Home-delivered meals: food quality, nutrient content, and characteristics of recipients.
Meals provided by a home-delivered meal program with the same supplier were evaluated for 5 consecutive days in each of 6 years. In the evaluations, meals were compared with federal guidelines for meal pattern, serving size, and temperature of hot food, and the quality was evaluated. Meal pattern and serving size guidelines were not always met by the meals. Problems included no delivery of milk with the meals and variations in serving sizes for meat or alternate, fruit, vegetable, and dessert. Temperatures of hot foods were often much lower than the 140 degrees or 150 degrees F specified in food safety guidelines. Food quality varied. Protein, iron, phosphorus, vitamin A, and niacin were consistently greater than 33% of the RDA; energy, thiamin, riboflavin, and vitamin C were less than 33% of the RDA some years, and calcium was consistently less than 33% of the RDA. Estimated total daily nutrient intakes of 27 recipients followed the same pattern as the nutrient content of the meals. For many recipients, estimated nutrient intakes from food other than the home-delivered meal was less than 33% of the RDA. Food preferences were fairly well satisfied. Recall of nutrition-related vocabulary was poor. In this study, home-delivered meals were found to make important contributions to the nutrition needs of the recipients.


Probiotics for cancer alternative prevention and treatment.
Cancer is a fatal malignancy with high clinical significance and remains one of the major causes of illness and death. It has no suitable cure existing till now. The safety and stability of the standard chemotherapeutics drugs and synthetic agents used to manage cancer are doubtful. These agents are affecting the quality of life or contributing for development of drug resistance and are not affordable to the majority of the patients. Therefore, scientists are looking into clinical management of the cancer with high efficiency. This review focuses on the role of probiotics as alternative prevention and treatment of cancer. In this regard, we discuss the alternative cancer biotherapeutic drugs including live or dead probiotics and their metabolites, such as short chain fatty acids, inhibitory compounds of protein, polysaccharide, nucleic acid and ferrichrome in in vitro, in vivo and clinical studies. We also discuss the effectiveness of these biotherapeutics in prevention and treatment of various types of cancer linked with probiotic bacterial or fungal strains, probiotic dose, and time of exposure. More in vivo mainly clinical trials are necessary to further reveal and approve the significant role of live and dead probiotics as well as their metabolic products in cancer prevention and treatment. Finally, the majority of the positive results provided by probiotic treatments are limited to experimental settings. To minimize side effects associated with probiotics, short and long term effect studies in the direction of methodology standardization are required.


Comparison of the active and inactive chromatin structures of genes transcribed by RNA polymerases I and II.
The coding sequences of the yeast 35S rDNA gene and of the yeast galactokinase gene both show clear staphylococcal nuclease nucleosome profiles under conditions in which the gene is inactive (galactokinase) or less active (rDNA). Under conditions of more active expression, the galactokinase gene shows marked smearing in the digestion profiles. The rDNA gene shows a qualitatively similar change in digestion patterns. There is a typical nucleosomal DNase I ladder on the coding sequences of both genes, regardless of the state of activity. In contrast to the coding sequences, the rDNA upstream region chromatin shows a nonnucleosomal profile. The nonnucleosomal character is more pronounced when the gene is more active. On the galactokinase upstream region chromatin, there is a nucleosomal structure, with some minor modifications, when the gene is inactive and a clear nonnucleosomal structure when the gene is expressed.


Prevalence of pseudoexfoliation syndrome in indigenous Australians within central Australia: The Central Australian Ocular Health Study.
Pseudoexfoliation syndrome (XFS) has been found to occur more commonly among indigenous Australians. This paper was designed to determine the prevalence of XFS within the indigenous Australian population living in central Australia. Clinic-based cross-sectional study. One thousand eight hundred eighty-four individuals living in one of 30 remote communities within the statistical local area of 'Central Australia' were recruited. This equated to 36% of those aged 20 years or older and 67% of those aged 40 years or older within this district. Participants aged 20 years or over were recruited as they presented to the eye clinic at each remote community. Slit-lamp examination was performed, and the presence of XFS in each eye was recorded and presented. Prevalence and associations of XFS. XFS was present in one or both eyes of 4.7% of the individuals recruited into the study. Prevalence increased with age (5.9% of those ≥40 years and 12.7% ≥ 60 years). There was a significant association between the presence of XFS and climatic keratopathy (χ(2) = 240.13; P < 0.00001). Notably, none of those with XFS had ocular hypertension or glaucoma. XFS was present in a significantly higher proportion of indigenous Australians compared with previously reported prevalence estimates among non-indigenous Australians. The association found between XFS and climatic keratopathy may represent a common causal link between the two conditions. The lack of association of XFS with ocular hypertension and glaucoma appears to be a unique feature of the indigenous Australian population, and this merits further investigation.


Protein kinase CK2 phosphorylates the cell cycle regulatory protein Geminin.
Geminin contributes to cell cycle regulation by a timely inhibition of Cdt1p, the loading factor required for the assembly of pre-replication complexes. Geminin is expressed during S and G2 phase of the HeLa cell cycle and phosphorylated soon after its synthesis. We show here that Geminin is an excellent substrate for protein kinase CK2 in vitro; and that the highly specific CK2 inhibitor tetrabromobenzotriazole (TBB) blocks the phosphorylation of Geminin in HeLa protein extracts and HeLa cells in vivo. The sites of CK2 phosphorylation are located in the carboxyterminal region of Geminin, which carries several consensus sequence motifs for CK2. We also show that a minor phosphorylating activity in protein extracts can be attributed to glycogen synthase kinase 3 (GSK3), which most likely targets a central peptide in Geminin. Treatment of HeLa cells with TBB does not interfere with the ability of Geminin to interact with the loading factor Cdt1.


Detection of amyloid-β fibrils using the DNA-intercalating dye YOYO-1: Binding mode and fibril formation kinetics.
Identification of the chemical and biological properties of amyloid fibrils is important for understanding their roles in human diseases and to clarify the mechanisms that govern their formation. In pursuit of these goals, small molecule fluorescent dyes have received increasing attention as probes of amyloid conformations. In this study, we report on the ability of YOYO-1, a homodimeric derivative of oxazole yellow, to detect fibrils formed by the Alzheimer's disease related Aβ(1-42) peptide. We find that YOYO-1 binds to Aβ(1-42) fibrils with the long axes of its oxazole yellow moieties parallel to the fibril axis, resulting in a 200x emission enhancement; a result that shows that YOYO-1 is a sensitive amyloid probe. Further, YOYO-1 exhibits characteristic absorption shifts upon binding to the Aβ(1-42) fibrils that we attribute to a self-stacking to non-stacking transition in its homodimer configuration; herein we show how this phenomenon can be exploited to estimate the degree of dye binding. Furthermore, we show that YOYO-1 can be used to monitor the kinetics of amyloid formation reactions. Taken together, our results show that YOYO-1 is a sensitive amyloid probe that can operate with both absorption and fluorescence read-outs, and this suggests that this commercially available dye could become a useful complement to thioflavin-T for in vitro amyloid-sensing applications.


Semiconductor interfacial carrier dynamics via photoinduced electric fields.
Solar photoconversion in semiconductors is driven by charge separation at the interface of the semiconductor and contacting layers. Here we demonstrate that time-resolved photoinduced reflectance from a semiconductor captures interfacial carrier dynamics. We applied this transient photoreflectance method to study charge transfer at p-type gallium-indium phosphide (p-GaInP2) interfaces critically important to solar-driven water splitting. We monitored the formation and decay of transient electric fields that form upon photoexcitation within bare p-GaInP2, p-GaInP2/platinum (Pt), and p-GaInP2/amorphous titania (TiO2) interfaces. The data show that a field at both the p-GaInP2/Pt and p-GaInP2/TiO2 interfaces drives charge separation. Additionally, the charge recombination rate at the p-GaInP2/TiO2 interface is greatly reduced owing to its p-n nature, compared with the Schottky nature of the p-GaInP2/Pt interface.


Effects of 17alpha-ethinylestradiol on immune parameters in the lizard Sceloporus occidentalis.
We examined the effect of 17alpha-ethinylestradiol on immunity of the Western fence lizard, Sceloporus occidentalis. Injection of 17alpha-ethinylestradiol resulted in dose-dependent suppression of peripheral blood leukocyte levels as determined by cell counts, whereas total spleen cell levels were decreased only at higher doses of 17alpha-ethinylestradiol. In contrast, spleen cell proliferation was enhanced by 17alpha-ethinylestradiol as measured by reduction of MTT to formazan following a two-way mixed lymphocyte reaction. Antibody responses were unaffected. Effects on peripheral blood leukocyte levels and spleen cell proliferation similar to those observed in response to injection of 17alpha-ethinylestradiol were observed following injection of a single dose of hydrocortisone. However, injection of lizards with 17alpha-ethinylestradiol did not result in a significant increase in serum cortisol. Results of this study suggest that exposure of Western fence lizards to 17alpha-ethinylestradiol leads to decreased numbers of circulating leukocytes and total spleen cell numbers and the enhancement of spleen cell proliferation in a two-way mixed lymphocyte reaction. These effects probably involve mechanisms other than or in addition to the induction of cortisol release.


Publisher Correction: Resolving acceleration to very high energies along the jet of Centaurus A.
An Amendment to this paper has been published and can be accessed via a link at the top of the paper.


CRISPR/Cas9, a promising approach for the treatment of β-thalassemia: a systematic review.
The CRISPR/Cas9 technique is easily programmable, fast, more powerful, and efficient at generating a mutation compared to previous gene therapy methods. β-thalassemia is the most common autosomal recessive disorder worldwide. Appropriate genomic changes in the β gene can be modified to alleviate the symptoms of the disease using the CRISPR/Cas9 system. PubMed/Medline, Scopus, Web of Science, and SID databases were searched in Persian and English from February 2000 to September 2022. Finally, 39 articles had inclusion criteria which were reviewed by two separate individuals. Among the reviewed articles, articles were divided into three categories. In the first group, studies attemped to increase the expression of γ-globin and production of hemoglobin F. The strategy of second group of studies were the reduction of the α-globin chain to prevent hemolysis of RBCs by accumulation of excessive α-globins. The third group corrected the mutations causing β-thalassemia. Studies have shown that the genome of β-thalassemia patients can be modified using the CRISPR/Cas9 technique, and this approach might be promising for the treatment of β-thalassemia.


