The New Bedford Harbor Superfund site long-term monitoring program (1993-2009).
New Bedford Harbor (NBH), located in southeastern Massachusetts, was designated as a marine Superfund site in 1983 due to sediment contamination by polychlorinated biphenyls (PCBs). Based on risks to human health and the environment, the first two phases of the site cleanup involved dredging PCB-contaminated sediments from the harbor. Therefore, a long-term monitoring program (LTM) was developed to measure spatial and temporal chemical and biological changes in sediment, water, and biota to assess the effects and effectiveness of the remedial activities. A systematic, probabilistic sampling design was used to select sediment sampling stations. This unbiased design allowed the three segments of the harbor to be compared spatially and temporally to quantify changes resulting from dredging the contaminated sediments. Sediment was collected at each station, and chemical (e.g., PCBs and metals), physical (e.g., grain size), and biological (e.g., benthic community) measurements were conducted on all samples. This paper describes the overall NBH-LTM approach and the results from the five rounds of sample collections. There is a decreasing spatial gradient in sediment PCB concentrations from the northern boundary (upper harbor) to the southern boundary (outer harbor) of the site. Along this same transect, there is an increase in biological condition (e.g., benthic community diversity). Temporally, the contaminant and biological gradients have been maintained since the 1993 baseline collection; however, since the onset of full-scale remediation, PCB concentrations have decreased throughout the site, and one of the benthic community indices has shown significant improvement in the lower and outer harbor areas.


Exploring regression dilution bias using repeat measurements of 2858 variables in ≤49 000 UK Biobank participants.
Measurement error in exposures and confounders can bias exposure-outcome associations but is rarely considered. We aimed to assess random measurement error of all continuous variables in UK Biobank and explore approaches to mitigate its impact on exposure-outcome associations. Random measurement error was assessed using intraclass correlation coefficients (ICCs) for all continuous variables with repeat measures. Regression calibration was used to correct for random error in exposures and confounders, using the associations of red blood cell distribution width (RDW), C-reactive protein (CRP) and 25-hydroxyvitamin D [25(OH)D] with mortality as illustrative examples. The 2858 continuous variables with repeat measures varied in sample size from 109 to 49 121. They fell into three groups: (i) baseline visit [529 variables; median (interquartile range) ICC = 0.64 (0.57, 0.83)]; (ii) online diet by 24-h recall [22 variables; 0.35 (0.30, 0.40)] and (iii) imaging measures [2307 variables; 0.85 (0.73, 0.94)]. Highest ICCs were for anthropometric and medical history measures, and lowest for dietary and heart magnetic resonance imaging.The ICCs (95% confidence interval) for RDW, CRP and 25(OH)D were 0.52 (0.51, 0.53), 0.29 (0.27, 0.30) and 0.55 (0.54, 0.56), respectively. Higher RDW and levels of CRP were associated with higher risk of all-cause mortality, and higher concentration of 25(OH)D with lower risk. After correction for random measurement error in the main exposure, the associations all strengthened. Confounder correction did not influence estimates. Random measurement error varies widely and is often non-negligible. For UK Biobank we provide relevant statistics and adaptable code to help other researchers explore and correct for this.


99mTc-3PRGD2 scintigraphy to stage liver fibrosis and evaluate reversal after fibrotic stimulus withdrawn.
Scintigraphy using 99mTc-3PRGD2 targeting integrin αvβ3 could assess activation of hepatic stellate cells (HSCs). Liver fibrogenesis is intimately associated with activation of HSCs, and the fibrolytic process is accompanied by the reduction of the activated HSCs. In this study, we aimed to evaluate the feasibility of this method to assess the severity of liver fibrosis and the reversal after the fibrotic stimulus withdrawal. Liver fibrosis of different stages was induced by thioacetamide (TAA) injection for 2, 4 and 6 weeks (n = 6 for each time point). Another 6 rats with 8-week TAA administration (the 8-week group) and 6 rats which were injected with TAA for 6 weeks, and then withdrawn of TAA for 2 weeks (spontaneous recovery rats, SRR) were designed. The ratios of radioactivity detected in the liver vs. the heart at 30 min post-injection of 99mTc-3PRGD2 (L/H30min), the collagen proportionate area (CPA), the protein and mRNA levels of integrin αv, integrin β3 were analyzed and compared among groups. The Ishak stage scores of the livers in the control and 2, 4, 6-week groups increased when the TAA administration period was extended. L/H30min increased with the upgrading of liver fibrosis and the differences between each pair of groups were statistically significant (p 30 min in the 8-week group was similar to that in the 6-week group (p > 0.05), but was significantly higher than that in the SRR group (p = 0.005). Scintigraphy using 99mTc-3PRGD2 may provide a non-invasive method for grading liver fibrosis and assessing liver fibrosis reversal.


Pacing for hypertrophic obstructive cardiomyopathy does it work?
Sixty-nine years old lady presented with sudden cardiac arrest, she was found to have hypertrophic obstructive cardiomyopathy, she refused septal myomectomy and had a dual chamber ICD implanted, she was put on right ventricular apical pacing with short AV interval, after pacing her max pressure gradient across left ventricular out flow tract (LVOT) dropped from 117 mmHg to 21 mmHg and her symptoms much improved over a follow up period of 1 year.


Viral studies in streptozotocin-induced pancreatic insulitis.
Multiple injections of streptozotocin to Charles River (CD-1) Laboratory mice resulted in a syndrome characterised by diabetes mellitus, insulitis and the induction of endogenous type C viruses in pancreatic beta cells. Within one week after the completion of five intraperitoneal injections of streptozotocin, the CD-1 mice exhibited irreversible hyperglycaemia and insulinopaenia. Light microscopic studies of pancreata from mice sacrificed at this time demonstrated insulitis and beta cell necrosis. Electron microscopic studies revealed spherical and atypical cylindrical type C viruses and occasional clusters of intracisternal type A viruses exclusively within beta cells. To clarify the identification of the type C viruses and their role in the genesis of the insulitis, type C virus specific antigens were identified within islet cells by immune fluorescence at various intervals after streptozotocin administration. Immune fluorescence studies demonstrated the presence of type C virus antigens within islets from streptozotocin treated mice but not in buffer-injected controls. Time course studies suggested that type C virus induction may precede the appearance of insulitis by two days and that insulitis is consistently accompanied by the presence of virus positive islet cells.


Elemental concentrations in air-exposed and vacuum-stored cryosections of rat liver cells.
Elemental concentrations in different compartments of cryosections of isolated rat liver cells cryotransferred and freeze-dried were compared with those obtained after storage under vacuum for 12 or 60 h and after exposure to room air for 2 min. Poorer image contrast and segregation artefacts are frequently found in air-exposed sections, together with a slight but significant decrease of the K concentration in the cytoplasm and an increase of the S concentration in the liver cell nuclei and the extracellular medium. Extreme distortions of both ultrastructure and elemental distributions are observed if the sections are even slightly colder than the surrounding atmosphere. While storage of frozen-dried cryosections under vacuum for less than 12 h does not lead to alterations in the sections, gross changes are found both in morphology and elemental distribution in sections stored under vacuum for about 60 h. Long-time vacuum storage of frozen-dried cryosections is, therefore, not recommended.


The immunochemistry of sandwich ELISAs--III. The stoichiometry and efficacy of the protein-avidin-biotin capture (PABC) system.
The protein-avidin-biotin capture (PABC) system was developed to decrease the adsorption-induced loss of antigen capture capacity (AgCC) of capture antibodies (CAb) used in sandwich ELISAs. This system involves immobilization of biotinylated CAbs through linkage by streptavidin (SA) to biotinylated carrier proteins adsorbed on polystyrene. Studies reported here describe the stoichiometry of the system and the influence of biotinylation of different carrier proteins and CAbs on the reaction stoichiometry and the AgCC of CAbs. Because of the widespread use of sandwich ELISAs to measure the concn of multivalent protein antigens, the AgCCs of monoclonal and polyclonal CAbs to pig IgG in the PABC system were compared with the AgCCs of these Abs immobilized on the plastic by direct adsorption. Optimal assay conditions for the carrier were obtained when 1 microgram/ml of the biotinylated protein was added to the polystyrene solid phase. An increasing degree of biotin substitution in three carrier proteins was paralleled by an increasing AgCC until a constant maximum was reached. Under conditions of maximal AgCC, 120 ng of the carrier rabbit gamma globulin (RGG; i.e. RGG25biot) was bound to polystyrene, which in turn yielded the maximum amount (i.e. 100 ng) of bound streptavidin (SA; Bdngmax) when 20 micrograms/ml of SA was added. Under conditions giving the Bdngmax for SA, CAb12biot yielded a higher Bdngmax than did CAb25biot or CAb2biot. When the AgCC of equal amounts of differentially biotinylated CAbs were compared, the following order of AgCC was observed: CAb12biot greater than CAb12biot greater than CAb25biot. Hence, while the maximal amount of CAb is immobilized on SA when CAb12biot is used, optimal AgCC is achieved with CAb2biot. The carrier:SA:CAb2biot ratio was 1:2:1 while that for carrier:SA:CAb12biot was 1:2:2. The same ratio was obtained using IgG2biot from four different species. Monoclonal antibodies to swine IgG showed a 5-6-fold increase in Bd%max when immobilized as CAbs using the PABC system versus when adsorbed on polystyrene. Plots of these data suggest that the differences result from a loss of functional affinity. On the contrary, no significant differences in Bd%max and hence functional affinity were observed when a polyclonal antibody to pig IgG was compared using the two assay configurations. Furthermore, when the globulin fraction of the anti-pig polyclonal was adsorbed on plastic, it behaved nearly as well as its affinity-purified counterpart immobilized by the PABC system. The PABC system appears to offer significant advantages for sandwich ELISAs utilizing monoclonal antibodies as the CAb, and may offer some advantages in other s


Mössbauer spectroscopic studies of deproteinised, sub-fractionated and reconstituted ferritins: the relationship between haemosiderin and ferritin.
In a previous study of human haemosiderin and ferritin by a combination of Mössbauer spectroscopy and electron microscopy, it was observed that the Mössbauer spectra of haemosiderin showed a very different temperature dependence to those of ferritin. These differences were related to the superparamagnetic behaviour of small particles of a magnetic material and suggested that the magnetic anisotropy constant of the haemosiderin was considerably larger than that of the ferritin. In the present work, samples of ferritin have been examined by Mössbauer spectroscopy following partial deproteinisation, subfractionation, and reconstitution with and without phosphate, in order to investigate whether these procedures lead to changes in the magnetic anisotropy constant of the iron-containing cores. There is no evidence from the present data that changes in the protein shell, in the size of the iron-containing cores of ferritin, or in the phosphate content lead to any significant changes in the magnetic anisotropy constant, as obtained from the temperature dependence of the Mössbauer spectra. These results indicate that the different magnetic anisotropy constant observed in the case of human haemosiderin resulting from transfusional iron overload must arise from other significant differences in the composition or structure of the iron-containing cores.


