Pregnancy planning and antenatal health behaviour: findings from one maternity unit in Turkey.
to determine the relationship between pregnancy planning and antenatal behaviours. a descriptive study using a questionnaire completed during face-to-face interviews. the obstetric and gynaecology department of one public hospital in Turkey. 1355 postpartum women. of the pregnancies among these women, 71.3% were planned, 17% were unplanned and 11.7% were unwanted. Women with unwanted or unplanned pregnancies smoked more often than the women whose pregnancies were planned; these women were also less likely to take recommended vitamins such as folic acid, and were less likely to have adequate nutrition or gain an appropriate level of weight during pregnancy. Women with unwanted pregnancies tended to attend later for antenatal care, to not attend as often as women with planned or unplanned pregnancies (p<0.01). This study found that pregnancy planning influenced antenatal health behaviour.


Intraguild predation among larval plethodontid salamanders: a field experiment in artificial stream pools.
Intraguild predation can be important in determining community structure and dynamics. Artificial stream pools were used to test for the impacts of intraguild predation among three species of larval plethodontid salamanders. Intraguild predators (large Gyrinophilus porphyriticus and Pseudotriton ruber) significantly decreased the survival of small Pseudotriton ruber. There was a trend toward reduced growth of Pseudotriton and Eurycea cirrigera in the presence of intraguild predators. The presence of large Gyrinophilus significantly reduced the growth rate of large Pseudotriton, both in the absence and presence of intraguild prey. The presence of intraguild prey did not significantly increase the growth rates of the intraguild predators. Intraguild predation is likely to be an important force shaping the evolution and ecology of these salamanders.


Cardiopulmonary Exercise Testing in the Age of New Heart Failure Therapies: Still a Powerful Tool?
New therapies with prognostic benefits have been recently introduced in heart failure with reduced ejection fraction (HFrEF) management. The aim of this study was to evaluate the prognostic power of current listing criteria for heart transplantation (HT) in an HFrEF cohort submitted to cardiopulmonary exercise testing (CPET) between 2009 and 2014 (group A) and between 2015 and 2018 (group B). Consecutive patients with HFrEF who underwent CPET were followed-up for cardiac death and urgent HT. CPET was performed in 487 patients. The composite endpoint occurred in 19.4% of group A vs. 7.4% of group B in a 36-month follow-up. Peak VO2 (pVO2) and VE/VCO2 slope were the strongest independent predictors of mortality. International Society for Heart and Lung Transplantation (ISHLT) thresholds of pVO2 ≤ 12 mL/kg/min (≤14 if intolerant to β-blockers) and VE/VCO2 slope > 35 presented a similar and lower Youden index, respectively, in group B compared to group A, and a lower positive predictive value. pVO2 ≤ 10 mL/kg/min and VE/VCO2 slope > 40 outperformed the traditional cut-offs. An ischemic etiology subanalysis showed similar results. ISHLT thresholds showed a lower overall prognostic effectiveness in a contemporary HFrEF population. Novel parameters may be needed to improve risk stratification.


The analytical and biomedical potential of cytosine-rich oligonucleotides: A review.
Polycytosine DNA strands are often found among natural sequences, including the ends of telomeres, centromeres, and introns or in the regulatory regions of genes. A characteristic feature of oligonucleotides that are rich in cytosine (C-rich) is their ability to associate under acidic conditions to form a tetraplex i-motif consisting of two parallel stranded cytosine-hemiprotonated cytosine (C·C+) base-paired duplexes that are mutually intercalated in an antiparallel orientation. Nanotechnology has been exploiting the advantages of i-motif pH-dependent formation to fabricate nanomachines, nanoswitches, electrodes and intelligent nanosurfaces or nanomaterials. Although a few reviews regarding the structure, properties and applications of i-motifs have been published, this review focuses on recently developed biosensors (e.g., to detect pH, glucose or silver ions) and drug-delivery biomaterials. Furthermore, we have included examples of sensors based on parallel C-rich triplexes and silver nanoclusters (AgNCs) fabricated on cytosine-rich DNA strands. The potential diagnostic and therapeutic applications of this type of material are discussed.


Oxidative stress markers in the follicular fluid of patients with polycystic ovary syndrome correlate with a decrease in embryo quality.
Elevated oxidative stress has been proposed as an important factor in the pathogenesis of polycystic ovary syndrome (PCOS)-related infertility. Our study was aimed at simultaneously exploring local and systemic oxidative stress in PCOS individuals and its relationship with embryo quality. We recruited 86 PCOS cases and 60 controls. Five representative oxidative stress markers, namely, total oxidant capacity (TOC), total antioxidant capacity (TAC), malonaldehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD), were measured in both follicular fluid (FF) and serum. Women with PCOS compared to normal controls had higher levels of TOC in both FF (10.13 ± 2.68 vs.7.03 ± 2.45, P < 0.001) and serum (11.76 ± 2.92 vs. 8.82 ± 2.57, P < 0.001). The oxidative stress index (OSI, the ratio of TOC to TAC) was also higher in PCOS cases. They were still significant after BMI adjustment (Padj<0.01). In addition, the serum OSI level was much higher than the FF OSI level in both groups. Correlation analysis showed that the FF and serum TOC were negatively correlated with the high-quality embryo rate on day 3 and the later blastocyst formation rate in the PCOS group (P < 0.05). The correlation coefficient was higher in FF. Moreover, as the regression analysis data showed, the FF MDA level was significantly associated with embryo quality indicators (P < 0.05). PCOS was accompanied by elevated oxidative stress in both serum and FF. Even though serum oxidative stress was severe, the study suggested that FF oxidative stress contributed more to embryo quality, to which we should give more attention in the future.


Development and applications of photo-triggered theranostic agents.
Theranostics, the fusion of therapy and diagnostics for optimizing efficacy and safety of therapeutic regimes, is a growing field that is paving the way towards the goal of personalized medicine for the benefit of patients. The use of light as a remote-activation mechanism for drug delivery has received increased attention due to its advantages in highly specific spatial and temporal control of compound release. Photo-triggered theranostic constructs could facilitate an entirely new category of clinical solutions which permit early recognition of the disease by enhancing contrast in various imaging modalities followed by the tailored guidance of therapy. Finally, such theranostic agents could aid imaging modalities in monitoring response to therapy. This article reviews recent developments in the use of light-triggered theranostic agents for simultaneous imaging and photoactivation of therapeutic agents. Specifically, we discuss recent developments in the use of theranostic agents for photodynamic-, photothermal- or photo-triggered chemotherapy for several diseases.


Association of the genetic variants of luteinizing hormone, luteinizing hormone receptor and polycystic ovary syndrome.
High circulating luteinizing hormone (LH) level is a typical biochemical feature of polycystic ovary syndrome (PCOS) whose pathophysiology is still unclear. Certain mutations of LH and LH receptor (LHR) may lead to changes in bioactivity of these hormones. The aim of this study was determine the role of the LH and LHR polymorphisms in the pathogenesis of PCOS using a genetic approach. 315 PCOS women and 212 controls were screened for the gene variants of LH G1052A and LHR rs61996318 polymorphisms by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). PCOS patients had significantly more A allele frequency of LH G1052A mutations than controls (p=0.001). Within PCOS group, carriers of LH 1052A allele had lower LH (p=0.05) and higher fasting glucose levels (p=0.04). No subjects were identified with LHR rs61996318 polymorphisms. A new LHR single nucleotide polymorphism (SNP) was found without clear association with PCOS. Results suggested LH G1052A mutation might influence PCOS susceptibility and phenotypes.


Evaluations of three different types of smiles in relation to social anxiety and psychopathic traits.
Research has identified three different types of smiles - the reward, affiliation and dominance smile - which serve expressions of happiness, connectedness, and superiority, respectively. Examining their explicit and implicit evaluations by considering a perceivers' level of social anxiety and psychopathy may enhance our understanding of these smiles' theorised meanings, and their role in problematic social behaviour. Female participants (N=122) filled in questionnaires on social anxiety, psychopathic tendencies (i.e. the affective-interpersonal deficit and antisocial lifestyle) and callous-unemotional (CU) traits. In order to measure explicit and implicit evaluations of the three smiles, angry and neutral facial expressions, an Explicit Valence Rating Task and an Approach-Avoidance Task were administered. Results indicated that all smiles were explicitly evaluated as positive. No differences in implicit evaluations between the smile types were found. Social anxiety was not associated with either explicit or implicit smile evaluations. In contrast, CU-traits were negatively associated with explicit evaluations of reward and dominance smiles. These findings support the assumptions of non-biased explicit information processing in social anxiety, and flattened emotional sensitivity in CU-traits. The importance of a multimethod approach to enhance the understanding of the effects of smile types on perceivers is discussed.


