Translating research to policy at the NCSE 2017 symposium "Microbiology of the Built Environment: Implications for Health and Design".
Here, we summarize a symposium entitled "Microbiology of the Built Environment: Implications for Health and Design" that was presented at the National Council for Science and the Environment (NCSE) 17th National Conference and Global Forum in January 2017. We covered topics including indoor microbial exposures and childhood asthma, the influence of hospital design on neonatal development, the role of the microbiome in our premise (i.e., building) plumbing systems, antibiotic resistance, and quantitative microbial risk assessment. This symposium engaged the broader scientific and policy communities in a discussion to increase awareness of this critical research area and translate findings to practice.


Discovery of new therapeutic redox targets for cardioprotection against ischemia/reperfusion injury and heart failure.
Global epidemiological studies reported a shift from maternal/infectious communicable diseases to chronic non-communicable diseases and a major part is attributable to atherosclerosis and metabolic disorders. Accordingly, ischemic heart disease was identified as a leading risk factor for global mortality and morbidity with a prevalence of 128 million people. Almost 9 million premature deaths can be attributed to ischemic heart disease and subsequent acute myocardial infarction and heart failure, also representing a substantial socioeconomic burden. As evidenced by typical oxidative stress markers such as lipid peroxidation products or oxidized DNA/RNA bases, the formation of reactive oxygen species by various sources (NADPH oxidases, xanthine oxidase and mitochondrial resperatory chain) plays a central role for the severity of ischemia/reperfusion damage. The underlying mechanisms comprise direct oxidative damage but also adverse redox-regulation of kinase and calcium signaling, inflammation and cardiac remodeling among others. These processes and the role of reactive oxygen species are discussed in the present review. We also present and discuss potential targets for redox-based therapies that are either already established in the clinics (e.g. guanylyl cyclase activators and stimulators) or at least successfully tested in preclinical models of myocardial infarction and heart failure (mitochondria-targeted antioxidants). However, reactive oxygen species have not only detrimental effects but are also involved in essential cellular signaling and may even act protective as seen by ischemic pre- and post-conditioning or eustress - which makes redox therapy quite challenging.


Phylogenetic analysis of receptor FgfrL1 shows divergence of the C-terminal end in rodents.
FGFRL1 is a member of the fibroblast growth factor receptor (FGFR) family. Similar to the classical receptors FGFR1-FGFR4, it contains three extracellular Ig-like domains and a single transmembrane domain. However, it lacks the intracellular tyrosine kinase domain that would be required for signal transduction, but instead contains a short intracellular tail with a peculiar histidine-rich motif. This motif has been conserved during evolution from mollusks to echinoderms and vertebrates. Only the sequences of FgfrL1 from a few rodents diverge at the C-terminal region from the canonical sequence, as they appear to have suffered a frameshift mutation within the histidine-rich motif. This mutation is observed in mouse, rat and hamster, but not in the closely related rodents mole rat (Nannospalax) and jerboa (Jaculus), suggesting that it has occurred after branching of the Muridae and Cricetidae from the Dipodidae and Spalacidae. The consequence of the frameshift is a deletion of a few histidine residues and an extension of the C-terminus by about 40 unrelated amino acids. A similar frameshift mutation has also been observed in a human patient with a craniosynostosis syndrome as well as in several patients with colorectal cancer and bladder tumors, suggesting that the histidine-rich motif is prone to mutation. The reason why this motif was conserved during evolution in most species, but not in mice, is not clear.


Biological Factors in the Workplace-Current Threats to Employees, the Effects of Infections, Prevention Options.
Infectious diseases or communicable diseases are spread from person to person by various routs [...].


Management of Severe Acute Pancreatitis.
There have been significant advancements in different aspects of management of severe acute pancreatitis (SAP). Our review of the most recent literature focuses on severity prediction, fluid resuscitation, analgesic administration, nutrition, and endoscopic intervention for SAP and its extra-pancreatic complications. Recent studies on serum cytokines for the prediction of SAP have shown superior prognostic performance when compared with conventional laboratory tests and clinical scoring systems. In patients with established SAP and vascular leak syndrome, intravenous fluids should be administered with caution to prevent intra-abdominal hypertension and volume overload. Endoscopic retrograde cholangiopancreatography improves outcomes only in AP patients with suspected cholangitis. Early enteral tube-feeding does not appear to be superior to on-demand oral feeding. Abdominal compartment syndrome is a highly lethal complication of SAP that requires percutaneous drainage or decompressive laparotomy. Endoscopic transmural drainage followed by necrosectomy (i.e., "step-up approach") is the treatment strategy of choice in patients with symptomatic or infected walled-off pancreatic necrosis. SAP is a complex clinical syndrome associated with a high mortality rate. Early prediction of SAP remains challenging due to the limited accuracy of the available prediction tools. Early fluid resuscitation, organ support, enteral nutrition, and prevention of/or prompt recognition of abdominal compartment syndrome remain cornerstones of its management. A step-up, minimally invasive drainage/debridement is the preferred approach for patients with infected pancreatic necrosis.


Sparse spike trains and the limitation of rate codes underlying rapid behaviours.
Animals live in dynamic worlds where they use sensorimotor circuits to rapidly process information and drive behaviours. For example, dragonflies are aerial predators that react to movements of prey within tens of milliseconds. These pursuits are likely controlled by identified neurons in the dragonfly, which have well-characterized physiological responses to moving targets. Predominantly, neural activity in these circuits is interpreted in context of a rate code, where information is conveyed by changes in the number of spikes over a time period. However, such a description of neuronal activity is difficult to achieve in real-world, real-time scenarios. Here, we contrast a neuroscientists' post-hoc view of spiking activity with the information available to the animal in real-time. We describe how performance of a rate code is readily overestimated and outline a rate code's significant limitations in driving rapid behaviours.


Survival benefit of liver resection for hepatocellular carcinoma associated with portal vein invasion.
The presence of portal vein tumor thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC) is regarded as indicating an advanced stage, and liver resection (LR) is not recommended. The aim of this study was to evaluate the survival benefit of LR for HCC patients with PVTT through the analysis of the data from a Japanese nationwide survey. We analyzed data for 6474 HCC patients with PVTT registered between 2000 and 2007. Of these patients, 2093 patients who underwent LR and 4381 patients who received other treatments were compared. The propensity scores were calculated and we successfully matched 1058 patients (66.1% of the LR group). In the Child-Pugh A patients, the median survival time (MST) in the LR group was 1.77years longer than that in the non-LR group (2.87years vs. 1.10years; p<0.001) and 0.88years longer than that in the non-LR group (2.45years vs. 1.57years; p<0.001) in a propensity score-matched cohort. A subgroup analysis revealed that LR provides a survival benefit regardless of age, etiology of HCC, tumor marker elevation, and tumor number. The survival benefit was not statistically significant only in patients with PVTT invading the main trunk or contralateral branch. In the LR group, the postoperative 90-day mortality rate was 3.7% (68 patients). As long as the PVTT is limited to the first-order branch, LR is associated with a longer survival outcome than non-surgical treatment. The presence of portal vein tumor thrombosis in patients with hepatocellular carcinoma is regarded as indicating an advanced stage, and liver resection is not recommended. We performed a multicenter, nationwide study to assess the survival benefit of liver resection in hepatocellular carcinoma patients with portal vein tumor thrombosis using propensity score-based matching. As long as the portal vein tumor thrombosis is limited to the first-order branch, liver resection is associated with a longer survival outcome than non-surgical treatment.


Influence of exogenous CO₂ on biomass and lipid accumulation of microalgae Auxenochlorella protothecoides cultivated in concentrated municipal wastewater.
The effects of exogenous CO₂ on the growth and lipid accumulation of a local screened facultative heterotrophic microalgae strain Auxenochlorella protothecoides (UMN280) as well as nutrient removal from concentrated municipal wastewater stream (centrate) were examined in this study. A 12-day batch experiment was conducted with CO₂ aeration at three levels, namely, 0%, 1%, and 5% (v/v) CO₂ mixed with air, under light intensity of 60 μmol/(m² @@s). A two-stage growth pattern was observed. The first stage (first-fifth day) was dominated by heterotrophic growth in which organic carbon was the main carbon source. The second stage (6th-12th day) was dominated by autotrophic growth in which exogenous CO₂ had a positive effect on algal biomass accumulation. The addition of 5% CO₂ was better than that of 1% CO₂ on the biomass and lipid production. The uptakes of nutrients were similar between injection and no injection of CO₂, except on phosphorus removal which was affected by the acidification of CO₂.


Associated Factors with Perceived Fear of COVID-19 among Vietnamese Hospital Healthcare Workers during Fourth Wave of the COVID-19 Pandemic: Policy Implications for Interconnected and Social- and Personal-Based Health Support.
(1) Background: The present study measures the fear of COVID-19 among hospital healthcare workers and identifies several factors associated with increasing fear of COVID-19. (2) Methods: A cross-sectional, hospital-based survey was conducted on healthcare workforce recruited from the National Hospital of Tropical Diseases from 1 October 2021 and 20 October 2021. We selected the participants who have been directly involved in diagnosing, treating, or providing nursing care to patients with COVID-19. The primary data was collected via sending the invitation directly to the participants, utilizing structured self-completed questionnaires. The seven-item fear of COVID-19 scale was used to measure the data. The responses of 208 hospital healthcare workers were included in the final analysis. (3) Results: Total score of COVID-19 fear was 19.62 (SD = 5.22). The COVID-19 fear score of 7 items ranged from 2.38 (SD = 0.83) to 3.21 (SD = 0.96). The lowest and highest scores were the item 'My hands become clammy when I think about Corona' and the item 'I am most afraid of corona' was the highest, respectively. Linear regression of the COVID-19 fear showed that the factors positively correlated with the fear of COVID-19 among hospital healthcare workers were: being influenced by the community (p = 0.001), feeling at very high risk of COVID-19 (p = 0.03), and experiencing traumatic stress with an academic event (p = 0.042). (4) Conclusions: Although these findings merit further elaboration, these preliminary findings suggest relatively great fear of the COVID-19 pandemic among Vietnamese hospital healthcare workers and that social and personal connections are necessary for maintaining the mental wellbeing.


