Identification of hepatocellular carcinoma-related subtypes and development of a prognostic model: a study based on ferritinophagy-related genes.
Hepatocellular carcinoma still has a high incidence and mortality rate worldwide, and further research is needed to investigate its occurrence and development mechanisms in depth in order to identify new therapeutic targets. Ferritinophagy is a type of autophagy and a key factor in ferroptosis that could influence tumor onset and progression. Although, the potential role of ferritinophagy-related genes (FRGs) in liver hepatocellular carcinoma (LIHC) is unknown. Single-cell RNA sequencing (scRNA-seq) data of LIHC were obtained from the Gene Expression Omnibus (GEO) dataset. In addition, transcriptome and clinical follow-up outcome data of individuals with LIHC were extracted from the The Cancer Genome Atlas (TCGA) dataset. FRGs were collected through the GeneCards database. Differential cell subpopulations were distinguished, and differentially expressed FRGs (DEFRGs) were obtained. Differential expression of FRGs and prognosis were observed according to the TCGA database. An FRG-related risk model was constructed to predict patient prognosis by absolute shrinkage and selection operator (LASSO) and COX regression analyses, and its prognosis predictive power was validated. Ultimately, the association between risk score and tumor microenvironment (TME), immune cell infiltration, immune checkpoints, drug sensitivity, and tumor mutation burden (TMB) was analyzed. We also used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to validate the expression of key genes in normal liver cells and liver cancer cells. We ultimately identified 8 cell types, and 7 differentially expressed FRGs genes (ZFP36, NCOA4, FTH1, FTL, TNF, PCBP1, CYB561A3) were found among immune cells, and we found that Monocytes and Macrophages were closely related to FRGs genes. Subsequently, COX regression analysis showed that patients with high expression of FTH1, FTL, and PCBP1 had significantly worse prognosis than those with low expression, and our survival prediction model, constructed based on age, stage, and risk score, showed better prognostic prediction ability. Our risk model based on 3 FRGs genes ultimately revealed significant differences between high-risk and low-risk groups in terms of immune infiltration and immune checkpoint correlation, drug sensitivity, and somatic mutation risk. Finally, we validated the key prognostic genes FTH1, FTL, using qRT-PCR, and found that the expression of FTH1 and FTL was significantly higher in various liver cancer cells than in normal liver cells. At the same time, immunohistochemistry showed that the expression of FTH1, FTL in tumor tissues was significantly higher than that in para-tumor tissues. This study identifies a considerable impact of FRGs on immunity and prognosis in individuals with LIHC. The collective findings of this research provide new ideas for personalized treatment of LIHC and a more targeted therapy approach for individuals with LIHC to improve their prognosis.


Isolation of single-copy-sequence clones from a yeast artificial chromosome library of randomly-sheared Arabidopsis thaliana DNA.
We describe the construction of a yeast artificial chromosome (YAC) library from the Arabidopsis thaliana genome. Randomly sheared high molecular weight source DNA was extracted from frozen, ground leaf tissue and blunt-end-ligated to the vector pYAC3. By size-fractionating the ligation products, we achieved an average clone size of 150 kb. Approximately 6% of the YACs contained inserts from the chloroplast genome. We screened clones equivalent to greater than four A. thaliana haploid nuclear genomes and isolated YACs homologous to five single-copy-sequence probes. The library should be useful for chromosome walking and genome mapping experiments. In addition, the approach used for its construction should be applicable to other higher plant species.


Assessment of spatial variation in breast cancer-specific mortality using Louisiana SEER data.
Previous studies suggest spatial differences in mortality for many types of cancer, including breast cancer. Identifying explanations for these spatial differences results in a better understanding of what leads to longer survival time. We used a Bayesian accelerated failure time model with spatial frailty terms to investigate potential spatial differences in breast cancer mortality following breast cancer diagnosis using 2000-2013 Louisiana SEER data. There are meaningful spatial differences in breast cancer mortality across the parishes of Louisiana, even after adjusting for known demographic and clinical risk factors. For example, the average survival time of a woman diagnosed in Orleans parish was 1.51 times longer than that of a woman diagnosed in Terrebonne parish. Additionally, there is evidence to suggest shorter survival times in lower income parishes along the Red and Mississippi Rivers, as well as parishes with lower socioeconomic status, less access to care and fresh food, worse quality of care, and more workers in certain industries. The addition of spatial frailties to account for an individual's geographic location is useful when analyzing breast cancer mortality data. Our findings suggest that survival following breast cancer diagnosis could potentially be improved if socioeconomic status differences were addressed, healthcare improved in quality and became more accessible, and certain industrial situations were improved for individuals diagnosed in parishes identified as having shorter average survival times.


Social comorbidities? A qualitative study mapping syndemic theory onto gender-based violence and co-occurring social phenomena among Brazilian women.
Gender-based violence is a globally recognized social problem impacting women and girls worldwide. Intimate partner violence (IPV) represents the most common form of gender-based violence. Among the countries grappling with gender-based violence is Brazil, which has identified high rates of IPV along with co-occurring social conditions such as adverse childhood experiences, community violence, and substance use. While the syndemic framework has incorporated IPV into understandings of HIV and other diseases, none have explicitly applied syndemic framework to understand IPV and co-occurring social conditions -- referred to here as "social comorbidities" -- in the absence of a biological outcome. This study aims to: (1) Examine perspectives on violence and relevant social comorbidities (substance use, community violence, and childhood abuse) among women living in Santo André, São Paulo State, Brazil; and (2) Apply the syndemic framework to a set of social comorbidities among women living in Santo André, São Paulo State, Brazil. This thematic analysis applies a syndemic framework to 28 in-depth interviews with women in Santo André, Brazil. Interviews were recorded and transcribed verbatim in Portuguese. Our analysis examined themes relating to IPV, community violence, substance use, and other individual experiences and community issues using syndemics as an organizing framework (e.g. diseases, adverse interactions, disparity conditions, and enhanced disease transmission). Most participants described experiencing multiple social comorbidities including IPV, adverse childhood experiences, community violence, family violence, and substance use. Adverse interactions included increased financial conflicts, a sense of isolation, and increased severity of violence due to substance use. Long term enhanced "disease" progression included injury, increased mental health symptoms, femicide, and death. Our results suggest that using a syndemic framework to understand IPV in the context of social comorbidities could be useful for understanding how these social phenomena may mutually reinforce each other and cause adverse interactions. Similar applications across other social phenomena may also be possible.


Nosocomial COVID: the moral and clinical imperative for worldwide data collection and action.
There is a wide disparity worldwide in data collection and sharing of rates of hospital-acquired coronavirus disease (COVID). There is an ethical imperative that such information is systematically gathered, distributed and acted on to reduce rates of this form of preventable and devastating transmission during a pandemic.


Lactococcus lactis carrying a DNA vaccine coding for the ESAT-6 antigen increases IL-17 cytokine secretion and boosts the BCG vaccine immune response.
A regimen utilizing Bacille Calmette-Guerin (BCG) and another vaccine system as a booster may represent a promising strategy for the development of an efficient tuberculosis vaccine for adults. In a previous work, we confirmed the ability of Lactococcus lactis fibronectin-binding protein A (FnBPA+) (pValac:ESAT-6), a live mucosal DNA vaccine, to produce a specific immune response in mice after oral immunization. In this study, we examined the immunogenicity of this strain as a booster for the BCG vaccine in mice. After immunization, cytokine and immunoglobulin profiles were measured. The BCG prime L. lactis FnBPA+ (pValac:ESAT-6) boost group was the most responsive group, with a significant increase in splenic pro-inflammatory cytokines IL-17, IFN-γ, IL-6 and TNF-α compared with the negative control. Based on the results obtained here, we demonstrated that L. lactis FnBPA+ (pValac:ESAT-6) was able to increase the BCG vaccine general immune response. This work is of great scientific and social importance because it represents the first step towards the development of a booster to the BCG vaccine using L. lactis as a DNA delivery system.


Wound healing: relationship of wound closing tension to tensile strength in rats.
A study was conducted to better define the relationship between closing tension and the resulting tensile strength of scars in incisional wounds. Five groups consisting of ten hairless rats were studied. Transverse wounds were created and closed on the back of each rat, with closing tension varied by excising amounts of skin in widths of 0 (control), 15, 30, 45, and 60 mm. The tensile strengths were determined at 28 days. Higher mean tensile strengths were demonstrated in the two groups requiring the highest closing tensions (45 mm and 60 mm of skin excision) with P = 0.0028 and P = 0.00016, respectively. A logarithmic relationship between closing tension and tensile strength was demonstrated using linear regression analysis with t = 6.18, p less than .0001, and R2 = .44.


The association between high parity and obesity in women living in South-eastern Turkey.
One of the major public health problems in Turkey is the high prevalence of obesity, which is particularly frequent among women. As it has been reported that parity affects body fat and BMI, the aim of this study was to evaluate the association between parity number, socioeconomic status and obesity. The study involved 286 married or divorced women aged 28- 80 years (mean age: 46.7+/-9.7), who were divided into two groups depending on whether they had experienced three or fewer pregnancies (group 1) or four or more pregnancies (group 2). We measured their body weight and height, and waist and hip circumferences, calculated their BMI, and determined their body fat percentage and fat mass by means of bioelectric impedance. The women in group 2 had a higher BMI, a greater fat percentage and fat mass, a larger waist circumference and higher waist/hip ratio values than those in group 1, and their mean age and illiteracy ratio were also higher. There was a significant correlation between parity number and body weight, BMI and hip circumference. Among other risk factors, a high parity number and socioeconomic indices may be associated with obesity in women.


Horizontal transmission might be a common route of hepatitis B virus exposure in highly endemic areas.
Hepatitis B virus (HBV) is a common viral pathogen that infects more than a third of the world's population; however, the transmission route remains to be further defined. The 18-year implementation of the free HBV vaccine for children has greatly changed the prevalence of HBV infection in China, which presents a unique real-world model for assessing the pattern of HBV transmission. Cross-sectional data of HBV seromarkers between July 2019 and April 2020 were collected from 53 371 individuals aged 1-60 years in four areas of North to South in Eastern China. Longitudinal data of HBV seromarkers between 2007 and 2020 were collected from 177 adults in an area of South China. The regional- and age-specific changes in HBV seromarkers were analyzed. Overall, positive rates of HBV surface antigen (HBsAg; from 3.44% to 15.1%) and antibody against HBV core antigen (anti-HBc; from 7.6% to 44.0%) significantly increased from North to South. Among persons aged ≤18 years, the positive rates of antibody against HBsAg (anti-HBs) and anti-HBc (+) remained at low levels in the North, while they were increasing among persons aged >12 years in the South, despite higher positive rates of anti-HBs (+). Among persons aged >18 years, the anti-HBs (+) rates remained relatively stable (~60%), while anti-HBc (+) rates increased significantly with age. Up to ~80% of the anti-HBs (+) adults in the South was anti-HBc (+) while it was 13.6% in the North. In the longitudinal cohort, the anti-HBc (+) rate among adults in the South increased by 14.2% during 10 years of follow-up. Horizontal transmission might be a common route in highly endemic areas, and may help to explain the high HBV exposure worldwide. The risk of horizontal transmission among children without seroprotective anti-HBs should be notified in highly endemic areas.