Growth and carbon allocation of Agropyron desertorum following autumn defoliation.
Growth and carbon allocation of a cool season tussock grass, Agropyron desertorum, following defoliation of newly initiated tillers in the autumn of 1988 and 1989 were investigated. Tiller density and mortality, reproductive shoot density, root density, biomass, individual tiller weight, carbon allocation, and soil water depletion were used to evaluate the response of A. desertorum to autumn grazing. Tiller recruitment was lower in the autumn-defoliated treatment in both years compared with the control because of the cessation of tiller development following autumn defoliation. Autumn defoliation also significantly reduced the movement of 13C to the roots in 1988 but not in 1989. Soils were cooler and drier in 1989. Other plant growth measurements and soil water depletion rates were not different between treatments. Autumn defoliation in 1988 did not influence tiller recruitment in the following autumn. Two consecutive years of autumn defoliation did not affect tiller overwinter mortality or peak standing crop in 1990.


Metabolic problems in the management of a traumatic pancreatic fistula.
A case of persistent, high output, traumatic pancreatic fistula, complicated by the development of a gastric fistula secondary to a pancreatic abscess, is described. The problems associated with the metabolic and nutritional management are discussed.


Stretching the point: an association between the occurrence of striae and pelvic relaxation?
Striae are seen in numerous clinical conditions, including pregnancy, and may be resultant from progressive, continuous skin stretching. Regardless of etiology, they appear as raised pink/purple lesions, which mature leaving depressed silver 'scars'. In this issue, Salter et al. explore the possibility that occurrence of striae may predict pelvic relaxation (prolapse of the pelvic organs) in later life.


Clinical significance of plasma PD-L1+ exosomes in the management of diffuse large B cell lymphoma.
PD-L1+ exosome have been reported to be a promising prognostic biomarker in various cancers. However, its clinical value in diffuse large B cell lymphoma (DLBCL) has not been defined yet. In this study, a total of 165 plasma samples from 78 patients with DLBCL undergoing standard first-line R-CHOP regimens were collected at three different time points (pretreatment, and after 3 and 6 cycles of R-CHOP) to determine the proportions of PD-L1+ exosomes by flow cytometry. We found that high pretreatment plasma PD-L1+ exosome correlated with indicators of poor clinical outcome that included high Ki-67 expression (P = 0.02), double expressor lymphoma (P = 0.005), immunohistochemical PD-L1+ tumor tissue (P = 0.006), and the baseline maximal standardized uptake values (P = 0.0003). Pretreatment plasma PD-L1+ exosome was an independent factor by multivariate analysis with logistic regression (P = 0.0301). Moreover, the pretreatment PD-L1+ exosome was a strong predictor of final treatment responses of either CR or non-CR by ROC analysis (P < 0.001). PD-L1+ exosome level declined significantly in patients who experienced CR (pretreatment vs. after 3 cycles/after 6 cycles, P < 0.05), but not in the non-CR group. Intriguingly, plasma PD-L1+ exosome after 3 cycles (AUC = 0.857; 95%CI: 0.728-0.939) might represent a more sensitive indicator than radiographic assessment after 3 cycles (AUC = 0.626; 95%CI: 0.477-0.758) for evaluating the therapeutic response of DLBCL patients (P = 0.0136). Our results suggest that plasma PD-L1+ exosomes may represent a new biomarker for the dynamic monitoring of treatment response.


Caffeine suppresses the progression of human glioblastoma via cathepsin B and MAPK signaling pathway.
Glioblastoma has aggressive proliferative and invasive properties. We investigated the effect of caffeine on the invasion and the anti-cancer effect in human glioblastomas. Caffeine reduced the invasion in U-87MG, GBM8401 and LN229 cells. Caffeine decreased mRNA, protein expression, and activity of cathepsin B. Besides, mRNA and protein expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) was upregulated by caffeine treatment, whereas matrix metalloproteinase-2 (MMP-2) was downregulated. The expression of Ki67, p-p38, phospforylated extracellular regulated protein kinases (p-ERK), and membranous integrin β1 and β3 was decreased by caffeine. The Rho-associated protein kinase (ROCK) inhibitor, Y27632, blocked the caffeine-mediated reduction of cathepsin B, phosphorylated focal adhesion kinase (p-FAK), and p-ERK, and invasion. Moreover, caffeine decreased the tumor size, cathepsin B and Ki67 expression in animal model. Caffeine reduced the invasion of glioma cells through ROCK-cathepsin B/FAK/ERK signaling pathway and tumor growth in orthotopic xenograft animal model, supporting the anti-cancer potential in glioma therapy.


In vitro cultivation methods for coccidian parasite research.
The subclass Coccidia comprises a large group of protozoan parasites, including important pathogens of humans and animals such as Toxoplasma gondii, Neospora caninum, Eimeria spp., and Cystoisospora spp. Their life cycle includes a switch from asexual to sexual stages and is often restricted to a single host species. Current research on coccidian parasites focuses on cell biology and the underlying mechanisms of protein expression and trafficking in different life stages, host cell invasion and host-parasite interactions. Furthermore, novel anticoccidial drug targets are evaluated. Given the variety of research questions and the requirement to reduce and replace animal experimentation, in vitro cultivation of Coccidia needs to be further developed and refined to meet these requirements. For these purposes, established culture systems are constantly improved. In addition, new in vitro culture systems lately gained considerable importance in research on Coccidia. Well established and optimized in vitro cultures of monolayer cells can support the viability and development of parasite stages and even allow completion of the life cycle in vitro, as shown for Cystoisospora suis and Eimeria tenella. Furthermore, new three-dimensional cell culture models are used for propagation of Cryptosporidium spp. (close relatives of the coccidians), and the infection of three-dimensional organoids with T. gondii also gained popularity as the interaction between the parasite and host tissue can be studied in more detail. The latest advances in three-dimensional culture systems are organ-on-a-chip models, that to date have only been tested for T. gondii but promise to accelerate research in other coccidians. Lastly, the completion of the life cycle of C. suis and Cryptosporidium parvum was reported to continue in a host cell-free environment following the first occurrence of asexual stages. Such axenic cultures are becoming increasingly available and open new avenues for research on parasite life cycle stages and novel intervention strategies.


MiR-24-3p regulates cell proliferation and milk protein synthesis of mammary epithelial cells through menin in dairy cows.
MiR-24-3p, a broadly conserved, small, noncoding RNA, is abundantly expressed in mammary tissue. However, its regulatory role in this tissue remains poorly understood. It was predicted that miR-24-3p targets the 3' untranslated region (3'-UTR) of multiple endocrine neoplasia type 1 (MEN1), an important regulatory factor in mammary tissue. The objective of this study was to investigate the function of miR-24-3p in mammary cells. Using a luciferase assay in mammary epithelial cells (MAC-T), miR-24-3p was confirmed to target the 3'-UTR of MEN1. Furthermore, miR-24-3p negatively regulated the expression of the MEN1 gene and its encoded protein, menin. miR-24-3p enhanced proliferation of MAC-T by promoting G1/S phase progression. MiR-24-3p also regulated the expression of key factors involved in phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin and Janus kinase/signal transducer and activators of transcription signaling pathways, therefore controlling milk protein synthesis in epithelial cells. Thus, miR-24-3p appears to act on MAC-T by targeting MEN1. The expression of miR-24-3p was controlled by MEN1/menin, indicating a negative feedback loop between miR-24-3p and MEN1/menin. The negatively inhibited expression pattern of miR-24-3p and MEN1 was active in mammary tissues at different lactation stages. The feedback mechanism is a new concept to further understand the lactation cycle of mammary glands and can possibly to be manipulated to improve milk yield and quality.


Starvation for ilvB operon leader amino acids other than leucine or valine does not increase acetohydroxy acid synthase activity in Escherichia coli.
Eleven different amino acids are encoded in the ilvB leader mRNA. Starvation for leucine or valine, but not for any of the other nine amino acids, resulted in high levels of acetohydroxy acid synthase I. These results are discussed in terms of a report (C.A. Hauser and G.W. Hatfield, Proc. Natl. Acad. Sci. U.S.A. 81:76-79, 1984) which suggests that threonine and alanine, in addition to leucine and valine, are involved in the regulation of the ilvB operon.


Analysis and Comparison of the Malignant Thyroid Nodules Not Recommended for Biopsy in ACR TIRADS and AI TIRADS With a Large Sample of Surgical Series.
To determine if the artificial intelligence-based Thyroid Imaging, Reporting and Data System (AI TIRADS) would perform better than the American College of Radiology (ACR) TIRADS in monitoring malignant thyroid nodules not recommended for biopsy using follow-up thresholds. A total of 3499 thyroid nodules with surgical histopathology and ultrasound features were retrospectively reviewed and categorized using ACR TIRADS and AI TIRADS. The recommendations for biopsy and follow-up divided nodules into three groups 1) fine needle aspiration (FNA), 2) follow-up ultrasound, and 3) no further evaluation. Of the total 1608 malignant nodules in this study, 974 malignant nodules would not be biopsied in ACR TIRADS compared with 967 in AI TIRADS. While 60.0% (584/974) of these non-biopsied malignancies could be followed-up by ultrasound in ACR TIRADS and 62.8% (607/967) in AI TIRADS. For the malignancies of no further evaluation, 97.4% (380/390) were sized <10 mm in ACR TIRADS and 93.3% (336/360) in AI TIRADS. Compared with ACR TIRADS, AI TIRADS had lower unnecessary FNA rate and missing cancer rate (41.0% vs 47.8% and 22.8% vs 27.5%, P < .05, respectively) while having higher specificity and AUC as well as lower sensitivity (65.0% vs 57.9%, 0.895 vs 0.881, and 96.1% vs 97.8%, all P < .05). Using the follow-up thresholds, more than half of the malignancies not being biopsied were monitored by ultrasound in both ACR TIRADS and AI TIRADS, and AI TIRADS had lower missing cancer rate. More than 90% of malignancies recommended for no further evaluation were <10 mm in diameter.


Possible role of hypothyroidism in the prognosis of COVID-19.
In patients with COVID-19, certain medical conditions could result in poorer clinical outcomes. However, the prognostic role of hypothyroidism in COVID-19 is still unknown. In the present retrospective study, we estimated the prevalence of hypothyroidism in COVID-19 admitted patients in Tehran, Iran. Among 390 COVID-19 admitted patients, 21 hypothyroid cases (5.4%) were found, in which nearly 90% were aged 50 years and older. Regarding the effect of hypothyroidism on COVID-19 mortality, 60 (15.3%) of total patients and 4 (19%) of hypothyroid patients died, and no significant difference was found between the two groups.