Fluorescent reporter systems for tracking probiotic lactic acid bacteria and bifidobacteria.
In the last two decades, there has been increasing evidence supporting the role of the intestinal microbiota in health and disease, as well as the use of probiotics to modulate its activity and composition. Probiotic bacteria selected for commercial use in foods, mostly lactic acid bacteria and bifidobacteria, must survive in sufficient numbers during the manufacturing process, storage, and passage through the gastro-intestinal tract. They have several modes of action and it is crucial to unravel the mechanisms underlying their postulated beneficial effects. To track their survival and persistence, and to analyse their interaction with the gastro-intestinal epithelia it is essential to discriminate probiotic strains from endogenous microbiota. Fluorescent reporter proteins are relevant tools that can be exploited as a non-invasive marker system for in vivo real-time imaging in complex ecosystems as well as in vitro fluorescence labelling. Oxygen is required for many of these reporter proteins to fluoresce, which is a major drawback in anoxic environments. However, some new fluorescent proteins are able to overcome the potential problems caused by oxygen limitations. The current available approaches and the benefits/disadvantages of using reporter vectors containing fluorescent proteins for labelling of bacterial probiotic species commonly used in food are addressed.


Single-dose trastuzumab monotherapy achieved pathological complete response (pCR) in a patient with HER2-positive breast cancer: a case report.
With advances in breast cancer treatment, the importance of de-escalation therapy to reduce harm during the treatment of elderly patients has attracted attention in recent years. Certain patient populations are expected to have a superior response to anti-HER2 drugs, particularly those with human epidermal growth factor receptor type 2 (HER2)-positive breast cancer. In this report, we describe our experience of dramatic anti-HER2 drug response in a patient who achieved pathological complete response (pCR) with a single dose of trastuzumab. An 88-year-old woman presented with a 2-cm palpable mass in the left breast. Vacuum-assisted breast biopsy, ultrasonography, and positron emission tomography-computed tomography revealed estrogen receptor-negative and HER2-positive, T1N0M0, stage I breast cancer. Mastectomy was scheduled within 2 months of the initial visit; however, the patient was anxious about the length of the waiting period and requested medication in the interim. Therefore, prior to surgery, one cycle of trastuzumab monotherapy was administered at the discretion of the attending physician. Postoperative pathology showed no remnant of invasive carcinoma and pCR with only a 0.2-mm ductal carcinoma in situ remnant. The patient refused further medication after surgery because of severe diarrhea after trastuzumab administration. Postoperative treatment was limited to follow-up, and no recurrence was observed at 1 year and 6 months postoperatively. This case suggests that trastuzumab monotherapy may be effective in certain patients with HER2-positive breast cancer. In the future, identifying patients who are more likely to respond to trastuzumab, as in this case, will allow for more options regarding de-escalation therapy without chemotherapy, particularly in elderly patients who are concerned about the side effects of chemotherapy.


Jordanian nurses' perceptions of their preparedness for disaster management.
To assess Jordanian RNs' perceptions regarding their knowledge, skills, and preparedness for disaster management. Current disaster knowledge, skills, and preparedness levels need to be evaluated to guide plans for effective educational programs. There is also a need to know where RNs received their knowledge, skills, and preparation, to enhance or improve future educational opportunities. Cross-sectional survey where the Disaster Preparedness Evaluation Tool (DPET(®)) was distributed to Jordanian RNs who work in three randomly selected Ministry of Health hospitals and two university hospitals. Four hundred and seventy-four participants completed the survey. Sixty-five per cent of respondents described their current disaster preparedness as weak: 18% medium: 12% good; and 5% felt their preparation was very good. Thirty-one per cent received disaster education in undergraduate programs; 8% in graduate nursing programs; 31% in facility drills, and 22% in continuing education courses. Eleven per cent had participated in a real disaster. Four hundred and thirty RNs wanted to learn more about RNs role in disasters, including knowledge and skills. Knowledge,skills, and disaster preparedness need continual reinforcement to improve self efficacy for disaster management. There is a need for a consistent national nursing curriculum for disaster preparedness and nationwide drills to increase disaster knowledge, skills, preparedness, and confidence.


Transfusion-associated hypoxemia in pediatric patients with solid tumors after autologous peripheral blood stem cell transplantation.
Although several types of transfusion-related adverse reactions (TRARs) have been reported, one of the most important involves respiratory features during and after blood transfusion. Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are the most severe adverse events following blood transfusion, whereas transfusion-associated dyspnea (TAD) is a less severe respiratory distress. However, there exists little evidence of these factors in pediatric populations. Here, two cases of atypical TRARs with respiratory features, in pediatric patients with solid tumors, appearing after transfusion of platelet concentrate following autologous peripheral blood stem cell transplantation are reported. Both patients developed mild hypoxemia during PC transfusion, which continued for approximately 2 weeks. Chest radiography in either patient did not reveal any abnormalities that are included in the criteria of either TRALI or TACO. Both patients recovered following oxygen administration. This complication of TRARs with respiratory features may occur more frequently in pediatric populations than realized because it may be under-recognized or under-reported. Accumulation of additional cases, including non-typical cases, is necessary to fully understand the pathology of TRARs, correctly classify these reactions, and improve care of patients receiving blood transfusions.


Cerebral amyloid angiopathy and astrocytic gliosis in Alzheimer's disease.
Astrocytic reaction at amyloid infiltrated cortical vessels was studied using glial fibrillary acidic protein (GFAP) stain in two cases of Alzheimer's disease (AD). Sections from the visual and prefrontal cortex were stained with H&E, Bodian, Congo red, and thioflavin S in addition to GFAP. Senile plaques and neurofibrillary tangles were present in both cases. The density of astrocytes surrounding vessels infiltrated with amyloid was variable. In the same area, there were vessels with minimal perivascular astrocytic reaction as well as vessels displaying more pronounced perivascular gliosis; there was no constant excessive gliosis around vessels with severe amyloid deposits. However, if amyloid infiltrating the vessel wall protruded into the perivascular neuropil of the cortex, then prolific reaction of astroglia, similar to that seen at interstitial senile plaques was apparent, and a neuritic component was distinct. It appears that once amyloid of AD type is deposited in the neuropil, whether in form of interstitial plaque or perivascular plaque, it causes a similar astroglial and neuritic reaction.


Hyposensitization in allergic rhinitis--a comparison of aqueous extracts and Allpyral by means of rhinomanometry.
Fifty-six patients with seasonal allergic rhinitis were hyposensitized with aqueous extracts (23 patients) and Allpyral extracts (33 patients). The clinical course was appraised objectively on the basis of rhinomanometry findings at examinations performed before hyposensitization and one year later. There was no essential difference between the two groups of patients as regards the relief of symptoms. A reduction of nasal congestion was recorded in 54 and 58% of the patients, respectively. Complications were less severe and less frequent in the Allpyral group.


Intravertebral vacuum phenomenon.
Intraosseous gas formation may occasionally be seen within vertebral crush fractures after spinal osteoporosis. This is due to a vacuum phenomenon which follows impaired fracture healing and may be related to avascular necrosis. Four cases are reported from rural Thailand. A high incidence may reflect inappropriate steroid therapy.


Automatic tuning of flexible interventional RF receiver coils.
Microcontroller-based circuitry was built and tested for automatically tuning flexible RF receiver coils at the touch of a button. This circuitry is robust to 10% changes in probe center frequency, is in line with the scanner, and requires less than 1 s to tune a simple probe. Images were acquired using this circuitry with a varactor-tunable 1-inch flexible probe in a phantom and in an in vitro porcine knee model. The phantom experiments support the use of automatic tuning by demonstrating 30% signal-to-noise ratio (SNR) losses for 5% changes in coil center frequency, in agreement with theoretical calculations. Comparisons between patellofemoral cartilage images obtained using a 3-inch surface coil and the surgically-implanted 1-inch flexible coil reveal a worst-case local SNR advantage of a factor of 4 for the smaller coil. This work confirms that surgically implanted coils can greatly improve resolution in small-field-of-view (FOV) applications, and demonstrates the importance and feasibility of automatically tuning such probes.