Adhesion molecules of the nervous system.
The structural and functional characterization of neural cell-cell adhesion molecules continues to progress at a rapid rate, exposing the complex nature of these large multidomain receptors and their intricate relationship with the cell. Over the past year, significant progress has been made in the description of multiple binding activities, signaling potentials, and cytoplasmic associations of cell-cell adhesion molecules. In addition, new modes for developmental regulation of adhesion molecule function have been identified.


No effect of maternal smoking in early pregnancy observed on chromosome aberrations in chorionic villus samples.
The effect of maternal smoking on first trimester chorionic villus samples (CVS) was studied by analysing the frequency of chromosome aberrations (CAs) among 20 non-smoking and 20 smoking mothers. The aberrations were classified as chromosome- and chromatid-type breaks and gaps. No statistically significant differences were found in the frequencies of CAs between non-smoking mothers (5.4% or 2.0% gaps excluded) and smoking mothers (3.5% or 1.0% gaps excluded).


Glycaemic and insulin index of four common German breads.
German-style breads are recommended as a lower glycaemic index (GI) alternative, yet little data is available. Our aim was to test the GI and insulin index (II) of four breads and rolls commonly consumed in Germany. Four German bread products were tested for their GI and II in 12 healthy subjects according to the International Standard Organization guidelines. Only the wholemeal rye bread with visible intact grains and sunflower seeds was identified as low GI (GI=55). Both the wholemeal spelt wheat (GI=63) and the rye wheat sourdough bread (GI=62) were classified as medium GI, whereas soft pretzel was high GI (GI=80, P<0.05 compared with other products). The II of soft pretzels (II=102) was also highest and differed significantly from wholemeal rye (II=70) and rye sourdough bread (II=72) but not from wholemeal spelt wheat (II=77). Contrary to popular belief, these German-style breads are medium to high GI, with the exception of the rye bread with intact grains and seeds. The results highlight the need to test, rather than 'guestimate', the GI of local products, and develop a broader range of low-GI breads.


Fusion of multiple segmentations of medical images using OV2ASSION and Deep Learning methods: Application to CT-Scans for tumoral kidney.
Nephroblastoma is the most common kidney tumour in children. Its diagnosis is based on imagery. In the SAIAD project, we have designed a platform for optimizing the segmentation of deformed kidney and tumour with a small dataset, using Artificial Intelligence methods. These patient's structures segmented by separate tools and processes must then be fused to obtain a unique numerical 3D representation. However, when aggregating these structures into a final segmentation, conflicting pixels may appear. These conflicts can be solved by IA techniques. This paper presents a synthesis of our segmentation contribution in the SAIAD project and a new fusion method. The segmentation method uses the FCN-8s network with the OV2ASSION training method, which allows segmentation by patient and overcomes the limited dataset. This new fusion method combines the segmentations of the previously performed structures, using a simple and efficient network combined with the OV2ASSION training method as well, in order to manage eventual conflicting pixels. These segmentation and fusion methods were evaluated on pathological kidney and tumour structures of 14 patients affected by nephroblastoma, included in the final dataset of the SAIAD project. They are compared with other methods adapted from the literature. The results demonstrate the effectiveness of our training method coupled with the FCN-8s network in the segmentation process with more patients, and in the case of the fusion process, its effectiveness coupled with a common network, in resolving the conflicting pixels and its ability to improve the resulting segmentations.


Prothrombotic state induced by COVID-19 infection as trigger for stroke in young patients: A dangerous association.
•COVID-19 infection could led to a pro-inflammatory and pro-thrombotic state.•Cerebrovascular involvement may occur in COVID-19 infection even in young patients.•Physicians should be aware that stroke may be the first COVID-19 manifestation.


Impact of market misallocations on green TFP: evidence from countries along the Belt and Road.
Based on the idea of a "Community of Human Destiny," the Chinese government proposed the "Belt and Road" initiative, and clearly proposed to promote green development and strengthen ecological environmental protection. However, a considerable number of countries are resource-rich economies with serious market misallocations. Using the stochastic frontier analysis (SFA) combined with the directional distance function (DDF) framework, this paper measures the green total factor productivity (GTFP) and its items (i.e., technical change and efficiency change) of 33 countries along the Belt and Road in 1995-2012, and then the impact of market misallocations on GTFP is analyzed. The following conclusions are drawn: (1) The main driving force for GTFP promotion in Asian countries came from technical change, while in European countries, it came from efficiency change. (2) Market misallocations had significantly hindered the GTFP of these economies. Countries with greater market misallocations have smaller GTFP. (3) Results based on counterfactual measures showed that GTFP could be increased by up to 4.04% and the average can be increased by 1.24% after eliminating market misallocations.


Social and behavioral determinants of attitudes towards and practices of hepatitis B vaccine birth dose in Vietnam.
Hepatitis B virus (HBV) infection is a significant public health issue in Vietnam. Our goal was to understand the determinants of attitudes towards and practices of hepatitis B vaccine birth dose (HepB-BD) in certain regions of Vietnam. A rapid qualitative assessment was conducted in three geographically diverse provinces that reported low coverage (<50%) of HepB-BD. Using purposive sampling of participants, 29 focus group discussions and 20 in-depth interviews were held with caregivers (n = 96), healthcare providers (n = 75), and healthcare administrators (n = 16). Summary notes from these were translated, and inductive coding was used to derive themes. The SAGE Vaccine Hesitancy Determinants Matrix was used as a theoretical framework to organize barriers and facilitators associated with the themes into three levels of influence. At the individual and group level, caregivers who had higher levels of knowledge about HepB-BD sought the vaccine proactively, while others with lower knowledge faced barriers to the vaccine. Some caregivers reported a negative attitude toward health services because of a language barrier or had generalized concerns about HepB-BD due to media reporting of the past adverse events. Distress arising from potential adverse events was equally common among healthcare providers. At the contextual level, the physical environment made it difficult for caregivers to access healthcare facilities and for providers to conduct outreach. Home births posed a challenge for timely administration of HepB-BD, while health facility births facilitated it. Vaccination-specific barriers included misinterpretation of pre-vaccination screening criteria and asking for the consent of caregivers. Inadequate resources for service delivery negatively influenced HepB-BD attitudes and practices. Given the diversity of barriers associated with attitudes towards and practices of HepB-BD in the three provinces, tailored interventions will be necessary for both demand- and supply-side factors. Rural areas, often with more home births and geographic barriers, may require focused attention.


Exploring intracellular space: function of the Min system in round-shaped Escherichia coli.
The MinCDE proteins help to select cell division sites in normal cylindrical Escherichia coli by oscillating along the long axis, preventing unwanted polar divisions. To determine how the Min system might function in cells with multiple potential division planes, we investigated its role in a round-cell rodA mutant. Round cells lacking MinCDE were viable, but growth, morphology and positioning of cell division sites were abnormal relative to Min+ cells. In round cells with a long axis, such as those undergoing cell division, green fluorescent protein (GFP) fusions to MinD almost always oscillated parallel to the long axis. However, perfect spheres or irregularly shaped cells exhibited MinD movement to and from multiple sites on the cell surface. A MinE-GFP fusion exhibited similar behavior. These results indicate that the Min proteins can potentially localize anywhere in the cell but tend to move a certain maximum distance from their previous assembly site, thus favoring movement along the cell's long axis. A new model for the spatial control of division planes by the Min system in round cells is proposed.


Tetramethylpyrazine induces heme oxygenase-1 expression and attenuates myocardial ischemia/reperfusion injury in rats.
The accumulation of oxygen free radicals and activation of neutrophils are strongly implicated as pathophysiological mechanisms mediating myocardial ischemia/reperfusion injury. Heme oxygenase-1 (HO-1) has been reported to play a protective role in oxidative tissue injuries. In this study, the cardioprotective activity of tetramethylpyrazine (TMP), an active ingredient of Chinese medicinal herb Ligusticum wallichii Franchat, was evaluated in an open-chest anesthetized rat model of myocardial ischemia/reperfusion injury. Pretreatment with TMP (5 and 10 mg/kg, i.v.) before left coronary artery occlusion significantly suppressed the occurrence of ventricular fibrillation. After 45 min of ischemia and 1 h of reperfusion, TMP (5 and 10 mg/kg) caused a significant reduction in infarct size and induced HO-1 expression in ischemic myocardium. The HO inhibitor ZnPP (50 microg/rat) markedly reversed the anti-infarct action of TMP. Superoxide anion production in ischemic myocardium after 10 min reperfusion was inhibited by TMP. Furthermore, TMP (200 and 500 microM) significantly suppressed fMLP (800 nM)-activated human neutrophil migration and respiratory burst. In conclusion, TMP suppresses ischemia-induced ventricular arrhythmias and reduces the infarct size resulting from ischemia/reperfusion injury in vivo. This cardioprotective activity of TMP may be associated with its antioxidant activity via induction of HO-1 and with its capacity for neutrophil inhibition.


[Cervical lymphadenopathy revealing differentiated thyroid cancer. Review of the literature and therapeutic approach].
Well-differentiated thyroid cancer (i.e. papillary microcarcinoma) may be revealed by a clinically palpable cervical node, especially in young patients. Primary tumor specificity (small-sized, superior location, invasion, multifocality) and characteristics of cervical node involvement (with synchronous central and lateral multiple node spread) require appropriate treatment by a skilled surgeon. Contrary to the primary tumor treatment (total thyroidectomy), surgical management of the cervical node basins remains controversial. Only a special knowledge of the specificity of this disease and cervical lymphatic anatomy will ensure a good prognosis for the patient.