Immunoglobulins and immunoglobulin genes of the horse.
Antibodies of the horse were studied intensively by many notable immunologists throughout the past century until the early 1970's. After a large gap of interest in horse immunology, additional basic studies on horse immunoglobulin genes performed during the past 10 years have resulted in new insights into the equine humoral immune system. These include the characterization of the immunoglobulin lambda and kappa light chain genes, the immunoglobulin heavy chain constant (IGHC) gene regions, and initial studies regarding the heavy chain variable genes. Horses express predominately lambda light chains and seem to have a relatively restricted germline repertoire of both lambda and kappa chain variable genes. The IGHC region contains eleven constant heavy chain genes, seven of which are gamma heavy chain genes. It is suggested that all seven genes encoding IgG isotypes are expressed and have distinct functions in equine immune responses.


Storage stability of biocrude oils from fast pyrolysis of poultry litter.
The unstable nature of biocrude oils produced from conventional pyrolysis of biomass is one of the properties that limits its application. In the disposal of poultry litter via pyrolysis technology, the biocrude oil produced as a value-added product can be used for on farm applications. In this study, we investigated the influence of bedding material (wood shavings) on the storage stability of biocrude oils produced from the fast pyrolysis of poultry litter. The biocrude oils produced from manure, wood (pine and oak), and mixtures of manure and wood in proportions (75:25 50:50, and 25:75w/w%) were stored under ambient conditions in sealed glass vials for a period of 6 months and their stability were monitored by measuring the changes in viscosity over time. The manure oil had the lowest rate of viscosity change and thus was relatively the most stable and the oils from the 50:50w/w% litter mixtures were the least stable. The rate of viscosity change of the manure biocrude oil was 1.33cP/day and that of the 50/50 litter mixture was 7.6cP/day for pine and 4.17cP/day for oak. The spectrometric analyses of the biocrude oils showed that the presence of highly reactive oxygenated functionalities in the oil were responsible for the instability characteristic of the litter biocrude oils. The poor stability of the biocrude oil from the 50:50w/w% litter mixtures was attributed to reactions between nitrogenous compounds (amides) from protein degradation and oxygenated compounds from the decomposition of polysaccharides and lignin. The addition of 10% methanol and 10% ethanol to the oil from 50% manure and 50% pine reduced the initial viscosity of the oil and was also beneficial in slowing down the rate of viscosity change during storage.


Forensic issues in Down syndrome fatalities.
Down syndrome, or trisomy 21, is the most common chromosomal abnormality associated with intellectual impairment. Premature death is a feature of the syndrome due to a wide variety of conditions including congenital heart disease, impaired immune responses resulting in respiratory infections, acute leukaemia, upper airway narrowing, pulmonary hypertension, Alzheimer disease and atlantoaxial instability. Cases of Down syndrome not uncommonly present for medicolegal autopsy, as the non-specificity of symptoms and signs often precludes accurate antemortem establishment of a cause of death. Manifestations of Down syndrome are reviewed with an analysis of possible mechanisms of death and findings at autopsy.


Predictors of the failure of treatment with chloroquine in children with acute, uncomplicated, Plasmodium falciparum malaria, in an area with high and increasing incidences of chloroquine resistance.
Resistance to chloroquine (CQ) in Plasmodium falciparum has reached unacceptably high levels in many endemic countries. The pre-treatment factors that identify the children who are at risk of treatment failure after being given CQ were evaluated in 385 children with acute, uncomplicated, Plasmodium falciparum malaria. These children each took part in one of six antimalarial drug trials conducted, between July 1996 and July 2004, in a hyper-endemic area of south-western Nigeria. Following treatment with CQ, 149 (39%) of the children failed treatment by day 7 or 14. In a multivariate analysis, an age of < or =7 years [giving an adjusted odds ratio (AOR) of 2.17, with a 95% confidence interval (CI) of 1.19-3.85; P = 0.01], an asexual parasitaemia of > or =100,000/microl (AOR = 2.17; CI = 1.08-4.35; P = 0.03), the presence of gametocytaemia (AOR = 2.08; CI = 1.14-3.85; P = 0.02) and enrolment >4 years after commencement of the study (i.e. after 2000; AOR = 2.13; CI = 1.3-4.0; P = 0.003) were found to be independent predictors at presentation of the subsequent failure of treatment with CQ. Compared with the other children, those who failed to clear their parasitaemias within 3 days and those who still had fever 1-2 days after commencing treatment were more likely to be treatment failures. Together, these findings may have implications for malaria-control efforts in all areas of sub-Saharan Africa where treatment of malaria depends almost entirely on antimalarial monotherapy.


Substance abuse treatment in human immunodeficiency virus: the role of patient-provider discussions.
Substance abuse treatment is associated with decreases in human immunodeficiency virus (HIV) risk behavior and can improve HIV outcomes. The purpose of this study was to examine factors associated with substance abuse treatment utilization, including patient-provider discussions of substance use issues. We surveyed 951 HIV-infected adults receiving care at 14 HIV Research Network primary care sites regarding drug and alcohol use, substance abuse treatment, and provider discussions of substance use issues. Although 71% reported substance use, only 24% reported receiving substance abuse treatment and less than half reported discussing substance use issues with their HIV providers. In adjusted logistic regression models, receipt of substance abuse treatment was associated with patient-provider discussions. Patient-provider discussions of substance use issues were associated with current drug use, hazardous or binge drinking, and Black race or ethnicity, though substance use was comparable between Blacks and Whites. These data suggest potential opportunities for improving engagement in substance abuse treatment services.


Female sexual function after spinal cord injury.
Over the past 10 years, studies of the impact of spinal cord injuries on female sexuality have expanded from questionnaire studies in small populations with unknown levels and degrees of injury to laboratory-based analyses of women with known injury patterns. These studies have provided detailed information on how specific injury patterns affect specific aspects of the female sexual response. Research findings have supported the hypothesis that the sympathetic nervous system is regulatory for psychogenic genital vasocongestion and that orgasm is a reflex response of the autonomic nervous system. Based on these results, a new system for the classification of sexual function in women with spinal cord injury (SCI) is proposed. Moreover, studies related to the treatment of sexual dysfunction in women with cord injury are reviewed.


Living-donor liver transplantation with hyperreduced left lateral segment grafts: a single-center experience.
In the setting of liver transplantation in small infants who receive left lateral segment (LLS) grafts, problems are encountered related to graft-size mismatching in the form of so-called "large-for-size" grafts. To address these problems, the feasibility of further reducing the size of LLS grafts to form hyperreduced LLS (HRLLS) grafts was investigated. Of the 175 pediatric living-donor liver transplantations performed between November 2005 and December 2011 at our institute, 31 cases were performed using HRLLS grafts. The medical records were reviewed and data were collected retrospectively. The graft-to-recipient body weight ratio was successfully reduced from 5.2% ± 2.0% to 2.9% ± 0.5%. Portal vein thrombosis was observed in one case, and biliary stenosis was seen in two cases. No hepatic artery thrombosis was encountered. The graft and patient 2-year survival rate was 87%. When the results categorized according to the original disease were verified, patients with fulminant hepatic failure (FHF) weighed less and had smaller abdominal cavities compared with patients with cholestatic or metabolic disease. Patients with FHF frequently required skin or partial skin closure to avoid graft compression. For this reason, the anteroposterior diameters in the recipients' abdominal cavities were not adequately large to accommodate the graft thickness, especially in patients with FHF. In conclusion, living-donor liver transplantation using HRLLS grafts offers a safe and useful option for treating smaller infants.


The effect of prior experience on a prey's current perceived risk.
The prior experience of prey may influence how they assess the level of predation risk associated with an information source. Here, I present the results from a set of experiments that demonstrate how the prior experience of green frog (Rana clamitans) tadpoles can influence their risk assessment during exposure to the chemical cue of predatory larval dragonflies (Anax spp.) consuming conspecific tadpoles. At the short-term scale, green frog tadpoles perceived a higher level of risk when consecutive cue exposures overlapped, but only when the total chemical cue concentration was weak. Weaker chemical cue concentrations may be less reliable than stronger cue concentrations, and overlapping cue exposures may increase the degree of certainty that tadpoles have in their perceived risk. When consecutive cue exposures did not overlap, tadpoles assessed the risk associated with each cue exposure independently. Predator-conditioned tadpoles responded longer during exposure to the Anax chemical cue than nonconditioned tadpoles, which suggests that a tadpole's long-term experience eventually does influence its risk assessment. In general, the results suggest that a prey's prior experience may influence its current perceived risk by influencing either the degree of certainty in or the level of its perceived risk. Understanding how the prior experience of prey influences their current risk assessment requires that the rate of decay of the value of prior experience should be identified at two timescales as an indicator of the current level of predation risk.


Traumatic injuries of the abdominal aorta.
Despite immediate operation, patients with abdominal aortic injuries and profound hypovolemic shock do not respond to the usual methods of resuscitation and die soon after celiotomy, prior to control and repair of the aortic injury. The rate of aortic hemorrhage exceeds the ability to restore blood volume. Shock becomes "irreversible." In such patients tamponade of the aortic injury may be effected by the use of an external counterpressure device such as a G-suit or MAST suit. These devices, used in conjunction with transthoracic aortic occlusion, may raise blood pressure sufficiently to perfuse the sritical coronary and cerebral circulation, allowing time to correct acidosis and locate, control, and repair the aortic injury. Early aggressive therapy should result in increased survival.


Sarcopenia in Inflammatory Bowel Diseases: Reviewing Past Work to Pave the Path for the Future.
Sarcopenia is the loss of muscle quantity and strength. It is highly prevalent in patients with inflammatory bowel disease (IBD) and is associated with periods of ongoing inflammation. This review will summarize the prior work in the field and highlight areas for future research. The presence of sarcopenia has been associated with adverse outcomes in different populations. Most recently, sarcopenia has been associated with adverse postoperative outcomes and an increased likelihood of surgery in IBD. Despite this, significant heterogeneity among these studies limits the ability to draw definitive conclusions. The importance of sarcopenia in inflammatory bowel disease (IBD) is only beginning to be recognized. Future studies assessing it utility both as a risk stratification tool and a modifiable factor in IBD are needed.