Enrichment, isolation, and biodegradation potential of long-branched chain alkylphenol degrading non-ligninolytic fungi from wastewater.
4-t-Octylphenol (4-t-OP) has become a serious environmental concern due to the endocrine disruption in animals and humans. The biodegradation of 4-t-OP by pure cultures has been extensively investigated only in bacteria and wood-decaying fungi. In this study we isolated and identified 14 filamentous fungal strains from wastewater samples in Taiwan using 4-t-OP as a sole carbon and energy source. The isolates were identified based on sequences from different DNA regions. Of 14 fungal isolates, 10 strains grew effectively on solid medium with a wide variety of endocrine disrupting chemicals as the sole carbon and energy source. As revealed by high-performance liquid chromatography analysis, the most effective 4-t-OP degradation (>70%) in liquid medium was observed in Fusarium falciforme after 15days. To our knowledge, this is the first report on the degradation of 4-t-OP as a sole carbon and energy source by non-ligninolytic fungi.


Chewing problems and mortality in older adults in home care: results from the Aged in Home Care study.
To assess the association between chewing problems and risk of mortality in an older population receiving home care in Europe. Retrospective cohort study. Eleven European countries. Two thousand seven hundred fifty-five older adults (mean age+/-standard deviation 82.2+/-7.2) in home care. Data were collected using the Minimum Data Set for Home Care. Study personnel recorded chewing problems (inability to chew food easily and without pain or difficulties, regardless of cause) that presented in the last 3 days before baseline assessment. Data on mortality were collected over a 1-year period. Three hundred ninety-five participants (14.3%) presented with chewing problems. One-year mortality differed significantly according to presence of chewing problems; 303 of 2,361 (12.8%) without chewing problems (crude incident rate per person-year (p-y)=0.15) and 80 of 394 (20.3%) participants with chewing problems (crude incident rate per p-y=0.24) died during follow-up. After adjusting for potential confounders, the risk of death was significantly higher for participants with chewing problems (adjusted hazard ratio (HR)=1.45, 95% confidence intervals (CI)=1.05-1.99). This association remained after exclusion of participants with cognitive impairment (adjusted HR=1.50, 95% CI=1.03-2.20) and those with unintended weight loss (adjusted HR=1.62, 95% CI=1.12-2.34). In older adults in home care in Europe, chewing problems are associated with greater risk of mortality.


Striping of orbital-order with charge-disorder in optimally doped manganites.
The phase diagrams of LaMnO3 perovskites have been intensely studied due to the colossal magnetoresistance (CMR) exhibited by compositions around the [Formula: see text] doping level. However, phase segregation between ferromagnetic (FM) metallic and antiferromagnetic (AFM) insulating states, which itself is believed to be responsible for the colossal change in resistance under applied magnetic field, has prevented an atomistic-level understanding of the orbital ordered (OO) state at this doping level. Here, through the detailed crystallographic analysis of the phase diagram of a prototype system (AMn[Formula: see text]Mn[Formula: see text]O12), we show that the superposition of two distinct lattice modes gives rise to a striping of OO Jahn-Teller active Mn3+ and charge disordered (CD) Mn3.5+ layers in a 1:3 ratio. This superposition only gives a cancellation of the Jahn-Teller-like displacements at the critical doping level. This striping of CD Mn3.5+ with Mn3+ provides a natural mechanism though which long range OO can melt, giving way to a conducting state.


Relationship of exercise, oral contraceptive use, and body fat to concentrations of plasma lipids and lipoprotein cholesterol in young women.
To investigate the relationship of exercise and oral contraceptive use to plasma lipids and lipoproteins, a cross-sectional study was designed to compare lipid levels in 96 exercising and non-exercising women who used or did not use oral contraceptives. Exercisers had significantly lower plasma triglyceride concentrations and low-density/high-density lipoprotein ratios than non-exercisers after adjustment for differences in pill type distribution between groups. Women using progestin-dominant pills had significantly lower plasma triglyceride and high-density lipoprotein concentrations and significantly higher low-density/high-density lipoprotein ratios compared with women using estrogen/progestin-balanced pills. As body fat was significantly associated with both pill type and physical activity, it is unclear how much of these lipoprotein differences were due to body fat, exercise, or pill use. Regular physical activity together with reduced body fat partially compensated for plasma lipoprotein differences associated with oral contraceptive use.


Predictive factors affecting early recurrence after hepatectomy for hepatocellular carcinoma in 5-year survivors.
This study was undertaken to establish a therapeutic strategy for long-term recurrence-free survival in hepatocellular carcinoma (HCC) patients treated by hepatectomy by determining the factors that predict intrahepatic recurrence. This study included 72 patients who survived more than 5 years after hepatectomy for HCC. Based on the interval between hepatectomy and intrahepatic recurrence, they were classified into 3 groups: those with early recurrence within 2 years after surgery (n=15), those with recurrence between 2 and 5 years (n=18), and those without recurrence within 5 years (n=39). Twenty-six parameters concerning host-related, tumor-related, treatment-related factors, and postoperative levels of serum transaminases were evaluated. Among host-related and tumor-related factors, serum albumin level, serum levels of transaminases, indocyanine green retention rate at 15 minutes, tumor number, intrahepatic metastasis and TNM stage were determined to be significantly different between the patients with recurrence within 5 years and those without recurrence. Among treatment-related factors, curability was highly associated with recurrence. The period until increase in the levels of transaminases after surgery was significantly shorter in patients with recurrence compared to the patients without recurrence. Curative operation minimizing intrahepatic metastasis and postoperative anti-inflammatory treatment lowering the occurrence of multicentric carcinogenesis are useful therapeutic strategies for achieving long-term recurrence-free survival for HCC patients treated with surgery.


Improved quantitative dynamic regional oxygen-enhanced pulmonary imaging using image registration.
Oxygen-enhanced MR imaging has been demonstrated in a number of recent studies as a potential method to visualize regional ventilation in the lung. A quantitative pixel-by-pixel analysis is hampered by motion and volume change due to breathing. In this study, image registration via active shape modeling is shown to produce significant improvements in the regional analysis of both static and dynamic oxygen-enhanced pulmonary MRI for five normal volunteers. The method enables the calculation of regional change in relaxation rate between breathing air and 100% oxygen, which is proportional to the change in regional oxygen concentration, and regional oxygen wash-in and wash-out time constants. Registration-corrected mapping of these parameters is likely to provide improved information in the regional assessment of a range of lung diseases.


The influence of age on steroidogenic enzyme activities of the rat adrenal gland: enhanced expression of cholesterol side-chain cleavage activity.
The ability of isolated adrenocortical cells to secrete corticosterone in response to ACTH challenge declines as rats age, but the site or mechanism(s) of this impairment is still unknown. To test the functionality of steroidogenic capacity per se, we measured the key enzyme activities involved in corticosterone biosynthesis. We also measured the mitochondrial cytochrome P-450 content and nonsteroidogenic enzymes specific for subcellular fractions. Mitochondria and microsomal fractions were isolated from the adrenals of 2-, 12-, and 18-month-old animals and used for various enzyme measurements. Mitochondrial side-chain cleavage enzyme activity (nanomoles per min mg protein-1) increased from a mean of 0.43 +/- 0.06 in 2-month-old rats to 1.26 +/- 0.11 and 1.51 +/- 0.06 in 12- and 18-month old rats, respectively. After incubation with 5-cholesten-3 beta,25-diol (25-hydroxycholesterol; 25 micrograms/ml) side-chain cleave activity rose to 5.0 +/- 0.6, 12.4 +/- 1.2, and 16 +/- 1.4 nmol min-1 mg protein-1 in adrenal mitochondrial fractions from 2-, 12-, and 18-month-old rats, respectively. In contrast, mitochondrial cytochrome P-450 content did not vary with advancing age. Microsomal delta 5-3 beta-hydroxysteroid dehydrogenase-delta 5-delta 4-isomerase activities were similar in 2- and 12-month-old rats, but 21-hydroxylase (nanomoles per min mg protein-1) activity was significantly increased in 12-month-old rats (2-month-old, 5.2 +/- 0.2; 12-month-old, 7.7 +/- 0.5). Finally, mitochondrial 11 beta-hydroxylase was comparable in both age groups. In addition, activities of mitochondrial nonsteroidogenic enzymes, such as monoamine oxidase, amytal insensitive NADH cytochrome c reductase, cytochrome c oxidase, succinate dehydrogenase, and malate dehydrogenase, did not change with age. It appears from the evidence presented that the activities of the steroidogenic enzymes are not responsible for the diminished capacity in corticosterone production seen with aging in the rat.


N-Heterocyclic carbene catalysed beta-lactam synthesis.
N-Heterocyclic carbenes promote the formal [2+2] cycloaddition of ketenes with N-tosyl imines to give the corresponding beta-lactams in good to excellent isolated yields; chiral NHCs give beta-lactams in high e.e. after crystallisation.


Tracking human footprints in Antarctica through passive sampling of polycyclic aromatic hydrocarbons in inland lakes.
Freely dissolved polycyclic aromatic hydrocarbons (PAHs) were monitored in seven inland lakes of Antarctica by a polyethylene (PE)-based passive sampling technique, with the objective of tracking human footprints. The measured concentrations of PAHs were in the range of 14-360 ng L(-1) with the highest values concentrated around the Russian Progress II Station, indicating the significance of human activities to the loading of PAHs in Antarctica. The concentrations of PAHs in the inland lakes were in the upper part of the PAHs levels in aquatic environments from remote and background regions across the globe. The composition profiles of PAHs indicated that PAHs in the inland lakes were derived mainly from local oil spills, which was corroborated by a large number of fuel spillage reports from ship and plane crash incidents in Antarctica during recent years. Clearly, local human activities, rather than long-range transport, are the dominant sources of PAH contamination to the inland lakes. Finally, the present study demonstrates the efficacy of PE-based passive samplers for investigating PAHs in the aquatic environment of Antarctica under complex field conditions.


Metastatic pulmonary, gastric, and renal calcification demonstrated on bone scintigraphy in a patient with malignant melanoma and renal failure.
This case report describes the clinical, scintigraphic, and pathologic findings in a patient with an unexpected finding of a cutaneous malignant melanoma. Multiple imaging studies were done, as was a pathologic examination of a suspicious pigmented lesion on the patient's back. A Tc-99m MDP bone scan showed diffuse uptake in the skeleton, lungs, kidneys, and stomach. Metastatic calcification, as shown by isotope scintigraphy, is an unusual manifestation of metastatic cancer from a primary cutaneous melanoma.


[Radiation induced skin reactions].
Radiotherapy is one of the most important treatment modality of cancers. Skin secondary effects are well known. Cutaneous complications are described. Physiopathogenic mechanisms are reported. Many preventative and treatment options have been used with varying degrees of evidence of success. Information of patients, further research studies and a multidisciplinary approach are necessary to increase the management of radiation induced skin reactions.