Bis-enzyme cascade CRISPR-Cas12a platform for miRNA detection.
MicroRNA (miRNA) play a vital role in the pathological development of many diseases. It is considered to be the diagnosis and potential biomarkers of prognosis. Herein, we proposed Bis-enzyme cascade Platform by combining T7 RNA polymerase and CRISPR-Cas12a (BPTC) for a miRNA detection. In the proposed BPTC, the RNA to DNA conversion ability of phi29 amplification and trans-cleavage of CRISPR-Cas12a are combined. The target miRNA can be amplified after binding to the recognizer ssDNA, and then transcribed the CRISPR-derived RNA (crRNA) by T7 RNA polymerase. The produced crRNA can thereby be assembled by CRISPR-Cas12a and recognized with its target dsDNA, thus triggered its trans-cleavage towards surrounding fluorescent reporters, labeled with a fluorophore and a corresponding quenching group. Based on the bis-enzyme cascade system, the biosensor shows highly sensitivity and excellent specificity. Moreover, this study provided a novel all-in-one detect strategy for miRNA and may open a new idea for the design of CRISR-Cas-based miRNA biosensing platforms.


Corrigendum: Clinical implications of atrial fibrillatioN detection using wearabLE devices in patients with cryptogenic stroke (CANDLE-AF) trial: Design and rationale.
[This corrects the article DOI: 10.3389/fcvm.2022.837958.].


Aniridia, cataracts, and Wilms' tumor in monozygous twins.
We studied the first instance of aniridia-Wilms' tumor syndrome in twins who were mentally retarded. Both of them had congenital aniridia, cataracts, and glaucoma; only one subsequently developed a Wilms' tumor. A two-allele, two-step mutation is the most likely explanation of this genetically abnormal syndrome in twins. The aniridia-Wilms' tumor syndrome in twins further documents the relationship of teratogenic malformations and neoplasias.


Ca(2+) -complex stability of GAPAGPLIVPY peptide in gas and aqueous phase, investigated by affinity capillary electrophoresis and molecular dynamics simulations and compared to mass spectrometric results.
Strong, sequence-specific gas-phase bindings between proline-rich peptides and alkaline earth metal ions in nanoESI-MS experiments were reported by Lehmann et al. (Rapid Commun. Mass Spectrom. 2006, 20, 2404-2410), however its relevance for physiological-like aqueous phase is uncertain. Therefore, the complexes should also be studied in aqueous solution and the relevance of the MS method for binding studies be evaluated. A mobility shift ACE method was used for determining the binding between the small peptide GAPAGPLIVPY and various metal ions in aqueous solution. The findings were compared to the MS results and further explained using computational methods. While the MS data showed a strong alkaline earth ion binding, the ACE results showed nonsignificant binding. The proposed vacuum state complex also decomposed during a molecular dynamic simulation in aqueous solution. This study shows that the formed stable peptide-metal ion adducts in the gas phase by ESI-MS does not imply the existence of analogous adducts in the aqueous phase. Comparing peptide-metal ion interaction under the gaseous MS and aqueous ACE conditions showed huge difference in binding behavior.


Differential antigen presentation regulates the changing patterns of CD8+ T cell immunodominance in primary and secondary influenza virus infections.
The specificity of CD8+ T cell responses can vary dramatically between primary and secondary infections. For example, NP366-374/Db- and PA224-233/Db-specific CD8+ T cells respond in approximately equal numbers to a primary influenza virus infection in C57BL/6 mice, whereas NP366-374/Db-specific CD8+ T cells dominate the secondary response. To investigate the mechanisms underlying this changing pattern of immunodominance, we analyzed the role of antigen presentation in regulating the specificity of the T cell response. The data show that both dendritic and nondendritic cells are able to present the NP366-374/Db epitope, whereas only dendritic cells effectively present the PA224-233/Db epitope after influenza virus infection, both in vitro and in vivo. This difference in epitope expression favored the activation and expansion of NP366-374/Db-specific CD8+ memory T cells during secondary infection. The data also show that the immune response to influenza virus infection may involve T cells specific for epitopes, such as PA224-233/Db, that are poorly expressed at the site of infection. In this regard, vaccination with the PA224-233 peptide actually had a detrimental effect on the clearance of a subsequent influenza virus infection. Thus, differential antigen presentation impacts both the specificity of the T cell response and the efficacy of peptide-based vaccination strategies.


Kinetics of force recovery following length changes in active skinned single fibres from rabbit psoas muscle: analysis and modelling of the late recovery phase.
Redevelopment of isometric force following shortening of skeletal muscle is thought to result from a redistribution of cross-bridge states. We varied the initial force and cross-bridge distribution by applying various length-change protocols to active skinned single fibres from rabbit psoas muscle, and observed the effect on the slowest phase of recovery ('late recovery') that follows transient changes. In response to step releases that reduced force to near zero ( approximately 8 nm (half sarcomere)(-1)) or prolonged shortening at high velocity, late recovery was well described by two exponentials of approximately equal amplitude and rate constants of approximately 2 s(-1) and approximately 9 s(-1) at 5 degrees C. When a large restretch was applied at the end of rapid shortening, recovery was accelerated by (1) the introduction of a slow falling component that truncated the rise in force, and (2) a relative increase in the contribution of the fast exponential component. The rate of the slow fall was similar to that observed after a small isometric step stretch, with a rate of 0.4-0.8 s(-1), and its effects could be reversed by reducing force to near zero immediately after the stretch. Force at the start of late recovery was varied in a series of shortening steps or ramps in order to probe the effect of cross-bridge strain on force redevelopment. The rate constants of the two components fell by 40-50% as initial force was raised to 75-80% of steady isometric force. As initial force increased, the relative contribution of the fast component decreased, and this was associated with a length constant of about 2 nm. The results are consistent with a two-state strain-dependent cross-bridge model. In the model there is a continuous distribution of recovery rate constants, but two-exponential fits show that the fast component results from cross-bridges initially at moderate positive strain and the slow component from cross-bridges at high positive strain.


Time parameters of contraction of inotropically responding cultured heart cells in relation to cellular cyclic AMP levels.
Television video microscopy combined with photoelectric recording was used to determine the influence of a number of positive inotropic agents on the amplitude (peak height) and the course of the contraction of electrically paced myocytes in 4-day monolayer cultures derived from the heart ventricles of 1 to 2-day old rats. Cyclic AMP was determined in parallel cultures of the same cell population. Reductions in time to 90% of peak height, 90% of relaxation time, and duration of contraction caused by peak height-augmenting concentrations of isoproterenol, epinephrine, dibutyryl cyclic AMP, and 1-methyl-3-isobutylxanthine, but not of theophylline, correlated with rises in cellular cyclic AMP levels. Ouabain, a rise in extracellular CaCl2, and, in some experiments, phenylephrine in the presence of propranolol increased peak height, but did not change time to 90% of peak height, 90% of relaxation time, duration of contraction, and cyclic AMP content. These responses are compared to those observed by other authors in intact cardiac muscle and are discussed in the light of evidence linking increased myocardial cyclic AMP levels with an abbreviation of systole.


Sarcopenia/Muscle Mass is not a Prognostic Factor for Short- and Long-Term Outcome After Esophagectomy for Cancer.
Recent studies have suggested that sarcopenia is a prognostic risk indicator of postoperative complications and predicts survival in cancer patients. The aim of this study is to investigate whether sarcopenia is associated with postoperative short-term outcome (morbidity and mortality) and long-term survival in patients undergoing esophagectomy for cancer after neoadjuvant chemoradiotherapy. All patients who underwent neoadjuvant chemoradiotherapy followed by esophagectomy for cancer, and of whom an adequate CT scan was available, were included in the current study. The presence of sarcopenia was defined by CT imaging using cut-off values of the total cross-sectional muscle tissue measured transversely at the third lumbar level. A total number of 120 patients were eligible for analysis. Almost half of the patients (N = 54, 45 %) were classified as having sarcopenia; 24 sarcopenic patients (44 %) had overweight and 5 sarcopenic patients (9 %) were obese. Overall morbidity and mortality rate did not differ significantly between sarcopenic and non-sarcopenic patients, nor did long-term overall or disease-free survival. Also sarcopenic obesity was not associated with worse outcome. The presence of sarcopenia was not associated with a negative short- and long-term outcome in this selected group of esophageal cancer patients after neoadjuvant chemoradiotherapy followed by esophagectomy.


High doses of hydrocortisone improved tracheal autograft revascularization.
Anti-inflammatory effects of steroid to revascularization of the tracheal autografts in pigs, with the use of pedicled muscle flaps of the abdominal rectus was evaluated. The research was done on 19 pigs. First group: eight pigs, no steroids were given. Second group: 11 pigs, a daily dose of 30 mg/kg hydrocortisone was given, starting on the day of operation. A segment of trachea ten rings long was skeletonized and excised, and reimplanted in the previous position. A muscle flap was sutured on the anterior aspect of the tracheal autograft. All eight animals in the first group died from graft failure. In the second group receiving steroids, only two animals succumbed (18.1%). Nine animals recovered, and were put to sleep 30-42 days following surgery. The average diameter of the grafts was 85%. Microscopically, all structures of the trachea were preserved. Grafts perfusion was on average 80.6%. Two conditions have to be fulfilled for tracheal autografts to survive: One, well vascularising muscular flaps have to be employed, and second, a high dose of steroids must be given starting on the day of operation.


Hydrocortisone and long-term outcomes in very-low-birthweight infants.
The long-term effects of hydrocortisone (HDC) used for very-low-birthweight (VLBW) infants with chronic lung disease (CLD) are not fully understood. The aim of this study was to examine the short-term clinical effects and long-term impact of a physiological replacement dose of HDC on acute deterioration of CLD in VLBW infants. This prospective case-control study included 110 of the 174 VLBW infants admitted to our facility between 2003 and 2006 who were followed up to a corrected age of 18 months. Infant deaths and infants with congenital deformities were excluded from the study. The infants were classified into the following three groups: infants with CLD and treated with HDC (1-2 mg/kg/dose) due to progressive deterioration in oxygenation (CLD treatment group; n = 24); infants with CLD but not treated with HDC (CLD untreated group; n = 40); and infants without CLD (non-CLD group; n = 46). The fraction of inspired oxygen (F(I) O(2) ) in the CLD treatment group improved significantly after treatment (P < 0.01). There were no significant differences among the three groups in terms of growth and neurodevelopmental quotient at the corrected age of 18 months following adjustment for birthweight, sex, and presence of light-for-date infants. There were also no significant intergroup differences in all three areas of developmental quotient. Physiological doses of HDC replacement are effective in treating acute deterioration in oxygenation in VLBW infants with CLD. Furthermore, this treatment modality did not adversely affect the growth and development of infants at the corrected age of 18 months.