Clinical, Radiological, Pathological Features and Seizure Outcome With Surgical Management of Polymorphous Low-Grade Neuroepithelial Tumor of the Young Associated With Epilepsy.
Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a novel distinct epileptogenic neoplasm, and its clinical, imaging, histopathological, and molecular features were already known in the existing literature. We aimed to analyze the surgical management of PLNTY combined with these known characteristics. Eight patients underwent surgical treatment in our center between December 2017 and December 2020, and the postoperative pathology was diagnosed as PLNTY. Their clinical data, imaging, pathological, molecular characteristics, and seizure outcome were retrospectively analyzed. Follow-up evaluations and a literature review were performed. The 8 patients included 1 woman and 7 men, aged between 5 and 51 years old (mean = 31.6, median = 29). The preoperative symptoms of all 8 cases were seizures. Four tumors were situated in the temporal lobes, and one of the four extratemporal tumors was in the occipital lobe and three were in the frontal lobe. Enlarged and gross total resections were performed in 2 cases and the other 6 cases, respectively. All cases exhibited intense labeling of CD34, and absence of 1p/19q codeletion and IDH1 or IDH2 mutation. B-Raf proto-oncogene (BRAF) V600E mutation was presented in 4 (66.7%) of 6 detected cases. The postoperative seizure outcome of Engel class I was achieved in 6 cases (75%). PLNTY represents distinctive histologic, immunophenotypic and biomolecular features, and has high epileptogenicity. Early surgical intervention and enlarged resection of PLNTY associated with epilepsy will help to improve the postoperative seizure-free rate.


Adding systematic biopsy to magnetic resonance ultrasound fusion targeted biopsy of the prostate in men with previous negative biopsy or enrolled in active surveillance programs: A prospective single center, randomized study.
Magnetic resonance imaging (MRI) targeted biopsy (TBx) of the prostate demonstrated to improve detection rate (DR) of clinically significant prostate cancer (csPCa) in biopsy-naive patients achieving strong level of evidence. Nevertheless, the csPCa yield for TBx alone versus TBx plus systematic biopsy (SBx) after accounting for overlapping of SBx cores with TBx cores, in prior-negative or active surveillance (AS) patients has not been well established.The objective of the study was to investigate benefits in terms of detection rate and pathological stratification of prostate cancer (PCa) using contextual SBx during MRI-TBx.Patients previously submitted to negative-SBx (cohort A) and those enrolled in an AS program (cohort B) who showed at least 1 suspicious area with a PIRADSv2 score ≥ 3 were prospectively and randomly assigned to only TBx strategy versus TBx plus SBx strategy. SBx locations could not encompass the TBx sites, so that the results of each type of biopsy were independent and did not overlap.A total of 312 patients were included in the 2 cohorts (cohort A: 213 cases; cohort B: 99 cases). No significant differences were found in terms of overall PCa-DR (77.6% vs 69.6% respectively; P = .36) and csPCa-DR (48.2% vs 60.9 respectively; P = .12). The MRI-TBx alone cohort showed higher csPCa/PCa ratio (87.5% vs 62.2%; P = .03). The MRI-TBx plus SBx group subanalysis showed significantly higher csPCa-DR obtained at the MRI-TBx cores when compared with the SBx cores (43.7% vs 24.1%, respectively; P = .01). Independently to age, prostatic-specific antigen and prostate imaging-reporting and data system score, either in rebiopsy (OR 0.43, 0.21-0.97) or AS (OR 0.46, 0.32-0.89) setting, SBx cores were negatively associated with the csPCa-DR when combined to TBx cores.MRI-TBx should be considered the elective method to perform prostate biopsy in patients with previous negative SBx and those considered for an AS program. Adding SBx samples to MRI-TBx did not improve detection rate of csPCa.


Amphibians as a model to study the role of immune cell heterogeneity in host and mycobacterial interactions.
Mycobacterial infections represent major concerns for aquatic and terrestrial vertebrates including humans. Although our current knowledge is mostly restricted to Mycobacterium tuberculosis and mammalian host interactions, increasing evidence suggests common features in endo- and ectothermic animals infected with non-tuberculous mycobacteria (NTMs) like those described for M. tuberculosis. Importantly, most of the pathogenic and non-pathogenic NTMs detected in amphibians from wild, farmed, and research facilities represent, in addition to the potential economic loss, a rising concern for human health. Upon mycobacterial infection in mammals, the protective immune responses involving the innate and adaptive immune systems are highly complex and therefore not fully understood. This complexity results from the versatility and resilience of mycobacteria to hostile conditions as well as from the immune cell heterogeneity arising from the distinct developmental origins according with the concept of layered immunity. Similar to the differing responses of neonates versus adults during tuberculosis development, the pathogenesis and inflammatory responses are stage-specific in Xenopus laevis during infection by the NTM M. marinum. That is, both in human fetal and neonatal development and in tadpole development, responses are characterized by hypo-responsiveness and a lower capacity to contain mycobacterial infections. Similar to a mammalian fetus and neonates, T cells and myeloid cells in Xenopus tadpoles and axolotls are different from the adult immune cells. Fetal and amphibian larval T cells, which are characterized by a lower T cell receptor (TCR) repertoire diversity, are biased toward regulatory function, and they have distinct progenitor origins from those of the adult immune cells. Some early developing T cells and likely macrophage subpopulations are conserved in adult anurans and mammals, and therefore, they likely play an important role in the host-pathogen interactions from early stages of development to adulthood. Thus, we propose the use of developing amphibians, which have the advantage of being free-living early in their development, as an alternative and complementary model to study the role of immune cell heterogeneity in host-mycobacteria interactions.


RNA interference to combat the Asian tiger mosquito in Europe: A pathway from design of an innovative vector control tool to its application.
The Asian tiger mosquito Aedes albopictus is currently spreading across Europe, facilitated by climate change and global transportation. It is a vector of arboviruses causing human diseases such as chikungunya, dengue hemorrhagic fever and Zika fever. For the majority of these diseases, no vaccines or therapeutics are available. Options for the control of Ae. albopictus are limited by European regulations introduced to protect biodiversity by restricting or phasing out the use of pesticides, genetically modified organisms (GMOs) or products of genome editing. Alternative solutions are thus urgently needed to avoid a future scenario in which Europe faces a choice between prioritizing human health or biodiversity when it comes to Aedes-vectored pathogens. To ensure regulatory compliance and public acceptance, these solutions should preferably not be based on chemicals or GMOs and must be cost-efficient and specific. The present review aims to synthesize available evidence on RNAi-based mosquito vector control and its potential for application in the European Union. The recent literature has identified some potential target sites in Ae. albopictus and formulations for delivery. However, we found little information concerning non-target effects on the environment or human health, on social aspects, regulatory frameworks, or on management perspectives. We propose optimal designs for RNAi-based vector control tools against Ae. albopictus (target product profiles), discuss their efficacy and reflect on potential risks to environmental health and the importance of societal aspects. The roadmap from design to application will provide readers with a comprehensive perspective on the application of emerging RNAi-based vector control tools for the suppression of Ae. albopictus populations with special focus on Europe.


Interobserver discordance in the classification of mechanisms of death in studies of heart failure.
Studies of the mechanism of death in heart failure are dependent on the reliability and validity of classification of deaths as pump failure or arrhythmias (sudden). Two recent trials differed in that the Vasodilator Heart Failure Trial II (V-HeFT II) reported a higher incidence of sudden death than the Studies of Left Ventricular Dysfunction Treatment Trial (SOLVD) and an effect of enalapril on sudden death was not observed in SOLVD. A similar classification system was used in the two studies, but deaths in V-HeFT were classified centrally from a narrative summary, whereas deaths in SOLVD were classified in the field by individual investigators. To examine reliability, 10 narratives used to classify V-HeFT deaths were independently classified by 21 SOLVD investigators. In only 5 of 10 cases did 75% of SOLVD investigators agree with the V-HeFT classification. In no deaths were all SOLVD investigators in agreement on classification. Although V-HeFT classified 5 of 10 cases as sudden death, 16 of 21 SOLVD investigators classified less than 5 deaths as sudden and 1 classified none as sudden. The kappa statistic for interobserver agreement of 0.22 (P < or = .01) indicated interobserver agreement only slightly better than chance agreement. Therefore, the incidence of sudden death in heart failure is critically dependent on the bias of the investigator. Central classification will minimize inconsistencies, but it does not solve the problem that the mechanism of death is difficult to assign. Total mortality may be the only reliable endpoint in heart failure trials.


Analysis of baseline factors associated with reduction in chest pain in patients with angina pectoris treated by enhanced external counterpulsation.
Data from the International Enhanced External Counterpulsation (EECP) Patient Registry were analyzed to determine which patient characteristics influence improvement in angina class with EECP treatment. Patients with severely disabling angina at baseline, men, and those without a history of smoking are more likely to improve their angina class after EECP, whereas those with diabetes mellitus, prior bypass surgery, and heart failure were less likely to benefit.


Enhanced microbial reduction of aqueous hexavalent chromium by Shewanella oneidensis MR-1 with biochar as electron shuttle.
Biochar, carbonaceous material produced from biomass pyrolysis, has been demonstrated to have electron transfer property (associated with redox active groups and multi condensed aromatic moiety), and to be also involved in biogeochemical redox reactions. In this study, the enhanced removal of Cr(VI) by Shewanella oneidensis MR-1(MR-1) in the presence of biochars with different pyrolysis temperatures (300 to 800 °C) was investigated to understand how biochar interacts with Cr(VI) reducing bacteria under anaerobic condition. The promotion effects of biochar (as high as 1.07~1.47 fold) were discovered in this process, of which the synergistic effect of BMBC700(ball milled biochar) and BMBC800 with MR-1 was noticeable, in contrast, the synergistic effect of BMBCs (300-600 °C) with MR-1 was not recognized. The more enhanced removal effect was observed with the increase of BMBC dosage for BMBC700+MR-1 group. The conductivity and conjugated O-containing functional groups of BMBC700 particles themselves has been proposed to become a dominant factor for the synergistic action with this strain. And, the smallest negative Zeta potential of BMBC700 and BMBC800 is thought to favor decreasing the distance from microbe than other BMBCs. The results are expected to provide some technical considerations and scientific insight for the optimization of bioreduction by useful microbes combining with biochar composites to be newly developed.


Variability of Clinical Practice Management of Type 1 and Type 2 Diabetes During Surgery Across Canada.
As part of a larger project to develop quality standards in perioperative diabetes management, the goal of this project was to assess self-reported management of surgical patients with diabetes across healthcare institutions and specialties in Canada. Current practice of perioperative management of patients with diabetes was assessed using multiple-choice questions based on commonly encountered clinical scenarios involving patients with type 1 and type 2 diabetes. The survey was sent to a broad stakeholder group of individuals involved in perioperative medicine in academic and community settings across Canada. Responses to clinical case scenarios demonstrated more consistent approaches for patients with type 1 diabetes undergoing cardiac surgery, possibly reflecting more robust evidence. There was more variability in the management of noninsulin antihyperglycemic agents and hyperglycemia in patients with type 2 diabetes undergoing noncardiac surgery. Given the variability in clinical practice, standards and clinical tools are required for perioperative and periprocedural glycemic management in Canada to inform practice, improve the experience and outcomes for people with diabetes and provide a foundation for quality improvement initiatives and benchmarking.