Hyperactivation of the JAK2/STAT5 Signaling Pathway and Evaluation of Baricitinib Treatment Among Patients With Eosinophilic Cellulitis.
The pathogenesis of eosinophilic cellulitis (EC) is poorly understood, limiting available treatment options. The current treatment paradigm focuses on delayed type 2 hypersensitivity reaction to various triggers. To gain further insight into the nature of EC inflammation and into the cellular signal transduction pathways that are activated in the context of EC. This case series was conducted in Lyon, France, from January 2018 to December 2021. Analysis of archival skin biopsy samples from patients with EC and from healthy control participants was performed using histology, Janus kinase (JAK)-signal transducer and activator of transcription (STAT) immunohistochemistry, and gene profiling. Data analysis was conducted between January 2020 and January 2022. Pruritus (visual analog score), percentage of body surface area with lesional skin, and RNA transcripts of inflammatory biomarkers from the skin (threshold cycle) were assessed in 1 index patient with refractory EC who received oral JAK1/JAK2 inhibitor baricitinib (4 mg/d). This study included samples from 14 patients with EC (7 men and 7 women) and 8 healthy control participants (4 men and 4 women). The mean (SD) age of patients was 52 (20) years. Marked type 2 inflammation (chemokines CCL17, CCL18, and CCL26 and interleukin 13) with preferential activation of the JAK1/JAK2-STAT5 pathways in EC lesions was observed. In the 1 index patient with refractory EC, complete clinical remission of skin lesions was observed after 1 month of treatment with baricitinib. These findings suggest that EC is a type 2 inflammatory disease with preferential activation of the JAK1/JAK2-STAT5 pathways. In addition, these results suggest the potential of treatment approaches targeting JAK1/JAK2 for patients with EC.


Endoscopic Evaluation of Pathological Complete Response Using Deep Neural Network in Esophageal Cancer Patients Who Received Neoadjuvant Chemotherapy-Multicenter Retrospective Study from Four Japanese Esophageal Centers.
Detecting pathological complete response (pCR) before surgery would facilitate nonsurgical approach after neoadjuvant chemotherapy (NAC). We developed an artificial intelligence (AI)-guided pCR evaluation using a deep neural network to identify pCR before surgery. This study examined resectable esophageal squamous cell carcinoma (ESCC) patients who underwent esophagectomy after NAC. The same number of histological responders without pCR and non-responders were randomly selected based on the number of pCR patients. Endoscopic images were analyzed using a deep neural network. A test dataset consisting of 20 photos was used for validation. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AI and four experienced endoscopists' pCR evaluations were calculated. For pathological response evaluation, Japanese Classification of Esophageal Cancer was used. The study enrolled 123 patients, including 41 patients with pCR, the same number of histological responders without pCR, and non-responders [grade 0, 5 (4%); grade 1a, 36 (30%); grade 1b, 21 (17%); grade 2, 20 (16%); grade 3, 41 (33%)]. In 20 models, the median values of sensitivity, specificity, PPV, NPV, and accuracy for endoscopic response (ER) detection were 60%, 81%, 77%, 67%, and 70%, respectively. Similarly, the endoscopists' median of these was 43%, 90%, 85%, 65%, and 66%, respectively. This proof-of-concept study demonstrated that the AI-guided endoscopic response evaluation after NAC could identify pCR with moderate accuracy. The current AI algorithm might guide an individualized treatment strategy including nonsurgical approach in ESCC patients through prospective studies with careful external validation to demonstrate the clinical value of this diagnostic approach including primary tumor and lymph node.


Metabolic impact of genetic and chemical ADP/ATP carrier inhibition in renal proximal tubule epithelial cells.
Mitochondrial dysfunction is pivotal in drug-induced acute kidney injury (AKI), but the underlying mechanisms remain largely unknown. Transport proteins embedded in the mitochondrial inner membrane form a significant class of potential drug off-targets. So far, most transporter-drug interactions have been reported for the mitochondrial ADP/ATP carrier (AAC). Since it remains unknown to what extent AAC contributes to drug-induced mitochondrial dysfunction in AKI, we here aimed to better understand the functional role of AAC in the energy metabolism of human renal proximal tubular cells. To this end, CRISPR/Cas9 technology was applied to generate AAC3-/- human conditionally immortalized renal proximal tubule epithelial cells. This AAC3-/- cell model was characterized with respect to mitochondrial function and morphology. To explore whether this model could provide first insights into (mitochondrial) adverse drug effects with suspicion towards AAC-mediated mechanisms, wild-type and knockout cells were exposed to established AAC inhibitors, after which cellular metabolic activity and mitochondrial respiratory capacity were measured. Two AAC3-/- clones showed a significant reduction in ADP import and ATP export rates and mitochondrial mass, without influencing overall morphology. AAC3-/- clones exhibited reduced ATP production, oxygen consumption rates and metabolic spare capacity was particularly affected, mainly in conditions with galactose as carbon source. Chemical AAC inhibition was stronger compared to genetic inhibition in AAC3-/-, suggesting functional compensation by remaining AAC isoforms in our knockout model. In conclusion, our results indicate that ciPTEC-OAT1 cells have a predominantly oxidative phenotype that was not additionally activated by switching energy source. Genetic inhibition of AAC3 particularly impacted mitochondrial spare capacity, without affecting mitochondrial morphology, suggesting an important role for AAC in maintaining the metabolic spare respiration.


Comparison of Exergames Versus Conventional Exercises on the Health Benefits of Older Adults: Systematic Review With Meta-Analysis of Randomized Controlled Trials.
Conventional exercises (CEs) can provide health benefits for older adults, but the long-term exercise adherence rate is low. As an emerging, stimulating, and self-motivating strategy, exergames (EGs) are defined as combinations of exercises and games that users carry out through physical actions. They can promote exercise, but the health effects of EGs versus CEs on the physical function and mental health (cognitive function, depression, and quality of life) of older adults remain controversial. The aim of the study is to compare the health benefits of EGs versus those of CEs for the physical function and mental health of older adults. A comprehensive search was conducted from the earliest available date to February 2023 in the following 6 databases: PubMed, Web of Science, Embase, Cochrane, CINAHL, and PsycINFO. All English-language randomized controlled trials comparing the effects of EGs versus those of CEs on the physical function and mental health of older adults, with nearly same physical activity between the 2 interventions, were included. Risk of bias was independently evaluated by 2 authors using the Cochrane risk of bias in randomized trials tool. Two authors independently extracted data. We followed the Cochrane Handbook of Systematic Reviews of Interventions to process and analyze the data for meta-analysis. Standardized mean differences (SMDs) and 95% CIs were used for continuous data, and random models were used for analyses. We included 12 studies consisting of 919 participants in total. Of these, 10 studies were eventually included in the meta-analysis. The results showed that EGs versus CEs exhibited no significant differences in physical (P=.13; τ2=0.31; χ26=26.6; I2=77%; SMD=0.37; 95% CI -0.11 to 0.86) or cognitive function (P=.63; τ2=0.01; χ23=3.1; I2=4%; SMD=0.09; 95% CI -0.27 to 0.44) effects. Our findings indicate no significant difference between EGs and CEs in improving the physical function and cognitive function of older adults. Future studies are required to compare the effects of EGs versus those of CEs on cognitive function according to cognitive status, quantify the "dose-effect" relationship between EGs and health benefits, and evaluate the effects of different types and devices of EGs with regard to the health benefits of older adults. PROSPERO CRD42022322734; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=322734.


Cytokine patterns differ seasonally between women with and without uterine leiomyomata.
Uterine leiomyomata are the most common reproductive tumor in women, and their cause is not known. Plasma samples from 155 women (74 with and 81 without ultrasound-confirmed leiomyoma) from a new study of leiomyoma risk factors in the Detroit, Michigan area, were examined for any cross-sectional associations between commonly examined cytokines and leiomyoma presence. Associations varied by season of sample collection defined a priori as winter (December-February) and non-winter seasons. In the winter months, interleukin (IL)13 and IL17 were positively and IP10 was inversely associated with having a leiomyoma. In the non-winter samples, VEGF, G-CSF, and IP10 were positively associated and Monocyte chemotactic protein-1, IL13, and IL17 were inversely associated with having a leiomyoma. Associations were not changed by adjustment for age or BMI. These data suggest that new insight into leiomyoma formation may be acquired through investigation of the immune system.