Pain-related evoked potentials with concentric surface electrodes in patients and healthy subjects: a systematic review.
Pain-related evoked potentials with concentric surface electrodes (PREP with CE) have been increasingly used in the diagnostics of polyneuropathies as well as in pain research. However, the study results are partly inconsistent regarding their utility to distinguish between normal and abnormal findings. The present systematic review aimed to summarise and compare study results, where PREP with CE were used in healthy subjects or patients and to identify possible influencing factors. We found 36 research articles, of which 21 investigated disorders in patients compared to healthy controls, while the other 15 focussed on basic research in healthy subjects. Patients with polyneuropathies showed the most consistent PREP results with similar prolonged latencies and reduced amplitude values. Findings in other patient groups or in healthy subjects were more heterogeneous. There was evidence for an influence by age and height as well as by central effects like emotions, which should be considered in further studies. Further systematic research analysing PREP results depending on individual and disease-specific factors is needed to develop optimal normative values.


Photodynamic activity of BAM-SiPc, an unsymmetrical bisamino silicon(IV) phthalocyanine, in tumour-bearing nude mice.
Ever since the discovery of photodynamic therapy, there has been a continuous search for more potent photosensitizers. Towards that end, we have synthesized a number of novel phthalocyanine derivatives. The unsymmetrical bisamino silicon(IV) phthalocyanine BAM-SiPc is one of the most potent compounds. In in vitro cell culture, it exhibits high phototoxicity against a number of cancer cell lines. In the present investigation, the in vivo effect of BAM-SiPc was studied in the tumour-bearing nude mice model. The biodistribution of BAM-SiPc was followed to evaluate its tumour selectivity and rate of clearance. The tumour volume in the hepatocarcinoma HepG2- and the colorectal adenocarcinoma HT29-bearing nude mice was measured after photodynamic therapy. The level of intrinsic toxicity induced was also investigated. Finally, the metabolism of BAM-SiPc in the 'normal' WRL68 liver cells and the hepatocarcinoma HepG2 cells was compared. The results not only showed significant tumour regression of HepG2 and growth inhibition of HT29 in the tumour-bearing nude mice, but also no apparent hepatic or cardiac injury with the protocol used. Histological analyses showed that apoptosis was induced in the solid tumour. BAM-SiPc could be metabolized by WRL68 liver cells but not by the hepatocarcinoma HepG2 cells. Unfortunately, BAM-SiPc did not show any specific targeting towards the tumour tissue. The efficiency of BAM-SiPc in inhibiting tumour growth makes it a good candidate for further evaluation. Enhancement of its uptake in tumour tissue by conjugation with biomolecules is currently under investigation.


Identification of two distinct isoforms of stathmin and characterization of their respective phosphorylated forms.
Stathmin is a ubiquitous soluble protein (Mr approximately 19,000, pI approximately 6.2-5.5) whose phosphorylation is associated with the intracellular mechanisms involved in the regulations of cell differentiation and functions by extracellular effectors. Its purification from rat brain and the preparation of specific antibodies allowed us to identify a set of immunologically related unphosphorylated (N1, N2) and phosphorylated (P1, P2a, P2b, P3) proteins of decreasing isoelectric points. All these proteins yielded identical silver-stained or 32P-radioactive peptide maps with the protease V8 from Staphylococcus aureus, indicating that they are also structurally related. In vitro phosphorylation with the exogenous catalytic subunit of the cAMP-dependent protein kinase, as well as dephosphorylation with alkaline phosphatase, indicated that P1, P2, and P3 derived from N1 and N2 by progressive phosphorylation. Phosphorylation of individual proteins extracted from semi-preparative two-dimensional polyacrylamide gels demonstrated the existence of two distinct isoforms of stathmin, alpha and beta: N1 and N2 are their respective unphosphorylated forms (alpha O and beta O), whereas proteins P1-P3 could be resolved as at least three increasingly phosphorylated forms of both alpha and beta stathmin (alpha 1, alpha 2, alpha(3) and beta 1, beta 2, beta(3]. In intact pituitary GH4C1 cells, hormones like thyrotropin-releasing hormone and vasoactive intestinal peptide induced a similar conversion from N1 and N2 to P1, P2, and P3. The phosphorylation of both alpha and beta isoforms of stathmin is therefore a physiologically significant response to specific extracellular regulatory agents. In conclusion, stathmin represents a family of at least two distinct protein isoforms, whose respective phosphorylation and expression might play a role in its likely function as an intracellular relay of various converging extracellular signals.


Simultaneous separation of Fe & Al and extraction of Fe from waste coal fly ash: Altering the charge sequence of ions by electrolysis.
A significant amount of coal fly ash is generated and this type of waste material causes severe environmental hazards. Metal (Al and Fe) extraction from coal fly ash is beneficial to the resource utilization of waste coal fly ash. However, the coexistence of Al and Fe in coal fly ash means that the separation of Al and Fe is required, which is a key and difficult step to prepare high value-added products from coal fly ash. This work presents a novel electrolysis method to alter the charge sequence of Al3+, Fe3+, and H2O, leading to a process different from their natural tendency for simultaneous separation of Fe3+ and Al3+, and extraction of Fe. The single iron removal efficiency was 43.48%, and the aluminum extraction efficiency was <0.30% under optimal conditions. The iron product had a purity of 98.3 wt% Fe, 0.45 wt% Al, and 0.18 wt% S. This process occurs without chemical additions and expensive membranes, avoiding impurity introduction, slag generation, and membrane limitations. Fe(s), H2(g), Al2(SO4)3(aq), and O2(g) are the main products during the electrolysis. Flake Fe is selectively produced instead of colloidal Fe(OH)3. Fe is a magnetic substance and is easier to remove from the solution by magnets than colloidal Fe(OH)3. H2 is a green fuel. Wastewater (Al2(SO4)3(aq)) can be directly used to further extract alumina. Therefore, this study provides an alternative method of zero pollution discharge for simultaneous separation of Fe3+ and Al3+, and extraction of Fe from coal fly ash leachate.


Transformation of a benign oral pigmentation to primary oral melanoma.
The objective is to report the serendipitous 7-year follow-up and transformation of a melanotic palatal lesion, which was initially diagnosed histologically as a benign oral melanotic macule, into primary oral melanoma and to provide long-term follow-up of a case of oral malignant melanoma. Nine formalin-fixed paraffin-embedded tissue blocks from several different facilities and microscopic slides of the patient's lesions were reviewed to study the transformation of a benign, oral, pigmented lesion into melanoma. Review of blocks and slides of the patient's lesions suggest that the onset of melanocytic hyperplasia (increased clear cell activity) heralded the transformation of the melanotic macule into melanoma. The histology of the first biopsies was totally benign, but retrospectively, the clinical appearance was not typical and was somewhat worrisome because of the size of the lesion and feathering of the pigmentation at the periphery. This clinical presentation, however, was unknown to the pathologists. This study documents a case of primary oral melanoma arising from an apparent oral melanotic macule and suggests that even histologically benign-appearing oral melanotic lesions should perhaps be viewed with caution if increased numbers of melanocytes (melanocytic hyperplasia or clear cell activity) are present. Careful correlation of clinical appearance and histology is necessary to arrive at an appropriate diagnosis and prognosis for oral pigmented lesions.


Increased glycosylation of proteins from cataractous lenses in diabetes.
The rates of glycosylation of lens proteins were determined in extracts of human 'diabetic' and 'senile' cataractous lenses by a method employing thiobarbituric acid. Incubation of soluble lens proteins (6,500 X g supernatant of homogenates) in vitro with various concentrations of D-glucose in sodium phosphate buffer (50 mmol/l, pH 7.2) resulted in a gradual glycosylation which was time and concentration dependent. Glycosylated proteins from the cataractous lenses of 21 senile and 12 diabetic subjects afforded 0.72 +/- 0.22 and 1.84 +/- 0.44 nmol 5-hydroxymethylfurfural/mg protein (mean +/- SD), respectively. The value is significantly higher in the diabetic than in the senile group (p less than 0.001), although the mean age of the diabetic patients (67 years) was significantly younger than that of senile subjects (75 years; p less than 0.01). These results indicate that human lens proteins can be glycosylated both in vitro and in vivo, and that hyperglycaemia can accelerate the non-enzymatic glycosylation of lens proteins in diabetic patients.


Extra-fibrillar matrix mechanics of annulus fibrosus in tension and compression.
The annulus fibrosus (AF) of the disk is a highly nonlinear and anisotropic material that undergoes a complex combination of loads in multiple orientations. The tensile mechanical behavior of AF in the lamellar plane is dominated by collagen fibers and has been accurately modeled using exponential functions. On the other hand, AF mechanics perpendicular to the lamella, in the radial direction, depend on the properties of the ground matrix with little to no fiber contribution. The ground matrix is mainly composed of proteoglycans (PG), which are negatively charged macromolecules that maintain the tissue hydration via osmotic pressure. The mechanical response of the ground matrix can be divided in the contribution of osmotic pressure and an elastic solid part known as extra-fibrillar matrix (EFM). Mechanical properties of the ground matrix have been measured using tensile and confined compression tests. However, EFM mechanics have not been measured directly. The objective of this study was to measure AF nonlinear mechanics of the EFM in tension and compression. To accomplish this, a combination of osmotic swelling and confined compression in disk radial direction, perpendicular to the lamella, was used. For this type of analysis, it was necessary to define a stress-free reference configuration. Thus, a brief analysis on residual stress in the disk and a procedure to estimate the reference configuration are presented. The proposed method was able to predict similar swelling deformations when using different loading protocols and models for the EFM, demonstrating its robustness. The stress-stretch curve of the EFM was linear in the range 0.9 < λ₃ < 1.3 with an aggregate modulus of 10.18±3.32 kPa; however, a significant nonlinearity was observed for compression below 0.8. The contribution of the EFM to the total aggregate modulus of the AF decreased from 70 to 30% for an applied compression of 50% of the initial thickness. The properties obtained in this study are essential for constitutive and finite element models of the AF and disk and can be applied to differentiate between functional degeneration effects such as PG loss and stiffening due to cross-linking.


[Cellulose decomposition under nitrogen deficiency by bacteria isolated from the intestines of phytophagous vertebrates].
A nitrogen-fixing strain identified as Klebsiella pneumonia 402-2 and two endoglucanase-synthesizing Bacillus strains were isolated from the intestines of phytophagous animals. One of the Bacillus strains was identified as Bacillus subtilis GL. Klebsiella pneumoniae 402-2 increased the endoglucanase activity of both Bacillus strains in mixed cultures. The data on the taxonomic position of strains 402-2 and GL and on the nitrogen-fixing capacity of strain 402-2 were confirmed by sequencing and analyzing their 16S rRNA genes and by amplifying the nitrogenase gene nifH.