Sentinel Event Alert says access control holds the key to reducing ED violence.
A new Joint Commission Sentinel Event Alert notes that EDs are the most vulnerable area of the hospital when it comes to violence and that access control is a key to preventing that violence. * Perform a risk assessment, so you know where your greatest threats lie. Examine physical control barriers, and consider access control products such as keypads. Position security personnel in the greeting area of the ED.


Novel spore lytic enzyme from a Bacillus phage leading to spore killing.
Bacterial spores maintain metabolic dormancy and have high resistance to external pressure. Germination requires degradation of the spore cortex and the participation of germination-specific cortex-lytic enzymes (GSLEs). Previously reported GSLEs have been identified in bacteria and facilitate germination. In this study, we have characterized a novel spore lytic enzyme, Ply67, from Bacillus pumilus phage vB_BpuM_BpSp. Ply67 had a similar cortex-lytic activity to GSLEs but disrupted the inner membranes (IMs) of spores, leading to spore killing rather than germination. The amino acid sequence of the complete protein, Ply67FL, exhibited 40% homology to the GSLE SleB. Domain prediction showed that Ply67FL was composed of three domains: a signal peptide, N-terminal domain protein and C-terminal domain protein. Ply67FL rapidly caused E. coli cells lysis when it was expressed in E. coli. The protein containing the C-terminal domain protein, Ply67C, could kill B. pumilus spores. The protein containing the N-terminal domain protein, Ply67N, could combine with the decoated B. pumilus spores, indicating that N-terminal was the binding domain and C-terminal was the hydrolase domain. The protein lacking the signal peptide but containing the N-terminal and C-terminal domain proteins, Ply67, had activity against spores of various Bacillus species. The surface of spores treated with Ply67 shrank and the permeability barrier was disrupted, and the inner contents leaked out. Immunoelectron microscopic observation showed that Ply67 was mainly acted on the spore cortex. Overall, Ply67 is a novel spore lytic enzyme that differs from other GSLEs not only in amino acid sequence but also in activity against spores, and Ply67 might have the potential to kill spores of pathogenic Bacillus species, e.g., B. cereus and B. anthracis.


Sevoflurane enhances nitroglycerin tolerance in rat aorta: implications for the desensitization of soluble guanylate cyclase possibly through the additive generation of superoxide anions and/or hydroxyl radicals within vascular smooth muscle.
Nitroglycerin (TNG) tolerance, defined as an impaired vasodilation response to TNG, has been recently demonstrated to be associated with increased production of reactive species. We designed this study to investigate the mechanisms that mediate TNG tolerance and to compare the effects of sevoflurane and isoflurane on the development of TNG tolerance. Tension changes in rat aortic rings without endothelium were recorded. The cumulative relaxant responses to TNG (10(-8)-10(-5) M) were assessed in phenylephrine-contracted rings. To induce TNG tolerance, the rings were then incubated in the bathing solution containing TNG (10(-5) M) for 30 min in the presence or absence of each anesthetic (1 to 3 MAC). After washout of TNG and anesthetic, the second response to TNG was obtained. Some rings were pretreated with oxygen radical scavengers or sulfhydryl supplements. The first and the second responses to TNG were compared. Sevoflurane at 3 MAC, but not sevoflurane at smaller concentrations or isoflurane, enhanced TNG tolerance when administered in combination with TNG. Sevoflurane alone had no effect on TNG tolerance. The enhancement of TNG tolerance in the case of a combined sevoflurane and TNG treatment was inhibited in the presence of oxygen radical scavengers or at a smaller oxygen concentration (25%). Sevoflurane at a concentration of 3 MAC in hyperoxic condition enhances the development of TNG tolerance, possibly by additive generation of superoxide anions or hydroxyl radicals within vascular smooth muscle. The effects of sevoflurane and isoflurane on the development of nitroglycerin (TNG) tolerance were investigated in isolated rat aorta. TNG tolerance was induced by incubation of the vascular tissue in the bathing media containing TNG (10-5 M) for 30 min. Sevoflurane, but not isoflurane, enhances TNG tolerance, possibly by additive generation of oxygen-derived free radicals.


3D printed PEKK bone analogs with internal porosity and surface modification for mandibular reconstruction: An in vivo rabbit model study.
Polyetheretherketone (PEEK) and its derivative polyetherketoneketone (PEKK) have been used as implant materials for spinal fusing and enjoyed their success for many years because of their mechanical properties similar to bone and their chemical inertness. The osseointegration of PEEKs is datable. Our strategy was to use custom-designed and 3D printed bone analogs with an optimized structure design and a modified PEKK surface to augment bone regeneration for mandibular reconstruction. Those bone analogs had internal porosities and a bioactive titanium oxide surface coating to promote osseointegration between native bone and PEKK analogs. Our workflow was 3D modeling, bone analog designing, structural optimization, mechanical analysis via finite element modeling, 3D printing of bone analogs and subsequently, an in vivo rabbit model study on mandibular reconstruction and histology evaluation. Our results showed the finite element analysis validated that the porous PEKK analogs provided a mechanical-sound structure for functional loadings. The bone analogs offered a perfect replacement for segmented bones in the terms of shape, form and volume for surgical reconstruction. The in vivo results showed that bioactive titanium oxide coating enhanced new bone in-growth into the porous PEKK analogs. We have validated our new approach in surgical mandibular reconstruction and we believe our strategy has a significant potential to improve mechanical and biological outcomes for patients who require mandibular reconstruction procedures.


Driver gene combinations dictate cutaneous squamous cell carcinoma disease continuum progression.
The molecular basis of disease progression from UV-induced precancerous actinic keratosis (AK) to malignant invasive cutaneous squamous cell carcinoma (cSCC) and potentially lethal metastatic disease remains unclear. DNA sequencing studies have revealed a massive mutational burden but have yet to illuminate mechanisms of disease progression. Here we perform RNAseq transcriptomic profiling of 110 patient samples representing normal sun-exposed skin, AK, primary and metastatic cSCC and reveal a disease continuum from a differentiated to a progenitor-like state. This is accompanied by the orchestrated suppression of master regulators of epidermal differentiation, dynamic modulation of the epidermal differentiation complex, remodelling of the immune landscape and an increase in the preponderance of tumour specific keratinocytes. Comparative systems analysis of human cSCC coupled with the generation of genetically engineered murine models reveal that combinatorial sequential inactivation of the tumour suppressor genes Tgfbr2, Trp53, and Notch1 coupled with activation of Ras signalling progressively drives cSCC progression along a differentiated to progenitor axis. Taken together we provide a comprehensive map of the cSCC disease continuum and reveal potentially actionable events that promote and accompany disease progression.


VX-809 and related corrector compounds exhibit secondary activity stabilizing active F508del-CFTR after its partial rescue to the cell surface.
The most common mutation causing cystic fibrosis (CF), F508del, impairs conformational maturation of CF transmembrane conductance regulator (CFTR), thereby reducing its functional expression on the surface of epithelia. Corrector compounds including C18 (VRT-534) and VX-809 have been shown to partially rescue misfolding of F508del-CFTR and to enhance its maturation and forward trafficking to the cell surface. Now, we show that there is an additional action conferred by these compounds beyond their role in improving the biosynthetic assembly. In vitro studies show that these compounds bind directly to the metastable, full-length F508del-CFTR channel. Cell culture and patient tissue-based assays confirm that in addition to their cotranslational effect on folding, certain corrector compounds bind to the full-length F508del-CFTR after its partial rescue to the cell surface to enhance its function. These findings may inform the development of alternative compounds with improved therapeutic efficacy.


Dissecting thoracic aorta and fusiform aneurysm of the abdominal aorta.
A 59-year-old woman with dissection of the thoracic aorta and a fusiform aneurysm of the abdominal aorta without evidence of Marfan's syndrome underwent aneurysmorrhaphy with a bifurcated expanded polytetrafluoroethylene graft. Histological specimens of the aneurysmal wall revealed the presence of idiopathic cystic medial necrosis. As typical findings of idiopathic cystic medial necrosis in the aortic wall are very rare except in cases of Marfan's syndrome, the present case is reported and the implications of this condition are discussed.


Melorheostosis of the thumb and trapezium bone.
Melorheostosis of the hand is rare. We report a 28-year-old woman with persistent pain associated with a slowly growing mass on the dorsum of the right thumb. The radiographs, computed tomography, and magnetic resonance imaging were used to examine characteristic of melorheostosis involving the trapezium bone, first metacarpal, and proximal phalange. The lesions underwent a surgical debulking of the hyperostotic cortex and a cortical fenestration.


Large cell neuroendocrine carcinoma of the submandibular gland: case report and literature review.
Large cell neuroendocrine carcinoma (LCNEC) of the salivary gland is extremely rare. We report on a case of LCNEC in the submandibular gland. A 58-year-old male had a four-month history of an enlarging mass in his left submandibular region. He underwent lymph node resection and metastasis of LCNEC was suspected. Magnetic resonance imaging of the neck showed a solid submandibular gland tumor with marginal blurring. Positron-emission tomography and upper gastrointestinal endoscopy showed no evidence of malignancy other than in the left submandibular gland. He underwent left submandibular gland resection and left upper neck dissection. The final diagnosis was LCNEC of the submandibular gland; surgical margin was negative. Fourteen months later he is free of tumors. This is the first report of LCNEC of the submandibular gland. LCNEC of the salivary gland shows high-grade malignancy like that of the lung. According to past reports, two of four patients died despite multidisciplinary treatments. There are no standard treatments for LCNEC of the salivary glands. More studies are needed to define prognostic factors and establish therapeutic methods.


Synthesis and evaluation of bifunctional chelating agents derived from bis(2-aminophenylthio)alkane for radioimaging with 99mTc.
Novel bifunctional chelating agents bearing an aromatic rigid backbone have been synthesized and characterized on the basis of spectroscopic techniques. These macrocyclic multidentate chelating agents were conjugated with monoclonal antibody which forms stable complexes with 99mTc with high radiochemical purity.