Porrocaecum parvum n. sp. and P. reticulatum (Linstow, 1899) (Nematoda: Ascaridoidea) from birds in China.
Porrocaecum parvum n. sp. is described from the grey-faced buzzard Butastur indicus (Gmelin) (Accipitriformes: Accipitridae) in China. The new species differs from its congeners in having well-developed cervical alae, small interlabia and very short intestinal caecum (0.34 mm long, representing 11.9% of oesophageal length) and in the number and arrangement of the caudal papillae (29 pairs in total, arranged as follows: 21 pairs precloacal, single double pair paracloacal and seven pairs postcloacal) and in the morphology of the male tail. In addition, Porrocaecum reticulatum (Linstow, 1899), collected from the purple heron Ardea purpurea L., the grey heron A. cinerea L. and the little egret Egretta garzetta (L.) (Pelecaniformes: Ardeidae) in China, was also studied using light and, for the first time, scanning electron microscopy. Previously unreported and erroneous morphological features of taxonomic significance are revealed, including the presence of narrow cervical alae, single pair of small, submedial pores and single, short medial ditch on each lip, interlabia with very pointed anterior prolongation, single medio-ventral precloacal papilla on anterior cloacal lip and double paracloacal papillae slightly posterior to cloaca.


Modulation of genomic and postgenomic alterations in noncancer diseases and critical periods of life.
Genomic and postgenomic changes are extensively investigated in cancer research. Similar alterations, affecting genome, transcriptome, mirnome and/or proteome end-points, have been detected in a variety of other chronic degenerative diseases, such as atherosclerosis, degenerative heart diseases, chronic obstructive pulmonary diseases, neurological disorders, eye diseases, diabetes, metabolic syndrome, skin ageing and alopecia. No generalization can be made due to the myriad of diverse clinical entities classified as chronic degenerative diseases. Moreover, the detection of molecular changes does not automatically imply their causal role. Nevertheless, common mechanisms, such as DNA damage, epigenetic alterations, oxidative stress, and chronic inflammation, in addition to genetic predisposition, are often involved in noncancer diseases. We debate here in more detail the subjects of cardiovascular diseases and of skin diseases. Moreover, we discuss our experimental studies suggesting that genomic and postgenomic changes do also occur during critical periods of life, including the prenatal life, the perinatal period, and ageing. In addition, we comment on the finding that stem-derived cells are more susceptible to molecular damage than more differentiated cells. All these data are viewed in the perspective of preventive medicine. In fact, there is evidence that the genomic and postgenomic alterations occurring not only in several pathological conditions but also in paraphysiological situations that affect critical periods of life can be modulated by means of dietary and pharmacological agents. The discovery that chemopreventive agents are also able to attenuate nucleotide damage in stem-derived cells warrants further studies in view of possible clinical applications.


Synthesis of both enantiomers of 12-methyl-13-tridecanolide and 14-methyl-15-pentadecanolide (muscolide).
Both enantiomers of 12-methyl-13-tridecanolide{(R)-(+)-1, (S)-(-)-1} and 14-methyl-15-pentadecanolide (muscolide) {(R)-(+)-2, (S)-(-)-2} were synthesized from either (S)-(+)- or (R)-(-)-3-bromo-2-methyl-1-propanol 8 as a chiral building block.


Human monoclonal antibodies and monoclonal antibody multispecificity.
The majority of human anti-tumour monoclonal antibodies (Mabs) isolated to date have been disappointing. Firstly, they react or cross react with intracellular cytoskeletal proteins or nuclear antigens and therefore are of limited value as blood borne agents. They are also generally of the IgM isotype and show relatively low intrinsic affinity for the primary epitope. Secondly, such Mabs can be generated from normal, non tumour bearing subjects at a frequency comparable to their production from tumour patients. This latter observation is true also for common autoantigens such as DNA and IgG since Mabs to these can also be generated from normal subjects in addition to autoimmune individuals. This article rationalises these observations in the context of the requirement for clinical use for human Mabs. It discusses the evidence that there is a potentially useful B cell response to be immortalised, and examines the consequences of the newly recognised phenomenon of monoclonal antibody multispecificity both on the methodology of their generation and on their subsequent use as imaging and therapeutic tools.


Intracellular pH and free calcium changes in single cells using quene 1 and quin 2 probes and fluorescence microscopy.
Photometric fluorescence microscopy has been used to measure intracellular pH (pHi) and free calcium concentrations [( Ca]i) in individual mouse thymocytes and 2H3 rat basophil leukaemic cells containing indicators for pH (quene 1) or calcium (quin 2). The pHi and [Ca]i measurements in individual 2H3 cells and mouse thymocytes and their responses to various stimuli were consistent with the corresponding data obtained from suspensions of these cells measured in a spectrofluorimeter. Photometric fluorescence microscopy of these indicators in individual cells provides a sensitive and fast method of following pHi and [Ca]i responses in individual cells.


Identification of potent maturation inhibitors against HIV-1 clade C.
Antiretroviral therapy has led to a profound improvement in the clinical care of HIV-infected patients. However, drug tolerability and the evolution of drug resistance have limited treatment options for many patients. Maturation inhibitors are a new class of antiretroviral agents for treatment of HIV-1. They act by interfering with the maturation of the virus by blocking the last step in Gag processing: the cleavage of the capsid-spacer peptide 1 (CA-SP1) intermediate to mature CA by the viral protease (PR). The first-in-class maturation inhibitor bevirimat (BVM) failed against a subset of HIV-1 isolates in clinical trials due to polymorphisms present in the CA-SP1 region of the Gag protein. Sequence analysis indicated that these polymorphisms are more common in non-clade B strains of HIV-1 such as HIV-1 clade C. Indeed, BVM was found to be ineffective against HIV-1 clade C molecular clones tested in this study. A number of BVM analogs were synthesized by chemical modifications at the C-28 position to improve its activity. The new BVM analogs displayed potent activity against HIV-1 clade B and C and also reduced infectivity of the virus. This study identifies novel and broadly active BVM analogs that may ultimately demonstrate efficacy in the clinic.


GraphDDP: a graph-embedding approach to detect differentiation pathways in single-cell-data using prior class knowledge.
Cell types can be characterized by expression profiles derived from single-cell RNA-seq. Subpopulations are identified via clustering, yielding intuitive outcomes that can be validated by marker genes. Clustering, however, implies a discretization that cannot capture the continuous nature of differentiation processes. One could give up the detection of subpopulations and directly estimate the differentiation process from cell profiles. A combination of both types of information, however, is preferable. Crucially, clusters can serve as anchor points of differentiation trajectories. Here we present GraphDDP, which integrates both viewpoints in an intuitive visualization. GraphDDP starts from a user-defined cluster assignment and then uses a force-based graph layout approach on two types of carefully constructed edges: one emphasizing cluster membership, the other, based on density gradients, emphasizing differentiation trajectories. We show on intestinal epithelial cells and myeloid progenitor data that GraphDDP allows the identification of differentiation pathways that cannot be easily detected by other approaches.


Hsa-let-7f-1-3p targeting the circadian gene Bmal1 mediates intervertebral disc degeneration by regulating autophagy.
The intervertebral disc has an intrinsic circadian rhythm, elimination of which leads to stress in nucleus pulposus cells (NPCs), contributing to intervertebral disc degeneration (IDD). Disruption or deletion of Bmal1 (a core transcription factor) results in complete loss of circadian rhythms, make mice susceptibility to IDD. However, the underlying mechanism by which Bmal1 mediates IDD is remains enigmatic, and whether there are other upstream factors regulating Bmal1 in NPCs. In our study, we first found that the decrease of Bmal1 was significantly correlated with the grades of IDD. With gain- and loss-of-function, Bmal1 shown a protective effect on NPC viability and functions. Transcriptomic and proteomic landscape reveals the functional contributions of Bmal1, and phosphoproteomic analysis links to autophagy. Bioinformatics analysis identified that a novel miRNA hsa-let-7f-1-3p was directly target Bmal1 3'UTR and negatively correlated with NPC function. Finally, our animal model confirmed the protective role of Bmal1 in rat IDD and this effect could be attenuated by hsa-let-7f-1-3p. The hsa-let-7f-1-3p/Bmal1/autophagy axis provides a potential therapeutic strategy for the clinical treatment of IDD.