The use of Liposuction to treat significant contour abnormalities associated with Lipomyeloeningocoele.
Since 1972 when first pioneered, liposuction has developed and is now one of the commonest aesthetic procedures performed worldwide. Evidence of its application in aesthetic lipomodelling is widely known, but there are scant reports in the literature on the use of liposuction in more unusual cases. We report its use as a safe and successful method of contour correction in two cases of lipomyelomeningocoele (LMMC), a form of spina bifida. To our knowledge, this has never been reported before. A prospective review was performed and both cases were followed up during the treatment period. Both patients were treated at the Royal Belfast Hospital for Sick Children. Patient charts were reviewed and magnetic resonance imaging was used. Two patients, aged 11 and 17 years, had a large LMMC over the lumbosacral area. Preoperative imaging was obtained in each case to ensure the procedure could safely avoid the underlying spinal cord structures. The use of the Microaire© suction device allowed precise fat extraction. Postoperative images demonstrate reduction of lipomatous bulk and improved contour. We have shown that when used with caution liposuction is a safe and effective technique for volume reduction of a LMMC in carefully selected cases.


Ovarian neoplasms in F344 rats and B6C3F1 mice.
The National Toxicology Program (NTP) classification system for rat and mouse ovarian tumors is presented. The classification system is based on previous classification systems and on a review of all the primary ovarian tumors from the archives of the National Cancer Institute (NCI) and NTP Carcinogenesis Testing Programs. The relative frequency and principal diagnostic features of 204 ovarian tumors from 39,851 female F344 rats and 587 ovarian tumors from 41,102 female B6C3F1 mice are described. The most frequently observed neoplasms in F344 rats were malignant granulosa cell tumors (29% of primary rat ovarian neoplasms observed), benign undifferentiated sex cord-stromal tumors (26%), benign granulosa cell tumors (16%), and benign Sertoli cell tumors (7%). The most frequent neoplasms in B6C3F1 mice were cystadenomas (24%), tubulostromal adenomas (24%), benign granulosa cell tumors (21%), and benign teratomas (8%).


A multicenter prospective cohort study to investigate the effectiveness and safety of apixaban in Japanese elderly atrial fibrillation patients (J-ELD AF Registry).
A global, randomized clinical trial indicated the efficacy and safety of apixaban in stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). However, data in the elderly NVAF patients ≥75 years, especially those on reduced dose, are limited. To confirm the current dose reduction criteria of apixaban in elderly NVAF patients. With a large-scale, multicenter prospective observational study, one-year outcomes after administration of on-label doses of apixaban were analyzed in Japanese NVAF patients aged ≥75 years. Endpoints were stroke or systemic embolism, bleeding requiring hospitalization, total death, and cardiovascular death. A total of 3031 patients (average age, 81.7 years; female, 48.2%) taking standard (5 mg bid) or reduced dose (2.5 mg bid) of apixaban were enrolled from 110 facilities. Standard and reduced apixaban doses were administered in 1284 (42.4%) and 1747 (57.6%) patients, respectively. Event rates (/100 person-years) in standard and reduced dose groups were 1.67 and 1.56, respectively, for stroke or systemic embolism, 1.42 and 2.25 for bleeding requiring hospitalization, 1.41 and 4.46 for total death, and 0.41 and 1.36 for cardiovascular death. Reduced apixaban dose was not significantly associated with stroke or systemic embolism and bleeding requiring hospitalization, but was independently associated with total and cardiovascular death. Incidences of stroke or systemic embolism and bleeding requiring hospitalization were similar between standard and reduced apixaban doses in the elderly NVAF patients. The incidences of total and cardiovascular death were significantly higher in the reduced dose group due to the coexisting higher risks in this group.


The role of ultrasound in the assessment and treatment of abdominal metastases from testicular tumours.
The para-aortic region has been investigated with ultrasound in 95 patients with testicular teratoma seen in the testicular tumour unit between 1973 and 1976. The liver was assessed in 110 patients. The technique has provided useful and reliable information. Para-aortic ultrasound can provide more information than existing diagnostic methods and is particularly useful for defining the volume of metastatic nodal masses. Its role should be regarded as complementary to that of lymphography. Ultrasonography is particularly useful to the radiotherapist since it can define the volume and limits of the tumour and thus influence choice of therapeutic approach and radiation planning technique. Ultrasound is also valuable in the assessment of response to treatment and in monitoring the patient during the subsequent follow-up period.


Suicide, misappropriation and impulsivity.
To describe a patient who survived a suicidal act in which lethal means were used and who subsequently cooperated with psychiatric examination. Case report. A 22-year-old man jumped from a bridge into the water 49 m below and survived. He was admitted to hospital for assessment. No psychiatric diagnosis could be made on either Axis I or II. He had misappropriated money and lost it gambling, and detection was imminent. He described his jumping as being the result of a sudden impulse. While he was falling he changed his mind and assumed an appropriate diving posture with the intention of preventing his death. This is an example of a person performing a highly lethal suicide act, in the absence of Axis I or II disorder. Threat of disgrace and possible prosecution; and impulsivity were significant factors.


Combined approach for gynecomastia.
Gynecomastia is a deformity of male chest. Treatment of gynecomastia varied from direct surgical excision to other techniques (mainly liposuction) to a combination of both. Skin excision is done according to the grade. In this study, experience of using liposuction adjuvant to surgical excision was described. Between September 2012 and April 2015, a total of 14 patients were treated with liposuction and surgical excision through a periareolar incision. Preoperative evaluation was done in all cases to exclude any underlying cause of gynecomastia. All fourteen patients were treated bilaterally (28 breast tissues). Their ages ranged between 13 and 33 years. Two patients were classified as grade I, and four as grade IIa, IIb or III, respectively. The first 3 patients showed seroma. Partial superficial epidermolysis of areola occurred in 2 cases. Superficial infection of incision occurred in one case and was treated conservatively. All grades of gynecomastia were managed by the same approach. Skin excision was added to a patient that had severe skin excess with limited activity and bad skin complexion. No cases required another setting or asked for 2(nd) opinion.


Acquired ichthyosis and hypertrichosis due to autoimmune thyroiditis: therapeutic response to thyroxine replacement.
Thyroid diseases may be associated with a wide variety of dermatologic disorders. We report a 15-year-old girl with acquired ichthyosis and hypertrichosis associated with hypothyroidism resulting from autoimmune thyroiditis. Her skin lesions progressively resolved after 8 months of replacement therapy with L-thyroxine. This result supports the hypothesis that hypothyroidism in our patient can be directly related to the pathogenesis of acquired ichthyosis and hypertrichosis.


Development of a matrix solid-phase dispersion method for the simultaneous determination of pyrethroid and organochlorinated pesticides in cattle feed.
A matrix solid-phase dispersion (MSPD) method was developed for the simultaneous extraction of 36 common pesticides and breakdown products (mostly pyrethroids and organochlorines) in cattle feed. Different parameters affecting the extraction efficiency (such as dispersing phase, clean-up adsorbent and elution volume) were investigated. The experimental procedure was optimized using a multivariate statistical approach and the final analyses were carried out by GC-muECD. Several protocols for extract purification were also studied. As far as we know, this is the first application of MSPD for the extraction of most of the target pesticides from animal feed. Using the optimized extraction conditions, the method was validated in terms of accuracy, and precision (within-a-day and among-days), using a certified reference material (CRM 115) as well as spiked cattle feedingstuffs at different concentration levels. A matrix effect study was also carried out using various real samples. The recoveries were satisfactory (>75% in most cases) and the quantification limits, at the sub-ngg(-1) or low-ngg(-1) level, complied with the regulated maximum residue levels (MRLs) in animal feed and in main crops used in the preparation of cattle feeding materials. Finally, the MSPD-GC-muECD methodology was applied to the analysis of real cattle feed samples collected in farms of dairy cattle from NW Spain.


Correction to: Testing an Online Program to Foster Need Crafting During the COVID‑19 Pandemic.
[This corrects the article DOI: 10.1007/s12144-022-03012-2.].


Summary Report Panel 2: Regulatory Issues.
The Effects of Noise on Aquatic Life 2013 Conference convened four panels to discuss specific topics related to the effects of anthropogenic noise on aquatic ecosystems. The second of these four panels, the Regulatory Issues Panel, brought together several different perspectives: representatives of agencies responsible for regulating activities that introduce anthropogenic noise into aquatic ecosystems: representatives of the regulated industries, agencies, and consultancies that advise regulators and regulated industries; and nongovernmental organizations and other stakeholders with an interest in anthropogenic noise. The goal of the panel was to help develop a more productive relationship between these groups.


Meal associated changes in brown fat thermogenesis and glycogen.
Data indicate a close association between a decrease in feeding-induced brown adipose tissue (BAT) thermogenesis and an increase in food consumption. The present study examines the hypothesis that feeding-induced BAT thermogenesis, or feeding-induced changes in BAT glycogen, a mobile form of energy store and a correlate of BAT thermogenesis, may modulate feeding behavior. We report that propranolol, which completely abolished meal-induced BAT thermogenesis, did not evoke intake of a larger meal. Though BAT glycogen concentration is a sensitive measure of the state of feeding, on a meal to meal basis it does not correlate with hunger and satiety. Hence the hypothesis is not supported by the current data. We also report that meal-induced BAT hypertrophy and glycogen deposition can be dissociated from meal-induced BAT thermogenesis.


Scaling up in vitro transcription synthesis of RNA standards for competitive quantitative RT-PCR: looking for bigger yields.
Because the acquisition of in vitro transcription kits, for production of RNA standards, might not be affordable for some small laboratories, the current work describes some alternatives to the commercial Promega protocols. Yields of tested reactions were all higher than the ones reported for the standard Riboprobe kit (1mug RNA/mug template, 1x) and the optimized variant for high yields (5-10x). They were also as good as the ones described for the high RNA production kit RiboMAX (10-20x), exceeding them in approximately 70% of reactions. Our best results, achieved in a 500-mul format, were three to five times higher than the ones reported for the Promega kit.


An Investigation Into Vortioxetine Salts: Crystal Structure, Thermal Stability, and Solubilization.
Three 1:1 salts containing vortioxetine (VOT), an orally antidepressant drug, and 3 aryl monoacids have been designed and successfully prepared by liquid-assisted grinding based on the ΔpKa rule. The C-O bond lengths (∼1.25 Å) in the COOH groups show that the proton transfer has occurred from aryl monoacid to piperazine N1 atom of vortioxetine in the crystal structures. Three salts feature cyclic [2 + 2] structural units through R(4)4 (12) N-H···O hydrogen bonding interactions which result in the remarkable thermal stabilities, and VOT-p-aminobenzoic acid shows 2-dimensional framework by linking cyclic [2 + 2] units through additional hydrogen bonding interactions. The equilibrium solubility of VOT in VOT-p-aminobenzoic acid salt can be largely improved up to 0.50 mg/mL (about 450% above the free base) at 25°C in water, which also accelerates the intrinsic dissolution rate.