Constriction of cat coronary arteries by synthetic thromboxane A2 and its antagonism.
Synthetic thromboxane A2 (TxA2S) induced rapid, concentration-dependent constriction of isolated perfused cat coronary arteries. Its potency was approximately 30 times that of the prostaglandin endoperoxide, PGH2. Pinane thromboxane A2 (PTA2), BM-13.505 and SQ-29,548, compounds previously shown to antagonize the effects of stable prostaglandin endoperoxide analogs, inhibited the constriction induced by TxA2S in a concentration-dependent fashion. These experiments provide further evidence that the oxetane structure proposed for TxA2 is correct and show that compounds that inhibit the effects of prostaglandin endoperoxides also antagonize the effects of TxA2.


Congenital diaphragmatic hernia-does the presence of a hernia sac improve outcome? A systematic review of published studies.
Early reports have suggested survival benefits associated with a hernia sac in congenital diaphragmatic hernia (CDH). However, these studies have included only small subsets of patients. This systematic review aimed to evaluate differences in outcomes of CDH newborns with and without a hernia sac. PubMed and Embase databases were searched using relevant key terms. Papers were independently reviewed by two authors with final selection approved by the senior author. Original search retrieved 537 papers; the final review included 8 studies (n = 837 patients). There were 168 CDH patients (20%) with a hernia sac with an overall survival of 93% vs 73% for CDH newborns without a sac (p < 0.001). Twenty-three percent of patients with a CDH sac required diaphragm patch repair vs 44% patients without a sac (p < 0.001). Pulmonary hypertension was manifested in 44% of CDH babies with a hernia sac vs 64% without a sac (p < 0.001). Three studies compared ECMO requirement: 15% with a hernia sac and 34% without sac, p < 0.001.Conclusion: This study shows significant survival benefits in newborns associated with presence of a CDH sac. This may be likely related to these infants having more favourable physiology with less severe pulmonary hypertension and/or smaller anatomical defects requiring primary closure only. What is Known: • Early reports have suggested survival benefits associated with a hernia sac in CDH. • Previous studies have included only a small number of patients. What is New: • A systematic review of published studies clearly shows that CDH newborns with a hernia sac have better overall survival outcomes and less severe pulmonary hypertension. • ECMO utilization and patch repair were also less often required in newborns with a hernia sac.


Artificial neural network approach for prediction of AuNPs biosynthesis by Streptomyces flavolimosus, characterization, antitumor potency in-vitro and in-vivo against Ehrlich ascites carcinoma.
Gold nanoparticles (AuNPs) have emerged as promising and versatile nanoparticles for cancer therapy and are widely used in drug and gene delivery, biomedical imaging, diagnosis, and biosensors. The current study describes a biological-based strategy for AuNPs biosynthesis using the cell-free supernatant of Streptomyces flavolimosus. The biosynthesized AuNPs have an absorption peak at 530-535 nm. The TEM images indicate that AuNPs were spherical and ranged in size from 4 to 20 nm. The surface capping molecules of AuNPs are negatively charged, having a Zeta potential of - 10.9 mV. FTIR analysis revealed that the AuNPs surface composition contains a variety of functional groups as -OH, C-H, N-, C=O, NH3+, amine hydrochloride, amide group of proteins, C-C and C-N. The bioprocess variables affecting AuNPs biosynthesis were optimized by using the central composite design (CCD) in order to maximize the AuNPs biosynthesis. The maximum yield of AuNPs (866.29 µg AuNPs/mL) was obtained using temperature (35 °C), incubation period (4 days), HAuCl4 concentration (1000 µg/mL) and initial pH level 6. Comparison was made between the fitness of CCD versus Artificial neural network (ANN) approach based on their prediction and the corresponding experimental results. AuNPs biosynthesis values predicted by ANN exhibit a more reasonable agreement with the experimental result. The anticancer activities of AuNPs were assessed under both in vitro and in vivo conditions. The results revealed a significant inhibitory effect on the proliferation of the MCF-7 and Hela carcinoma cell lines treated with AuNPs with IC50 value of 13.4 ± 0.44 μg/mL and 13.8 ± 0.45 μg/mL for MCF-7 and Hela cells; respectively. Further, AuNPs showed potential inhibitory effect against tumor growth in tumor-bearing mice models. AuNPs significantly reduced the tumor volume, tumor weight, and decreased number of viable tumor cells in EAC bearing mice.


Value of simple otoscopy in diagnosing otitis media with effusion in children.
To explore the value of otoscopy in diagnosing OME when performed by otorhinolaryngology, pediatrics, and primary care physicians; to evaluate the interobserver and intraobserver agreement of interpretation of otoscopy images. A cross-sectional study using an anonymous mailed survey was used. We presented pre-recorded otoscopy images of pediatric patients to otorhinolaryngology, pediatrics, and primary care physicians (ten volunteer specialists and residents from each medical specialty). All participants had to answer "yes" or "no" if they considered that the image corresponded or not to an OME case, respectively. We considered that the images were positive for OME whenever the respective tympanogram was type B. Thirty-one otoscopy images and 1860 responses provided by sixty physicians were analyzed. The accuracy of otoscopy in diagnosing OME was highest in the Otolaryngologists group (mean 74.8%), with the worst rate observed in the primary care residents group (mean 51.3%). Overall sensitivity, specificity, and positive predictive value of otoscopy for diagnosing OME were significantly higher when performed by otorhinolaryngologists (75.8%, 72.8%, 66.8%, respectively). Fleiss' kappa showed that interobserver agreement was globally weak within each group of specialties, with overall better interobserver agreement observed among otorhinolaryngologists (κ = 0.30; 95% CI 0.27-0.32). According to our data, simple otoscopy as a single diagnostic method in pediatric OME is insufficient, even for otorhinolaryngologists. Current recommendations must be followed to improve diagnostic accuracy.


A noncanonical RNA-binding domain of the fragile X protein, FMRP, elicits translational repression independent of mRNA G-quadruplexes.
Loss of functional fragile X mental retardation protein (FMRP) causes fragile X syndrome, the leading form of inherited intellectual disability and the most common monogenic cause of autism spectrum disorders. FMRP is an RNA-binding protein that controls neuronal mRNA localization and translation. FMRP is thought to inhibit translation elongation after being recruited to target transcripts via binding RNA G-quadruplexes (G4s) within the coding sequence. Here, we directly test this model and report that FMRP inhibits translation independent of mRNA G4s. Furthermore, we found that the RGG box motif together with its natural C-terminal domain forms a noncanonical RNA-binding domain (ncRBD) that is essential for translational repression. The ncRBD elicits broad RNA-binding ability and binds to multiple reporter mRNAs and all four homopolymeric RNAs. Serial deletion analysis of the ncRBD identified that the regions required for mRNA binding and translational repression overlap but are not identical. Consistent with FMRP stalling elongating ribosomes and causing the accumulation of slowed 80S ribosomes, transcripts bound by FMRP via the ncRBD cosediment with heavier polysomes and were present in puromycin-resistant ribosome complexes. Together, this work identifies a ncRBD and translational repression domain that shifts our understanding of how FMRP inhibits translation independent of mRNA G4s.


Synthesis and Evaluation of N-substituted (Z)-5-(Benzo[d][1,3]dioxol-5- ylmethylene)-2-Thioxothiazolidin-4-one Derivatives and 5-Substituted- Thioxothiazolidindione Derivatives as Potent Anticonvulsant Agents.
Epilepsy is a serious and common neurological disorder threatening the health of humans. Despite enormous progress in epileptic research, the anti-epileptic drugs present many limitations. These limitations prompted the development of more safer and effective AEDs. A series of N-substituted (Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)- 2-thioxothiazolidin-4- one derivatives and 5-substituted-thioxothiazolidindione derivatives were designed, synthesized and tested for anticonvulsant activity against maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ). Neurotoxicity was determined by the rotarod test. Among them, the most potent 4e displayed high protection against MES-induced seizures with an ED50 value of 9.7 mg/kg and TD50 value of 263.3 mg/kg, which provided 4e with a high protective index (TD50/ED50) of 27.1 comparable to reference antiepileptic drugs. 4e clearly inhibits the NaV1.1 channel in vitro. The molecular docking study was conducted to exploit the results. Stiripentol is a good lead compound for further structural modification. Compound 4e was synthesized, which displayed remarkable anticonvulsant activities, and the NaV1.1 channel inhibition was involved in the mechanism of action of 4e.


Inheritance of F cell frequency in heterocellular hereditary persistence of fetal hemoglobin: an example of allelic exclusion.
Two kindreds are described in which F cell frequency is inherited. These families differ in ethnic origin, the mean quantity of HbF per F cell, and in G gamma: A gamma ratios. Heterozygotes have approximately 50% F cells while homozygotes have close to 100%. Semiquantitative single cell immunodiffusion assays establish that F cells contain all of the HbF found in heterozygotes. Our finding that the gene for this heterocellular form of hereditary persistence of fetal hemoglobin is expressed in only half the cells provides the first example of allelic exclusion known apart from immunoglobulin expression.


Management of venous thromboembolism in pediatric patients: Quality assessment of clinical practice guidelines and variations in recommendations.
We performed a quality assessment and comparison of clinical practice guidelines (CPGs) for the prevention and treatment of venous thromboembolism (VTE) in pediatric patients and to provide a clinical reference. Electronic databases, guideline development organizations, and professional societies were searched to identify CPGs for VTE in pediatric patients between January 1, 2012, and April 7, 2022. The Appraisal of Guidelines Research & Evaluation (AGREE) II instrument was used to evaluate quality. Recommendations for preventing and treating VTE in pediatric patients were extracted via descriptive synthesis. Six CPGs were included. The median scores (interquartile range [IQR]) for each AGREE II domain were as follows: scope and purpose, 88.89 % (IQR: 8.33 %); stakeholder involvement, 88.89 % (25 %); rigor of development, 67.71 % (24.47 %); clarity and presentation, 88.89 % (0 %); applicability, 50 % (42.71 %); and editorial independence, 66.67 % (50.00 %). In total, 268 key recommendations were extracted, and traditional anticoagulants (heparin and warfarin) remain the standard treatment. However, in recent years direct oral anticoagulants (DOACs) have shown similar efficacy and safety results for the treatment of VTE in children to those reported in adults; therefore, this practice is recommended in recent guidelines. Variability exists in the development and reporting of CPGs for VTE in pediatric patients. There may be changes to the recommendations for the prevention and treatment of VTE in pediatrics in the future due to the efficacy of DOACs in children, and recommendations should be revised periodically as new evidence emerges.