Atypical ventricular tachycardia and alternating Osborn waves induced by spontaneous mild hypothermia.
A one-month-old infant developed atypical ventricular tachycardia, complete right bundle branch black, and alternating 2:1 Osborn waves during spontaneous mild hypothermia; 10 h after rewarming, the electrocardiogram was normal.


The platelet-to-lymphocyte ratio, superior to the neutrophil-to-lymphocyte ratio, correlates with hepatitis C virus infection.
The platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) have been studied widely in cancer diseases. However, their correlation with hepatitis C virus (HCV) infection is unknown. The aim of this study was to investigate the correlation of PLR and NLR with disease severity in patients with HCV-related liver disease and the virological response in chronic hepatitis C (CHC) patients. The clinical data of 120 HCV-infected patients and 40 healthy controls were analyzed. The clinical data of 24 CHC patients who had been followed up regularly were collected for the following time points: before treatment (week 0) and weeks 4, 48, and 72 during treatment. These data were also analyzed. All data were collected from the database of the hospital patient electronic medical record system. The HCV-related cirrhosis group and HCV-related hepatocellular carcinoma group were found to have lower PLRs (61±31 and 51±23) than the healthy controls (115±23). The PLR of the HCV cleared group (154±85) was significantly higher than that of the HCV untreated group and HCV uncleared group (90±28 and 88±40, respectively). Receiver operating characteristics curve analysis for the PLR showed an area under the curve of 0.772 (95% confidence interval 0.674-0.869, p<0.000); for NLR, the area under the curve was 0.612 (95% confidence interval 0.495-0.730, p=0.063). Furthermore, an increasing PLR in CHC patients indicated a good virological response, and a stable PLR or a downward trend in PLR could predict no rapid virological response being achieved by week 4, and even no sustained virological response by week 72. The PLR is closely related to disease severity in patients with HCV-related liver disease and to the virological response in CHC patients. Dynamic continuous monitoring of the PLR will contribute to disease surveillance, with an increasing tendency predicting a good virological response.


Effects of microbial DNA on human DNA profiles generated using the PowerPlex® 16 HS system.
Most crime scenes are not sterile and therefore may be contaminated with environmental DNA, especially if a decomposing body is found. Collecting biological evidence from this individual will yield DNA samples mixed with microbial DNA. This also becomes important if postmortem swabs are collected from sexually assaulted victims. Although genotyping kits undergo validation tests, including bacterial screens, they do not account for the diverse microbial load during decomposition. We investigated the effect of spiking human DNA samples with known concentrations of DNA from 17 microbe species associated with decomposition on DNA profiles produced using the Promega PowerPlex® HS system. Two species, Bacillus subtilis and Mycobacterium smegmatis, produced an extraneous allele at the TPOX locus. When repeated with the PowerPlex® Fusion kit, the extra allele no longer amplified with these two species. This experiment demonstrates that caution should be exhibited if microbial load is high and the PowerPlex® 16HS system is used.


Skeletal muscle area correlates with body surface area in healthy adults.
Depletion of skeletal muscle mass (sarcopenia) predicts survival in patients with cancer or liver cirrhosis. Recently, many reports have used computed tomography (CT) to measure muscle area to define sarcopenia. However, the definition of sarcopenia using CT has not been fully determined. The aim of this study was to establish formulae to calculate the standard area of skeletal muscle. Forty-five healthy adults (24 men and 21 women, aged 21-66 years) who wished to donate part of their liver for transplantation underwent CT. Cross-sectional areas (cm(2) ) of skeletal muscle were measured at the caudal end of the third lumbar vertebra. Regression analysis was performed to establish formulae to calculate the standard area of skeletal muscle. A validation conducted on 30 other healthy adults was performed to check the accuracy of formulae. Men had a median skeletal muscle area of 155.0 cm(2) (range, 114.0-203.0), compared with 111.7 cm(2) (range, 89.8-139.3) in women (P < 0.001). Furthermore, skeletal muscle area significantly correlated with body surface area (BSA) in men (P < 0.0001, r(2) = 0.60) and women (P < 0.0001, r(2) = 0.78). The formulae to calculate skeletal muscle area were 126.9 × BSA - 66.2 in men and 125.6 × BSA - 81.1 in women. The estimated muscle area significantly correlated with actual muscle area in men (P = 0.003, r(2) = 0.64) and women (P = 0.0001, r(2) = 0.70). Sarcopenia can be defined by the difference between measured data and calculated data using our new formulae.


Tubulin-specific chaperones: components of a molecular machine that assembles the α/β heterodimer.
The tubulin heterodimer consists of one α- and one β-tubulin polypeptide. Neither protein can partition to the native state or assemble into polymerization competent heterodimers without the concerted action of a series of chaperone proteins including five tubulin-specific chaperones (TBCs) termed TBCA-TBCE. TBCA and TBCB bind to and stabilize newly synthesized quasi-native β- and α-tubulin polypeptides, respectively, following their generation via multiple rounds of ATP-dependent interaction with the cytosolic chaperonin. There is free exchange of β-tubulin between TBCA and TBCD, and of α-tubulin between TBCB and TBCE, resulting in the formation of TBCD/β and TBCE/α, respectively. The latter two complexes interact, forming a supercomplex (TBCE/α/TBCD/β). Discharge of the native α/β heterodimer occurs via interaction of the supercomplex with TBCC, which results in the triggering of TBC-bound β-tubulin (E-site) GTP hydrolysis. This reaction acts as a switch for disassembly of the supercomplex and the release of E-site GDP-bound heterodimer, which becomes polymerization competent following spontaneous exchange with GTP. The tubulin-specific chaperones thus function together as a tubulin assembly machine, marrying the α- and β-tubulin subunits into a tightly associated heterodimer. The existence of this evolutionarily conserved pathway explains why it has never proved possible to isolate α- or β-tubulin as stable independent entities in the absence of their cognate partners, and implies that each exists and is maintained in the heterodimer in a nonminimal energy state. Here, we describe methods for the purification of recombinant TBCs as biologically active proteins following their expression in a variety of host/vector systems.


Progesterone receptor signalling in retinal photoreceptor neuroprotection.
'Norgestrel', a synthetic form of the female hormone progesterone has been identified as potential drug candidate for the treatment of the degenerative eye disease retinitis pigmentosa. However, to date, no work has looked at the compound's specific cellular target. Therefore, this study aimed to identify the receptor target of Norgestrel and begin to examine its potential mechanism of action in the retina. In this work, we identify and characterize the expression of progesterone receptors present in the C57 wild type and rd10 mouse model of retinitis pigmentosa. Classical progesterone receptors A and B (PR A/B), progesterone receptor membrane components 1 and 2 (PGRMC1, PGRMC2) and membrane progesterone receptors α, β and γ were found to be expressed. All receptors excluding PR A/B were also found in the 661W photoreceptor cell line. PGRMC1 is a key regulator of apoptosis and its expression is up-regulated in the degenerating rd10 mouse retina. Activated by Norgestrel through nuclear trafficking, siRNA knock down of PGRMC1 abrogated the protective properties of Norgestrel on damaged photoreceptors. Furthermore, specific inhibition of PGRMC1 by AG205 blocked Norgestrel-induced protection in stressed retinal explants. Therefore, we conclude that PGRMC1 is crucial to the neuroprotective effects of Norgestrel on stressed photoreceptors. The synthetic progestin 'Norgestrel' has been identified as a potential therapeutic for the treatment of Retinitis Pigmentosa, a degenerative eye disease. However, the mechanism behind this neuroprotection is currently unknown. In this work, we identify 'Progesterone Receptor Membrane Component 1' as the major progesterone receptor eliciting the protective effects of Norgestrel, both in vitro and ex vivo. This furthers our understanding of Norgestrel's molecular mechanism, which we hope will help bring Norgestrel one step closer to the clinic.


Solid-phase synthesis of O-glycosylated Nalpha-Fmoc amino acids and analysis by high-resolution magic angle spinning NMR.
Direct O-glycosylation of amino acids bound to TentaGel resin with a number of glycosyl trichloroacetimidate donors results in high yields. The glycosylation reaction can be easily monitored by analyzing the bead-bound amino acids with high-resolution magic angle spinning (HR-MAS) NMR. These studies pave a new way for the construction of "one-bead one-compound" O-glycopeptide libraries with standard amino acid building blocks and appropriate glycosyl trichloroacetimidate donors.


Does your dermatology classifier know what it doesn't know? Detecting the long-tail of unseen conditions.
Supervised deep learning models have proven to be highly effective in classification of dermatological conditions. These models rely on the availability of abundant labeled training examples. However, in the real-world, many dermatological conditions are individually too infrequent for per-condition classification with supervised learning. Although individually infrequent, these conditions may collectively be common and therefore are clinically significant in aggregate. To prevent models from generating erroneous outputs on such examples, there remains a considerable unmet need for deep learning systems that can better detect such infrequent conditions. These infrequent 'outlier' conditions are seen very rarely (or not at all) during training. In this paper, we frame this task as an out-of-distribution (OOD) detection problem. We set up a benchmark ensuring that outlier conditions are disjoint between the model training, validation, and test sets. Unlike traditional OOD detection benchmarks where the task is to detect dataset distribution shift, we aim at the more challenging task of detecting subtle differences resulting from a different pathology or condition. We propose a novel hierarchical outlier detection (HOD) loss, which assigns multiple abstention classes corresponding to each training outlier class and jointly performs a coarse classification of inliers vs. outliers, along with fine-grained classification of the individual classes. We demonstrate that the proposed HOD loss based approach outperforms leading methods that leverage outlier data during training. Further, performance is significantly boosted by using recent representation learning methods (BiT, SimCLR, MICLe). Further, we explore ensembling strategies for OOD detection and propose a diverse ensemble selection process for the best result. We also perform a subgroup analysis over conditions of varying risk levels and different skin types to investigate how OOD performance changes over each subgroup and demonstrate the gains of our framework in comparison to baseline. Furthermore, we go beyond traditional performance metrics and introduce a cost matrix for model trust analysis to approximate downstream clinical impact. We use this cost matrix to compare the proposed method against the baseline, thereby making a stronger case for its effectiveness in real-world scenarios.