Distribution of urocortin in the rat's gastrointestinal tract and its colocalization with tyrosine hydroxylase.
Urocortin (Ucn), a newly identified member of the corticotropin-releasing factor (CRF) family, is not only expressed in the brain, but also abundantly present in the peripheral tissues, especially in the gastrointestinal tract (GI) as determined by radioimmuoassay. In order to determine the precise localization of urocorin in the GI, we mapped the distribution of urocortin-like immunoreactivity (ir) in the GI of the rat using an immunofluorescence histochemical technique. Ucn, both in the brain and the peripheral tissues, is involved in the regulatory control of host-defense mechanism during stress. In order to study the possible involvement of the sympathetic system in the expression of GI urocortin in response to stress, we examined the effect of chemical sympathectomy on urocortin-ir and its colocalization with tyrosine hydroxylase (TH). UCn was expressed in all parietal cells of the stomach, myenteric and submucosal plexuses as well as in cells in Lieberkühn crypts of the small and large intestine. Most of the acid secreting parietal cells contained both Ucn and TH. Chemical sympathectomy did not affect Ucn immunoreactivity of parietal cells.


Trypanosoma cruzi: Biological characterization of lineages I and II supports the predominance of lineage I in Colombia.
The causes of the particular distribution of both Trypanosoma cruzi lineages throughout the American continent remain unknown. In Colombia, T. cruzi I is the predominant group in both domestic and sylvatic cycles. Here, we present the biological characterization of T. cruzi parasites belonging to both T. cruzi I and T. cruzi IIb groups. Our results show the inability of the T. cruzi IIb clones to infect mammalian cells, produce trypomastigotes and replicate in Rhodnius prolixus, the main vector species in this country. Moreover, this result was confirmed when other species from the same genus, such as R. pallescens and R. robustus, were infected with the same TcIIb clone and its parental strain, while the infection in other genera such as Triatoma and Panstrongylus was successful. Furthermore, the growth kinetics and duplication time in vitro suggest that the high prevalence of T. cruzi I in Colombia results from more successful interactions between parasite lineage, vector, and host species. This type of study may help to understand the factors influencing the particular epidemiological patterns of Chagas disease transmission in different endemic regions.


Validity of the γ-Ray Evaluation with iodoamphetamine for Cerebral Blood Flow Assessment (REICA) method for quantification of cerebral blood flow including acetazolamide challenge test.
The γ-Ray Evaluation with iodoamphetamine for Cerebral Blood Flow Assessment (REICA) is a new method for quantifying cerebral blood flow (CBF) using single-photon emission computed tomography (SPECT) and [123I]N-isopropyl-p-iodoamphetamine (123I-IMP). The present study aimed to validate the REICA method using data including acetazolamide challenge test. The REICA and Graph-Plot (GP) methods were used to calculate mean CBF (mCBF) for 92 acquisitions (rest: 57, stress: 35) and cerebrovascular reactivity (CVR) in 33 patients. To obtain stress data, 15 mg/kg of acetazolamide was injected intravenously 10 min before the administration of 123I-IMP, and blood samples were collected under the same conditions as rest data. The reference standard was the Autoradiograph (ARG) method using arterial blood sampling, and the accuracy of the REICA method was analyzed by comparing it with each method. For mCBF, the correlation coefficients (r) were 0.792 for the REICA method and 0.636 for the GP method. For CVR, r values were 0.660 for the REICA method and 0.578 for the GP method. In both acquisitions, the REICA method had a stronger correlation with the ARG method than the GP method. For mCBF, there was a significant difference in the correlation coefficient between the two correlation coefficients (p < 0.01). The REICA method was more accurate than the GP method in quantifying CBF and closer to the ARG method. The REICA method, which is a noninvasive method of cerebral blood flow quantification using 123I-IMP, has great medical usefulness.


A novel G143D mutation in the NADH-cytochrome b5 reductase gene in an Indian patient with type I recessive hereditary methemoglobinemia.
We report a novel homozygous mutation responsible for NADH-b(5)R deficiency in a family from Ratnagiri district in western India with recessive congenital methemoglobinemia (RCM) type I. The propositus was a 20-year-old female with a history of increasing cyanosis exacerbated by fever and weakness. There was no history of cardiac illness or exposure to drugs and chemicals. The methemoglobin level was 38.0% in the propositus with 70% reduction in NADH-b(5)R activity. Spectroscopic analysis of the hemolysate showed normal peaks suggesting absence of Hb-M. There was no hemoglobin instability and G6PD activity was normal. This novel G-->A homozygous mutation at codon 143 in exon 5 was identified by SSCP followed by DNA sequencing and results in a glycine to aspartic acid substitution in the cytochrome b(5) reductase protein. This mutation, which is located outside the FAD and NADH binding domain, leads to mild cyanosis. Investigations of the family members revealed that both the parents and a brother of the propositus were heterozygous for the G143D mutation.


Improved real-time PCR detection of 'Candidatus Liberibacter asiaticus' from citrus and psyllid hosts by targeting the intragenic tandem-repeats of its prophage genes.
'Candidatus Liberibacter asiaticus' (CLas) is a Gram-negative α-proteobacterium, and the prominent species of Liberibacter associated with a devastating worldwide citrus disease known as huanglongbing (HLB). This fastidious bacterium resides in phloem sieve cells of host plants and is vectored by the Asian citrus psyllid (Diaphorina citri). Due to its uneven distribution in planta and highly variable bacterial titers, detection of HLB bacteria can be challenging. Here we demonstrated a new utility of nearly identical tandem-repeats of two CLas prophage genes for real-time PCR by SYBR Green 1 (LJ900fr) and TaqMan(®) (LJ900fpr). When compared with conventional 16S rDNA-based real-time PCR, targeting the repeat sequence reduced the relative detectable threshold by approximately 9 and 3 real-time PCR cycles for LJ900fr and LJ900fpr, respectively. Additionally, both LJ900 methods detected CLas from otherwise non-detectable samples by other methods. CLas was also detected from globally derived samples including psyllids, various citrus varieties, periwinkle, dodder, and orange jasmine, suggesting the new detection method can be applicable worldwide. Additionally, we demonstrated the presence of the hyv(I)/hyv(II) repeat sequence within the 'Ca. Liberibacter americanus' strain. The method thereby provides sensitive HLB detection with broad application for scientific, regulatory, and citrus grower communities.


Organization of trigeminothalamic tracts and other thalamic afferent systems of the brainstem in the rat: presence of gelatinosa neurons with thalamic connections.
Thalamic projections from trigeminal and certain other nuclei of the brainstem of the rat have been investigated using the technique of retrograde transport of horseradish peroxidase (HRP). The pattern of trigeminothalamic projections is very specifically related to the individual subnuclei of the complex. The Main Sensory Nucleus (MSN) provides profuse cross connections to the ventrobasal thalamus (VB); these arise exclusively from medium and small-sized neurons, but never from the large cells. In addition to these crossed connections, a small ipsilateral dorsal trigeminothalamic tract arises from the dorsal third of the most rostral part of the MSN; this is the only ipsilateral connection to VB found in the trigeminal complex. Subnucleus Oralis has no projections to the thalamus; it is suggested that it may be concerned primarily with reflex activation of the facial nucleus, with which it is co-extensive in the rostro-caudal axis. Subnucleus Interpolaris has a well-defined crossed projection of moderate size which arises from the large, medium and some of the small neurons. Subnucleus Caudalis has a sparse output to the thalamus and differs in its projections from rostral to caudal. At the most rostral level, all layers (marginal, transitional gelatinosa and magnocellularis) contain neurons which project to the thalamus; particularly conspicuous in this respect are the marginal neurons, most of which are strongly labelled. The presence of gelatinosa neurons projecting to the thalamus emphasizes a point made in earlier reports, that these neurons do not form an homogeneous population. At caudal levels, the marginal neurons are the major source of thalamic projections, while connections to the thalamus form deeper lying neurons are infrequent. With a single exception, the medullary reticular nuclei contained no neurons with thalamic connections; a small number of reticulo-thalamic neurons were found in the ventral pontine area. Marked labelling of the medial cuneate nucleus and moderate labelling of the gracilis and lateral cuneate nuclei occurred contralaterally to the injection site. A small numebr of medial cuneate and gracile neurons project to the ipsilateral thalamus. Projections from the solitary nucleus were always ipsialteral. The boundaries of individual subnuclei of the lateral sensory trigeminal complex in the rat have been redefined on the basis of cytological criteria; these are in good accord with the corresponding thalamic projection patterns.


Etiologies and outcomes of status epilepticus in children.
Status epilepticus (SE) is a medical emergency with significant associated mortality and morbidity. This study was conducted to determine the etiology and outcome of SE in children. All patients from 1 month to 15 years old with SE admitted to Nemazee Hospital, Shiraz, Iran, the main pediatric hospital in the area, between 1999 and 2004, were studied in a retrospective cross-sectional study. Outcomes were rated according to the Glasgow Outcome Score (GOS). In all, 135 patients (76 boys, 59 girls) were studied. The most common cause of SE was fever. Etiology of SE did not differ significantly between various age groups and also between boys and girls (P=0.736 and P=0.156, respectively). Fourteen patients died in hospital and 81 were discharged in good health. Outcome did not differ significantly between the age groups (P=0.695) or between boys and girls (P=0.386). When classified as good (GOS=5) and bad (GOS=1-4), outcome was significantly correlated with etiology of SE (P=0.017). Prolonged febrile seizures had the best, and symptomatic SE the worst, outcome. In this study, even in children above 3 years of age, fever was the most common cause of SE. This is noteworthy and heralds the need to pay more attention to febrile seizures, especially in children at risk for their occurrence. Outcome was not related to age and sex, but etiology of SE significantly influenced outcome.


A method for the massive separation of highly purified, adult porcine islets of Langerhans.
A method for the massive and reproducible isolation of highly purified, adult porcine islets of Langerhans is described. The successful combination of donor animal-strain selection with original procedures for pancreas retrieval and enzymatic digestion permitted us to separate uniquely massive concentrations of pure porcine islets with no need for mechanical disruption of the pancreatic tissue. Following our procedure, porcine islets, which fully retain viability and function, can be harvested easily and rapidly. Xenotransplantation of such islets, immunoprotected within algin/polyaminoacidic microcapsules, was associated with complete reversal of hyperglycemia in rodents with either spontaneous or streptozotocin-induced diabetes mellitus.