Progressive pathology of the caudate nucleus, the substantia nigra pars reticulata and the deeper layers of the colliculus superior: acute behavioural and metabolic effects of intrastriatal kainic acid.
The acute behavioural and metabolic consequences of functional changes following unilateral intracaudate kainic acid at the level of the feline caudate nucleus, the substantia nigra pars reticulata and the deeper layers of the colliculus superior were investigated. The present study became possible since it was previously found that unilateral changes in neurotransmission processes in these structures all result in behavioural alterations that can be distinguished from each other. During the first 17 min after kainic acid, all animals displayed contralateral forced staccato head turning; these movements are characteristic for an activation of dopamine receptors and/or inhibition of GABA receptors in the rostromedial caudate nucleus. Between 15 and 50 min, all animals displayed fast, uninterrupted contralateral forced head, torso or body turning; these movements are characteristic for an activation of nigral GABA receptors. From about 48 min, all animals displayed sequences of short contralateral forced ear, head, torso and body turnings; these movements are characteristic for an inhibition of collicular GABA receptors. Furthermore, most cats displayed ipsilateral orofacial dyskinetic movements during the whole 180 min observation period. Metabolism was analysed in three cats that received [14C]2-D-deoxyglucose immediately before, 5 min after, or 70 min after kainic acid. Metabolism was increased in the ipsilateral caudate nucleus; this effect was most pronounced in the cat that received deoxyglucose immediately before kainic acid. Metabolic activity was increased in the ipsilateral substantia nigra pars reticulata; this effect was most pronounced in the cat treated with deoxyglucose 5 min after kainic acid. Metabolism was increased in the ipsilateral deeper layers of the colliculus superior in the cat that received deoxyglucose 70 min after kainic acid. The present behavioural and metabolic data suggest that kainic acid produces an increasing pathology resulting successively in functional changes in the caudate nucleus, its output-station the substantia nigra pars reticulata and the nigral output-station the deeper layers of the colliculus superior. It is suggested that the successive appearance of the latter effects is inherent in the hierarchical order of the brain structures under study. The occurrence of orofacial dyskinetic movements during the whole observation period suggests that the former movements were not mediated via the striato-nigro-collicular pathway. Finally, apomorphine injected in the ipsilateral caudate nucleus 1 week after kainic acid was significantly less effective compared to apomorphine injected 1 week before kainic acid. The c


HIF1α promotes tumor chemoresistance via recruiting GDF15-producing TAMs in colorectal cancer.
Chemoresistance is a tremendous challenge to efficacy of systemic chemotherapy which is the preferred treatment for the advanced CRC patients. More tumor-associated macrophages (TAMs) are recruited into the CRC tumor under chemotherapy, which are highly implicated in the chemoresistance development, but the underlying molecular mechanism is unclear. Here, we present that activated HIF1α signaling in CRC cells under chemotherapy drives the expression of HMGB1to promotes macrophage infiltration and in turn chemoresistance development. Chemotherapeutic treatment with 5-FU leads to increased recruitment of macrophages into tumors, which display tumor-protective alternative activation. Mechanistically, tumor HIF1α signaling activated by chemo-induced ROS drives the transcription of HMGB1 to promote more macrophage infiltration into CRC tumor. Furthermore, high levels of GDF15 produced by TAMs impair the chemosensitity of tumor cells via enhancing fatty acids β-oxidation. Together, our current study reveals a new insight into the cross-talking between tumor cells and immune cells, and provides novel drug targets for clinic treatments for CRC.


Lead systems for the abdominal fetal electrocardiogram.
The literature on abdominal FECG has been studied for design principals of a lead system for recording FECG signals at the maternal abdomen. The indications are compared, contrasted, and combined with the results obtained from basic FECG data collected in a recent study on the modelling of the FECG.


Minimal invasive surgery for coronoid fracture: technical note.
Operative treatment of coronoid fracture often requires a large dissection of soft tissue, resulting in elbow stiffness and functional limitation. The authors present a minimal invasive, safe technique, useful in the case of isolated coronoid fracture associated with elbow dislocation. This technique does not require soft tissue dissection and allows an early unlimited resumption of sports activities.


A fair test of the effect of a shadow-incompatible luminance gradient on the simultaneous lightness contrast.
Shadow-compatibility of simultaneous lightness contrast is discussed by Alexander D Logvinenko and Paola Bressan, with examples claiming to provide a test of the hypothesis.


A coumarin-based fluorescent probe for NIR imaging-guided photodynamic therapy against S. aureus-induced infection in mouse models.
A coumarin-based viscosity-responsive fluorescent probe (HZAU800) was designed and synthesized. The probe, containing a strong electron-donating and rigid group on the 7-position of coumarin and a rhodamine derivative containing an oxonium ion on 3-position, could not only shift the emission wavelength to near-infrared region (NIR, λem = 800 nm) but also deliver a good PDT effect due to its high rigid planarity. The NIR fluorescence of HZAU800 can be lighted up in the S. aureus-infected region due to its high viscous environment. Under the laser's irradiation at 690 nm, the PDT effect was effectively triggered up, and the antibacterial evaluation in vitro and in vivo was successfully carried out. This study not only offers a new strategy for constructing coumarin-based phototherapy agents but also facilitates the exploration of the next generation of antibacterial materials based on coumarin architectures.


[Treatment of premature labour and antagonization of the side effects of tocolytic therapy with verapamil (author's transl)].
167 cases of threatened premature birth were treated with Fenoterol, Fenoterol + Verapamil and Ritodrine. In 70-79% of cases a newborn of over 2500 g was achieved. In 70-76% it was possible to prolong the pregnancy for over 7 days and in 61-64% a gestation age of 37 weeks and more was reached. Special attention was paid to the facts as to whether the general side effects of Fenoterol can be antagonized with Verapamil.


Propofol-based sedation does not negatively influence oxygenator running time compared to midazolam in patients with extracorporeal membrane oxygenation.
Patients on extracorporeal membrane oxygenation are frequently in need for sedation. Use of propofol has been associated with impaired oxygenator function due to adsorption to the membrane as well as lipid load. The aim of our retrospective analysis was to compare two different sedation regimens containing either propofol or midazolam with respect to oxygenator running time. Midazolam was used in 73 patients whereas propofol was used in 49 patients, respectively. In the propofol group, veno-arterial-extracorporeal membrane oxygenation was used predominantly (84%), while veno-venous-extracorporeal membrane oxygenation was used more often in the midazolam group (64%). Oxygenator running time until first exchange was 7 days in both groups ( p = 0.759). No statistically significant differences could be observed between the subgroup of patients receiving lipid-free (n = 24) and lipid-containing (n = 31) parenteral nutrition, respectively. Laboratory parameters like triglycerides, free hemoglobin, fibrinogen, platelets, and activated partial thromboplastin time were not significantly different between both sedation regimens ( p = 0.462, p = 0.489, p = 0.960, p = 0.134, and p = 0.843) and were not associated with oxygenator running time. The use of propofol as sedative seems suitable in patients undergoing extracorporeal membrane oxygenation therapy.


A rare cause of fatal right ventricular cardiac decompensation.
Hereditary hemorrhagic telangiectasia is an autosomal dominant vascular disease often manifesting with epistaxis, telangiectasia, and intraparenchymatous arteriovenous malformations. We report on the case of a 71-year-old man who was admitted to hospital due to a tricuspid valve insufficiency. During the following days, the patient developed liver and renal failure; the clinical condition worsened rapidly. Computed tomographic diagnostics revealed arteriovenous malformations in the lung and in the liver portal. Additionally, mucocutaneous telangiectasia in the mouth was found. Hereditary hemorrhagic telangiectasia was assumed; nevertheless, an effective treatment was impossible because of the patient's worse clinical state; he died a few days later. Autopsy affirmed the diagnosis of hereditary hemorrhagic telangiectasia; molecular genetic analysis revealed a heterozygous mutation in the ALK-1 gene. Despite its relatively high prevalence, hereditary hemorrhagic telangiectasia is not considered as a diagnosis as frequently as it should be, and clinicians need to be aware of the signs of hereditary hemorrhagic telangiectasia as well as the appropriate diagnostic workup.


Selective staining of the same set of nucleolar phosphoproteins by silver and Giemsa. A combined biochemical and cytochemical study on staining of NORs.
Gel electrophoresis of nucleolar isolates from Zajdela ascites hepatoma cells followed by various staining procedures revealed a common set of bands that stained selectively with silver and Giemsa. The gel bands, corresponding to molecular weights of 104, 78, 37, and 29 kilodaltons (kd), appeared to contain phosphoproteins that were at least partly associated with oligo-deoxyribonucleotides. Enzyme digestion studies showed that the Giemsastainability was due to the phosphorylated state of the proteins. The positive selective silver-staining reaction in gels could be most likely attributed to the high content of carboxyl groups present in these phosphoproteins. The significance of these findings in relation to cytological results produced by selective silver staining of nucleolus organizing regions (NORs) and by Giemsa N-banding is discussed.


The Directions of psychiatric research by Emil Kraepelin. 1887.
This classic text reproduces Emil Kraepelin's inaugural lecture at the University of Dorpat in 1887. It represents one of the most succinct contemporary surveys of German psychiatric discourse in the 1880s. It also outlines Kraepelin's own research priorities in the early years of his career, providing important historical background to the motives that drove him to place such great emphasis on (and hope in) experimental psychology. Contrary to our contemporary image of Kraepelin as a grand clinical nosologist, this text shows that he was much more of a diagnostician and experimental psychologist than historians have generally assumed. The document also reflects a wider 'psychological turn' in German psychiatry, away from patho-anatomic study - a turn that has often been overlooked in the historiographic literature.


Whole-brain radiotherapy with 20 Gy in 5 fractions for brain metastases in patients with cancer of unknown primary (CUP).
Whole brain radiotherapy (WBRT) is the most common treatment for brain metastases. Survival of patients with cancer of unknown primary (CUP) presenting with brain metastases is extremely poor. A radiation program with a short overall treatment time (short-course RT) would be preferable to longer programs if it provides similar outcomes. This study compares short-course RT with 20 Gy in 5 fractions (5 x 4 Gy) given over 5 days to longer programs in CUP patients. Data regarding 101 CUP patients who received either short course WBRT (n=34) with 5 x 4 Gy or long-course WBRT (n=67) with 10 x 3 Gy given over 2 weeks or 20 x 2 Gy given over 4 weeks for brain metastases were analyzed retrospectively. Six additional potential prognostic factors were investigated: age, gender, Karnofsky performance score (KPS), number of brain metastases, extracranial metastases, RPA-(Recursive Partitioning Analysis-)class. On univariate analysis, the radiation program was not associated with survival (p=0.88) nor intracerebral control (p=0.36). Improved survival was associated with KPS >or= 70 (p<0.001), absence of extracranial metastases (p<0.001), and RPA-class 1 (p<0.001). On multivariate analyses, KPS (risk ratio [RR]: 4.55; p<0.001), extracranial metastases (RR: 1.70; p=0.018), and RPA-class (RR: 2.86; p<0.001) maintained significance. On univariate analysis, KPS (p<0.001) and RPA-class (p<0.001) were significantly associated with intracerebral control. On multivariate analyses, KPS (RR: 2.72; p<0.001) and RPA-class (RR: 2.09; p<0.001) remained significant. Short-course WBRT with 5 x 4 Gy provided similar intracerebral control and survival as longer programs for the treatment of brain metastases in CUP patients. 5 x 4 Gy appears preferable because it is more convenient for patients.