Exploring the effect of napping on sleep quality and duration in collegiate athletes.
Purpose: The purpose of this study was to extend research on napping and sleep behaviors in collegiate athletes, and to compare nappers and non-nappers on sleep quality and duration. Methods: Current varsity, club, and intramural athletes between 18-29 years completed the Short Napping Behavior Scale, Pittsburgh Quality Sleep Index, Generalized Anxiety Disorder-7, and the Patient Health Questionnaire-9. Results: Approximately 72% (129/179) reported napping. There were no significant differences in outcomes between nap frequency groups on sleep quality (Χ2(3)=4.97, p=.17) or duration (Χ2(3)=1.20, p=.75). Moreover, there was no significant differences for nap length groups on sleep quality (Χ2(3)=7.03, p=.07) or duration (Χ2(3)=1.32, p=.72). Furthermore, there were no significant differences for nap timing groups on sleep quality (Χ2(3)=1.54, p=.67) or duration (Χ2(3)=2.43, p=.49). Conclusion: In a sample of collegiate athletes, nap frequency, length, and timing were not associated with worse sleep quality or duration.


Pneumonia in newly diagnosed patients infected with the Omicron variant: a population-based study of Chinese patients in Chongqing.
Pneumonia is the main complication of the Omicron variant of SARS-CoV-2; however, the incidence proportions and prognostic factors for Omicron-associated pneumonia have not been established. We conducted this study to characterise the incidence proportions and influence of various factors on prognosis of Omicron-associated pneumonia. We collected data from 714 patients infected with the Omicron variant in The First Affiliated Hospital of Chongqing Medical University (Chongqing, China) who were divided into different groups for analysis. We identified 313 patients with Omicron-associated pneumonia at the time of diagnosis of patients infected with the Omicron variant, representing 43.8% of the entire cohort. A total of 82 were 15-59 years old, 71 were 60-69 years old, 76 were 70-79 years old and 84 were >80 years old. 133 were female and 180 were male. Incidence proportions of pneumonia were highest among patients with cardiovascular (82.4% of the basic disease of the cardiovascular system subset) or kidney disease (92.3% of the kidney disease subset), whereas patients with lung cancer (35.7% of the lung cancer subset) had a lower incidence proportion. Several factors were associated with the prognosis of pneumonia in patients infected with the Omicron variant. Patients with a thrombosis or pleural effusion had a longer hospitalisation time. Paxlovid and immunoglobulins improved the prognosis of patients with severe pneumonia. The following measures were significantly different in patients as a function of disease severity: number of neutrophils and lymphocytes, partial oxygen pressure; and myoglobin, lactic dehydrogenase, aspartate transaminase and procalcitonin levels. Patients infected with the Omicron variant with coexisting cardiovascular or kidney disease, but not respiratory disease, had a higher incidence proportion of pneumonia. Paxlovid and immunoglobulins can be used in patients with severe infections to improve prognosis.


Impact of susceptibility-induced distortion correction on perfusion imaging by pCASL with a segmented 3D GRASE readout.
The consensus for the clinical implementation of arterial spin labeling (ASL) perfusion imaging recommends a segmented 3D Gradient and Spin-Echo (GRASE) readout for optimal signal-to-noise-ratio (SNR). The correction of the associated susceptibility-induced geometric distortions has been shown to improve diagnostic precision, but its impact on ASL data has not been systematically assessed and it is not consistently part of pre-processing pipelines. Here, we investigate the effects of susceptibility-induced distortion correction on perfusion imaging by pseudo-continuous ASL (pCASL) with a segmented 3D GRASE readout. Data acquired from 28 women using pCASL with 3D GRASE at 3T was analyzed using three pre-processing options: without distortion correction, with distortion correction, and with spatial smoothing (without distortion correction) matched to control for blurring effects induced by distortion correction. Maps of temporal SNR (tSNR) and relative perfusion were analyzed in eight regions-of-interest (ROIs) across the brain. Distortion correction significantly affected tSNR and relative perfusion across the brain. Increases in tSNR were like those produced by matched spatial smoothing in most ROIs, indicating that they were likely due to blurring effects. However, that was not the case in the frontal and temporal lobes, where we also found increased relative perfusion with distortion correction even compared with matched spatial smoothing. These effects were found in both controls and patients, with no interactions with the participant group. Correction of susceptibility-induced distortions significantly impacts ASL perfusion imaging using a segmented 3D GRASE readout, and this step should therefore be considered in ASL pre-processing pipelines. This is of special importance in clinical studies, reporting perfusion across ROIs defined on relatively undistorted images and when conducting group analyses requiring the alignment of images across different subjects.


Association between early ambulation exercise and short-term postoperative recovery after open transforaminal lumbar interbody fusion: a single center retrospective analysis.
Early ambulation in patients undergoing transforaminal lumbar interbody fusion (TLIF) surgery is recommended, however, the precise time interval after open surgery has never been specified. Current retrospective analysis was conducted aiming to clarify an accurate time interval. A retrospective analysis of eligible patients was conducted using the databases of the Bone Surgery Department, Third Affiliated Hospital of Sun Yat-sen University from 2016 to 2021. Data pertaining to postoperative hospital stay length, expenses, incidence of complications were extracted and compared using Pearson's χ2 or Student's t-tests. A multivariate linear regression model was conducted to identify the relationship between length of hospital stay (LOS) and other outcomes of interest. A propensity analysis was conducted to minimize bias and to evaluate the reliability of results. A total of 303 patients met the criteria and were included for the data analysis. Multivariate linear regression results demonstrated that a high ASA grade (p = 0.016), increased blood loss (p = 0.003), cardiac disease (p < 0.001), occurrence of postoperative complications(p < 0.001) and longer ambulatory interval (p < 0.001) was significantly associated with an increased LOS. The cut-off analysis manifested that patients should start mobilization within 3 days after open TLIF surgery (B = 2.843, [1.395-4.292], p = 0.0001). Further comparative analysis indicated that patients who start ambulatory exercise within 3 days have shorter LOS (8.52 ± 3.28d vs 12.24 ± 5.88d, p < 0.001), total expenses ( 9398.12 ± 2790.82vs 10701.03 ± 2994.03 [USD], p = 0.002). Propensity analysis revealed such superiority was stable along with lower incidence of postoperative complications (2/61 vs 8/61, p = 0.0048). The current analysis suggested that ambulatory exercise within 3 days for patients who underwent open TLIF surgery was significantly associated with reduced LOS, total hospital expenses, and postoperative complications. Further causal relationship would be confirmed by future randomized controlled trials.


Diagnosis and management of renal angiomyolipoma.
Renal angiomyolipoma (hamartoma) is an uncommon benign tumor of the kidney. Although about 400 cases of renal angiomyolipoma have been reported, it still causes difficulties in diagnosis and treatment. Until a few years ago it was almost impossible to arrive at a correct diagnosis preoperatively, and most of the cases underwent nephrectomy with the wrong diagnosis of renal carcinoma. More recently, abdominal computerized tomography and renal sonography have made it possible to reach the correct preoperative diagnosis in many cases, and thus to avoid unnecessary nephrectomies. We report on our experience with 13 cases of renal angiomyolipoma, and our conservative approach in a number of cases, which has enabled us to preserve renal tissue and function.


Combined sequencing of mRNA and DNA from human embryonic stem cells.
Combined transcriptome and whole genome sequencing of the same ultra-low input sample down to single cells is a rapidly evolving approach for the analysis of rare cells. Besides stem cells, rare cells originating from tissues like tumor or biopsies, circulating tumor cells and cells from early embryonic development are under investigation. Herein we describe a universal method applicable for the analysis of minute amounts of sample material (150 to 200 cells) derived from sub-colony structures from human embryonic stem cells. The protocol comprises the combined isolation and separate amplification of poly(A) mRNA and whole genome DNA followed by next generation sequencing. Here we present a detailed description of the method developed and an overview of the results obtained for RNA and whole genome sequencing of human embryonic stem cells, sequencing data is available in the Gene Expression Omnibus (GEO) database under accession number GSE69471.


Developing implantable optical biosensors.
Nanobiotechnologists are developing devices that can measure specific enzymes and proteins. These devices are expected to detect single enzyme or protein molecules accurately, providing highly sensitive biosensing applications. A recent study by Strano and co-workers shows that single-walled carbon nanotubes (SWNTs) hold great promise as implantable biosensors. Although most researchers have focused on substrate-oriented biosensors, Strano and colleagues have shown that the inherent fluorescent properties of suspended individual SWNTs can be used for solution-phase beta-D-glucose sensing.


Effectiveness of Switching From Intravenous to Subcutaneous Infliximab in Patients With Inflammatory Bowel Diseases: the REMSWITCH Study.
We assessed the effectiveness of switching from intravenous to subcutaneous infliximab in patients with inflammatory bowel diseases (IBDs) treated with or without intensified intravenous regimen. In this multicenter observational study, IBD patients in clinical remission (partial Mayo score ≤2 or Harvey-Bradshaw index ≤4) were switched to a unique dose of subcutaneous infliximab (120 mg every other week). Pharmacological and biological data were collected at baseline, visit 1 (4-8 weeks postswitch), visit 2 (8-16 weeks postswitch), and visit 3 (16-24 weeks postswitch). Relapse was defined as clinical relapse or fecal calprotectin increase ≥150 μg/g compared with baseline. Among 184 eligible patients, 72.3% (n = 133 of 184) agreed to switch to subcutaneous infliximab. At visit 3, a relapse occurred in 10.2% (n = 6 of 59), 7.3% (n = 3 of 38), 16.7% (n = 3 of 18), and 66.7% (n = 10 of 15) (P < .001) of patients receiving 5 mg/kg every 8 weeks, 10 mg/kg every 8 weeks, 10 mg/kg every 6 weeks, and 10 mg/kg every 4 weeks, respectively. Dose escalation to 240 mg every other week led to recapture clinical remission in 93.3% (n = 14 of 15). Infliximab serum levels increased after the switch (P < .0001) except for patients receiving 10 mg/kg every 4 weeks. In multivariable analysis, 10 mg/kg every 4 weeks regimen (odds ratio, 12.4; 95% confidence interval, 1.6-98.4; P = .017) and fecal calprotectin >250 μg/g at baseline (odds ratio, 5.4; 95% confidence interval, 1.1-27.6; P = .042) had a higher risk of relapse as well as reduced (41.7%) or stable (36.8%) infliximab serum levels between baseline and visit 1 compared with increased serum levels (12.7%) (P = .020 and P = .019, respectively). Patients' acceptability (10-point scale) was improved by the switch (6.9 ± 1.6 vs 8.6 ± 1.4; P < .0001). No severe adverse event was reported. Switching from intravenous to subcutaneous infliximab 120 mg every other week is safe and well accepted, leading to a low risk of relapse in IBD patients except for those receiving 10 mg/kg every 4 weeks requiring 240 mg every other week.