Elevated plasma level of differentiation inhibitory factor nm23-H1 protein correlates with risk factors for myelodysplastic syndrome.
We measured plasma nm23-H1 level (nm23-H1), a differentiation inhibitory factor, by an enzyme-linked immunosorbent assay (ELISA) in patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS). The nm23-H1 in AA was not significantly elevated when compared to normal subjects (6.66 +/- 1.20 ng/ml vs 5.13 +/- 0.81 ng/ml; P = 0.274). In contrast, MDS patients had significantly high levels of nm23-H1 compared not only to normal subjects (11.16 +/- 1.42 vs 5.13 +/- 0.81 ng/ml; P = 0.0004) but also to those of the AA group (11.16 +/- 1.42 ng/ml vs 6.66 +/- 1.20 ng/ml; P = 0.018). In the MDS group of patients, no significant difference was observed in the nm23-H1 levels between patients with refractory anemia (RA) and RA with excess blasts (RAEB)/RAEB in transformation (10.71 +/- 1.61 ng/ml vs 9.24 +/- 2.66 ng/ml; P = 0.672). Of the patients with RA, patients with low risk according to the International Prognostic Scoring System (IPSS) had significantly low levels of nm23-H1 compared to those of IPSS INT-1 level cases (6.40 +/- 1.36 ng/ml vs 13.05 +/- 2.50 ng/ml; P = 0.0028), suggesting that nm23-H1 may be useful as a prognostic marker for MDS, especially in low risk patients.


Effects of thromboprophylactic doses of apixaban and rivaroxaban on coagulation and thrombin generation in association with total hip replacement.
Factor Xa inhibitors (FXaI) apixaban and rivaroxaban are used for thromboprophylaxis after major elective orthopaedic surgery. Because few patient sample studies exist, we postoperatively assessed patients undergoing unilateral total hip arthroplasty, including 22 treated with apixaban (2.5 mg BID) and 20 treated with rivaroxaban (10 mg OD). We collected blood samples before and 3 h after drug intake at 4 time points, preoperatively, as well as on day 1, week 1 (day 2-8) and day 28 post-operation. APTT and PT were immediately analysed. Calibrated anti-FXa activity, Russel's Viper Venom Time (RVVT) and thrombin generation (TG; Calibrated Automated Thrombogram®) captured the effects of FXaI on coagulation and TG. APTT and PT remained within the reference interval throughout, and did not correlate with FXaI levels (PT R2 = 0.44, APTT R2 = 0.07). Mean apixaban concentration at the peak varied by eightfold (19-153 ng/mL), but rivaroxaban only by 1.5-fold (111-183 ng/mL). Rivaroxaban, but not apixaban prolonged RVVT at peak levels. Both FXaIs had a prolonged lag time of TG (p < 0.001). Rivaroxaban decreased ETP peak at all time points and reached a minimum at day 28 (540 nM/min at rivaroxaban 184 ng/mL, p < 0.001), while rivaroxaban trough levels were low and ETP values normal. However, with apixaban, after an initial decrease, ETP did not differ between peak and trough levels until decreasing on day 28 at peak (990 nM/min at apixaban 112 ng/mL, p = 0.005). In conclusion, due to different dosing and pharmacology rivaroxaban and apixaban distinctly inhibited TG under postoperative conditions.


In vitro digestibility of dietary proteins and in vitro DIAAS analytical workflow based on the INFOGEST static protocol and its validation with in vivo data.
The FAO recommends the digestible indispensable amino acid score (DIAAS) to determine protein quality in foods, preferably tested in vivo. Here, the INFOGESTin vitrodigestion protocol was applied and supplemented with an analytical workflow allowing the assessment of protein digestibility and DIAAS calculation. The protocol was applied to selected samples WPI, zein, collagen, black beans, pigeon peas, All-Bran®, and peanuts. The total protein digestibility, digestibility of individual amino acids (AA), and DIAAS values were established and compared with in vivo data for the same substrates. Total protein digestibility (total Nitrogen, r = 0.7, P < 0.05; primary amines (OPA), r = 0.6, P < 0.02; total AA, r = 0.6, P < 0.02) and digestibility of individual AA (r = 0.6, P < 0.0001) were in good agreement, between in vitro and in vivo, with a mean difference of 1.2 %. In vitro DIAAS was highly correlated with DIAAS obtained from in vivo true ileal digestibility values (r = 0.96, R2 = 0.89, P < 0.0001) with a mean difference of 0.1 %.


Hierarchical core-shell-structured bimetallic nickel-cobalt phosphide nanoarrays coated with nickel sulfide for high-performance hybrid supercapacitors.
High-performance supercapacitors have attracted considerable interests due to their high-power density, fast charge/discharge process and long cycle life. However, the wide application of supercapacitors is limited by their low energy density. Herein, the hierarchical core-shell structured NiCoP@NiS nanoarrays have been successfully synthesized by using the vertically grown nickel-cobalt bimetallic phosphide (NiCoP) nanowire as the core and the nickel sulfide (NiS) by electrodeposition as the shell. As the "super channel" for electron transfer, the NiCoP core is coupled with the NiS shell to promote rapid diffusion of electrons and improve cycle stability of the electrode. Consequently, the optimized NiCoP@NiS nanoarrays display an extremely good specific capacitance (2128F g-1 at 1 A g-1) and a superior long cycle life (the capacitance retention of 90.36 % after 10,000 cycles). A hybrid supercapacitor (HSC) has been assembled using the NiCoP@NiS as the positive and the activated carbon (AC) as the negative, which displays a superior energy density of 30.47 Wh kg-1 at a remarkable power energy of 800 W kg-1. This study shows that the prepared hierarchical core-shell structured nanoarrays have great prospects as a novel electrode material in energy storage.


Spectral and Photochemical Properties of Rhodobacter sphaeroides R-26 Reaction Center Films in Vacuum.
Using absorption spectroscopy in the visible/near-IR and mid-IR regions, spectral and photochemical properties of isolated reaction centers (RCs) from Rhodobacter sphaeroides R-26 were studied in dried films on the inorganic support surface (quartz or CaF2 plates) under vacuum dehydration conditions (10-2 or 7·10-5 mm Hg). Three detergents, N,N-dimethyldodecylamine N-oxide (LDAO), Triton X-100 (TX100), and n-dodecyl-β-D-maltoside (DM), were tested for their ability to stabilize the RC-detergent complexes in the vacuum-dried state. It was shown that in the presence of LDAO, RC complexes underwent destruction in vacuum. In contrast, DM provided an environment that minimized irreversible disruptive changes in the RCs in vacuum. The effects of vacuum dehydration on the RC-DM films included a small increase in the content of α-helices in the RC protein, a short-wavelength reversible shift in the optical transitions of pigments, and minor changes in the electronic structure of the P+ dimer. The films retained their photochemical activity upon excitation with high-intensity light (200 mW/cm2). TX100 also helped to maintain spectral and functional properties of the RCs in vacuum; however, in this case, the stabilizing effect was less pronounced than in the presence of DM, especially, at high detergent concentrations. The results are discussed within the framework of a model suggesting that the detergent-protein interactions and the properties of detergent micelles play a dominant role in maintaining the structure of the RCs upon vacuum dehydration of the RC complexes. The obtained data can be useful for developing hybrid photoconverting systems based on bacterial RCs.


Isolated peripancreatic necrosis (PPN) is associated with better clinical outcomes compared with combined pancreatic and peripancreatic involvement (CPN)- a systematic review and meta-analysis.
Peripancreatic necrosis (PPN) is considered as a distinct entity with a better outcome when compared with combined pancreatic and peripancreatic necrosis (CPN), but there is no systematic review to summarize the evidence. Our study aimed to perform a meta-analysis of existing observational studies comparing the outcomes of PPN with CPN. Studies in adult patients comparing the outcomes of PPN and CPN from PubMed, Medline, and Scopus databases from inception to November 2018 were systematically searched. The primary outcome was mortality, and secondary outcomes included multi-organ failure, persistent organ failure, infected necrosis, need for interventions including open necrosectomy. Pooled adjusted odds ratios, and 95% confidence intervals (CI) were obtained by the random-effects model. Forrest plots were constructed to show the summary pooled estimate. Heterogeneity was assessed by using I2 measure of inconsistency. A total of 6 studies involving 1851 patients (1295 (70%) with CPN and 556 (30%) with PPN) were included. Patients with CPN had a significantly higher mortality (OR 2.49, 95% CI: 1.61-3.87), risk for multi-organ failure (OR 3.24, 95% CI: 2.38-4.43), persistent organ failure (OR 2.79, 95% CI: 1.53-5.08), and infected necrosis (OR 6.21, 95% CI: 3.85-10.03). They underwent more interventions (OR 5.86, 95% CI: 3.69-9.32), including open necrosectomy (OR 5.04, 95% CI: 3.33-7.63). Heterogeneity was low (I2 = 18.1, p = 0.296), and there was no publication bias. Isolated peripancreatic necrosis portends an overall better prognosis when compared to necrosis involves pancreatic parenchyma. Clinicians should recognize this distinction for management decisions.