Increased incidence of cardiac anomalies in pregnancies complicated by gastroschisis.
The purpose of this study was to determine the incidence of congenital heart defects (CHD) in infants with gastroschisis. Infants with gastroschisis repair were identified from California hospital discharge data during the years 1992 to 1997. The frequency of concomitant diagnosis of CHD and other demographic, neonatal, and pregnancy outcomes were examined. Sixty-nine of the 621 infants had a diagnosis of CHD, with 16 having more than 1 lesion. Excluding cases possibly attributable to persistent fetal circulation, 25 infants with CHD remained, for an incidence rate of 4%. There was a significant (P = .014) increase in incidence of CHD in cases of gastroschisis complicated by bowel atresia. African American infants with gastroschisis had an increased risk of CHD (P = .009) compared with infants of other ethnicities. Contrary to conventional teaching that gastroschisis is an isolated anomaly, we found an increased incidence of concomitant CHD. Our data would suggest that detailed antepartum and/or postnatal cardiac evaluations are indicated in fetuses identified with gastroschisis.


Stereochemistry and functions of the new cysteinyl-resolvin, 4S,5R-RCTR1, in efferocytosis and erythrophagocytosis of human senescent erythrocytes.
Specialized pro-resolving lipid mediators play key functions in the resolution of the acute inflammatory response. Herein, we elucidate the stereochemical structure of the new 4S,5R-RCTR1, a cysteinyl-resolvin, recently uncovered in human leukocytes incubated with a 4S,5S-epoxy-resolvin intermediate, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and ultra-violet (UV) spectrophotometry. With this approach, the physical properties of the new mediator prepared by total organic synthesis were matched to enzymatically produced biogenic material. In addition, we confirmed the potent biological actions of 4S,5R-RCTR1 with human M2-like macrophage phagocytosis of live bacteria, efferocytosis of apoptotic neutrophils, and erythrophagocytosis of senescent human red blood cells in a concentration-dependent manner from 0.1 to 10 nM. Taken together, these results establish the complete stereochemistry of 4S,5R-RCTR1 as 5R-glutathionyl-4S,17S-dihydroxy-6E,8E,10Z,13Z,15E,19Z-docosahexaenoic acid and give evidence of its novel bioactivities in human phagocyte responses. Moreover, they confirm and extend the stereoselective functions of the 4S,5R-RCTR1 with isolated human phagocytes of interest in the resolution of inflammation.


Synergistic γ-In2 Se3 @rGO Nanocomposites with Beneficial Crystal Transformation Behavior for High-Performance Sodium-Ion Batteries.
Crystal transformation of metal compound cathodes during charge/discharge processes in alkali metal-ion batteries usually generates profound impact on structural stability and electrochemical performance, while the theme in anode materials, which always occurs and completes during the first redox cycle, is rarely explored probably due to the fast transformation dynamics. Herein, for the first time, a unique crystal transformation behavior with slow dynamics in anode of sodium-ion batteries (SIBs) is reported, which further promotes electrochemical performance. Specifically, irreversible γ → β crystal transformation of In2 Se3 is observed, induced by the persistent size degradation of In2 Se3 particles during repeated sodiation/desodiation, supported by a series of ex situ characterizations, such as HRTEM, XRD, and XPS of γ-In2 Se3 /reduced graphene oxide (γ-In2 Se3 @rGO) nanocomposite. The hybrid electrode shows ultrahigh long-term cycling stability (378 mA h g-1 at 1.0 A g-1 after 1000 cycles) and excellent rate capability (272 mA h g-1 at 20.0 A g-1 ). Full battery with Na3 V2 (PO4 )3 cathode also manifests superior performance, promising β-In2 Se3 dominated electrode materials in high-power and long-life SIBs. The first-principle calculations suggest the crystal transformation enhances electric conductivity of β-In2 Se3 and facilitates its accessibility to sodium. In combination with the synergistic effect between rGO matrix, substantially enhanced electrochemical performance is realized.


Maintaining weight loss after bariatric surgery: when the spectator role is no longer enough.
Bariatric (weight loss) surgery is the gold standard treatment for severe obesity. Concern exists that patients are regaining weight in the longer term. Success and cost-effectiveness of surgery are threatened due to the re-emergence of related conditions such as diabetes. This exploratory qualitative study investigates patients' expectations and experiences of weight regain (WR) 2 years or more after Roux-en-Y gastric bypass (RYGB). Ten participants (two men and eight women) who experienced WR were interviewed between 2 and 6 years following surgery. Findings highlight that participants reacted to initial weight loss as passive spectators and were unprepared for subsequent WR. Their tolerability of WR reduced as the amount of regain increased, suggesting a 'line of tolerance' for WR. WR was influenced by a new vulnerability arising from weight loss over time, and participants struggled to manage their own weight actively as surgical effects waned. They considered self-management skills, and carer and professional support to be limited at the time when WR was most likely to occur. Degrees of tolerability are noted in individuals regaining weight after RYGB. More studies are needed to further understand these problems. Pre- and post-operative support and teaching patients self-management skills may be helpful to minimize WR.


Efficacy of the fixed 1.2% clindamycin phosphate, 0.025% tretinoin gel formulation (Velac) and a proprietary 0.025% tretinoin gel formulation (Aberela) in the topical control of facial acne.
A formulation containing agents affecting the non-inflammatory as well as the inflammatory lesions of acne vulgaris at the same time would be efficient, probably showing a high efficacy and possibly a considerable shortening of the duration of treatment. One single formulation would simplify drug administration thereby enhancing patient compliance and possibly leading to improved therapeutic results. In two studies this seems to have been corroborated for the fixed clindamycin phosphate-tretinoin gel formulation. This study was designed to assess whether the recently developed fixed formulation of 1.2% clindamycin phosphate and 0.025% tretinoin in a gel base (Velac), further referred to as Clindamycin phosphate Tretinoin Gel is at least as effective as a proprietary 0.025% tretinoin gel formulation (Aberela, Janssen Cilag Ab, Sollentuna, Sweden; further defined as tretinoin) showing an additional anti-inflammatory effect in the treatment of moderate to severe acne vulgaris. In a double-blind, randomised study 72 patients were treated with CTG and 73 with tretinoin gel in a once daily regimen for 12 weeks. Responses, irritation as well as possible systemic and other adverse effects were recorded after 4, 8 and 12 weeks of treatment and the improvement, compared to baseline, assessed in all included patients. An additional assessment of the safety parameters was carried out at week 2. Parameters of efficacy were the various acne lesion counts, the overall acne severity grade and the calculated totals of acne lesion counts. CTG was statistically significantly more effective than tretinoin at the P = 0.05 level in the papular and the total mean inflammatory lesion counts as well as in the estimated or calculated mean overall acne severity scores. CTG and tretinoin gel were equally effective in the remaining parameters: open and closed comedones, the calculated total mean comedone, the pustule as well as the nodule lesion counts. The onset of action was faster for CTG than for tretinoin gel and evident in all assessed parameters except in open comedone lesion counts. In the calculated total mean acne lesion counts, half of all acne lesions had disappeared by week 6 of treatment with CTG, whereas this was recorded at week 9 for tretinoin gel. No clinically relevant changes in the parameters of safety as a consequence of treatment were observed, although the burning component of irritation was shown to be significantly less for CTG than for tretinoin gel. The observed adverse effects were considered minor. Treatment had to be discontinued in five patients on CTG and three on tretinoin. The addition of clindamycin to tretinoin, as in CTG, enhances the comedolytic efficacy of tretinoin in moderate to severe acne of the face, maintaining at the same time its anti-inflammatory efficacy thus accelerating resolution of all types of acne lesions without affecting the safety of response to both components.


A Labor of Love.
It is natural to want to avoid the sadness and powerlessness that come with losing, especially a young patient to a ravaging cancer. But there is gratification for the clinician and a deep sense of connection and support on the part of the patient and their family when we instead lean into and share those feelings, bringing our human self to the relationship when it feels that our medical self can offer so little.


MAP kinase mediates growth factor-induced nuclear translocation of estrogen receptor alpha.
In addition to mediating the classical transcriptional effects of estrogen, estrogen receptors (ERs) are now known to regulate gene expression in the absence of estrogen by ligand-independent activation pathways, and to mediate the rapid, non-genomic effects of estrogen as well. ERs have been shown to associate with the cell membrane, and recent studies demonstrate that this subpopulation of membrane-associated ER mediates the rapid effects of estrogen. To date, however, little is known regarding the pathways that regulate the distribution of the ER between the nuclear and membrane fractions. In the current study, we demonstrate membrane localization of transiently transfected ERalpha in human vascular smooth muscle cells, and translocation of ERalpha from the membrane to the nucleus in response to both estrogen-dependent and estrogen-independent stimulation. Mutational analyses identified serine 118 as the critical residue regulating nuclear localization following estrogen-independent stimulation, but not following estrogen stimulation. Induction of nuclear localization of ERalpha by estrogen-independent, but not estrogen-dependent stimulation was blocked by both pharmacologic and genetic inhibition of mitogen-activated protein (MAP) kinase activation. Furthermore, constitutive activation of MAP kinase resulted in nuclear translocation of ERalpha. These overexpression studies support that MAP kinase-mediated phosphorylation of ERalpha induces nuclear localization of the ER in response to estrogen-independent, but not estrogen-dependent stimulation, demonstrating stimulus-specific molecular pathways regulate the nuclear localization of the ER. These findings identify a previously unrecognized pathway that regulates the intracellular localization of the ER, and represent the first demonstration that the distribution of the ER between membrane and nuclear compartments is regulated by physiologic stimuli.


Successful treatment of severe fetal chylothorax resistant to repeated pleuroamniotic shunting by OK-432 pleurodesis.
We report the first case of successful fetal pleurodesis with OK-432 for recurrent severe fetal primary chylothorax after failing repeated pleuroamniotic shunting. Shunting and pleurodesis could be complementary to each other in the treatment of fetal chylothorax.