Unusual infrared-absorption mechanism in thermally reduced graphene oxide.
Infrared absorption of atomic and molecular vibrations in solids can be affected by electronic contributions through non-adiabatic interactions, such as the Fano effect. Typically, the infrared-absorption lineshapes are modified, or infrared-forbidden modes are detectable as a modulation of the electronic absorption. In contrast to such known phenomena, we report here the observation of a giant-infrared-absorption band in reduced graphene oxide, arising from the coupling of electronic states to the asymmetric stretch mode of a yet-unreported structure, consisting of oxygen atoms aggregated at the edges of defects. Free electrons are induced by the displacement of the oxygen atoms, leading to a strong infrared absorption that is in phase with the phonon mode. This new phenomenon is only possible when all other oxygen-containing chemical species, including hydroxyl, carboxyl, epoxide and ketonic functional groups, are removed from the region adjacent to the edges, that is, clean graphene patches are present.


Circadian rhythm sleep disorders: characteristics and entrainment pathology in delayed sleep phase and non-24-h sleep-wake syndrome.
This paper presents a clinical review of delayed sleep phase syndrome (DSPS) and non-24-h sleep-wake syndrome (non-24). These syndromes seem to be common and under-recognized in society, not only in the blind, but also typically emerging during adolescence. Both types of syndrome can appear alternatively or intermittently in an individual patient. Psychiatric problems are also common in both syndromes. DSPS and non-24 could share a common circadian rhythm pathology in terms of clinical process and biological evidence. The biological basis is characterized by a longer sleep period, a prolonged interval from the body temperature nadir-to-sleep offset, a relatively advanced temperature rhythm, lower sleep propensity after total sleep deprivation, and higher sensitivity to light than in normal controls. There are multiple lines of evidence suggesting dysfunctions at the behavioral, physiological and genetic levels. Treatment procedures and prevention of the syndromes require further attention using behavioral, environmental, and psychiatric approaches, since an increasing number of patients in modern society suffer from these disorders.


Rational Design of a Facially Coordinating P,N,N Ligand for Manganese-Catalysed Enantioselective Hydrogenation of Cyclic Ketones.
DFT calculations on the full catalytic cycle for manganese catalysed enantioselective hydrogenation of a selection of ketones have been carried out at the PBE0-D3PCM //RI-BP86PCM level. Mn complexes of an enantiomerically pure chiral P,N,N ligand have been found to be most reactive when adopting a facial coordination mode. The use of a new ligand with an ortho-substituted dimethylamino-pyridine motif has been calculated to completely transform the levels of enantioselectivity possible for the hydrogenation of cyclic ketones relative to the first-generation Mn catalysts. In silico evaluation of substrates has been used to identify those likely to be reduced with high enantiomer ratios (er), and others that would exhibit less selectivity; good agreements were then found in experiments. Various cyclic ketones and some acetophenone derivatives were hydrogenated with er's up to 99 : 1.


Complementary and Alternative Treatments for Alopecia: A Comprehensive Review.
The treatment of alopecia is limited by a lack of therapies that induce and sustain disease remission. Given the negative psychosocial impact of hair loss, patients that do not see significant hair restoration with conventional therapies often turn to complementary and alternative medicine (CAM). Although there are a variety of CAM treatment options on the market for alopecia, only a few are backed by multiple randomized controlled trials. Further, these modalities are not regulated by the Food and Drug Administration and there is a lack of standardization of bioactive in gredients in over-the-counter vitamins, herbs, and supplements. In this article, we provide a comprehensive review of the efficacy, safety, and tolerability of CAM, including natural products and mind and body practices, in the treatment of hair loss. Overall, there is a need for additional studies investigating CAM for alopecia with more robust clinical design and standardized, quantitative outcomes.


Age peculiarities of changes in the contractile function of isolated rat hearts during prolonged perfusion.
The experiments on the isolated hearts from adult and old rats have shown that during first hours of prolonged perfusion the contractile function decreased to a greater degree in adult rats compared to the old. Following a 3-h perfusion, there occurred a marked fall of the contractile function in old animals. The creatine phosphokinase activity in a perfusate grew sharply in the old rats and changed insignificantly in the adult. The Na,K-ATPase got activated in adult rats, which was prevented by the preliminary injection of actinomycin D, and declined in the old. It appeared that adult hearts had a better endurance of prolonged perfusion and kept sustaining a definite level of performance almost twice as long as the old. Under prolonged perfusion conditions, there has been synthesized a regulatory factor (invertor) in the heart of adult animals, which reduced the myocardial contractile function. The latter was evidenced from a fact that perfusate from adult hearts 'donors' promoted the decrease of contractility of the adult hearts 'recipients'. The preliminary injection of actinomycin D to adult rats prevented a developing decrease of the contractile function but did not induce any changes in the old. This permits to conclude that synthesis of the regulatory peptide factor promotes an economization and adaptation of the adult animal heart.


Effect of teriparatide on ligamentum flavum mesenchymal stem cells isolated from patients with ossification of the posterior longitudinal ligament.
Ossification of the posterior longitudinal ligament (OPLL) within the spinal canal sometimes leads to severe myelopathy. Teriparatide (TPD) is a recombinant human parathyroid hormone (PTH) (1-34), which promotes osteogenesis of mesenchymal stem cells (MSCs) via PTH 1 receptor (PTH1R). Although ligamentum flavum (LF)-MSCs from patients with OPLL have a high osteogenic potency, the effect of TPD on them remains unknown. In this study, we determined PTH1R expression in LF-MSCs from patients with OPLL and investigated whether TPD promotes osteogenic differentiation in them. First, LF-MSCs were isolated from patients with OPLL and cervical spondylotic myelopathy (CSM) (controls). Cultured LF-MSCs were treated with different concentrations of TPD on days 0, 7, and 14. On day 21, osteogenic gene expression was quantified. Mineralization was measured based on optical density after Alizarin Red S staining. LF-MSCs from both groups expressed PTH1R at the same level. TPD did not enhance osteogenic gene expression and mineralization in LF-MSCs from both groups. TPD did not promote the osteogenic differentiation of LF-MSCs from patients with OPLL. Thus, it may be safe for patients with OPLL. However, further confirmation of our results with in vivo studies is necessary.


Expression and regulation of the crucial plant-like ferredoxin of cyanobacteria.
The Synechocystis fedI gene (petF, ssl0020) was found to be strongly expressed under the negative control of H2O2 or heavy metals, and the positive control of light fluence (regulation dependent on active photosynthesis) or carbon availability [under the control of NdhR, the regulator of the ndh3 operon encoding NAD(P)H dehydrogenase subunits]. The basic and constitutive promoter (BP) of fedI extending from -62 to +25 (relative to the transcription start point) is weakly active, presumably because it harbours a long (30 bp) spacer between the two crucial motifs: the -10 box (5'-TAgtAT-3', -13 to -8) and the '-35' box (5'-TTGctA-3', -49 to -44). BP strength is strongly enhanced by the two upstream regions, -113 to -82 and -151 to -114, mediating the 30-fold constitutive stimulation and the fourfold light activation respectively. Three well-conserved transcriptional elements were characterized for the first time, namely the -19 box (5'-TTTT-3') that is essential to transcription, and the two twice repeated elements that are both critical to light induction: the TTGyCA-3' box (-35 to -30, and -125 to -120) and the 5'-ATTTyA-3' box (-55 to -50, and -134 to -129). That two of these light induction motifs (5'-TTGtCA-3', -35 to -30; 5'-ATTTcA-3', -55 to -50) occur in the constitutive BP promoter indicate that in the fedI gene light activation and transcription per se are closely interacting. Interestingly, the fedI gene from marine strains was found to lack the three transcriptional elements presently described, as well as the 5'-AGGA-3' Shine-Dalgarno sequence, which are all conserved among the fedI from non-marine strains.


Radiology of trauma to the wrist: dislocations, fracture dislocations, and instability patterns.
Radiologic changes from trauma to the carpus are described. Emphasis is placed upon pathomechanics and characterization of greater and lesser arc injury patterns. Finally, the various posttraumatic instability patterns of the wrist are discussed.


Single-cell molecular biology: implications for diagnosis and treatment of neurologic disease.
The continued discovery of basic pathologic mechanisms underlying neuropsychiatric illnesses will be critical to the development of improved diagnostic tests and more targeted therapeutic strategies. Molecular biological methods capable of evaluating gene expression at the single-cell level have great potential for advancing our knowledge of these processes. This review describes two techniques that are providing new insights into the intracellular regulation of ribonucleic acid trafficking and processing. These technologies promise to accelerate our understanding of both normal and abnormal molecular processes within neurons, and they have the potential for direct application to the study of human neurologic disease.


Differential regulation of the interferon induced gene ISG12A by serum from healthy and preeclamptic pregnancies.
Endothelial-cell dysfunction is central in the preeclamptic pathogenesis. Several components present in the blood of the preeclamptic mother are capable of mediating this dysfunction. We analyzed the regulation of the ISG12A gene by serum from the third trimester, to elucidate the role of type 1 interferon ISGs late in both healthy and preeclamptic pregnancies. The ISG12A transcription was up-regulated by serum from healthy pregnant women, but not by preeclamptic serum in HeLa and human umbilical vein endothelial cells (HUVEC). However, the ISG12A up-regulation by healthy pregnancy serum was not due to a general type 1 interferon response, since 6-16 and OAS1 were not up-regulated similarly. Also, the up-regulation of ISG12A was independent of the interferon-alpha receptor 2, but dependent on STAT1. Stimulation with folic acid alone or in combination with preeclamptic serum up-regulated ISG12A and 6-16. We conclude that type 1 interferon is not increased in third trimester serum, neither from healthy nor preeclamptic pregnancies. However, since ISG12A mRNA is up-regulated in healthy pregnancies, the ISG12A protein might take part in maintaining endothelial stability, as this function is lacking in preeclamptic pregnancies. Folic acid may ameliorate endothelial cell stability in preeclampsia by up-regulating ISG12A.


Population regulation of Serengeti Wildebeeest: a test of the food hypothesis.
The food hypothesis proposes that density dependent mortality regulates populations through food shortage. For Serengeti wildebeest, we found an empirical relationship between dry season adult mortality rate, density and food supply. This relationship predicted that: (1) the population would stabilize between 1.0 and 1.5 million animals, (2) dry season mortality would be density dependent and sufficient to account for the levelling off of this large ungulate population. Recent observations have tested and confirmed these predictions.


[Painful cutaneous leiomyosarcoma].
Leiomyosarcomas are derived from smooth muscles and only rarely involve the skin. A 73-year-old male presented with progressive tumor painful on the chest which had been present for 3 years and was tender to palpation, a finding more often associated with benign leiomyomas. immunohistochemical staining demonstrated multiple nerve fibers entrapped by atypical myofibrils, perhaps explaining the tenderness. Since 1996, we have excised five painless cutaneous leiomyosarcomas, in which entrapped nerves could not be demonstrated.