[Late complications after surgery for high congenital intestinal obstruction in children].
The work analyses the experience in examination and treatment of 31 patients with late-term complications after operations for various types of acute and chronic high congenital ileus. Five groups of children were set apart according to the character and anatomical cause of the complication. The characteristics of late-term complications, their clinical manifestations, and methods of repeated surgical interventions are given. The most difficult for treatment were complications which had developed after creation during the primary operation of gastroentero-anastomoses for an annular pancreas (5 patients) and membranous atresia of the duodenum (one patient). It is concluded that the performance of this operation is not advisable.


Symptoms of attention-deficit/hyperactivity disorder, overeating, and body mass index in men.
The high prevalence of obesity currently poses a global health crisis. Previous research has identified a novel link between obesity and Attention-Deficit/Hyperactivity Disorder (AD(H)D). Davis, Levitan, Smith, Tweed and Curtis [Davis, C., Levitan, R. D., Smith, M., Tweed, S., & Curtis, C. (2006). Associations among overeating, overweight, and attention deficit/hyperactivity disorder: A structural equation modeling approach. Eating Behaviors, 7, 266-274] recently tested a structural equation model predicting that AD(H)D symptoms foster overeating and subsequently contribute to the variation in Body Mass Index (BMI) in a sample of healthy adult females. The data were an excellent fit to the model. In order to extend the generalizability of these findings, the present study tested the same model in 145 non-clinical adult males. Similar to the findings in females, AD(H)D symptoms positively predicted overeating in males, which in turn positively predicted BMI. Results highlight mechanisms whereby AD(H)D symptoms could influence body mass and stress the importance of addressing AD(H)D symptoms in both the prevention and treatment of overeating and obesity.


Long-term effect of COVID-19 infection on kidney function among COVID-19 patients followed in post-COVID-19 recovery clinics in British Columbia, Canada.
We investigated the effect of Post-Acute COVID Syndrome or "long-COVID" on kidney function among patients followed in post-COVID recovery clinics (PCRC) in British Columbia, Canada. Long-COVID patients referred to PCRC between July 2020 to April 2022, aged ≥18 years who had an estimated glomerular filtration rate (eGFR) value recorded at 3 months from the coronavirus disease 2019 (COVID-19) diagnosis (index) date were included. Those requiring renal replacement therapy prior to index date were excluded. Primary outcome was change in eGFR and urine albumin-creatinine ratio (UACR) after COVID-19 infection. The proportion of patients in each of the six eGFR categories (<30, 30-44, 45-59, 60-89, 90-120 and >120 mL/min/1.73 m2) and three UACR categories (<3, 3-30 and >30 mg/mmol) in all of the study time points were calculated. Linear mixed model was used to investigate change in eGFR over time. The study sample included 2212 long-COVID patients. Median age was 56 years, 51% were male. Half (∼47%-50%) of the study sample had normal eGFR (≥90 mL/min/1.73 m2) from COVID-19 diagnosis to 12 months post-COVID and <5% of patients had an eGFR <30 mL/min/1.73 m2. There was an estimated 2.96 mL/min/1.73 m2 decrease in eGFR within 1 year after COVID-19 infection that was equivalent to 3.39% reduction from the baseline. Decline in eGFR was highest in patients hospitalized for COVID-19 (6.72%) followed by diabetic patients (6.15%). More than 40% of patients were at risk of CKD. People with long-COVID experienced a substantial decline in eGFR within 1 year from the infection date. The prevalence of proteinuria appeared to be high. Close monitoring of kidney function is prudent among patients with persistent COVID-19 symptoms.


Assessing patient-caregiver communication in cancer--a psychometric validation of the Cancer Communication Assessment Tool (CCAT-PF) in a German sample.
The recently introduced Cancer Communication Assessment Tool (CCAT-PF) measures congruence in patient-caregiver communication and was initially validated in lung cancer patients. Contributing to a greater proportion of the variance in the conflict scores, primary caregivers were hypothesized to experience greater stress. For a detailed understanding of conflicting communication patterns of cancer-affected families, our study aimed for psychometric validation of the CCAT-PF in a sample covering heterogeneous tumor entities. Subsequent to a cross-sectional survey of 189 pairs of cancer patients (31 % gastrointestinal, 34 % lung, and 35 % urological) and their caregivers' exploratory factor analysis with principal component condensation and varimax rotation was conducted (response rate, 74.2 %). Reliability and construct validity were assessed calculating Cronbach's α and Pearson correlation coefficients for CCAT-P and CCAT-F scales and related constructs, respectively. Cancer-related communication according to the CCAT-PF can be subdivided into four factors including the scales Disclosure, Limitation of treatment, Family involvement in treatment decisions, and Continuing treatment. Reliability ranged from α = .51-.68. The Disclosure scale, describing poor cancer-related communication of the patient, was correlated with patient's distress (QSC-R10: r = .30, p < .0001), unmet needs in several areas (SCNS-SF-34: r = .25-.32, p < .001), and negatively with social/family well-being (FACT: r = -0.31, p < .0001). Higher scores on the scale were significantly associated with considerable decrements in emotional well-being especially for caregivers perceiving patients' disclosure as problematic. The Disclosure scale originating from the CCAT-PF emerged as a short, valid, and reliable stand-alone instrument for identifying conflicting communication in patient-caregiver-dyads at risk.


Prevention and Treatment of SARS-CoV2 Infection in People Living with HIV: The Need for Specific Data.
The HIV pandemic has led to close to 40 million people living with HIV (PLWH) worldwide. To date, SARS-CoV2 has affected > 220 million people, and unprecedented global efforts have resulted in almost 6000 million doses of SARS-CoV2 vaccines being administered. Although several specific COVID-19 antiviral and anti-inflammatory treatments and SARS-CoV2 vaccines have been approved, the data available to support their use in specific populations such as PLWH remain limited. PLWH includes a range of individuals from practically unaffected immunity to severely immunocompromised individuals, and preventive and therapeutic interventions should be tailored for these subgroups . However, in most randomized clinical trials regarding antivirals, immunomodulators and vaccines for COVID-19, PLWH have been excluded or only enrolled in small numbers leading to a paucity of data. We briefly discuss the current evidence for prevention and treatment of COVID-19 in PLWH and identify key areas where more information is required.


Recruiting "Talent": School Choice and Teacher Hiring in New Orleans.
The purpose of this study is to examine school leaders' preferences and practices in an environment of widespread decentralization, privatization, and school choice. In New Orleans, such reforms have been enacted citywide since Hurricane Katrina, making it an ideal site to examine what happens when policy makers lift restrictions for school leaders-and remove protections for teachers-related to teacher hiring on a large scale. In this exploratory study, I analyze qualitative data to examine school leaders' preferences and practices when recruiting teachers in New Orleans. The data for the study come from 94 interviews with principals, district leaders, and charter network leaders. School leaders had different conceptions of "talent" and "fit," and used a variety of strategies to recruit teachers. School districts and charter networks both supported and constrained school leaders' autonomy and recruitment practices by screening applicants or setting guidelines and criteria. Other intermediary organizations also played a role in shaping the teacher labor market. School choice also posed unique challenges for teacher recruitment. Overall, expansive choice policies in New Orleans appear to foster flexibility and variation in teacher hiring strategies (although not in salary), as expected in a decentralized system. However, these policies and strategies appear also to have other consequences, including greater instability or "churn," unpredictability, and a bifurcated teaching force.


Synthesis of activated biochar from sustainable bamboo resources: An environment-friendly and low-cost solution for palladium (II) removal from wastewater.
This article highlights the developing capabilities of low-cost activated biochar from bamboo waste used for Palladium (II) (Pd(II)) separation from man-made electroless plating solutions (ELP). From a novelty perspective, this article addresses the effect of coupled sonication and surfactant for the adsorptive elimination of Pd(II) on Bamboo stem activated carbon (BSAC) from ELP. The optimal activation procedure referred to an acid-to-bamboo ratio of 4:1 at sintering of 600-900 °C, which provided an activated carbon (AC) adsorbent with surface area analysis (BET) of 1014.36 m2/g, a value comparable to the commercially procured AC. Pd(II) adsorption characteristics in the solution of Pd with 50-500 mg/L concentration range were evaluated utilizing both agitation and sonication. Adsorption time, pH, dose, and adsorbate concentration were among the pertinent optimal batch adsorption parameters that were found. When utilizing ELP solutions without surfactant, the proposed adsorbent for agitation-assisted adsorption had a simultaneous improvement in metal intake of 6.68-43.2 mg/g and removal efficiency of 72.96-54.5% (cTAB). For cTAB-containing solutions, sonication and agitation-assisted adsorption were outperformed in terms of removal efficiency of 80.32-60.16% and metal uptake of 6.69-50.13 mg/g. Equilibrium, kinetic, and thermodynamic models with good fitting to the reported Pd(II) adsorption properties have been developed.