Combination of dual-energy computed tomography and iterative metal artefact reduction to increase general quality of imaging for radiotherapy patients with high dense materials. Phantom study.
To evaluate the use of pseudo-monoenergetic reconstructions (PMR) from dual-energy computed tomography, combined with the iterative metal artefact reduction (iMAR) method. Pseudo-monoenergetic CT images were obtained using the dual-energy mode on the Siemens Somatom Definition AS scanner. A range of PMR combinations (70-130 keV) were used with and without iMAR. A Virtual Water™ phantom was used for quantitative assessment of error in the presence of high density materials: titanium, alloys 330 and 600. The absolute values of CT number differences (AD) and normalised standard deviations (NSD) were calculated for different phantom positions. Image quality was assessed using an anthropomorphic pelvic phantom with an embedded hip prosthesis. Image quality was scored blindly by five observers. AD and NSD values revealed differences in CT number errors between tested sets. AD and NSD were reduced in the vicinity of metal for images with iMAR (p < 0.001 for AD/NSD). For ROIs away from metal, with and without iMAR, 70 keV PMR and pCT AD values were lower than for the other reconstructions (p = 0.039). Similarly, iMAR NSD values measured away from metal were lower for 130 keV and 70 keV PMR (p = 0.002). Image quality scores were higher for 70 keV and 130 keV PMR with iMAR (p = 0.034). The use of 70 keV PMR with iMAR allows for significant metal artefact reduction and low CT number errors observed in the vicinity of dense materials. It is therefore an attractive alternative to high keV imaging when imaging patients with metallic implants, especially in the context of radiotherapy planning.


Bell's palsy and its recurrences.
The purpose of this study was to evaluate the incidence and the prognosis of patients with recurrences of Bell's palsy. Yanagihara's classification of recurrent palsies was used, and all palsies were separated into five different types. A total of 304 patients with Bell's palsy were examined. The recurrent ipsilateral attacks (i.e., the unilateral recurrent palsies) showed a worse prognosis when compared with the non-recurrent palsies. In contrast, the recurrent attacks involving the contralateral facial nerve (bilateral alternating palsies) presented a better facial recovery. In reviewing the recurrent cases, the stapedial reflex demonstrated no prognostic value. Our results suggest that in presenting data of Bell's palsy it is advisable to differentiate the recurrences from the common (non-recurrent) palsies.


The relative effectiveness of 6-thioguanine and 8-azaguanine in selecting resistant mutants from two V79 Chinese hamster cells in vitro.
The frequency of surviving colonies in two V79 cell lines exposed to either 6-thioguanine or 8-azaguanine was dependent on initial plating density. Different degrees of metabolic-co-operation were found to occur in the two cell lines and the loss of both spontaneous and added mutants occurred at a lower cell density when 6TG was used for selection than when 8 AZ was used in both cell lines. Both analogues were degraded on incubation in medium plus serum in the absence of added cells. Variation in serum batch had little effect on the rate of degradation or on the frequency of colonies recovered after treatment of V79 cell lines with 8AZ. The reasons for preferring 8AZ to 6TG as a selective agent are discussed.


In vivo gene expression profiling of human intestinal epithelial cells: analysis by laser microdissection of formalin fixed tissues.
The small intestinal epithelium mediates vital functions of nutrient absorption and host defense. The spatial organization of the epithelial cells along the crypt-villus axis segregates them into regions of specialized function. However, the differences in transcriptional programming and the molecular machinery that governs the migration, adhesion, and differentiation of intestinal epithelial cell lineages in humans remain under-explored. To increase our understanding of these mechanisms, we have evaluated gene expression patterns of ileal epithelial cells isolated by laser capture microdissection from either the villus epithelial or crypt cell regions of healthy human small intestinal mucosa. Expression profiles in villus and crypt epithelium were determined by DNA microarray, quantitative real-time PCR, and immunohistochemistry based methods. The expression levels of selected epithelial biomarkers were also compared between gastrointestinal tissues. Previously established biomarkers as well as a novel and distinct set of genes believed to be linked to epithelial cell motility, adhesion, and differentiation were found to be enriched in each of the two corresponding cell populations (GEO accession: GSE10629). Additionally, high baseline expression levels of innate antimicrobials, alpha defensin 5 (HD5) and regenerating islet-derived 3 alpha (Reg3A), were detected exclusively within the small bowel crypt, most notably in the ileum in comparison to other sites along the gastrointestinal tract. The elucidation of differential gene expression patterns between crypt and villus epithelial cell lineages in human ileal tissue provides novel insights into the molecular machinery that mediates their functions and spatial organization. Moreover, our findings establish an important framework of knowledge for future investigations of human gastrointestinal diseases.


Efficacy of a Hip Brace for Hip Displacement in Children With Cerebral Palsy: A Randomized Clinical Trial.
There is no consensus on interventions to slow the progress of hip displacement in patients with cerebral palsy. To investigate the efficacy of a novel hip brace in preventing progressive hip displacement in patients with cerebral palsy. This 2-group randomized clinical trial was conducted at 4 tertiary hospitals in South Korea from July 2019 to November 2021. Participants included children aged 1 to 10 years with nonambulatory cerebral palsy (Gross Motor Function Classification System level IV or V). Block randomization was used to assign an equal number of patients to the study and control groups via computerized random allocation sequences. Data were analyzed from November to December 2021. The intervention group wore the hip brace for at least 12 hours a day for the study duration (ie, 12 months). Follow-up evaluations were performed after 6 and 12 months of wearing the brace. Both groups proceeded with conventional rehabilitation therapy during the trial. The primary outcome was the Reimers migration index (MI) on radiography, as assessed by 3 blinded investigators. Primary outcome variables were analyzed using linear mixed models. Secondary outcomes include change in the Caregiver Priorities & Child Health Index of Life with Disabilities, on which lower scores indicate better quality of life. A total of 66 patients were included, with 33 patients (mean [SD] age, 68.7 [31.6] months; 25 [75.8%] boys) randomized to the intervention group and 33 patients (mean [SD] age, 60.7 [24.9] months; 20 [60.6%] boys) randomized to the control group. The baseline mean (SD) MI was 37.4% (19.3%) in the intervention group and 30.6% (16.3%) in the control group. The mean difference of the MI between the intervention group and control group was -8.7 (95% CI, -10.2 to -7.1) percentage points at 6 months and -12.7 (95% CI, -14.7 to -10.7) percentage points at 12 months. The changes in the Caregiver Priorities & Child Health Index of Life with Disabilities were favorable in the study group and reached statistical significance at the 6-month follow-up compared with the control group (difference, -14.2; 95% CI, -25.2 to -3.3). In this randomized clinical trial, the novel hip brace was significantly effective in preventing the progression of hip displacement, compared with the control group. It effectively improved quality of life in patients with nonambulatory cerebral palsy. Therefore, hip brace use could be a promising treatment method to delay hip surgery and improve the quality of life of patients with nonambulatory cerebral palsy. ClinicalTrials.gov Identifier: NCT04033289.


Perceived identity threat and organizational cynicism in the recursive relationship between psychological contract breach and counterproductive work behavior.
Counterproductive work behavior toward the organization (CWB-O) or supervisor (CWB-S) is commonly treated as a consequence of psychological contract breach (PCB). However, drawing from Self-Consistency Theory, the authors in this article argue that the PCB-CWB relationship is recursive through two mediating mechanisms: self-identity threat and organizational cynicism. Furthermore, the authors predict that the relationship between feelings of violation and CWB-O (or CWB-S) would depend on the extent to which the victim attributed blame to the organization (or supervisor). Using weekly and daily survey data, the study found that identity threat was a stronger mediator for recursive CWB-PCB relationships. Moreover, it was found that PCB related positively to violation feelings, which in turn related positively to CWB-O and CWB-S over time. As predicted, the former was moderated by organizational blame attributions, whereas the latter was moderated by supervisor blame attributions. The authors discuss the theoretical implications and propose novel practical implications based on these reciprocal findings.


Molecular mechanism responsible for the hyperexpression of baculovirus polyhedrin.
One of the amazing phenomena in the baculovirus life cycle is the hyperexpression of the very late gene, polyhedrin (polh), causing the production of the occlusion bodies where progeny virions are embedded. However, to date, the molecular mechanism underlying its hyperexpression is not completely elucidated. Considering that, in this review, the mechanism responsible for its hyperexpression from the previous studies up to now was comprehensively summarized from three aspects, namely, the structure characteristics of the polh promoter and transcription regulation, the structure and translation regulation of the polh mRNA, and especially the regulators that influence the expression of polh gene. Moreover, this review will help us obtain a better understanding about the hyperexpression of polh, and also provide guidance for improving the expression efficiency of the foreign proteins by adopting the baculovirus expression vector system.


Circular dichroism studies on cytochrome c peroxidase and cytochrome c-551 of Pseudomonas aeruginosa.
Circular dichroism (CD) spectra of ferric, ferrous and ferrous-carbonyl forms of Pseudomonas cytochrome c peroxidase have been recorded in the wave length range 200 to 650 nm. CD spectra in the Soret region show that in the oxidized enzyme the two hemes are degenerate, whereas in the reduced form the hemes are perturbed differently and one of the hemes appears to be non-degenerate. Changes in optical activity upon formation of the carbonylderivative suggest a spin-state conversion and indicate the presence of one high-spin and a low-spin heme. A histidine residue is proposed for the axial ligand of the heme iron. The alpha-helical content of the enzyme is estimated to be 34%. Ligand binding or changes in the oxidation state of the heme iron do not alter the conformation of the protein backbone. The dichroic spectra of oxidized and reduced cytochrome c-551 (P. aeruginosa) are included for comparison. In the visible region the cytochrome exhibits CD spectra similar to those of the peroxidase, whereas in the Soret region the dichroic spectra of the cytochrome are simpler. CD spectra in the far-ultraviolet region show the cytochrome to have a high alpha-helix content.


Nocturnal blood pressure, 3-methoxy-4-hydroxyphenylglycol and carotid intima-media thickness: The SABPA study.
Research demonstrated a significant relationship between elevated nocturnal blood pressure and sympathetic hyperactivity. The study aimed to investigate possible associations between norepinephrine metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), nocturnal BP and carotid intima-media thickness (CIMT) in urban African and Caucasian men. The study included 82 African and 100 Caucasian male teachers, aged 33-56 years, recruited in the North-West Province, South Africa. Ambulatory BP and fasting saliva and blood samples were collected. B-mode ultrasound images were obtained to determine CIMT. Despite higher usage of anti-hypertensive medication usage (p=0.039), a large number of the African men were nocturnal hypertensives (75, 61%). The nocturnal systolic blood pressure (SBP) (p<0.001), diastolic blood pressure (DBP) (p<0.001) and heart rate (p<0.001) of the African men were higher. After stratifying groups into only nocturnal hypertensives the trend was the same (SBP p<0.001; DBP p<0.001; heart rate p=0.058). In the African and Caucasian men, CIMT was linearly predicted by SBP (β=0.33, p<0.001) and DBP (β=0.24, p=0.016) respectively, but not MHPG. No associations were firstly demonstrated between MHPG as sympathetic activity marker and CIMT or secondly, between MHPG and nocturnal blood pressure. Novel findings of elevated nocturnal BP evidently seem to promote structural vascular disease in urban African and Caucasian men.