Role of extra-articular procedure.
This article describes the 1993 role of extra-articular procedures in the treatment of anterior cruciate-deficient knees. Twenty years ago, most operative effort was concentrated on elimination of the pivot shift phenomenon. Newer operative reconstructions made most of the advantages attributed to extraarticular procedures (shorter operating room time, less soft tissue injury, shorter postoperative rehabilitation) no longer true.


A simple and rapid radioimmunoassay for human interleukin-6.
Studies were undertaken to develop a sensitive radioimmunoassay for human IL-6 using commercially available reagents. The assay utilized a polyclonal rabbit anti-IL-6 binding to iodinated IL-6; the reaction was carried out in solution and the immune complexes were precipitated using anti-rabbit IgG coupled to magnetic particles. Using a format where sample IL-6 was added in advance of the radiolabelled IL-6, the working range of the assay was found to fall between 0.1 and 10 ng/ml (IC50 around 1 ng/ml) for a 50 microliters sample volume, and was run overnight. However, the assay could be completed in 2 h, using a direct competitive format when less sensitivity is required (working range 1.5-25 ng/ml, IC50 12 ng/ml). The RIA correlated directly with a standard functional assay for IL-6 (proliferation of the mouse hybridoma B9.9) for both recombinant IL-6 and natural IL-6 from human monocytes. The total assay variance was less than 12% and no reactivity with interleukins-1-5 was found. Using the RIA, IL-6 produced in culture by human monocytes in response to various stimuli (LPS, IL-1, dibutyryl cAMP) was measured.


Two different clinical entities of small vessel occlusion in TOAST classification.
Small deep infarcts might be classified into 2 types: lacunar and branchatheromatous infarcts. However, since their initial description, small deep infarcts were still regarded as the same category of the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, small vessel occlusion (SVO). We hypothesized that the 2 types of small deep infarcts would be distinct clinical entities. This study was conducted to investigate the clinical characteristics in the 2 groups of patients according to lesion pattern and combined atherosclerotic diseases. We included patients with small deep infarcts in the subcortical area. The patients were divided into 2 groups: (1) island lesions and (2) linear lesions on coronal diffusion weighted imaging. The status of the relevant artery was categorized as no stenosis, non-significant (<50% of luminal narrowing) and significant (≥ 50% of luminal narrowing). We compared the clinical and imaging characteristics of two lesion types according to various arterial status. This study analyzed a total of 248 patients. Independent factors for island lesions on coronal DWI were male, severe leukoaraiosis, microbleeds, abnormal glycated hemoglobin (HbA1C), and abnormal estimated glomerular filtration ratio (eGFR) adjusted by age, sex, and initial National Institutes of Health Stroke Scale. In addition, in patients without significant relevant arterial stenosis, island lesion patterns were more frequently associated with severe periventricular white matter hyperintensity, diabetes mellitus, abnormal eGFR and abnormal HbA1C than linear lesion patterns. This study demonstrated that SVO of TOAST classifications had different imaging and clinical characteristics according to the lesion patterns of coronal imaging. It suggests that two types of SVO should be regarded as the different categories of stroke classification.


Clinical characteristics and prognosis of 69 cases of neonatal appendicitis.
Neonatal appendicitis (NA) is a rare and potentially fatal neonatal disease. However, misdiagnosis is common owing to atypical clinical manifestations and non-specific laboratory tests. The aim of this study was to summarize the clinical characteristics, treatments, and prognoses of infants with NA. This retrospective analysis included 69 patients diagnosed with NA admitted to Beijing Children's Hospital between 1980 and 2019. The patients were divided into surgical and non-surgical groups based on whether surgery was performed. Their clinical characteristics were analyzed using the chi-square test, t-test, or the Mann-Whitney U test. The study included 47 males and 22 females with NA. The primary symptoms were abdominal distension (n = 36, 52.2%), fever (n = 19, 27.5%), refusal to feed or decreased feeding (n = 16, 23.2%), and vomiting (n = 15, 21.7%). Sixty-five patients underwent abdominal ultrasound examinations; 43 had definite appendiceal abnormalities, 10 had right lower abdominal adhesive masses, and 14 had neonatal enterocolitis manifestations. Twenty-nine and 40 patients were in the surgical and non-surgical groups, respectively. No statistically significant differences were observed between the groups regarding sex, age at onset, birth weight, admission weight, or hospitalization time. However, parenteral nutrition was prolonged in the surgical group (P = 0.001). Additionally, two patients (2.9%) died. NA is a rare neonatal disease with atypical clinical manifestations. Abdominal ultrasonography may aid in the diagnosis. Similarly, appropriate treatment can improve the prognosis.


Neonatal circumcision and penile dorsal nerve block--a painless procedure.
Circumcision is the only surgical procedure, excluding cord-clamping and cutting, which is routinely performed on normal, healthy newborn infants, usually during the first two or three days of life. Apparently no analgesic technique has been described nor suggested in association with neonatal circumcision. This is the first description of a technique of penile dorsal nerve block in neonatal circumcision. In 52 instances using 0.5 ml of 1% lidocaine (Xylocaine) and a 1.2 cm number 27 gauge needle PDNB was successfully and safely introduced with consistent elimination of pain, rendering NC a painless surgical procedure.


Nonactivated Protein C in the Treatment of Neonatal Sepsis: A Retrospective Analysis of Outcome.
Previously, we found that plasma protein C (PC) activity ≤10% significantly increased the probability of the occurrence of death during neonatal sepsis. Accordingly, if the activity of plasma PC declined during the course of sepsis to ≤10%, we administered a nonactivated PC zymogen to increase a PC activity. The aim of that retrospective analysis was to explore treatment effects of PC zymogen supplementation in septic infants, with plasma PC activity ≤10%. A database was used to locate 85 newborns treated with PC from among 458 analyzed infants with confirmed sepsis. The median birth weight and gestational age of treated infants were, respectively, 1010.0 g and 29 weeks. In 47 infants, early-onset sepsis developed, whereas in 38 neonates, late-onset sepsis was recognized. PC was given as a single dose of 200 IU/kg. Among 458 septic patients, death occurred in 19 newborns (4.2%), exclusively in infants with plasma PC activity ≤10%. In 15 infants, death occurred in the course of early-onset sepsis and 4 newborns died of late-onset sepsis (early-onset sepsis vs. late-onset sepsis; P = 0.036; χ with the Yates correction). An increased risk of death in septic neonates with plasma PC activity ≤10% suggests the necessity for its evaluation and possibility of supplementation of PC zymogen.


Transneuronal retrograde degeneration of retinal ganglion cells after damage to striate cortex in macaque monkeys: selective loss of P beta cells.
We examined the retinae of two monkeys whose left striate cortex had been removed eight years previously and compared the transneuronally degenerated hemiretina of each eye with the normal hemiretina, and with the retinae of normal monkeys. All retinae were prepared as whole mounts. One from each pair was stained with Cresyl Violet; the other was reacted for horseradish peroxidase two days after placing pellets of the enzyme in the optic nerve. Measurements of ganglion cell density in the Nissl-stained retina of the contralateral right eye showed that approximately 80% of retinal ganglion cells were missing in the central 30 degrees of the degenerated hemiretinae. More peripherally the percentage loss was less extensive. Measurements of cell soma size and dendritic field size of peroxidase-labelled classified surviving cells in the degenerated temporal hemiretina of the ipsilateral eye showed them to be morphologically normal. In comparison with the normal hemiretina, however, the mean soma size at three selected eccentricities was larger than normal, suggesting selective loss of smaller ganglion cells. Classification of peroxidase-labelled ganglion cells in the normal and degenerated hemiretinae revealed that the population of P beta cells was reduced by as much as 85% in the degenerated region. There was comparable change in the density of P alpha or P gamma cells. The degeneration of the great majority of P beta cells, which are believed to be the morphological substrate of ganglion cells with small and colour-opponent receptive fields, must set limits on the visual sensitivity and discrimination that survive damage to striate cortex.


A circadian study of liver antioxidant enzyme systems of female Fischer-344 rats subjected to dietary restriction for six weeks.
We examined the influences of dietary restriction (DR) on the circadian profile of liver catalase (CAT), glutathione peroxidase (GPx), and interacting systems required for removal of H2O2 (support systems), in 18-week old female Fischer 344 rats fed 60% of their ad libitum (AL) diet for six weeks. Food was presented to the DR animals during the early light-span. Regardless of diet, enzyme levels were generally consistent with circadian patterns. In CR animals, maximum activities often occurred at the time of food presentation. CAT and GPx activities generally were significantly higher in DR animals than in AL animals at the time of feeding. When assessing glucose-6-phosphate dehydrogenase (G6PDH) activity using saturating substrate (NADP(+)) concentrations, higher activities were seen at all times of day in the AL animals; however, when activity was measured in the presence of lower (i.e., physiologic) NADP(+) concentrations, the reverse was true. In contrast, glutathione reductase (GR) activity was not influenced by DR. Cytosolic levels of NADPH peaked and were higher in DR than in AL rodents prior to feeding. NADH levels were not influenced by diet, but did manifest a significant circadian pattern with a maximum occurring toward the middle of the dark span. These data suggest that even at a young age and following only a relatively brief duration of DR, there exists an enhanced enzymatic capability in rats subjected to DR to remove free radicals generated as a consequence of normal oxidative metabolism. Further, these data support emerging trends suggesting metabolic regulation of antioxidant defense systems in response to free radical generation.


A case of choroidal neovascular membrane in 6-year-old boy with juvenile idiopathic arthritis.
The purpose of this study is to report a case of choroidal neovascular membrane (CNVM) in a patient of juvenile idiopathic arthritis (JIA). The design of this study is an interventional case report. A 6-year-old boy, a known patient of JIA, presented with a complaint of redness and ocular pain with mild diminution of vision in his left eye. Fundus examination revealed a CNVM with retinal thickening and subretinal fluid which was confirmed on OCT. Treatment with intravitreal injection of anti-VEGF (ranibizumab) and oral immunosuppressive showed resolution of the CNVM. The result of this study is a successful treatment of CNVM with a single anti-VEGF injection and systemic immunosuppression. Although a rare complication, CNVM can occur in patients with JIA.


[The application and research progress of in-situ tissue engineering technology in bone and cartilage repair].
To review the application and research progress of in-situ tissue engineering technology in bone and cartilage repair. The original articles about in-situ tissue engineering technology in bone and cartilage repair were extensively reviewed and analyzed. In-situ tissue engineering have been shown to be effective in repairing bone defects and cartilage defects, but biological mechanisms are inadequate. At present, most of researches are mainly focused on animal experiments, and the effect of clinical repair need to be further studied. In-situ tissue engineering technology has wide application prospects in bone and cartilage tissue engineering. However, further study on the mechanism of related cytokines need to be conducted.