Usefulness of the Clavien-Dindo Classification to Rate Complications after Carotid Endarterectomy and Its Implications in Patient Prognosis.
Our primary objective was to test if the Clavien-Dindo classification (C-D-C) is also applicable for the assessment of carotid surgery and how well it correlates with patient prognosis in the mid-term follow-up. From January 2011 to March 2014, a total of 248 consecutive open surgical carotid revascularization procedures were performed at one academic institution. All patients, symptomatic and asymptomatic, had a high-grade (>70%) stenosis and were operated on under general anesthesia. Physicians graded all complications that were identified in the first 30 days after surgery according to C-D-C. Complications were considered "minor" if they were of C-D-C grades I or II. Complications were considered "major" if they were of C-D-C grades III (those requiring surgical, endoscopic, or radiological intervention) or IV (those that are life-threatening). In the analysis of the overall survival, we have found the following differences: (1) survival at 12 months (no complication [NC]: 96.3%, minor complications [Cmin]: 94.3%, major complications [Cmaj]: 85.7%), (2) at 24 months (NC: 93.1%, Cmin: 92.8%, Cmaj: 64.3%), and (3) at 36 months (NC: 87.7%, Cmin: 81.7%, Cmaj: 64.3%). These differences were significant (P = 0.014). When analyzing the stroke-free survival after surgery, the survival rates were as follows: (1) at 12 months (NC: 94.2%, Cmin: 91.3%, Cmaj: 84.6%), (2) at 24 months (NC: 87.7%, Cmin: 82.3%, Cmaj: 61.5%), and (3) at 36 months (NC: 81.13%, Cmin: 76.5%, Cmaj: 61.5%). The significance of the difference is P = 0.016. In the analysis of cardiovascular event-free survival, taking into account not only stroke and myocardial infarction but also major amputation, the survival analysis shows the following results: (1) at 12 months (NC: 90.3%, Cmin: 76.1%, Cmaj: 60%), (2) at 24 months (NC: 81.1%, Cmin: 61.1%, Cmaj: 50%), and (3) at 36 months (NC: 73%, Cmin: 56.8%, Cmaj: 0%). These data also show a difference between the groups (P < 0.001). The C-D-C is applicable for patients who underwent a carotid endarterectomy, and the classification seems to make a good correlation of the grade of the complication and the prognosis during follow-up. More studies are needed with larger numbers of patients and longer follow-up times to clarify the use of the C-D-C after vascular surgery and identify high-risk patients. It can also be helpful to homogenize reports and make them comparable.


Physiomimetic biocompatibility evaluation of directly printed degradable porous iron implants using various cell types.
Additively manufactured (AM) degradable porous metallic biomaterials offer unique opportunities for satisfying the design requirements of an ideal bone substitute. Among the currently available biodegradable metals, iron has the highest elastic modulus, meaning that it would benefit the most from porous design. Given the successful preclinical applications of such biomaterials for the treatment of cardiovascular diseases, the moderate compatibility of AM porous iron with osteoblast-like cells, reported in earlier studies, has been surprising. This may be because, as opposed to static in vitro conditions, the biodegradation products of iron in vivo are transported away and excreted. To better mimic the in situ situations of biodegradable biomaterials after implantation, we compared the biodegradation behavior and cytocompatibility of AM porous iron under static conditions to the conditions with dynamic in situ-like fluid flow perfusion in a bioreactor. Furthermore, the compatibility of these scaffolds with four different cell types was evaluated to better understand the implications of these implants for the complex process of natural wound healing. These included endothelial cells, L929 fibroblasts, RAW264.7 macrophage-like cells, and osteoblastic MG-63 cells. The biodegradation rate of the scaffolds was significantly increased in the perfusion bioreactor as compared to static immersion. Under either condition, the compatibility with L929 cells was the best. Moreover, the compatibility with all the cell types was much enhanced under physiomimetic dynamic flow conditions as compared to static biodegradation. Our study highlights the importance of physiomimetic culture conditions and cell type selection when evaluating the cytocompatibility of degradable biomaterials in vitro. STATEMENT OF SIGNIFICANCE: Additively manufactured (AM) degradable porous metals offer unique opportunities for the treatment of large bony defects. Despite the successful preclinical applications of biodegradable iron in the cardiovascular field, the moderate compatibility of AM porous iron with osteoblast-like cells was reported. To better mimic the in vivo condition, we compared the biodegradation behavior and cytocompatibility of AM porous iron under static condition to dynamic perfusion. Furthermore, the compatibility of these scaffolds with various cell types was evaluated to better simulate the process of natural wound healing. Our study suggests that AM porous iron holds great promise for orthopedic applications, while also highlighting the importance of physio-mimetic culture conditions and cell type selection when evaluating the cytocompatibility of degradable biomaterials in vitro.


Adherence to fecal immunochemical test screening among adults at average risk for colorectal cancer.
This study examined adherence to screening for fecal immunochemical test (FIT). Adults (≥ 50-75) with a FIT between 1/1/2014 and 6/30/2019 in MarketScan administrative claims were selected (index = earliest FIT). Patients were followed for 10 years pre- and 3 years post-index. Patients at increased risk for CRC or with prior screening were excluded. Year over year adherence was measured post-index. Of 10,253 patients, the proportion adherent to repeat testing at year 2 was 23.4% and 10.6% at year 3. Of 76.6% not adherent in year 2, 5.4% were adherent in year 3. Results suggest adherence to FIT tests is poor, minimizing potential benefits. Future studies are needed to consider alternative test options and whether more choice will improve long-term adherence.


Is routine blood cross-matching necessary in elective laparoscopic colorectal surgery?
Routine pre-operative cross-matching of two units of packed red cells (PRC) is current practice in most hospitals for patients undergoing elective laparoscopic colorectal surgery (LCS). To determine the usage of PRC in patients undergoing elective LCS & its cost implications. Retrospective analysis of 116 consecutive laparoscopic colorectal resections under the care of 2 consultant surgeons. Surgical procedures were anterior resection (31.9%; n = 37), right hemicolectomy (22.4%; n = 26), sigmoid colectomy (22.4%; n-26), subtotal colectomy (7.8%; n = 9), APR (4.3%; n = 5), panproctocolectomy (3.4%; n = 4), completion proctectomy (1.7%, n = 2), left hemicolectomy (0.9%, n = 1), total colectomy (0.9%; n = 1) & resection rectopexy (0.9%; n = 1). The median age was 65 years, 58% female. The median pre-operative haemoglobin was 131 g/L, median blood loss 100 ml and median post-operative haemoglobin 111.5 g/L. Eleven cases were converted. Three patients required perioperative blood transfusion, 2 of whom underwent open conversion. The cost of carrying out a group & save (G&S) in our hospital is £40.60 excluding laboratory staff labour cost. A 2 unit cross-match costs £294.60. There is potential for substantial cost savings with change of practice to G&S only. G&S is sufficient to allow safe & cost-effective operative practice in laparoscopic colorectal surgery.


Insight to biotechnological utility of phycochemicals from cyanobacterium Anabaena sp.: An overview.
Cyanobacteria (blue-green algae) are well-known for the ability to excrete extra-cellular products, as a variety of cyanochemicals (phycocompounds) of curio with several extensive therapeutic applications. Among these phycocompound, the cyanotoxins from certain water-bloom forming taxa are toxic to biota, including crocodiles. Failure of current non-renewable source compounds in producing sustainable and non-toxic therapeutics led the urgency of discovering products from natural sources. Particularly, compounds of the filamentous N2-fixing Anabaena sp. have effective antibacterial, antifungal, antioxidant, and anticancer properties. Today, such newer compounds are the potential targets for the possible novel chemical scaffolds, suitable for mainstream-drug development cascades. Bioactive compounds of Anabaena sp. such as, anatoxins, hassallidins and phycobiliproteins have proven their inherent antibacterial, antifungal, and antineoplastic activities, respectively. Herein, the available details of the biomass production and the inherent phyco-constituents namely, alkaloids, lipids, phenols, peptides, proteins, polysaccharides, terpenoids and cyanotoxins are considered, along with geographical distributions and morphological characteristics of the cyanobacterium. The acquisitions of cyanochemicals in recent years have newly addressed several pharmaceutical aliments, and the understanding of the associated molecular interactions of phycochemicals have been considered, for plausible use in drug developments in future.


Betaine protects against rotenone-induced neurotoxicity in PC12 cells.
Rotenone is an inhibitor of mitochondrial complex I-induced neurotoxicity in PC12 cells and has been widely studied to elucidate the pathogenesis of Parkinson's disease. We investigated the neuroprotective effects of betaine on rotenone-induced neurotoxicity in PC12 cells. Betaine inhibited rotenone-induced apoptosis in a dose-dependent manner, with cell viability increasing from 50 % with rotenone treatment alone to 71 % with rotenone plus 100-μM betaine treatment. Flow cytometric analysis demonstrated cell death in the rotenone-treated cells to be over 50 %; the number of live cells increased with betaine pretreatment. Betaine pretreatment of PC12 cells attenuated rotenone-mediated mitochondrial dysfunction, including nuclear fragmentation, ATP depletion, mitochondrial membrane depolarization, caspase-3/7 activation, and reactive oxygen species production. Western blots demonstrated activation of caspase-3 and caspase-9, and their increased expression levels in rotenone-treated cells; betaine decreased caspase-3 and caspase-9 expression levels and suppressed their activation. Together, these results suggest that betaine may serve as a neuroprotective agent in the treatment of neurodegenerative diseases.


Combined total body irradiation and local radiation therapy in oat cell carcinoma of the bronchus.
Use of total body irradiation (TBI) as a systematic therapy has been evaluated in controlling subclinical and established metastases in oat cell bronchus carcinoma. Preliminary results suggest that patients without clinical evidence of distant metastases do better than those with metastases. No patient in this series developed brain metastases. This could be related to TBI but may again be just a coincidence. The booster radiation dose (1000 rad) given to the liver seems to be inadequate in preventing metastases there, as all the deaths were due to liver metastases. In view of this, a higher dose to the liver is recommended.


Mandibular distraction osteogenesis: at what age to proceed.
To evaluate if there is a difference in mandibular distraction osteogenesis (MDO) treatment success rates and adverse outcomes in newborns, early infants, and older pediatric patients. Retrospective medical review spanning a nine-year period. Ten newborn (≤ 35 days old), five early infant (36 days-5 months) and eight older pediatric (> 5 months) patients underwent MDO for treatment of micrognathia with a severe tongue-based obstruction. Success was defined as avoidance of tracheostomy or CPAP, and decannulation of patients with tracheotomies. Postoperative complications were grouped into minor and major. MDO successfully treated 90% of newborns, 100% of early infants and 100% of older pediatric patients. There was no difference in the rates of success (p=0.48), minor (p=1.00) and major (p=1.00) postoperative complications between newborns and early infants. Older pediatric patients had no treatment failures, tended to have fewer minor (p=0.18) and significantly fewer major (p= 0.04) postoperative complications compared to younger patients. The distractor pin mobility (9%) and scar revisions (13%) were uncommon. Mandibular distraction osteogenesis is a reliable method for relieving severe tongue-based obstructions in pediatric patients. When comparing newborns and early infant patients, treatment success rates and the occurrence of complications were not found to be different. Older pediatric patients had no treatment failures, and tended to have fewer postoperative complications compared to younger patients.