Long-term biometric optic components of diode laser-treated threshold retinopathy of prematurity at 9 years of age.
To assess quantitatively the biometric optic components and its relationship with refractive status in preterm school children with diode laser-treated threshold retinopathy of prematurity (ROP). A prospective, cross-sectional study in which ultrasound biometric measurement of optic components and cycloplegic refraction were performed on 24 consecutive preterm children with diode laser-treated threshold ROP at the age of 9 years. The study results were compared with 1021 age-matched full-term control children from a national survey. The eyes with laser-treated ROP showed statistically significantly thicker lens (3.94 versus 3.39 mm), steeper vertical corneal curvature (7.47 versus 7.67 mm) and shallower anterior chamber depth (ACD) (2.91 versus 3.58 mm) than age-matched full-term controls, but no difference in axial length (23.32 versus 23.24 mm). The laser-treated eyes had a mean spherical equivalent (SE) of -4.49 D compared with mean SE of -0.44 D in controls. Of 46 eyes studied, 93% of eyes were myopic and 28.3% with high myopia (<-6.0 D) compared with the 32% prevalence of myopia in controls. In preterm children, younger gestational age tended to correlate with shallower ACD (r = 0.352) and thicker lens (r = -0.298); lower birth weight tended to correlate with shallower ACD (r = 0.372) and steeper cornea (r = 0.360). There were higher prevalence and greater magnitude of myopia in preterm children. The significantly thicker lens, steeper corneal curvature and shallower anterior chamber depth are the major factors contributing to the development of myopia in preterm school children with laser-treated threshold ROP.


Measuring the kinetics of membrane phase transitions.
This article presents a brief review of literature on the physical chemistry of lipid phase transitions with emphasis on their kinetic properties. The theoretical foundations of perturbation techniques, and specifically the volume-perturbation technique are discussed in some detail. These are presented as a rationale for, and introduction to, a volume-perturbation kinetic calorimeter that we have constructed for measurement of the kinetics of lipid phase transitions. The instrument has been applied to study the gel-liquid crystalline phase transition in a variety of phospholipid bilayer systems. The design and implementation of the volume-perturbation calorimeter are presented along with a discussion of the techniques of data analysis. Finally, we present typical results obtained with this methodology for a multilamellar vesicle dispersion of dipalmitoylphosphatidylcholine.


Histopathological study of experimentally induced endolymphatic hydrops with emphasis on Reissner's membrane.
We investigated the histopathological changes of the guinea pig cochlea in experimentally induced endolymphatic hydrops 1, 2, 4 and 8 months after obliteration of the endolymphatic sac. In this paper special attention is given to the morphological changes created in Reissner's membrane. Reissner's membrane showed various foldings, bony wall connections, local thickenings, duplications, mesothelial defects, ruptures and atrophy. The incidence of these changes increased with survival time. The stria vascularis and hair cells showed degeneration starting apically and proceeding towards the cochlear base. The possible implications of these findings are discussed.


ADP-ribosylation factor-like GTPase 15 enhances insulin-induced AKT phosphorylation in the IR/IRS1/AKT pathway by interacting with ASAP2 and regulating PDPK1 activity.
Decreased phosphorylation in the insulin signalling pathway is a hallmark of insulin resistance. The causes of this phenomenon are complicated and multifactorial. Recently, genomic analyses have identified ARL15 as a new candidate gene related to diabetes. However, the ARL15 protein function remains unclear. Here, we show that ARL15 is upregulated by insulin stimulation. This effect was impaired in insulin-resistant pathophysiology in TNF-α-treated C2C12 myotubes and in the skeletal muscles of leptin knockout mice. In addition, ARL15 localized to the cytoplasm in the resting state and accumulated in the Golgi apparatus around the nucleus upon insulin stimulation. ARL15 overexpression can enhance the phosphorylation of the key insulin signalling pathway molecules IR, IRS1 and AKT in C2C12 myotubes. Moreover, ARL15 knockdown can also specifically inhibit the phosphorylation of PDPK1 Ser241, thereby reducing PDPK1 activity and its downstream phosphorylation of AKT Thr308. Co-immunoprecipitation assays identified ASAP2 as an ARL15-interacting protein. In conclusion, we have identified that ARL15 acts as an insulin-sensitizing effector molecule to upregulate the phosphorylation of members of the canonical IR/IRS1/PDPK1/AKT insulin pathway by interacting with its GAP ASAP2 and activating PDPK1. This research may provide new insights into GTPase-mediated insulin signalling regulation and facilitate the development of new pharmacotherapeutic targets for insulin sensitization.


Spiritual distress-proposing a new definition and defining characteristics.
To identify the definition and defining characteristics (DCs) of spiritual distress (00066). Integrative literature review. Thirty-seven articles and 35 DCs were identified. Spiritual distress as a response to health problems in the context of nursing care is different from an impaired ability to experience and integrate meaning in life. The diagnosis misses some DCs that emerged from the literature review and lacks comprehensiveness. The domain and the class are reductionist toward its meaning. The taxonomy lacks a spiritual domain to include this and other diagnoses currently dispersed in other domains. Further content and clinical validation is needed, as well as an assessment, to determine the diagnosis' class and domain.


Vacuolated neurons in the hypogastric ganglion of the rat.
The vacuolated neurons (VN) of the main hypogastric ganglion of the male rat were studied using the formaldehyde-induced fluorescence (FIF) method for the histochemical demonstration of catecholamines. Microspectrofluorimetry was performed to identify the fluorophores and to quantify the FIF. The thiocholine method (Koelle-Gomori) was used to demonstrate acetylcholinesterase activity. The fine structure of the VN was studied using glutaraldehyde/OsO4 fixation. (1) In the untreated adult male rat VN represent only a small population of the total number of hypogastric neurons (0.8--1.2%). The vacuoles are similar to those of the VN from the corresponding female ganglion. (2) The VN are considered to be adrenergic due to the nature of their fluorophore, indicating a primary catecholamine. (3) The first VN appear in the hypogastric ganglia at the age of 7 weeks. After testosterone administration to young rats, VN are found at the age of 4 weeks. (4) The basic fine structure of the VN is similar to that of other ordinary neurons of the hypogastric ganglia. (5) The content of the vacuoles could not be identified. (6) Indications of degeneration were not observed in the VN. (7) The VN are interpreted as being a functional stage of the "short" adrenergic neurons, which are under the control of steroid hormones. (8) Fifteen months after castration, no VN could be found in the hypogastric ganglia, while their number was normal in the corresponding control animals.


How challenges in auditory fMRI led to general advancements for the field.
In the early years of fMRI research, the auditory neuroscience community sought to expand its knowledge of the underlying physiology of hearing, while also seeking to come to grips with the inherent acoustic disadvantages of working in the fMRI environment. Early collaborative efforts between prominent auditory research laboratories and prominent fMRI centers led to development of a number of key technical advances that have subsequently been widely used to elucidate principles of auditory neurophysiology. Perhaps the key imaging advance was the simultaneous and parallel development of strategies to use pulse sequences in which the volume acquisitions were "clustered," providing gaps in which stimuli could be presented without direct masking. Such sequences have become widespread in fMRI studies using auditory stimuli and also in a range of translational research domains. This review presents the parallel stories of the people and the auditory neurophysiology research that led to these sequences.


Reduced expression of thrombospondin-1 correlates with a poor prognosis in patients with non-small cell lung cancer.
Thorombospondin-1 (TSP-1) is a 450 kDa extracellular matrix glycoprotein, with anti-angiogenic activity. We analyzed the relationship in TSP-1 expression and Microvessel count (MVC), and also clinical factors, using immunohistochemical methods for non-small cell cancer (NSCLC). Histopathologically, there was inverse correlation between TSP-1 expression and MVC for squamous cell carcinoma, but not for adenocarcinoma cases. Among 199 completely resected cases of NSCLC, the 5-year survival was 77.0% when the expression of TSP-1 was maintained and 55.1% when the expression were reduced, respectively (P=0.0046). When compared with TSP-1 expression in the high MVC subgroup, there was significantly shorter survival time when TSP-1 expression was reduced (P=0.0091), and no significant difference was seen for the low MVC subgroup. Multivariate analysis revealed that expression of TSP-1 is as a prognostic factor of NSCLC. Our present data suggest that TSP-1 might not be a direct anti-angiogenic factor and the TSP-1 expression is a prognostic indicator of NSCLC.


Surgically induced astigmatism in phacoemulsification, pars plana vitrectomy, and combined phacoemulsification and vitrectomy: a comparative study.
To study the surgically induced astigmatism (SIA) in combined phacoemulsification and vitrectomy, and compare with that when either procedure is performed alone. This is a prospective comparative interventional trial comprising of 60 eyes of 60 consecutive patients with cataract and/or vitreo-retinal pathology. They were divided equally into three groups based on the type of procedure: Group A, phacoemulsification alone group, using a 3.0-3.2 mm wide unsutured sclero-corneal tunnel incision at 1.0 mm post-limbus at 10 o'clock; Group B, par plana vitrectomy alone group, using three sclerotomies at 3.5 mm post-limbus at 2, 8, and 10 o'clock (right eye) or at 2, 4, and 10 o'clock (left eye) positions; and Group C, combined phacoemulsification and pars plana vitrectomy group. Main outcome measures were the amplitude (K-induced) and the axis of SIA calculated by rectangular coordinate method using the Holladay-Cravy-Koch formula. The mean K-induced amplitudes were 0.19+/-0.14 D, 0.17+/-0.11 D, and 0.23+/-0.19 D for groups A, B, and C, respectively. The range of K-induced amplitudes for the entire cohort was 0.00-0.77 D. No overall statistically significant differences in the pre- and postoperative topographic astigmatism amplitudes and the K-induced between groups A, B, and C were found (all P>0.05). Minor shifts, of doubtful clinical significance, in the axes of SIA were present. Combined phacoemulsification and pars plana vitrectomy does not induce significant astigmatic change per se, and its amount is similar to that when either procedure is performed alone.