Effect of some peptides on dopaminergic function in man.
Thyrotropin-releasing hormone (TRH) (200 micrograms iv) and 1-desamino-8-D-arginine vasopressin (DDAVP) (4 micrograms iv) antagonized the growth hormone (GH) response to apomorphine HCl (Apo) (0.5 mg sc) in 10 normal men. Apo had no effect on basal prolactin (PRL) levels but antagonized the PRL response to TRH. DDAVP plus Apo decreased PRL compared to placebo or DDAVP alone. These observations are compatible with (a) an inhibitory effect of TRH on hypothalamic and pituitary lactotrophe dopamine (DA) function (b) a facilitory effect of DDAVP on lactotrophe DA function and an inhibitory effect on hypothalamic DA function. Whether these are direct or indirect effects on DA mechanisms is unclear.


[Resection of recurrent neck cancers with replacement of the carotid artery].
The management of patients with recurrent neck cancer invading the carotid artery is controversial. The aim of this study was to evaluate the overall survival and healthy survival years (QALY) as well as the patency of carotid revascularization after enbloc tumor resection followed by complementary radiotherapy. From 2000 to 2016, 42 consecutive patients with recurrent neck cancer invading the carotid artery underwent resection of the tumor associated with reconstruction of the carotid artery with a PTFE prosthesis (n=31) or with a saphenous vein graft (n=11). In 11 cases, resection was associated with musculocutaneous flap coverage. The primary tumor was a squamous cell carcinoma of the larynx (20 patients) or of the pharynx (9 patients), undifferentiated carcinoma of unknown origin (10 patients) and anaplastic thyroid carcinoma (3 patients). All patients had postoperative radiotherapy (50-70Gy) supplemented in 16 of them by chemotherapy. Nine patients had metastatic dissemination at the time of reoperation with a recurrent tumor ulcerated to the skin in 5 of them. The combined 30-day mortality and stroke rate was nil. Postoperative morbidity included dysphagia (n=8), vocal cord paralysis (n=6), late wound healing delay (n=2), transient mandibular claudication (n=1) and partial necrosis of the musculocutaneous flap (n=1). No infection and no thrombosis of the bypass were observed during follow-up [median: 31 months, range: 8-167 months]. Twenty-one patients (50%) died from the consequences of the spread of cancer, which had become metastatic, but without local recurrence. The 5-year survival rate was 50.9±8.3%. The median healthy survival year (QALY) was 3.38 [95% CI: 1.70-4.54] with a significant difference between patients without metastasis at the time of reoperation [n=33; QALY=4.02] and those with metastases [n=9; QALY=0.43; P=0.005]. Healthy life expectancy was also significantly longer in patients with laryngeal cancer [n=20, QALY=4.95] compared to patients with other types of tumors [n=22, QALY=1.67; P=0.032]. In the absence of metastases, enbloc resection of recurrent neck cancers invading the carotid artery improves the duration and quality of patient survival.


International rankings of infant mortality and the United States' vital statistics natality data collecting system--failure and success.
International rankings of infant mortality rates have been consistently lower for the US than other industrialized countries, and this ranking has been falling. This study examines the influence of birth registrations among very low birthweight infants on these international rankings. Birth rates of infants weighing < 1500 g (VLBW) reported by Japan, Sweden, the Netherlands, France, the UK and Canada were compared to the rates of infants of this weight born in the US, and these rates were correlated with the infant mortality rates reported by these countries. Also, deaths in the first 24 hours after birth were correlated with the reported mortality rates. Countries with the lowest infant mortality rates tended to have the lowest incidence of births < 500 g (correlation coefficient, r = 0.73) and of births 500-999 g (correlation coefficient, r = 0.81). When white and black newborns in the US were reported separately, the correlation coefficients were 0.96 and 0.97 for these weights. Furthermore, the countries with the lowest infant mortality rates registered the fewest number of deaths in the first 24 hours after birth, correlation coefficient, r = 0.78; when white and black newborns were reported separately, r = 0.95. In addition, the international rankings of the US, 1969-1988, when correlated with the annual birth rate of white infants < 500 g registered in this country was r = 0.78. Differences in birth registration practices for infants weighing < 1500 g are primarily responsible for the poor, deteriorating performance by the US in the international rankings of neonatal mortality rates.


Autocorrelation length of normal and myopathic human myocardium measured by acoustic microscopy: implications for clinical ultrasonic tissue characterization.
The pattern of acoustic speckle present in ultrasonic images of tissue may be affected by pathological changes in the tissue. To investigate the possibility for such an effect in dilated cardiomyopathy, we examined acoustic micrographs of frozen sections of normal (autopsy) and myopathic (transplant recipient) human myocardium. The resulting images were digitized, and the major axis autocorrelation length calculated for each image. For the normal specimens (n = 75, four patients), the mean autocorrelation length was 37 +/- 18 microns, with the maximum value of 92 microns. The myopathic specimens (n = 64, four patients) had a mean of 52 +/- 19 microns, with a maximum of 100 microns. We conclude that the changes in structure between normal and myopathic myocardium are significant (p less than 0.001), but on so small a scale in relation to the wave length of clinical ultrasound that there will only be changes in the intensity of the backscattered signal, not the pattern of speckle.


Visual outcomes and rotational stability of a new non-diffractive extended-vision toric intraocular lens.
To evaluate visual outcomes and intraocular lens (IOL) rotational stability of patients undergoing immediate sequential bilateral cataract surgery with a non-diffractive extended-depth-of-focus toric IOL. Non-comparative single-centre cohort study. Twenty patients (40 eyes) with significant cataracts and corneal astigmatism who underwent immediate sequential bilateral cataract surgery with the AcrySof IQ Vivity Extended Vision Lens (Alcon Laboratories Inc, Fort Worth, Tex.). Binocular uncorrected visual acuities (UCVA) and monocular best-corrected visual acuities (BCVA) were assessed at distance (6 m), intermediate (66 cm), and near (40 cm) postoperatively at 1 week and 3 months. The rotational stability of each IOL was assessed at 1 day, 1 week, and 3 months postoperatively. A validated questionnaire (Questionnaire for Visual Disturbances [QUVID]) was used for patient-reported subjective visual disturbances preoperatively at a 3-month follow-up. Binocular distance, intermediate, and near UCVAs (mean ± SD) were 0.00 ± 0.16, 0.09 ± 0.08, and 0.14 ± 0.11 logMAR at 1 week and 0.01 ± 0.06, 0.08 ± 0.08, and 0.14 ± 0.07 logMAR at 3 months postoperatively, respectively. Distance monocular BCVA improved from 0.22 ± 0.23 logMAR preoperatively to 0.02 ± 0.06 logMAR at 3 months. Monocular BCVAs at 3 months were 0.08 ± 0.08 logMAR at intermediate distance and 0.05 ± 0.08 logMAR at near distance. IOL rotation from the intended placement axis was 2.5 ± 1.7 degrees at 1 week and 1.7 ± 1.7 degrees at 3 months postoperatively. The AcrySof IQ Vivity Extended Vision IOL achieved good UCVAs and BCVAs for distance, intermediate, and near vision. This IOL also provided excellent rotational stability for astigmatism correction.


From liver fibrosis to hepatocarcinogenesis: Role of excessive liver H2O2 and targeting nanotherapeutics.
Liver fibrosis and hepatocellular carcinoma (HCC) have been worldwide threats nowadays. Liver fibrosis is reversible in early stages but will develop precancerosis of HCC in cirrhotic stage. In pathological liver, excessive H2O2 is generated and accumulated, which impacts the functionality of hepatocytes, Kupffer cells (KCs) and hepatic stellate cells (HSCs), leading to genesis of fibrosis and HCC. H2O2 accumulation is associated with overproduction of superoxide anion (O2 •-) and abolished antioxidant enzyme systems. Plenty of therapeutics focused on H2O2 have shown satisfactory effects against liver fibrosis or HCC in different ways. This review summarized the reasons of liver H2O2 accumulation, and the role of H2O2 in genesis of liver fibrosis and HCC. Additionally, nanotherapeutics targeting H2O2 were summarized for further consideration of antifibrotic or antitumor therapy.


Editorial for the 'Reciprocal Links between RNA Metabolism and DNA Damage' Special Issue: July 2023.
Two central parts of molecular biology are the control of genome integrity and genome expression [...].


Co-application of copper oxide nanoparticles and Trichoderma harzianum with physiological, enzymatic and ultrastructural responses for the mitigation of salt stress.
Chemical contamination or nutrient pollution is concerning for health, environmental, and economic reasons. Ecofriendly surface modification of nanoparticles is a consistent challenge for agricultural purposes. In response to this environmental concern, CuO-NPs synthesized through biological method using green source and characterized for morphological and structural features through SEM (scanning electron microscope) and TEM (transmission electron microscope) spectroscopy. Our research findings illustrate that the presence of salt stress induces a notable decline in both physiological and biochemical parameters within plants. Nevertheless, the utilization of T. harzianum and CuO-NPs exhibited a mitigating effect on the detrimental consequences induced by salt stress in plants. The application of T. harzianum and the simultaneous co-inoculation with CuO-NPs notably enhanced fresh biomass and facilitated vegetative growth in comparison to the control group. Furthermore, the exposure of both T. harzianum inoculum and Copper oxide nanoparticles resulted in a significant reduction of oxidative stresses, including reactive oxygen species (ROS) levels, H2O2, and lipid peroxidation (MDA) levels in the above-ground parts of the plant, while also minimizing electrolyte leakage (EL) by reducing root growth. Additionally, the co-inoculation of the endophyte and CuO-NPs led to a significant enhancement in antioxidant enzymatic activities, such as superoxide dismutase (SOD) and chitinase (CAT) activity in the above-ground parts, under salt stress conditions. The inoculum, along with its combination with CuO-NPs, decreased electrolyte conductivity and improved total chlorophyll contents as compared to the control. The combined application of T. harzianum and CuO-NPs improved salt tolerance in A. thaliana plants by triggering salt-associated gene expression. These findings suggest that the application of T. harzianum and CuO-NPs can considerably promote leaf anatomical changes in A. thaliana and have ability to enhance salt tolerance, particularly in saline areas.