Effects of nutrients on the production of AK-111-81 macrolide antibiotic by Streptomyces hygroscopicus.
The influence of different carbon and nitrogen sources on the production of AK-111-81 nonpolyenic macrolide antibiotic by Streptomyces hygroscopicus 111-81 was studied. Substitution of glucose with lactose or glycerol significantly affected maximal antibiotic AK-111-81 productivity as the growth rate was close to that of the basal fermentation medium. Addition of ammonium succinate to the fermentation medium markedly increased the antibiotic productivity as the growth rate was low. Divalent ions as Mn2+, Cu2+, Fe2+ stimulated AK-111-81 antibiotic biosynthesis. These results allow us to develop a new fermentation medium showing 6-fold increase of AK-111-81 antibiotic formation compared with the basal fermentation medium.


Concentrations and assessment of exposure to siloxanes and synthetic musks in personal care products from China.
We investigated the concentrations and profiles of 15 siloxanes (four cyclic siloxanes, D(4)-D(7); 11 linear siloxanes, L(4)-L(14)), four synthetic musks (two polycyclic musks, HHCB and AHTN; two nitro musks, MX and MK), and HHCB-lactone, in 158 personal care products marketed in China. Siloxanes were detected in 88% of the samples analyzed, at concentrations as high as 52.6 mg g(-1); Linear siloxanes were the predominant compounds. Among synthetic musks, more than 80% of the samples contained at least one of these compounds, and their total concentrations were as high as 1.02 mg g(-1). HHCB was the predominant musk in all of the samples analyzed, on average, accounting for 52% of the total musk concentrations. Based on the median concentrations of siloxanes and musks and the average daily usage amounts of consumer products, dermal exposure rates in adults were calculated to be 3.69 and 3.38 mg d(-1) for siloxanes and musks, respectively.


Pilocarpine-induced status epilepticus causes N-methyl-D-aspartate receptor-dependent inhibition of microsomal Mg(2+)/Ca(2+) ATPase-mediated Ca(2+) uptake.
Status epilepticus is associated with sustained and elevated levels of cytosolic Ca(2+). To elucidate the mechanisms associated with changes of cytosolic Ca(2+) after status epilepticus, this study was initiated to evaluate the effect of pilocarpine-induced status epilepticus on Mg(2+)/Ca(2+) ATPase-mediated Ca(2+) uptake in microsomes isolated from rat cortex, because the Ca(2+) uptake mechanism plays a major role in regulating intracellular Ca(2+) levels. The data demonstrated that the initial rate and overall Ca(2+) uptake in microsomes from pilocarpine treated animals were significantly inhibited compared with those in microsomes from saline-treated control animals. It was also shown that the inhibition of Ca(2+) uptake caused by status epilepticus was not an artifact of increased Ca(2+) release from microsomes, selective isolation of damaged microsomes from the homogenate, or decreased Mg(2+)/Ca(2+) ATPase protein in the microsomes. Pretreatment with the NMDA antagonist dizocilpine maleate blocked status epilepticus-induced inhibition of the initial rate and overall Ca(2+) uptake. The data suggest that inhibition of microsomal Mg(2+)/Ca(2+) ATPase Ca(2+) uptake is involved in NMDA-dependent deregulation of cytosolic Ca(2+) homeostasis associated with status epilepticus.


Evaluation of theranostic perspective of gold-silica nanoshell for cancer nano-medicine: a numerical parametric study.
Using gold-silica nanoshell as a reference nano-agent, this work has performed preliminary numerical parametric study to investigate the feasibility and if feasible the efficiency of using a single nano-agent to achieve theranostic goals. In total, seven generics of gold-silica nanoshells have been tested including the R[50,10] (radius of the silica core is 50 nm and thickness of the gold shell is 10 nm), R[40,15], R[55,25], R[40,40], R[75,40], R[104,23], and R[154,24] nanoshells. A planar tissue model has been constructed as the platform for parametric study. For mathematical modeling, radiant transport equation (RTE) has been applied to describe the interactions among laser lights, the hosting tissue, and the hosted nanoshells and Penne's bio-heat equation has been applied to describe the hyperthermia induced by such interactions. Effects of different nanoshell generics on the diffuse reflectance signal and hyperthermia temperature transition have been simulated, basing on which the potential of a certain nanoshell generic as theranostic nano-agent has been evaluated. It has been found that it is highly feasible for gold-silica nanoshells to be engineered for theranostic purpose and nanoshell generics that are preferentially scattering should be explored for good theranostic candidates. On the condition that nanoshell generic with the right optical properties has been located, a moderate nanoshell retention in the target tissue site is already sufficient to induce effective theranostic effects, which indicates that theranostic nano-medicine might not have a stringent requirement for the delivery technique. Among nanoshells that have been tested, the R[55,25] nanoshell seems to be a promising candidate as theranostic nano-agent. Further testing on it is highly recommended. Nanoshells that are preferentially absorbing such as the R[50,10] and R[40,15] nanoshells are efficient photothermal agent and could be used for therapeutic purpose only. However, it is not recommended that preferentially absorbing nanoshells being used for theranostic purpose due to possible negative effects such nanoshells might bring to the diffuse reflectance signal.


Percutaneous gastric tube placement: Comparison of trans-abdominal and trans-oral approach in patients with chronic ascites.
The purpose of this study was to compare the trans-abdominal (TA) and trans-oral (TO) approaches for fluoroscopic-guided gastrostomy tube placement in patients with chronic ascites. A 10-year review of clinical imaging and medical records at a single institution identified 29 patients with chronic recurrent ascites who underwent gastrostomy (GT) or gastro-jejunostomy tube (GJT) placement. In 22 patients (18 women, 4 men) aged from 22 to 76 years of age (mean age, 57.7±13.1 years), a GT or GJT was placed with the TO approach, and in 7 (7 women) from 31 to 86 years of age (mean age, 63±16.8 years) with the TA approach. Technical success was 100% in both groups with one (1/22; 5%) immediate complication in the TO group. Fluoroscopy time was significantly greater in the TO group (P=0.002). Leakage of ascites was significantly more frequent in the TA group (P=0.04). There was no significant difference in bleeding or inflammation (P=0.14 and P=0.43, respectively). The cumulative tract related complication rate was significantly greater in the TA group (P=0.03). Fluoroscopy times and the overall incidence of tract-related complications, in particular leakage of ascites from the stoma, are more frequent in patients in chronic ascites who underwent TA gastrostomy tube placement compared to those who underwent TO placement.


Proton relaxation enhancement by manganese(III)TPPS4 in a model tumor system.
Managanese(III)tetraphenylporphine sulfonate [Mn(III)TPPS4] has been investigated as a tumor specific paramagnetic contrast agent for magnetic resonance imaging (MRI) of L1210 solid tumors in mice. Mn(III)TPPS4 was found to clear rapidly from the blood and concentrate in the kidneys, tumor and liver. Although relatively high ratios of tumor to normal tissues could be obtained (e.g., greater than 90 for tumor/muscle), the kidneys were found to have the highest concentration of the metalloporphyrin at all doses and time periods tested. A significant decrease in the longitudinal relaxation time was measured for excised tissues (kidney, tumor, liver, muscle) from mice that were treated with Mn(III)TPPS4. A linear correlation was observed between the longitudinal relaxation rate determined for L1210 tumor and the corresponding concentration of Mn(III)TPPS4 found at various injected doses and time intervals between the injection and analysis. A small animal radiofrequency receiver coil designed for use with a 0.15-T clinical imager was employed to evaluate the ability of Mn(III)TPPS4 to selectively increase the signal intensity of the implanted L1210 tumor. The images show a conspicuous enhancement in the contrast between the tumor and adjacent tissue upon treatment with this agent. The results indicate that Mn(III)TPPS4 is a useful prototype paramagnetic metalloporphyrin MRI contrast agent with a significant affinity for the L1210 tumor.


Quantitative and Systems-Based Approaches for Deciphering Bacterial Membrane Interactome and Gene Function.
High-throughput genomic and proteomic methods provide a concise description of the molecular constituents of a cell, whereas systems biology strives to understand the way these components function as a whole. Recent developments, such as genome editing technologies and protein epitope-tagging coupled with high-sensitivity mass-spectrometry, allow systemic studies to be performed at an unprecedented scale. Available methods can be successfully applied to various goals, both expanding fundamental knowledge and solving applied problems. In this review, we discuss the present state and future of bacterial cell envelope interactomics, with a specific focus on host-pathogen interactions and drug target discovery. Both experimental and computational methods will be outlined together with examples of their practical implementation.


The effects of initial population density on the competition for limiting nutrients in two freshwater algae.
Eighteen long-term competition experiments were performed on two freshwater algae, a blue-green alga, Anabaena flos-aquae, and a diatom, Cyclotella sp., under controlled light and temperature conditions and various nutrient limitations. As predicted, Anabaena displaced Cyclotella when nitrate was in short supply to both species, whereas Cyclotella became dominant when both species were phosphate-limited. The two species stably coexisted when phosphate and silicate were limited. Anabaena either displaced or coexisted with Cyclotella when nitrate and phosphate or nitrate, phosphate and silicate were limited, depending on their initial density ratios. This study revealed strong effects of initial population densities on the outcomes of algal competition for limiting nutrients.


Sodium handling in pediatric patients on maintenance dialysis.
The risk of cardiovascular disease remains exceedingly high in pediatric patients with chronic kidney disease stage 5 on dialysis (CKD 5D). Sodium (Na+) overload is a major cardiovascular risk factor in this population, both through volume-dependent and volume-independent toxicity. Given that compliance with a Na+-restricted diet is generally limited and urinary Na+ excretion impaired in CKD 5D, dialytic Na+ removal is critical to reduce Na+ overload. On the other hand, an excessive or too fast intradialytic Na+ removal may lead to volume depletion, hypotension, and organ hypoperfusion. This review presents current knowledge on intradialytic Na+ handling and possible strategies to optimize dialytic Na+ removal in pediatric patients on hemodialysis (HD) and peritoneal dialysis (PD). There is increasing evidence supporting the prescription of lower dialysate Na+ in salt-overloaded children on HD, while improved Na+ removal may be achieved in children on PD with an individual adaptation of dwell time and volume and with icodextrin use during the long dwell.


