimate demand elasticities and compare the pre- and post- taxation and regulation terms. The results presented in the paper confirm that taxation and regulation have affected the long-term dynamics of demand for cigarettes. The price and income elasticities of demand for cigarettes are significantly higher than the previous literature on Turkey. Demand elasticities have increased on average in the anti-tobacco policies period.


The Human Tic Detector: An automatic approach to tic characterization using wearable sensors.
Current rating scales for Tourette syndrome (TS) are limited by recollection bias or brief assessment periods. This proof-of-concept study aimed to develop a sensor-based paradigm to detect and classify tics. We recorded both electromyogram and acceleration data from seventeen TS patients, either when voluntarily moving or experiencing tics and during the modified Rush Video Tic Rating Scale (mRVTRS). Spectral properties of voluntary and tic movements from the sensor that captured the dominant tic were calculated and used as features in a support vector machine (SVM) to detect and classify movements retrospectively. Across patients, the SVM had an accuracy, sensitivity, and specificity of 96.69 ± 4.84%, 98.24 ± 4.79%, and 96.03 ± 6.04%, respectively, when classifying movements in the test dataset. Furthermore, each patient's SVM was validated using data collected during the mRVTRS. Compared to the expert consensus, the tic detection accuracy was 85.63 ± 15.28% during the mRVTRS, while overall movement classification accuracy was 94.23 ± 5.97%. These results demonstrate that wearable sensors can capture physiological differences between tic and voluntary movements and are comparable to expert consensus. Ultimately, wearables could individualize and improve care for people with TS, provide a robust and objective measure of tics, and allow data collection in real-world settings.


Miltefosine decreases the cytotoxic effect of epirubicine and cyclophosphamide on mouse spermatogenic, thymic and bone marrow cells.
A new class of potent anticancer drugs, alkylphosphocholines has been recognized lately. Miltefosine (Hexadecylphosphochlorine, HPC) has been found to express select antineoplastic effect on human breast cancer skin metastases with simultaneous preservation of bone marrow proliferative activity and low clastogenicity. In the current study, we present data about the specific effect of two widely used cytostatics Cyclophosphamide (CP) and Epirubicine (ERb) applied separately or in combination with Miltefosine. C57BL6 mice were treated per os or intraperitonieally in doses corresponding to that in clinical use. Morphological, autoradiographic, ultrastructural and cytogenetic studies on spermatogenic, thymic and bone marrow cells were performed. It is found that compared with separate application, combinations of ERb or CP with Miltefosine slightly decreases spermatogonial proliferation and exerts milder effect on the structure of germinal and thymic cells. In addition, a lot of plasmocytes showed signs of active protein (antibody) synthesis. A significant reduction of aberrant chromosomes (clastogenicity) without changes in proliferative activity of bone marrow cells were recorded. In conclusion, the combine application of Miltefosine with ERb and CP decreased the destructive cytotoxic effects of ERb and CP on mouse spermatogenic and hematopoietic cells.


Statins in heart failure.
This article reviews the results from several recent reports describing the safety and efficacy of statin therapy in the setting of heart failure. It additionally discusses the ongoing controversy regarding the lipid paradox and possible mechanisms responsible for potential benefit of statin therapy in heart failure.


Treatment of hypertrophic burn scars by combination laser-cision and pinhole method using a carbon dioxide laser.
Hypertrophic burn scars induce cosmetic and functional complications. Although there are various treatment modalities, an ideal method has not yet been found. Recently, numerous laser treatment modalities have been introduced with encouraging results. To assess the efficacy and safety of combination therapy with laser-cision and pinhole method using a carbon dioxide (CO2 ) laser. We conducted retrospective chart review of patients with hypertrophic burn scars treated by combination laser-cision and pinhole method from January 2007 to December 2012. Nine patients with hypertrophic burn scars (mean age 31.2 years; range, 13-52 years) were treated with combination therapy over the past 6 years. Subjects were treated with one to three treatment sessions at 1-year intervals by laser-cision and five to eight treatment sessions at 2- to 3-month intervals by pinhole method. Two blinded observers evaluated photographs taken at baseline and 6 months after the final treatment. Compared with baseline, there was a mild to moderate improvement in all the patients (Grades 1-4; mean score: 2.89). The patient satisfaction survey revealed a mean improvement score of 3.11. Combination laser-cision and pinhole method using a CO2 laser may be a new effective treatment option for patients with hypertrophic burn scars.