Assessment of toxicologic interactions resulting from acute inhalation exposure to sulfuric acid and ozone mixtures.
Studies examining effects of air pollutants often use single compounds, while "real world" exposures are to more than one chemical. Thus, it is necessary to assess responses following inhalation of chemical mixtures. Rabbits were exposed for 3 hr to sulfuric acid aerosol at 0, 50, 75, or 125 micrograms/m3 in conjunction with ozone at 0, 0.1, 0.3, or 0.6 ppm, following which broncho-pulmonary lavage was performed. Various pulmonary response endpoints related to general cytotoxicity and macrophage function were examined. In addition, a goal of the study was to define an improved approach to the analysis of data sets involving binary pollutant mixtures. Results were evaluated using analysis of variance with multiple linear contrasts to determine the significance of any effect in the pollutant-exposed groups compared to sham control animals and to assess the type, and extent, of any toxicological interaction between acid and ozone. Interaction was considered to occur when the effects of combined exposure were either significantly greater or less than additive. Pollutant exposures had no effect on lavage fluid levels of lactate dehydrogenase, prostaglandins E2 and F2 alpha, nor on the numbers, viability, or types of immune cells recovered by lavage. Phagocytic activity of macrophages was depressed at the two highest acid levels and at all levels of ozone. Exposure to all mixtures showed significant antagonism. Superoxide production by stimulated macrophages was depressed by acid exposure at the two highest concentrations, while ozone alone had no effect. Significant antagonistic interaction was observed following exposure to mixtures of 75 or 125 micrograms/m3 acid with 0.1 or 0.3 ppm ozone. The activity of tumor necrosis factor elicited from stimulated macrophages was depressed by acid at 75 and 125 micrograms/m3 while ozone had no effect. Exposure to mixtures of 125 micrograms/m3 acid with 0.3 or 0.6 ppm ozone resulted in synergistic interaction. This study provided additional evidence for antagonism between two common air pollutants and demonstrated that the type of interaction between sulfuric acid and ozone depended upon the endpoint but that the magnitude of any interaction was not always related to the exposure concentrations of the constituent pollutants.


Myelin-associated glycoprotein is produced before myelin basic protein in cultured oligodendrocytes.
Mixed glial cell cultures from neonatal dog cerebellum were harvested daily between 3 and 21 days after seeding and studied with immunocytochemical techniques for the demonstration of myelin-associated glycoprotein (MAG) and myelin basic protein (MBP). Both MAG and MBP were detected in the cultures and by means of double labelling techniques shown to be produced by the same cells. MAG+ cells occurred earlier and were always more numerous than MBP+ cells. These results suggest that the oligodendrocyte in vitro expresses MAG before MBP. The findings are discussed in respect to oligodendroglial differentiation and myelination in vivo.


Blockade by phentolamine of the potentiation of histamine-induced vasoconstriction caused by serotonin and methysergide in the rabbit ear artery.
1. In subconstrictor doses, both serotonin and methysergide potentiated the vasoconstrictor responses to histamine in the isolated artery of the rabbit ear. 2. In the presence of phentolamine (5 microgram/ml) the potentiating actions of serotonin and methysergide were significantly reduced. 3. This blocking action of phentolamine could be overcome by increasing the concentration of serotonin or by washing the preparation. 4. In arteries taken from rabbits pretreated with reserpine, serotonin still potentiated the response to histamine and phentolamine still blocked this potentiation. 5. The concentration of phentolamine required to block potentiation also blocked the direct constrictor response to serotonin. It did, however, produce a significantly greater blockade of the vasoconstrictor response to noradrenaline. 6. The results indicate that the action of phentolamine in blocking the vascular potentiation produced by serotonin and methysergide is not due to a blockade of alpha-receptors.


Daratumumab for the Treatment of Multiple Myeloma: A Review of Clinical Applicability and Operational Considerations.
To review the available data for the efficacy and safety of daratumumab in the treatment of multiple myeloma (MM), both in the newly diagnosed and relapsed/refractory settings, as well as provide additional guidance to clinicians on operational, safety, and supportive care considerations. A literature search of PubMed (1966 to October 2021) was conducted using the keywords daratumumab, Darzalex, and myeloma. Data were also obtained from prescribing information and unpublished abstracts from meetings. All relevant published articles, prescribing information, and unpublished meeting abstracts on daratumumab for the treatment of MM were reviewed. Daratumumab is an anti-CD38 monoclonal antibody indicated for the treatment of MM. The addition of daratumumab to proteasome inhibitor and immunomodulatory drug-based regimens has led to a consistent improvement in progression-free survival and response rates in relapsed/refractory MM as per the POLLUX, CASTOR, APOLLO, and CANDOR trials. The ALCYONE and MAIA phase III trials have demonstrated an overall survival benefit when adding daratumumab to frontline regimens for transplant-ineligible patients with newly diagnosed MM. In transplant-eligible patients, daratumumab-based quadruplet regimens have improved depth of response in the CASSIOPIEA and GRIFFIN trials. Operational and safety considerations that clinicians need to account for do exist, including different administration and infusion strategies, infusion-related reactions, increased risk for infectious complications, and interference with blood transfusion management. Daratumumab has led to a shift in the treatment paradigm of both newly diagnosed and relapsed/refractory MM, leading to improvements in outcomes such as response rates, depth of response, and progression-free survival.


Phosphorylation of translation initiation factor eIF2alpha in the brain during pilocarpine-induced status epilepticus in mice.
In this work, we show extensive phosphorylation of the alpha subunit of translation initiation factor 2 (eIF2alpha) occurring in the brain of mice subjected to 30 min of status epilepticus induced by pilocarpine. eIF2alpha(P) immunoreactivity was detected in the hippocampal pyramidal layer CA1 and CA3, cortex layer V, thalamus and amygdala. After 2 h of recovery, there was a marked decrease in total brain eIF2alpha(P), with the cortex layer V showing the most pronounced loss of anti-eIF2alpha(P) labeling, whereas the CA1 subregion had a significant increase in eIF2alpha(P). These results indicate that inhibition of protein synthesis in experimental models of epilepsy might be due to low levels of eIF2-GTP caused by the phosphorylation of eIF2alpha, and suggest that translational control may contribute to cell fate in the affected areas.


Serum factor in cystic fibrosis: correlation with clinical parameters.
The relationship between the activity of the cystic fibrosis serum ciliary dyskinesia factor, detected by the rabbit tracheal bioassay, and clinical status of the patient has been investigated in children, 1-24 years old, with cystic fibrosis. No significant correlation was found between the amount of serum factor activity and age, clinical status assessed by the Schwachman score, pulmonary function (vital capacity, functional residual capacity, total lung capacity, residual volume, maximum breathing capacity, maximal midinspiratory flow, and maximal midexpiratory flow) or blood gas levels (pCO2, pO2). The activity showed no significant relationship to serum galactosyltransferase activity in children with cystic fibrosis.


Spectroscopy analysis of phenolic and sugar patterns in a food grade chestnut tannin.
Tannin of chestnut (Castanea sativa Mill.) wood, commonly used in winemaking was characterised with a spectroscopy qualitative approach that revealed its phenolic composition: several vibrational diagnostic bands assigned using the Attenuated Total Reflectance-Infrared Spectroscopy, and fragmentation patterns obtained using the Laser-Desorption-Ionization Time-of-Flight technique evidenced polygalloylglucose, e.g. castalagin/vescalagin-like structures as the most representative molecules, together with sugar moieties. The implication of these findings on winemaking application and the potential influence of the chemical structure on the sensory properties of wine are discussed.


Use of differentiating embryonic stem cells in pharmacological studies.
Adipocytes and osteoblasts are derived from a common precursor cell. It has been proposed that the bone loss commonly seen during aging or in the pathology of osteoporosis might be partly caused by a deregulation of the normal balance between osteoblast and adipocyte differentiation. In vitro differentiation of mouse embryonic stem cells toward the adipogenic and the osteogenic lineages provides a powerful system for testing effects of compounds on the developmental switch between adipogenesis and osteogenesis and identification of pharmacological targets. In this chapter, an improved protocol to commit mouse embryonic stem cells into both lineages at a correct rate is detailed.