A One Precursor One siRNA Model for Pol IV-Dependent siRNA Biogenesis.
RNA-directed DNA methylation in Arabidopsis thaliana is driven by the plant-specific RNA Polymerase IV (Pol IV). It has been assumed that a Pol IV transcript can give rise to multiple 24-nt small interfering RNAs (siRNAs) that target DNA methylation. Here, we demonstrate that Pol IV-dependent RNAs (P4RNAs) from wild-type Arabidopsis are surprisingly short in length (30 to 40 nt) and mirror 24-nt siRNAs in distribution, abundance, strand bias, and 5'-adenine preference. P4RNAs exhibit transcription start sites similar to Pol II products and are featured with 5'-monophosphates and 3'-misincorporated nucleotides. The 3'-misincorporation preferentially occurs at methylated cytosines on the template DNA strand, suggesting a co-transcriptional feedback to siRNA biogenesis by DNA methylation to reinforce silencing locally. These results highlight an unusual mechanism of Pol IV transcription and suggest a "one precursor, one siRNA" model for the biogenesis of 24-nt siRNAs in Arabidopsis.


Stroke in the elderly.
Stroke remains the second leading cause of death in the world, and its prevalence is projected to rise in the United States and globally. The main driver for increased stroke prevalence is aging of the population; however, best evidenced-based strategies for stroke treatment and prevention are not always followed for older patients. Furthermore, considerable gaps in knowledge exist for stroke prevention and treatment in elderly and very elderly patients. In this chapter, we discuss various aspects of stroke care in the elderly, including the evidence that guides stroke prevention and treatment. We focus on the challenges in managing stroke in the very elderly including the paucity of data to guide management. The sections span the continuum of stroke care, from primary prevention to management of stroke complications. Finally, we highlight the most significant unanswered questions regarding stroke care in the elderly.


Hypertonic saline solution for prevention of renal dysfunction in patients with decompensated heart failure.
Renal dysfunction is associated with increased mortality in patients with decompensated heart failure. However, interventions targeted to prevention in this setting have been disappointing. We investigated the effects of hypertonic saline solution (HSS) for prevention of renal dysfunction in decompensated heart failure. In a double-blind randomized trial, patients with decompensated heart failure were assigned to receive three-day course of 100mL HSS (NaCl 7.5%) twice daily or placebo. Primary end point was an increase in serum creatinine of 0.3mg/dL or more. Main secondary end point was change in biomarkers of renal function, including serum levels of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin-NGAL and the urinary excretion of aquaporin 2 (AQP2), urea transporter (UT-A1), and sodium/hydrogen exchanger 3 (NHE3). Twenty-two patients were assigned to HSS and 12 to placebo. Primary end point occurred in two (10%) patients in HSS group and six (50%) in placebo group (relative risk 0.3; 95% CI 0.09-0.98; P=0.01). Relative to baseline, serum creatinine and cystatin C levels were lower in HSS as compared to placebo (P=0.004 and 0.03, respectively). NGAL level was not statistically different between groups, however the urinary expression of AQP2, UT-A1 and NHE3 was significantly higher in HSS than in placebo. HSS administration attenuated heart failure-induced kidney dysfunction as indicated by improvement in both glomerular and tubular defects, a finding with important clinical implications. HSS modulated the expression of tubular proteins involved in regulation of water and electrolyte homeostasis.


[Primary and secondary reconstruction of the frontal sinus using the titanium screen system].
The objective of surgically maintaining shape and lumen after frontal sinus injuries can be achieved by using various types of osteosynthesis and reconstructive materials. In cases with extensive fracture defects we recommend alloplastic anterior wall reconstruction using titanium screens as an alternative to conventional procedures.


Biopsy prostate cancer perineural invasion and tumour load are associated with positive posterolateral margins at radical prostatectomy: implications for planning of nerve-sparing surgery.
Radical prostatectomy (RP) for prostate cancer is frequently complicated by erectile dysfunction and urinary incontinence. However, sparing of the nerve bundles adjacent to the posterolateral sides of the prostate reduces the number of complications at the risk of positive surgical margins. Preoperative selection of men eligible for safe, nerve-sparing surgery is therefore needed. Our aim was to identify pathological factors associated with positive posterolateral surgical margins in men undergoing bilateral nerve-sparing RP. Prostate cancer patients undergoing RP with standardised intra-operative surgical margin assessment according to the NeuroSAFE technique were included. Preoperative biopsies were reviewed for grade group (GG), cribriform and/or intraductal carcinoma (CR/IDC), perineural invasion (PNI), cumulative tumour length and extraprostatic extension (EPE). Of 624 included patients, 573 (91.8%) received NeuroSAFE bilaterally and 51 (8.2%) unilaterally, resulting in a total of 1197 intraoperative posterolateral surgical margin assessments. Side-specific biopsy findings were correlated to ipsilateral NeuroSAFE outcome. Higher biopsy GG, CR/IDC, PNI, EPE, number of positive biopsies and cumulative tumour length were all associated with positive posterolateral margins. In multivariable bivariate logistic regression, ipsilateral PNI [odds ratio (OR) = 2.98, 95% confidence interval (CI) = 1.62-5.48; P < 0.001] and percentage of positive cores (OR = 1.18, 95% CI = 1.08-1.29; P < 0.001) were significant predictors for a positive posterolateral margin, while GG and CR/IDC were not. Ipsilateral PNI and percentage of positive cores were significant predictors for a positive posterolateral surgical margin at RP. Biopsy PNI and tumour volume can therefore support clinical decision-making on the level of nerve-sparing surgery in prostate cancer patients.


Differential transfer of C and E apolipoproteins from very-low-density lipoprotein to lysophosphatidylcholine-phosphatidylcholine micelles.
Rat plasma VLDL was incubated with lysoPC/PC micelles consisting of 45-90 mol% lysoPC at micelle/VLDL phospholipid ratios of 0.33-6. Following incubation, the VLDL and micellar particles were reisolated by ultracentrifugation and the lipid and apolipoprotein composition determined by high-temperature gas chromatography and polyacrylamide gel electrophoresis, respectively. Lysophosphatidylcholine was found to equilibrate between the very-low-density lipoproteins and micellar fraction without transfer of phosphatidylcholine or sphingomyelin between these fractions. This produced reisolated VLDL and micellar particles with nearly identical lysoPC/PC ratios. Only apolipoprotein E transferred to reisolated micellar fractions with less than 35 mol% lysoPC. The C apolipoproteins were also transferred to the micellar fraction when the reisolated micelles contained more than 35 mol% lysoPC. It is concluded that apolipoproteins E and C can bind to HDL-size micellar particles of appropriate composition. The differential transfer of apolipoproteins E and C indicates that fundamental differences exist between these apolipoproteins in their interaction with lipid interfaces.


Mass spectrometric analysis of mucin core proteins.
Mucins are difficult to handle for their identification and characterization via proteomic applications due to their heavily glycosylated nature (up to 90%), high molecular weight (200 kDa-200 MDa), and size (Rg 10-300 nm). Their core proteins are extremely large and highly substituted with oligosaccharides, which only allow access to a highly restricted portion of their protein. For this reason, conventional 1D or 2D polyacrylamide gel-based proteomic approaches are not effective for identification and characterization of mucin molecules. In this chapter, we present our current protocol employing a modified shotgun proteomic approach to identify these complex glycoproteins.


Sudden anosmia and ageusia in a child: A COVID-19 case report.
COVID-19 in children has a spectrum of clinical presentations ranging from asymptomatic infection to severe illness and death. The recognition of COVID-19 in children has been challenging due to overlap with symptoms of common respiratory and gastrointestinal tract infections. We describe isolated sudden anosmia and ageusia as an uncommon clinical presentation of a child with COVID-19. Chart of a 17-year-old male referred to a tertiary care pediatric hospital for assessment of anosmia and ageusia was reviewed. Data included relevant history and physical examination, diagnostic work up, and management. The child presented with sudden anosmia and ageusia for 3 months. The patient did not have symptoms of upper respiratory tract infection or gastrointestinal infection. There was no history of trauma. Examination of the ears, nose, and throat were all unremarkable. Magnetic resonance imaging documented the presence of both olfactory bulbs and olfactory sulci. SARS-CoV-2 IgG test was positive. Anosmia was confirmed by The University of Pennsylvania Smell Identification Test with a score of 27.5%. The clinical picture of our patient represents a non-classical presentation of COVID-19 in a child. Clinicians should be cognizant about uncommon presentations of COVID-19 in previously asymptomatic children.


Quality improvement to evaluate and provide treatment for chronic hepatitis C postpartum.
Chronic hepatitis C virus (HCV) infections are increasing among reproductive age individuals. Direct acting antivirals (DAAs) can cure HCV, but the use of DAAs is not currently recommended during pregnancy and breastfeeding. Individuals with HCV commonly have inadequate prenatal and postnatal care. The purpose of our study was to demonstrate the success of a quality improvement program to increase evaluation during pregnancy and ensuring access to DAA treatment medication during the postpartum period for individuals with chronic HCV to achieve cure 12 weeks after completing therapy. The primary outcome was documented HCV cure rate compared among individuals who received immediate treatment with DAA after delivery or after weaning or a traditional approach of referral to an infectious diseases specialist or hepatologist. The secondary outcome was the proportion of infants exposed to HCV evaluated. An interdisciplinary team developed a program to increase evaluation and HCV treatment for postpartum individuals. Individuals who received prenatal care from March 2017 to May 2021 were eligible. Individuals with chronic HCV had a laboratory evaluation before delivery, and appropriate DAAs were selected for postpartum treatment. The health system specialty pharmacy dispensed DAA prescriptions immediately after delivery to those who were not breastfeeding. Individuals who did breastfeed had the option to begin treatment after weaning. Cure was defined as a sustained viral response or undetectable HCV RNA collected 12 weeks after completing DAA treatment. We demonstrate the success of an interdisciplinary team to ensure access to therapy for the treatment of postpartum chronic HCV. Only 3 infants (25%) with mothers referred were evaluated at our institution compared with 44% of infants (n = 10) whose mothers were treated after delivery. An interdisciplinary team for HCV treatment improves access to treatment therapy with DAAs leading to the cure of chronic HCV after delivery.