Probing domain swapping for the neuronal SNARE complex with electron paramagnetic resonance.
Highly conserved soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) proteins control membrane fusion at synapses. The target plasma membrane-associated SNARE proteins and the vesicle-associated SNARE protein assemble into a parallel four-helix bundle. Using a novel EPR approach, it is found that the SNARE four-helix bundles are interconnected via domain swapping that is achieved by substituting one of the two SNAP-25 helices with the identical helix from the second four-helical bundle. Domain swapping is likely to play a role in the multimerization of the SNARE complex that is required for successful membrane fusion. The new EPR application employed here should be useful to study other polymerizing proteins.


Exosomal Delivery of AntagomiRs Targeting Viral and Cellular MicroRNAs Synergistically Inhibits Cancer Angiogenesis.
Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated cancer characterized by a high degree of recurrence, angiogenesis, and metastasis. The importance of alternative pro-angiogenesis pathways including viral factors has emerged after decades of directly targeting various signaling components. Using NPC as a model, we identified an essential oncogenic pathway underlying angiogenesis regulation that involves the inhibition of a tumor suppressor, Spry3, and its downstream targets by EBV-miR-BART10-5p (BART10-5p) and hsa-miR-18a (miR-18a). Overexpression of EBV-miR-BART10-5p and hsa-miR-18a strongly promotes angiogenesis in vitro and in vivo by regulating the expression of VEGF and HIF1-α in a Spry3-dependent manner. In vitro or in vivo treatment with iRGD-tagged exosomes containing antagomiR-BART10-5p and antagomiR-18a preferentially suppressed the angiogenesis and growth of NPC. Our findings first highlight the role of EBV-miR-BART10-5p and oncogenic hsa-miR-18a in NPC angiogenesis and also shed new insights into the clinical intervention and therapeutic strategies for nasopharyngeal carcinoma and other virus-associated tumors.


Results after intraoperative open and endovascular revascularization of acute mesenteric ischemia requiring a laparotomy.
Acute mesenteric ischemia (AMI) is a dreaded condition with a difficult diagnosis and high mortality. Due to different baseline situations, the frequently performed comparison between endovascular and open surgical treatment is interfered with selection bias. The purpose of this study was to review outcomes in AMI treatment with an open or endovascular approach in association with laparotomy and to evaluate the endovascular-first strategy in similar clinical situations. The clinical data of 74 patients treated for AMI from 2007 to 2021 were retrospectively reviewed and compared. In-hospital mortality was appointed as the primary study endpoint. Risk factors for mortality were identified by using univariate and multivariate analysis. In total, 61 patients (82%) were treated open surgically (OT) and, 13 patients (18%) with an endovascular approach (ET) in combination with laparatomy. The etiology of AMI was 49% arteriosclerotic and 51% thromboembolic occlusions. The total in-hospital mortality manifested at 43% (n =32) (OT 41% vs. ET 53.8%; P=0.54). As independent risk factors for in-hospital mortality, pneumatosis intestinalis (P=0.01), increased lactate concentration (P=0.04), and ischemic intestinal sections (P=0.01) were identified. Additionally, on univariate analysis patient age, congestive heart failure (> NYHA II) and atrial fibrillation were related with higher mortality. Morbidity and mortality of AMI remains at a high level. Conventional open or intraoperative endovascular therapy achieved similar results in patients with indication for laparotomy. Advanced disease stage with ischemic intestinal sections at presentation and cardiovascular comorbidities were associated with adverse outcome.


On 2D-FTIR-XRF microscopy - A step forward correlative tissue studies by infrared and hard X-ray radiation.
Correlative Fourier Transform Infra-Red (FTIR) and hard X-Ray Fluorescence (XRF) microscopy studies of thin biological samples have recently evolved as complementary methods for biochemical fingerprinting of animal/human tissues. These are seen particularly useful for tracking the mechanisms of neurological diseases, i.e., in Alzheimer/Parkinson disease, in the brain where mishandling of trace metals (Fe, Cu, Zn) seems to be often associated with ongoing damage to molecular components via, among others, oxidative/reductive stress neurotoxicity. Despite substantial progress in state-of-the-art detection and data analysis methods, combined FTIR-XRF experiments have never benefited from correlation and co-localization analysis of molecular moieties and chemical elements, respectively. We here propose for the first time a completely novel data analysis pipeline, utilizing the idea of 2D correlation spectrometry for brain tissue analysis. In this paper, we utilized combined benchtop FTIR - synchrotron XRF mapping experiments on thin brain samples mounted on polypropylene membranes. By implementing our recently developed Multiple Linear Regression Multi-Reference (MLR-MR) algorithm, along with advanced image processing, artifact-free 2D FTIR-XRF spectra could be obtained by mitigating the impact of spectral artifacts, such as Etalon fringes and mild scattering Mie-like signatures, in the FTIR data. We demonstrated that the method is a powerful tool for co-localizing and correlating molecular arrangements and chemical elements (and vice versa) using visually attractive 2D correlograms. Moreover, the methods' applicability for fostering the identification of distinct (biological) materials, involving chemical elements and molecular arrangements, is also shown. Taken together, the 2D FTIR-XRF method opens up for new measures for in-situ investigating hidden complex biochemical correlations, and yet unraveled mechanisms in a biological sample. This step seems crucial for developing new strategies for facilitating the research on the interaction of metals/nonmetals with organic components. This is particularly important for enhancing our understanding of the diseases associated with metal/nonmetal mishandling.


Research Progress on Mono-ADP-Ribosyltransferases in Human Cell Biology.
ADP-ribosylation is a well-established post-translational modification that is inherently connected to diverse processes, including DNA repair, transcription, and cell signaling. The crucial roles of mono-ADP-ribosyltransferases (mono-ARTs) in biological processes have been identified in recent years by the comprehensive use of genetic engineering, chemical genetics, and proteomics. This review provides an update on current methodological advances in the study of these modifiers. Furthermore, the review provides details on the function of mono ADP-ribosylation. Several mono-ARTs have been implicated in the development of cancer, and this review discusses the role and therapeutic potential of some mono-ARTs in cancer.


Distinct receptors underlie glutamatergic signalling in inspiratory rhythm-generating networks and motor output pathways in neonatal rat.
Despite the enormous diversity of glutamate (Glu) receptors and advances in understanding recombinant receptors, native Glu receptors underlying functionally identified inputs in active systems are poorly defined in comparison. In the present study we use UBP-302, which antagonizes GluR5 subunit-containing kainate (KA) receptors at < or = 10 microm, but other KA and AMPA receptors at > or = 100 microm, and rhythmically active in vitro preparations of neonatal rat to explore the contribution of non-NMDA receptor signalling in rhythm-generating and motor output compartments of the inspiratory network. At 10 microm, UBP-302 had no effect on inspiratory burst frequency or amplitude. At 100 microm, burst amplitude recorded from XII, C1 and C4 nerve roots was significantly reduced, but frequency was unaffected. The lack of a frequency effect was confirmed when local application of UBP-302 (100 microm) into the pre-Bötzinger complex (preBötC) did not affect frequency but substance P evoked a 2-fold increase. A UBP-302-sensitive (10 microm), ATPA-evoked frequency increase, however, established that preBötC networks are sensitive to GluR5 activation. Whole-cell recordings demonstrated that XII motoneurons also express functional GluR5-containing KA receptors that do not contribute to inspiratory drive, and confirmed the dose dependence of UBP-302 actions on KA and AMPA receptors. Our data provide the first evidence that the non-NMDA (most probably AMPA) receptors mediating glutamatergic transmission within preBötC inspiratory rhythm-generating networks are pharmacologically distinct from those transmitting drive to inspiratory motoneurons. This differential expression may ultimately be exploited pharmacologically to separately counteract depression of central respiratory rhythmogenesis or manipulate the drive to motoneurons controlling airway and pump musculature.


Cancer detection and complications of transperineal prostate biopsy with antibiotics when indicated.
To describe the prostate cancer (PCa) detection rate, including clinically significant prostate cancer (csPCa), in a large cohort of patients who underwent transperineal ultrasonography-guided systematic prostate biopsy (TPB-US) using a probe-mounted transperineal access system, with magnetic resonance imaging (MRI) cognitive fusion in case of a Prostate Imaging-Reporting and Data System grade 3-5 lesion, under local anaesthesia in an outpatient setting. Additionally, to compare the incidence of procedure-related complications with a cohort of patients undergoing transrectal ultrasonography-guided (TRB-US) and transrectal MRI-guided biopsies (TRB-MRI). This was an observational cohort study in men who underwent TPB-US prostate biopsy in a large teaching hospital. For each participant, prostate-specific antigen level, clinical tumour stage, prostate volume, MRI parameters, number of (targeted) prostate biopsies, biopsy International Society of Uropathology (ISUP) grade and procedure-related complications were assessed. csPCa was defined as ISUP grade ≥2. Antibiotic prophylaxis was only given in those with an increased risk of urinary tract infection. A total of 1288 TPB-US procedures were evaluated. The overall detection rate for PCa in biopsy-naive patients was 73%, and for csPCa it was 63%. The incidence of hospitalization was 1% in TPB-US (13/1288), compared to 4% in TRB-US (8/214) and 3% in TRB-MRI (7/219; P = 0.002). Contemporary combined systematic and target TPB-US with MRI cognitive fusion is easy to perform in an outpatient setting, with a high detection rate of csPCa and a low incidence of procedure-related complications.


Randomised Controlled Clinical Study of Injection Caroverine and Ginkgo Biloba Extract in Cochlear Synaptic Tinnitus.
Tinnitus, also known as phantom auditory perception, is an annoying symptom and 13-17% of population reports bothersome tinnitus. Cochlear synaptic tinnitus is the most common type. Many treatments have been tried but none is yet considered to be well established. To evaluate effect of Inj.Caroverine and Ginkgo Biloba extract in cochlear synaptic tinnitus in terms of improving tinnitus grading, tinnitus matching and quality of life of patient. It is Randomised controlled study, conducted in department of ENT, on 86 patients, who met inclusion criteria, divided into 4 groups. Gr1-Inj Caroverin, Gr2-Inj Placebo, Gr3-Ginkgo Biloba extract, Gr4-Placebo as extract. A single dose infusion of caroverine immediately improves tinnitus grading and matching and provides immediate relief in reducing severity of tinnitus in 54.54% cases but improvement was not sustained in caroverine group at 3 month and 6 month follow-up after infusion. Ginkgo biloba also is effective in improving tinnitus grading and matching in 31.8% cases and improvement was sustained in ginkgo biloba group even after 3 month of cessation of treatment i.e. at 6 month follow-up. It is suggested that Inj.Caroverine as intravenous infusion should be given in severe cases of tinnitus to reduce its severity immediately and then patient should be put on Tab.Ginkgo biloba for a period of 3 months to provide sustained and long lasting relief. Thus combination therapy of Inj.Caroverin and Tab.Ginkgo Biloba, appropriately tailored to the need of patient will provide better results in greater majority of patients.