Reliability of ophthalmic accident and emergency referrals: a new role for the emergency nurse practitioner?
Annual attendances at the accident and emergency (A&E) department of St Bartholomew's and The Royal London NHS Trust exceed 100,000 people of which 6% are ophthalmic. This study evaluated the accuracy of eye referrals from A&E senior house officers (SHOs) and emergency nurse practitioners (ENPs) and the impact any inaccuracies may have had on out of hours work. Over a four week period a record of all referrals from the A&E department was made. The doctor receiving the referral made a note of clinical variables as reported by the referring clinician. When the patient was subsequently reviewed by an ophthalmologist, a record was again made of these findings. Any discrepancies were recorded. A total of 67 patients were recruited. ENPs were found to be consistently more accurate than SHOs in every aspect of the assessment, most notably in visual acuity (p = 0.0029), and provisional diagnosis (p = 0.012). Furthermore, had the examination findings been accurate, 58% of all SHO referrals seen after hours would have been triaged to the next available clinic but only 10% of ENP referrals could have been seen at the next clinic session (p = 0.027). This study found ENPs to be more accurate than A&E SHOs in history taking, recording visual acuity, describing ocular anatomy, and making provisional diagnoses. A significant reduction in out of hours ophthalmic workload may be achieved in the authors' unit if ENPs were to see all eye emergencies.


In-person versus remote CBT groups during COVID-19 for adolescents with mood disorders or psychosis-risk syndromes.
Since the COVID-19 pandemic, psychosocial therapies have been provided in varying formats, including remote, in-person, and hybrid services. It is unclear whether varying formats are similarly efficacious in improving psychiatric symptoms and functioning, lead to similar rates of treatment retention, and are equally acceptable to patients. This study compared youth with mood disorders and/or psychosis-risk syndromes who participated in a group cognitive behavioral therapy (CBT) in-person prior to COVID-19, to youth in the same treatment given remotely during the pandemic. Adolescents ages 13-17 years participated in 9 sessions of group-based CBT given in-person (2018-2019) or remotely (2020-2021). Youth participants provided self-report ratings of psychiatric symptoms, psychosocial functioning, and emotional regulation at the study baseline and post-treatment and ratings of treatment satisfaction and burden at post-treatment. There were no differences between in-person and remote treatment improvements in psychiatric symptoms, psychosocial functioning or emotional regulation. However, youth in remote treatment had increased retention compared to youth who received treatment in person. Youth in the remote treatment reported similar levels of satisfaction but reported lower burden compared to those who received in-person treatment. Participants were not randomized into remote or in-person treatment. Participants prior to COVID did not have the same frame of reference for alternative treatment delivery options as those during or post-COVID. Remote group treatment can provide similar levels of psychiatric benefit but less burden than in-person treatment for youth with mood disorders and/or psychosis-risk syndromes.


Regeneration of test in testate amoebae of the genus Arcella (Tubulinea, Arcellinida).
Although the presence of test is the most fundamental synapomorphy of arcellinid lobose amoebae, the significance of tests in maintenance of the biological functions of these organisms is still largely unclear. This paper demonstrates the effect of the artificial test removal on the behaviour, ultrastructure and reproduction of the testate lobose amoebae belonging to the two species of the genus Arcella. The studied cells can survive after artificial removal of their test, and many specimens are capable of building a test de novo. We investigated this process and found that test-free cells of Arcella in culture remained alive for weeks; they are able to move and feed, but never undergo normal cell division accompanied by mitosis. Test-free cells can restore the test in three different ways: (1) building almost normal test; (2) building a very small single-chambered test; (3) building a test which consisted of several small chambers attached to each other. Although newly constructed tests are abnormal, cells restore shape, size and other characteristic features of the test in the next one or two generations of descendants. The results obtained suggest that the test may be critically important for completing a life cycle of an amoeba.


Whole-body DHA synthesis-secretion kinetics from plasma eicosapentaenoic acid and alpha-linolenic acid in the free-living rat.
Whole body docosahexaenoic acid (DHA, 22:6n-3) synthesis from α-linolenic acid (ALA, 18:3n-3) is considered to be very low, however, the daily synthesis-secretion of DHA may be sufficient to supply the adult brain. The current study aims to assess whether whole body DHA synthesis-secretion kinetics are different when comparing plasma ALA versus eicosapentaenoic acid (EPA, 20:5n-3) as the precursor. Male Long Evans rats (n=6) were fed a 2% ALA in total fat diet for eight weeks, followed by surgery to implant a catheter into each of the jugular vein and carotid artery and 3h of steady-state infusion with a known amount of (2)H-ALA and (13)C-eicosapentaenoic acid (EPA, 20:5n3). Blood samples were collected at thirty-minute intervals and plasma enrichment of (2)H- and (13)C EPA, n-3 docosapentaenoic acid (DPAn-3, 22:5n-3) and DHA were determined for assessment of synthesis-secretion kinetic parameters. Results indicate a 13-fold higher synthesis-secretion coefficient for DHA from EPA as compared to ALA. However, after correcting for the 6.6 fold higher endogenous plasma ALA concentration, no significant differences in daily synthesis-secretion (nmol/day) of DHA (97.6±28.2 and 172±62), DPAn-3 (853±279 and 1139±484) or EPA (1587±592 and 1628±366) were observed from plasma unesterified ALA and EPA sources, respectively. These results suggest that typical diets which are significantly higher in ALA compared to EPA yield similar daily DHA synthesis-secretion despite a significantly higher synthesis-secretion coefficient from EPA.


Position statement on priorities for artificial intelligence in GI endoscopy: a report by the ASGE Task Force.
Artificial intelligence (AI) in GI endoscopy holds tremendous promise to augment clinical performance, establish better treatment plans, and improve patient outcomes. Although there are promising initial applications and preliminary clinical data for AI in gastroenterology, the field is still in a very early phase, with limited clinical use. The American Society for Gastrointestinal Endoscopy has convened an AI Task Force to develop guidance around clinical implementation, testing/validating algorithms, and building pathways for successful implementation of AI in GI endoscopy. This White Paper focuses on 3 areas: (1) priority use cases for development of AI algorithms in GI, both for specific clinical scenarios and for streamlining clinical workflows, quality reporting, and practice management; (2) data science priorities, including development of image libraries, and standardization of methods for storing, sharing, and annotating endoscopic images/video; and (3) research priorities, focusing on the importance of high-quality, prospective trials measuring clinically meaningful patient outcomes.


Carbon relations and competition between woody species in a Central European hedgerow : III. Carbon and water balance on the leaf level.
Annual carbon and water balances of sun leaves were measured in the field for five competing woody hedgerow species of different successional stages. They were compared with carbon and water budgets of climax species from the literature. Climatic limitation of primary production, the effectiveness of leaf photosynthetic capacity in relation to actual carbon gain, costs and time of leaf formation and amortization, and net dry matter gain from the leaf were determined. Their relevance for a species' position during a natural succession from pioneer-invaded fallow land to a climax beech forest in Central Europe is discussed.


Intra-lineage Plasticity and Functional Reprogramming Maintain Natural Killer Cell Repertoire Diversity.
Natural killer (NK) cell repertoires are made up of phenotypically distinct subsets with different functional properties. The molecular programs involved in maintaining NK cell repertoire diversity under homeostatic conditions remain elusive. Here, we show that subset-specific NK cell proliferation kinetics correlate with mTOR activation, and global repertoire diversity is maintained through a high degree of intra-lineage subset plasticity during interleukin (IL)-15-driven homeostatic proliferation in vitro. Slowly cycling sorted KIR+CD56dim NK cells with an induced CD57 phenotype display increased functional potential associated with increased transcription of genes involved in adhesion and immune synapse formation. Rapidly cycling cells upregulate NKG2A, display a general loss of functionality, and a transcriptional signature associated with increased apoptosis/cellular stress, actin-remodeling, and nuclear factor κB (NF-κB) activation. These results shed light on the role of intra-lineage plasticity during NK cell homeostasis and suggest that the functional fate of the cell is tightly linked to the acquired phenotype and transcriptional reprogramming.


Ex vivo stimulation of cord blood mononuclear cells by dexamethasone and interleukin-7 results in the maturation of interferon-gamma-secreting effector memory T cells.
The effects of dexamethasone phosphate and interleukin-7 upon the proliferation of T-cells and the production of interferon-gamma in the newborn's cord blood mononuclear cell cultures were studied. The capability of dexamethasone to enhance T-cell proliferation induced by anti-CD3 with interleukin-7 in some newborn cord blood mononuclear cell cultures was identified. Dexamethasone suppressed production of interferon-gamma in 68-h cell cultures stimulated with anti-CD3 both in the presence of interleukin-7 and without it. However, a 68-h cultivation of newborn blood cells with dexamethasone, anti-CD3 and interleukin-7 resulted in the accumulation of T-lymphocytes capable of producing interferon-gamma after restimulation. As a result of it the amount of interferon-gamma producing CD7(+) T-cells and the concentration of interferon-gamma in cultural supernatants were maximal in the cell cultures incubated with anti-CD3, interleukin-7 and dexamethasone during the first 68 h and subsequently restimulated with phorbol 12-myristate 13-acetate and ionomycin. The stimulation of neonatal or adult blood cells by dexamethasone, anti-CD3 and interleukine-7 also causes a decrease in the number of naïve T-cells and central memory cells and an increase in the number of effector memory CD7(+)CD45RA(+)CD62L(-) cells in cultures. It is possible that these effects are caused by the influence of dexamethasone on IL-7 receptor expression: it is known that IL-7 receptor alpha-chain gene is a glucocorticoid-inducible gene.