Ligand-mediated dephosphorylation signaling for MAP kinase.
Extracellular signal-regulated kinase (ERK), also known as classical mitogen-activated protein kinase, plays critical roles in cell regulation. ERK is activated through phosphorylation by a cascade of protein kinases including MEK. Various ligands activate the MEK/ERK pathway through receptor-dependent cell signaling. In cultured cells, many ligands such as growth factors, hormones, cytokines and vasoactive peptides elicit transient activation of MEK/ERK, often peaking at ~10 min after the cell treatment. Here, we describe a novel biological event, in which ligand-mediated cell signaling results in the dephosphorylation of MEK/ERK. Neuromedin N and neurotensin, peptides derived from the same precursor polypeptide, elicit cell signaling through the neurotensin receptors. In cultured human pulmonary artery smooth muscle cells (PASMCs), but not in human pulmonary artery endothelial cells (PAECs), we found that both neuromedin N and neurotensin promoted the dephosphorylation of ERK and MEK. Human PASMCs were found to express neurotensin receptor (NTR)-1, -2 and -3, while human PAECs only express NTR3. Neuromedin N-mediated dephosphorylation was suppressed by small chemical inhibitors of protein phosphatase 1/2A and peptidyl-prolyl isomerase. Transmission electron microscopy showed the formation of endocytic vesicles in response to neuromedin N treatment, and dephosphorylation did not occur when sorting nexin 9, a critical regulator of the endocytic vesicle formation, was knocked down. We conclude that neuromedin N and neurotensin elicit a unique dephosphorylation signaling in the MEK/ERK pathway that is regulated by endocytosis. Considering the pathophysiological importance of the MEK/ERK pathway, this discovery of the dephosphorylation mechanism should advance the field of cell signaling.


Total parenteral nutrition by peripheral vein--substitute or supplement to the central venous route? A prospective trial.
51 consecutive gastroenterological patients who required total parenteral nutrition (TPN) were entered into this study. Two patients were withdrawn because of specific nutritional requirements, leaving 49 patients for randomisation. 23 patients were allocated to receive peripheral parenteral nutrition (PPN) and 26 to receive feeding through a central venous line (CPN). There was no significant difference between the groups with respect to the median duration of feeding (9.4 +/- 3.6 days; 12.0 +/- 7.8 days) but significant morbidity occurred more frequently in the CPN group (11%) compared to the PPN group (0%). TPN by the designated route was not possible in 4 patients in the PPN group and in 3 of the CPN group. Of the 19 patients commenced on PPN, 13 continued without complication until resumption of oral feeding (median 10.7 +/- 3.2 days); 6 of these patients had to be converted to central venous feeding for completion of their nutritional requirements. Of the 23 patients commenced on CPN, 21 completed their nutritional course (median 11.8 +/- 5.3 days), 2 patients in the CPN group required conversion to PPN to complete their nutritional course. This study shows that PPN is a feasible, safe alternative to CPN in many patients. It is not necessary to subject all patients who require TPN to the risks and expense of central venous cannulation.


Association between delayed cesarean section and severe maternal and adverse newborn outcomes in the Somaliland context: a cohort study in a national referral hospital.
In a critical obstetric situation, the time interval between the decision of performing a caesarean section (CS) and delivery can influence maternal and newborn outcomes. In Somaliland, consent for surgical procedures, such as CS needs to be sought from family members. To determine the association between a delay in performing a CS and severe maternal and newborn outcomes in a national referral hospital in Somaliland. The type of barriers leading to delayed performance of CS after a doctor's decision were also explored. Women were followed from the time of decision to perform CS until discharge from the hospital between 15 April 2019 and 30 March 2020. No delay was defined as < 1 hour and delayed CS was defined as 1-3 hours and >3 hours from decision of CS to delivery. Information was collected on barriers leading to delayed CS and maternal and newborn outcomes. Data was analysed using binary and multivariate logistic regression. Overall, 1255 women were recruited from a larger cohort of 6658 women. A delay in CS >3 hours was associated with higher odds of severe maternal outcomes (aOR 1.58, 95% CI [1.13-2.21]). On the contrary, delay in performing a CS >3 hours was associated with lower odds of stillbirth (aOR 0.48, 95% CI [0.32-0.71]) compared to women without delay. Further, family decision-making for consent was the most important barrier leading to delays of >3 hours as compared to financial factors and barriers related to healthcare providers (48% vs 26% and 15%, respectively, p < 0.001). In this setting, delay in performing CS >3 hours was associated with higher risk of severe maternal outcomes. A standardised system of performing a CS by primarily addressing the barriers associated with family decision-making, financial aspects and healthcare providers is needed.


Effects of tacrolimus on antioxidant status and oxidative stress in glioma cells.
After organ transplantation, some patients suffer from mild neurologic symptoms, ranging from tremor to severe complications, including seizures and encephalopathy. Among the immunosuppressants, tacrolimus can cause neurologic side effects. However, the mechanisms of encephalopathy by tacrolimus are not fully understood. We measured the antioxidant status, hydrogen peroxide level, and malondialdehyde level in glioma cells after tacrolimus treatment. The production of hydrogen peroxide was determined by the modified xylenol orange method. The amount of malondialdehyde was measured by the thiobarbituric acid assay, which is based on malondialdehyde reaction with thiobarbituric acid to give a red species absorbing at 535 nm. Total antioxidant status (TAS) was measured using TAS kits (NX2332). Tacrolimus resulted in dose- and time-dependent increases in the production of hydrogen peroxide by glioma cells. The antioxidant status decreased in the glioma cells after tacrolimus treatment. Malondialdehyde level was unchanged in the glioma cells after tacrolimus treatment. Increased production of reactive oxygen species and decreased antioxidant status by tacrolimus in glioma cells may contribute to neurologic side effects.


Plasma RNA viral load in HIV-1 group O infection by real-time PCR.
HIV-1 group O strains are highly divergent, and are found mainly in central Africa. The clinical course of group O infection is identical to that of HIV-1 group M infection, with rapid onset of immunodeficiency. The important divergence of the HIV-1 group O strains lead to high limitations of the commercial tests. We describe here a method based on real-time polymerase chain reaction (PCR) to quantify plasma HIV-1 group O RNA. Primers amplify both HIV-1 group O and HIV-1 group M strains. Conversely, the probe is HIV-1 group O-specific. The standard used to quantify the clinical samples is an RNA solution resulting from the transcription of a plasmid including the amplified fragment of PCR. Our technique is capable of amplifying a wide range of HIV-1 group O strains belonging to the three current clades. This technique can be used to monitor HIV-1 group O viral load, which has previously been difficult.


Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein.
Plasmodium falciparum engineer infected erythrocytes to present the malarial protein, VAR2CSA, which binds a distinct type chondroitin sulfate (CS) exclusively expressed in the placenta. Here, we show that the same CS modification is present on a high proportion of malignant cells and that it can be specifically targeted by recombinant VAR2CSA (rVAR2). In tumors, placental-like CS chains are linked to a limited repertoire of cancer-associated proteoglycans including CD44 and CSPG4. The rVAR2 protein localizes to tumors in vivo and rVAR2 fused to diphtheria toxin or conjugated to hemiasterlin compounds strongly inhibits in vivo tumor cell growth and metastasis. Our data demonstrate how an evolutionarily refined parasite-derived protein can be exploited to target a common, but complex, malignancy-associated glycosaminoglycan modification.


Determination of oral anti-diabetic agents in human body fluids using high-performance liquid chromatography.
Two widely prescribed anti-diabetic agents for which no simple assay method was previously available can now be determined by high-performance liquid chromatography using a UV detection system. The two drugs investigated were tolbutamide (a sulphonylurea) and phenformin (a biguanide). Tolbutamide can be assayed directly, after a single extraction step, on a reversed-phase system, illustrating the simplicity of the technique for carrying out analyses on underivatised drug compared with gas chromatography. Phenformin was not so easily chromatographhed using straightforward partition systems; however, by the choice of a suitable ion-pair agent it was possible to chromatograph the underivatised drug in a relatively simple reversed-phase system.


Glycoside Hydrolase family 30 harbors fungal subfamilies with distinct polysaccharide specificities.
Efficient bioconversion of agro-industrial side streams requires a wide range of enzyme activities. Glycoside Hydrolase family 30 (GH30) is a diverse family that contains various catalytic functions and has so far been divided into ten subfamilies (GH30_1-10). In this study, a GH30 phylogenetic tree using over 150 amino acid sequences was contructed. The members of GH30 cluster into four subfamilies and eleven candidates from these subfamilies were selected for biochemical characterization. Novel enzyme activities were identified in GH30. GH30_3 enzymes possess β-(1→6)-glucanase activity. GH30_5 targets β-(1→6)-galactan with mainly β-(1→6)-galactobiohydrolase catalytic behavior. β-(1→4)-Xylanolytic enzymes belong to GH30_7 targeting β-(1→4)-xylan with several activities (e.g. xylobiohydrolase, endoxylanase). Additionally, a new fungal subfamily in GH30 was proposed, i.e. GH30_11, which displays β-(1→6)-galactobiohydrolase. This study confirmed that GH30 fungal subfamilies harbor distinct polysaccharide specificity and have high potential for the production of short (non-digestible) di- and oligosaccharides.


A single-variable proof of the omega SPT congruence family over powers of 5.
In 2018, Liuquan Wang and Yifan Yang proved the existence of an infinite family of congruences for the smallest parts function corresponding to the third-order mock theta function ω(q). Their proof took the form of an induction requiring 20 initial relations, and utilized a space of modular functions isomorphic to a free rank 2 Z[X]-module. This proof strategy was originally developed by Paule and Radu to study families of congruences associated with modular curves of genus 1. We show that Wang and Yang's family of congruences, which is associated with a genus 0 modular curve, can be proved using a single-variable approach, via a ring of modular functions isomorphic to a localization of Z[X]. To our knowledge, this is the first time that such an algebraic structure has been applied to the theory of partition congruences. Our induction is more complicated, and relies on sequences of functions which exhibit a somewhat irregular 5-adic convergence. However, the proof ultimately rests upon the direct verification of only 10 initial relations, and is similar to the classical methods of Ramanujan and Watson.


C-reactive protein is elevated in atypical but not nonatypical depression: data from the National Health and Nutrition Examination survey (NHANES) 1999-2004.
Little is known about the association of depression subtypes with inflammatory markers predictive of coronary artery disease. In a sample of younger adults representative of the U.S. population, we examined differences in serum C-reactive protein (CRP) among individuals with atypical major depressive disorder (MDD; n = 16), nonatypical MDD (n = 93), and no MDD (n = 1,682). Adults with atypical MDD exhibited higher CRP levels than those with no MDD (mean difference = 1.56 mg/L) or nonatypical MDD (mean difference = 1.40 mg/L), even after adjustment for potential cofounders, anxiety disorders, body mass, and smoking. Nearly twice as many adults with atypical MDD had CRP levels in the high cardiovascular risk range than did those with no MDD or nonatypical MDD. CRP levels of adults with nonatypical MDD or no MDD did not differ. Individuals with atypical depression may be partially driving the overall depression-inflammation relationship and may be a subgroup at elevated risk for coronary artery disease.