Optical performance of monofocal and multifocal intraocular lenses in the human eye.
To study the optical performance of intraocular lenses (IOLs) in the human eye to ascertain how multifocality affects the optical performance of refractive and diffractive technologies and the relationship to pupil size. Vissum-Instituto de Oftalmológico de Alicante, Alicante, Spain. Ten eyes each received the monofocal AcrySof MA60 IOL (Alcon) or 1 of the following multifocal pupil-dependent IOLs: diffractive AcrySof ReSTOR (Alcon) or refractive ReZoom (Advanced Medical Optics). The intraocular optical quality in vivo with 3.0 mm and 5.0 mm pupils was characterized by comparing the means of the difference between the total and corneal optical aberrations 3 months postoperatively. The main outcomes measures were total, higher-order, spherical, and coma aberrations (root-mean-square values); modulation transfer function values; point-spread function; and the Strehl ratio. The ReZoom group had higher in vivo intraocular aberrations than the AcrySof ReSTOR and AcrySof MA60 groups (P = .022). The difference in spherical aberration between the AcrySof ReSTOR and ReZoom groups was statistically significant with 5.0 mm pupils (P = .003) and 3.0 mm pupils (P = .001). The AcrySof ReSTOR group had statistically significant lower coma aberration values with a 5.0 mm pupil (P = .012); there were no differences between IOLs with a 3.0 mm pupil (P = .185). Multifocal refractive IOLs resulted in higher intraocular aberrations. The hybrid refractive-diffractive IOL was the least affected by pupil diameter in terms of intraocular aberrations and showed significantly less increase in optical aberrations when the pupil was enlarged.


Comparing sensitivity across different processing measures under metacontrast masking conditions.
In the so-called metacontrast dissociation, masked primes with a target-congruent shape facilitate responses to visible targets, whereas masked shape-incongruent primes interfere with them, even if participants cannot successfully discriminate between masked imperative primes (comprising congruent and incongruent shape primes) and non-imperative primes (with a shape different from that of all targets). Previous research suggests that visual motion perception can be spared from metacontrast masking [Kolers, P. (1963). Vision Research, 3, 191-206]. Here, we confirmed that detection of visual rotation is spared to a larger degree than detection of visual shape (Experiment 1) and that even shapes of masked stimuli can be detected if the shape-detection task is easier (Experiment 2). Implications of our findings for the conclusion that performance in masked priming studies depends on processing of non-conscious inputs are discussed.


netview p: a network visualization tool to unravel complex population structure using genome-wide SNPs.
Network-based approaches are emerging as valuable tools for the analysis of complex genetic structure in wild and captive populations. netview p combines data quality control with the construction of population networks through mutual k-nearest neighbours thresholds applied to genome-wide SNPs. The program is cross-platform compatible, open-source and efficiently operates on data ranging from hundreds to hundreds of thousands of SNPs. The pipeline was used for the analysis of pedigree data from simulated (n = 750, SNPs = 1279) and captive silver-lipped pearl oysters (n = 415, SNPs = 1107), wild populations of the European hake from the Atlantic and Mediterranean (n = 834, SNPs = 380) and grey wolves from North America (n = 239, SNPs = 78 255). The population networks effectively visualize large- and fine-scale genetic structure within and between populations, including family-level structure and relationships. netview p comprises a network-based addition to other population analysis tools and provides user-friendly access to a complex network analysis pipeline through implementation in python.


Turning waste into valuables: In situ deposition of polypyrrole on the obsolete mask for Cr(VI) removal and desalination.
The global mask consumption has been exacerbated because of the coronavirus disease 2019 (COVID-19) pandemic. Simultaneously, the traditional mask disposal methods (incineration and landfill) have caused serious environmental pollution and waste of resources. Herein, a simple and green mass-production method has been proposed to recycle carbon protective mask (CPM) into the carbon protective mask/polydopamine/polypyrrole (CPM/PDA/PPy) composite by in situ polymerization of PPy. The CPM/PDA/PPy composite was used for the removal of Cr(VI) and salt ions to produce clean water. The synergistic effect of PPy and the CPM improved the removal capability of Cr(VI). The CPM/PDA/PPy composite provided high adsorption capacity (358.68 mg g-1) and economic value (811.42 mg $-1). Consequently, the CPM/PDA/PPy (cathode) was combined with MnO2 (anode) for desalination in CDI cells, demonstrated excellent desalination capacity (26.65 mg g-1) and ultrafast salt adsorption rate (6.96 mg g-1 min-1), which was higher than conventional CDI cells. Our work proposes a new low-carbon strategy to recycle discarded masks and demonstrates their utilization in Cr(VI) removal and seawater desalination.


In vitro bioactivity of insulin analogues: lipogenic and anti-lipolytic potency and their interaction with the effect of native insulin.
This paper presents a survey of the biological potencies of a variety of naturally-occurring and semi-synthetic insulin analogues and a study of the joint biological action of some of these materials with native insulin. Biological activity was tested on isolated rat fat cells using lipogenesis from glucose as the metabolic index. A brief comparison using inhibition of fat cell lipolysis was included. The results indicated: 1. Analogue potencies varied considerably (0.4-100% insulin activity). Values obtained were mainly confirmatory but included two further B1-modified materials and a tricarbamylated insulin. The results supported previous indications on the relative roles of the A1, B1, and B29 residues of insulin for hormone activity. 2. Analogue bioactivities, whether assessed by stimulation of lipogenesis or inhibition of lipolysis, were similar for the four materials tested in both systems. The response of fat cells with respect to both metabolic indices occurred over a comparable range of insulin concentrations, with half maximal effects at 30-35 pmol 1(-1) insulin. 3. The presence of modified insulins appeared to alter the biological action of native insulin in vitro. Small effects of both potentiation and antagonism were identified.


Study of the expression of a glycoprotein of retroviral origin in the plasma of patients with hematologic disorders and in the plasma of normal individuals.
A 74,000 molecular weight glycoprotein was purified from the plasma of a patient with chronic myelogenous leukemia in blast crisis. Monoclonal antibodies were produced in the mouse and used to characterize this protein. It was shown to contain p15E antigenic determinants and portions of a reverse transcriptase. The level of this protein was found to be elevated in leukemic patients with high white blood cell counts and also in some patients with other hematopoietic disorders as compared to the level measured in normal individuals. The level of the protein was strongly reduced in acute leukemia patients after intense chemotherapy treatment. We tentatively conclude that this protein is of endogenous retroviral origin and perhaps regulates hematopoietic tissues.


Serial polysomnograms in Creutzfeldt-Jakob disease.
This is a report of the case of a patient with Creutzfeldt-Jakob disease, whose electroencephalograms and polysomnograms were repeatedly recorded throughout the course of the illness with details of the alterations of periodic synchronous discharges. In the advanced stage of the disease, the appearance of peculiar paroxysms was noted, predominantly in the early morning. Furthermore, apnea of the central type was observed during the same time period. Discussions were held on the mechanisms inducing the EEG paroxysms and apneas.


Activity and Capacity Profile of Transplant Physicians and Centers in Australia and New Zealand.
We conducted a study to analyze and report on indicators of hematopoietic cell transplant (HCT) physician time use and HCT center output measures. HCT centers in Australia and New Zealand (A&NZ) were invited to provide demographic and time use details for physicians participating in HCT patient care (HCT physicians). Resource details for adult and pediatric centers were included. From a total of 46 centers that were invited to participate, completed data were received from 37 centers (80%) representing 185 HCT physicians, with a median age of 48 (range, 33 to 72), of whom 31% were women. Just over half of HCT physicians cited prior work experience in large overseas HCT centers (97, 52%) and over one-third (79, 43%) possessed postgraduate qualifications other than specialist training. Total annual mean HCTs per HCT physician full-time equivalent (FTE) were 14.2 for centers performing both allogeneic and autologous HCT, 6.6 for autologous only centers, and 10.6 for all centers. For all HCT physicians surveyed the mean proportion of time spent on HCT related tasks was 31.7%. In A&NZ, for centers that perform both allografts and autografts, there was a mean of 4.0 allogeneic HCT annually per HCT bed, compared with 2.6 for the United States and 7.1 allogeneic HCT annually per HCT physician FTE (United States, 6.3). Projections of the A&NZ HCT physician workforce indicated that the numbers of HCT physicians are likely to stay within the region of 170 to 190 for the next 10 years, whereas HCT activity will likely continue to climb steadily. Healthcare and government authorities should be prepared to enable and support greater HCT activity in A&NZ in the future.


The endocannabinoid system as a possible target to treat both the cognitive and emotional features of post-traumatic stress disorder (PTSD).
Post-traumatic stress disorder (PTSD) is a psychiatric disorder of significant prevalence and morbidity, whose pathogenesis relies on paradoxical changes of emotional memory processing. An ideal treatment would be a drug able to block the pathological over-consolidation and continuous retrieval of the traumatic event, while enhancing its extinction and reducing the anxiety symptoms. While the latter benefit from antidepressant medications, no drug is available to control the cognitive symptomatology. Endocannabinoids regulate affective states and participate in memory consolidation, retrieval, and extinction. Clinical findings showing a relationship between Cannabis use and PTSD, as well as changes in endocannabinoid activity in PTSD patients, further suggest the existence of a link between endocannabinoids and maladaptive brain changes after trauma exposure. Along these lines, we suggest that endocannabinoid degradation inhibitors may be an ideal therapeutic approach to simultaneously treat the emotional and cognitive features of PTSD, avoiding the unwanted psychotropic effects of compounds directly binding cannabinoid receptors.


Effectiveness and safety of CT-guided (125)I seed brachytherapy for postoperative locoregional recurrence in patients with non-small cell lung cancer.
To retrospectively evaluate the effectiveness and safety of CT-guided (125)I seed brachytherapy (CTISB) in 38 non-small cell lung cancer (NSCLC) patients with locoregional recurrence (LRR). In total, we analyzed 38 NSCLC patients with LRR treated with percutaneous CTISB in our hospital between 2001 and 2008; among them, 15 also received combined chemotherapy: 1-6 cycles (median, 2) of platinum-based regimens. The change in tumor volume was evaluated based on followup contrast material-enhanced CT or positron emission tomography scans. The median Day 0 dosimetry was as follows: The volume treated with the prescription dose (V100) was 96.3% (90.1-123.5%), and the minimum dose received by at least 90% of the tumor volume (D90) was 124.8 Gy (116.0-130.7 Gy). The median duration of the followup period calculated from the first CTISB treatment was 22.5 months (range, 8-98 months). Two months after CTISB, complete response, partial response, and progressive disease were observed in 50%, 37%, and 8% of patients, respectively. Median overall survival (OS) after CTISB was 21 months (95% confidence interval, 7.4-34.6), and the rates of 2-year OS, progression-free survival, and local control were 47.4%, 39.5%, and 83.5%, respectively. Both univariate and multivariate analysis indicated that D90 was significant prognostic factors for OS and progression-free survival. For selected NSCLC patients with limited LRR, CTISB is effective and can provide a high rate of local cancer control with minimal trauma.


Iron loading and erythrophagocytosis increase ferroportin 1 (FPN1) expression in J774 macrophages.
The expression of ferroportin1 (FPN1) in reticuloendothelial macrophages supports the hypothesis that this iron-export protein participates in iron recycling from senescent erythrocytes. To gain insight into FPN1's role in macrophage iron metabolism, we examined the effect of iron status and erythrophagocytosis on FPN1 expression in J774 macrophages. Northern analysis indicated that FPN1 mRNA levels decreased with iron depletion and increased on iron loading. The iron-induced induction of FPN1 mRNA was blocked by actinomycin D, suggesting that transcriptional control was responsible for this effect. After erythrophagocytosis, FPN1 mRNA levels were also up-regulated, increasing 8-fold after 4 hours and returning to basal levels by 16 hours. Western analysis indicated corresponding increases in FPN1 protein levels, with maximal induction after 10 hours. Iron chelation suppressed FPN1 mRNA and protein induction after erythrophagocytosis, suggesting that FPN1 induction results from erythrocyte-derived iron. Comparative Northern analyses of iron-related genes after erythrophagocytosis revealed a 16-fold increase in FPN1 levels after 3 hours, a 10-fold increase in heme oxygenase-1 (HO-1) after 3 hours, a 2-fold increase in natural resistance macrophage-associated protein 1 (Nramp1) levels after 6 hours, but no change in divalent metal ion transporter 1 (DMT1) levels. The rapid and strong induction of FPN1 expression after erythrophagocytosis suggests that FPN1 plays a role in iron recycling.


Clinical applications of smart wearable sensors.
Smart wearable sensors are electronic devices worn on the body that collect, process, and transmit various physiological data. Compared to traditional devices, their advantages in terms of portability and comfort have made them increasingly important in the medical field. This review takes a unique clinical physician's standpoint, diverging from conventional sensor-type-based classifications, and provides a comprehensive overview of the diverse clinical applications of wearable sensors in recent years. In this review, we categorize these applications according to different diseases, encompassing skin diseases and injuries, cardiovascular diseases, abnormal human motion, as well as endocrine and metabolic disorders. Additionally, we discuss the challenges and perspectives hindering the development of sensors for clinical use, emphasizing the critical need for interdisciplinary collaboration between medical and engineering professionals. Overall, this review would serve as an important reference for the future direction of sensor devices in clinical use.


An XBP-1 dependent bottle-neck in production of IgG subtype antibodies in chemically defined serum-free Chinese hamster ovary (CHO) fed-batch processes.
The optimization of production processes for therapeutic antibodies is a continuing challenge in pharmaceutical biotechnology. Although it could be demonstrated that vector design and host cell engineering can improve transcriptional and translational efficiency and thereby result in generation of high producer cell lines, it is not clear whether introduction of transgenes that regulate protein transport or affect post-translational modifications could further improve such industrial processes. Here, we show that heterologous expression of the transcription factor X-box binding protein-1 (XBP-1) can lead to an increase in endoplasmic reticulum (ER) content and specific therapeutic antibody productivity of Chinese hamster ovary (CHO)-DG44 cells in inoculum suspension cultures. This effect translates into 40% increased overall antibody titers in a fed-batch format where cells are grown in chemically defined serum-free media. Protein-A purified antibody products from mock-transfected cells and XBP-1 transfected cells were found to be of comparable quality with regard to glycosylation pattern and physicochemical characteristics. The data demonstrate the potential of XBP-1 engineering to improve mammalian cell culture production processes to yield high amounts of a therapeutic protein product of desired quality.


Temperature dependence of single channel currents and the peptide libration mechanism for ion transport through the gramicidin A transmembrane channel.
A study of the temperature dependence of gramicidin A conductance of K+ in diphytanoyllecithin/n-decane membranes shows the plot of In (single channel conductance) as a function of reciprocal temperature to be nonlinear for the most probable set of conductance states. These results are considered in terms of a series of barriers, of the dynamics of channel conformation, vis-a-vis the peptide libration mechanism, and of the effect of lipid viscosity on side chain motions again as affecting the energetics of peptide libration.


A comparison of the effects of maternally administered meptazinol and pethidine on neonatal acid-base status.
A randomized double-blind study compared the effects of equi-analgesic doses of maternally administered meptazinol (1.5 mg/kg) and pethidine (1.5 mg/kg) on neonatal acid-base status. Heel-prick samples were taken for assessment of acid-base status at 10 and 60 min after delivery. Maternal antenatal history, details of labour and neonatal status at delivery were also recorded. Meptazinol produced less neonatal respiratory depression than pethidine: the mean 10 min acid-base data from 16 infants whose mothers received pethidine were indicative of a respiratory acidosis (pH 7.13, SD 0.08, PCO2, 9.11, SD 2.2 kPa; standard bicarbonate 22.3, SD 3.1 mmol/l). This was not evident in the mean acid-base data from 16 infants whose mothers received meptazinol (pH 7.23, SD 0.07; PCO2 6.83, SD 1.6 kPa; standard bicarbonate 20.9, SD 4.2 mmol/l). The mean pH and PCO2 in the two treatment groups were significantly different (P less than 0.002) at 10 min but not at 60 min after delivery.


Comparison between chondroprotective effects of glucosamine, curcumin, and diacerein in IL-1beta-stimulated C-28/I2 chondrocytes.
To compare the effects of glucosamine (GlcN), curcumin, and diacerein in immortalized human C-28/I2 chondrocytes at the cellular and the gene expression level. This study aimed to provide insights into the proposed beneficial effects of these agents and to assess the applicability of the C-28/I2 cell line as a model for the evaluation of chondroprotective action. Interleukin-1beta (IL-1beta)-stimulated C-28/I2 cells were cultured in the presence of GlcN, curcumin, and diacerein prior to the evaluation of parameters such as viability, morphology and proliferation. The impact of GlcN, curcumin, and diacerein on gene expression was determined using quantitative real-time RT-PCR (qPCR). At the transcriptional level, 5 mM GlcN and 50 microM diacerein increased the expression of cartilage-specific genes such as aggrecan (AGC) and collagen type II (COL2), while reducing collagen type I (COL1) mRNA levels. Moreover, the IL-1beta-mediated shift in gene expression pattern was antagonized by GlcN and diacerein. These effects were associated with a significant reduction in cellular proliferation and the development of chondrocyte-specific cell morphology. In contrast, curcumin was not effective at lower concentrations but even damaged the cells at higher amounts. Both GlcN and diacerein promoted a differentiated chondrocytic phenotype of immortalized human C-28/I2 chondrocytes by altering proliferation, morphology, and COL2/COL1 mRNA ratios. Moreover, both agents antagonized inhibitory effects of IL-1beta by enhancing AGC and COL2 as well as by reducing COL1 mRNA levels.


Genome-wide search for QTLs for apolipoprotein A-I level in elderly Swedish DZ twins: evidence of female-specific locus on 15q11-13.
The effect of genetic variants underlying atherosclerosis is thought to be mediated through intermediate phenotypes such as serum cholesterol levels. Localization of quantitative trait loci influencing levels of serum lipids and (apo)lipoproteins may aid in the search for determinants of susceptibility to atherosclerotic diseases. Since apolipoprotein A-I is the primary protein constituent of high-density lipoprotein, it is considered to be critical for the antiatherogenic effect of high-density lipoproteins. We describe here an effort to map loci influencing apolipoprotein A-I levels. Measurements of apolipoprotein A-I levels and genome scans with more than 1000 microsatellite markers were successfully performed in both members of 501 pairs of fraternal twins from Sweden. Variance component linkage analysis was undertaken to map quantitative trait loci. In the total study sample, two loci showed comparable suggestive evidence of linkage, 6p21-12 (LOD=2.4) and 12q23 (LOD=2.4). Sex-limited analyses revealed significant female-specific linkage at marker D15S156 on 15q11-13 (LOD=4.1). The loci on 12q and 15q in the present study confirm previously reported loci for apolipoprotein A-I, while the peak on chromosome 6p lends further support to a locus influencing several phenotypes related to atherosclerosis. Intriguingly, the presence of genes belonging to the phospholipase A2 superfamily under three out of four observed linkage peaks would lend some support to the view that this group of genes might collectively represent candidates as apolipoprotein A-I level regulators.


Effects of procaine and caffeine on the contractility of enzymatically isolated myocytes and intact cardiac tissue.
1. Procaine and caffeine exerted opposite effects on the contractility of rat cardiac tissue. 2. Procaine enhanced and caffeine depressed isometric contractile force of right ventricular strips. 3. In enzymatically isolated cells, caffeine increased the frequency and decreased the amplitude of spontaneous contractions, while procaine retarded the beating rate but concomitantly raised the shortening amplitude of the myocyte. 4. Both drugs depressed the propagation velocity of the contractile waves. 5. The results are suggested to be due to the opposite effects of the two drugs on the Ca-release process of the sarcoplasmic reticulum.


16K Fractionation of 3T3-L1 Adipocytes to Produce a Crude GLUT4-Containing Vesicle Fraction.
The insulin-sensitive pool of glucose transporter isoform 4 (GLUT4) can be isolated from total cell membranes using the 16K fractionation protocol, described here. This method produces a light membrane-containing supernatant that includes the insulin-sensitive pool of GLUT4 in GLUT4 storage vesicles. The 16K pellet fraction contains the heavy membranes (including the plasma membrane, mitochondria, nuclei, Golgi apparatus, and endoplasmic reticulum). The distribution of proteins between the two fractions is determined via immunoblotting. By subjecting insulin-stimulated versus unstimulated cells to this protocol, the mobilization of proteins out of the insulin-sensitive GLUT4 pool can be assessed.


A comparison of two methods of oral endotracheal tube stabilization in neonatal patients.
To determine if an endotracheal tube stabilization method using an umbilical clamp reduces accidental extubations when compared with a more traditional method of endotracheal tube stabilization. From January 1, 1994 through April 30, 1997, the frequency of accidental extubations per 100 ventilator days was tracked for the Neonatal Intensive Care Unit (NICU) Quality Assurance Committee of William Beaumont Hospital (Royal Oak, MI). From January 1, 1994 through December 31, 1995, all endotracheal tubes were stabilized using a traditional taping method. From March 1, 1996 through April 30, 1997, the endotracheal tubes were stabilized using a modified umbilical clamp and tape. The incidence of extubation using each stabilization method was compared by chi2 analysis. The umbilical clamp resulted in a significantly lower (p=0.001) rate of accidental extubations. The umbilical clamp taping method appears to have lowered the incidence of accidental extubation in our NICU when compared with a standard method of oral endotracheal tube stabilization.