Epidural analgesia? A prospective analysis of perioperative coagulation in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is beneficial in peritoneal carcinomatosis. Epidurals provide excellent pain relief for laparotomies. Coagulopathy (platelet count <100 × 109/L, INR>1.5 or PTT >45) occurs with CRS and HIPEC, increasing risk for bleeding complications with epidurals. This prospective study characterizes clot kinetics with thromboelastography (TEG) to determine suitability for epidural analgesia. After Research Ethics approval, thirty consented patients had blood collected. Primary data collected included TEG and conventional coagulation measures (platelets, PTT and INR). Secondary data collected included demographics, disease, surgical, intraoperative factors and complications from epidural placement. Of 30 patients analyzed, two had incomplete data. Four developed abnormal coagulation between the second and fifth post-operative day. For all patients, TEG values remained normal. Postoperative INR was elevated until day 3 (all INR < 1.5). 17 patients received epidural analgesia, 3 demonstrated abnormal conventional coagulopathic criteria despite normal TEG. In this study CRS and HIPEC do not contribute to the conventional definition of clinical coagulopathy. Clot kinetics indicate that epidural catheters may be recommended for post-operative analgesia.


Natural deep eutectic solvents for the extraction of lentinan from shiitake mushroom: COSMO-RS screening and ANN-GA optimizing conditions.
Using natural deep eutectic solvents (NDES) for green extraction of lentinan from shiitake mushroom is a high-efficiency method. However, empirical and trial-and-error methods commonly used to select suitable NDES are unconvincing and time-consuming. Conductor-like screening model for realistic solvation (COSMO-RS) is helpful for the priori design of NDES by predicting the solubility of biomolecules. In this study, 372 NDES were used to evaluate lentinan dissolution capability via COSMO-RS. The results showed that the solvent formed by carnitine (15 wt%), urea (40.8 wt%), and water (44.2 wt%) exhibited the best performance for the extraction of lentinan. In the extraction stage, an artificial neural network coupled with genetic algorithm (ANN-GA) was developed to optimize the extraction conditions and to analyze their interaction effects on lentinan content. Therefore, COSMO-RS and ANN-GA can be used as powerful tools for solvent screening and extraction process optimization, which can be extended to various bioactive substance extraction.


Neurochemical plasticity and the role of neurotrophic factors in bladder reflex pathways after spinal cord injury.
Transection of the spinal cord that interrupts the spinobulbospinal micturition reflex pathway, abolishes voluntary voiding and initially produces an areflexic bladder with complete urinary retention. However, depending upon the species, reflex bladder activity slowly recovers over the course of weeks or months. In chronic spinal animals, reflex mechanisms in the lumbosacral spinal cord are capable of duplicating many of the functions performed by reflex pathways in animals with an intact spinal cord and can induce bladder hyperreflexia. However, the bladder does not empty efficiently due to a loss of bladder-sphincter coordination (bladder-sphincter dyssynergia). In contrast to normal animals in which the sphincter relaxes during voiding, animals with a spinal cord injury exhibit sphincter contractions during voiding, an increase in urethral outlet resistance, urinary retention, bladder hyperreflexia, bladder overdistension, and an increase in bladder afferent cell size. Changes in electrophysiological or neurochemical properties of bladder afferent cells in the dorsal root ganglia and of spinal pathways could contribute to the emergence of the spinal micturition reflex, bladder hyperreflexia and changes in the pharmacologic responses of reflex pathways in the lumbosacral spinal cord after spinal cord injury. Urinary bladder hyperreflexia after spinal cord injury may reflect a change in the balance of neuroactive compounds in bladder reflex pathways. This review will detail: (1) changes in the neurochemical phenotype of bladder afferent neurons and of spinal neurons mediating micturition reflexes after spinal cord injury, with an emphasis on three neuroactive compounds, neuronal nitric oxide synthase (nNOS), galanin, and pituitary adenylate cyclase activating polypeptide (PACAP); (2) possible functional consequences on bladder reflexes of changes in spinal cord neurochemistry after spinal cord injury, and (3) the potential role of neurotrophic factors expressed in the urinary bladder or spinal cord after spinal cord injury in mediating these neurochemical changes.


Combining staged laparoscopic colectomy with robotic completion proctectomy and ileal pouch-anal anastomosis (IPAA) in ulcerative colitis for improved clinical and cosmetic outcomes: a single-center feasibility study and technical description.
Robotic proctectomy has been shown to lead to better functional outcomes compared to laparoscopic surgery in rectal cancer. However, in ulcerative colitis (UC), the potential value of robotic proctectomy has not yet been investigated, and in this indication, the operation needs to be adjusted to the total colectomy typically performed in the preceding 6 months. In this study, we describe the technique and analyze outcomes of a staged laparoscopic and robotic three-stage restorative proctocolectomy and compare the clinical outcome with the classical laparoscopic procedure. Between December 2016 and May 2021, 17 patients underwent robotic completion proctectomy (CP) with ileal pouch-anal anastomosis (IPAA) for UC. These patients were compared to 10 patients who underwent laparoscopic CP and IPAA, following laparoscopic total colectomy with end ileostomy 6 months prior by the same surgical team at our tertiary referral center. 27 patients underwent a 3-stage procedure for refractory UC (10 in the lap. group vs. 17 in the robot group). Return to normal bowel function and morbidity were comparable between the two groups. Median length of hospital stay was the same for the robotic proctectomy/IPAA group with 7 days [median; IQR (6-10)], compared to the laparoscopic stage II with 7.5 days [median; IQR (6.25-8)]. Median time to soft diet was 2 days [IQR (1-3)] vs. 3 days in the lap group [IQR 3 (3-4)]. Two patients suffered from a major complication (Clavien-Dindo ≥ 3a) in the first 90 postoperative days in the robotic group vs. one in the laparoscopic group. Perception of cosmetic results were favorable with 100% of patients reporting to be highly satisfied or satisfied in the robotic group. This report demonstrates the feasibility of a combined laparoscopic and robotic staged restorative proctocolectomy for UC, when compared with the traditional approach. Robotic pelvic dissection and a revised trocar placement in staged proctocolectomy with synergistic use of both surgical techniques with their individual advantages will likely improve overall long-term functional results, including an improved cosmetic outcome.


Dataset supporting the proteomic characterization of human corneal epithelial cells with HSV-1 infection.
HSV-1 infection in cornea can cause corneal ulcer, scar formation and neovascularization, and finally lead to severe visual impairment. The corneal epithelium is the first barrier against HSV-1 infection, but the host-virus interaction in human corneal epithelial cells (HCECs) in the process is still not well understood. We applied iTRAQ based proteomic approach to investigate the dynamic change of the protein expression profile in HCECs with a view to gain insight into the host response to HSV-1 infection. Bioinformatic analysis of these dysregulated proteins help us to find the potential gene function and signaling pathway with which these dysregulated proteins are associated. In this work, we present the supporting information for the proteomic characterization for better share and reuse. The main methodological approaches and major findings of the proteomic experiments are described in [1].


Probucol Quantitative Regression Swedish Trial: new angiographic technique to measure atheroma volume of the femoral artery.
The Probucol Quantitative Regression Swedish Trial is studying the development of atherosclerosis in hyperlipidemic patients through the use of digitized femoral arteriographic examinations. In a 20-cm segment of the femoral artery, cross-sectional areas are calculated using an algorithm that was introduced by Hilal and Crawford. Changes in atheroma volume are measured in repeat arteriographic examinations. This report describes the radiologic technique, the scanning procedure and the image analysis.


Multiple-dose granulocyte-macrophage-colony-stimulating factor plus 23-valent polysaccharide pneumococcal vaccine in patients with chronic lymphocytic leukemia: a prospective, randomized trial of safety and immunogenicity.
For the current study, the authors sought to determine whether administration of multiple-dose granulocyte-macrophage-colony-stimulating factor (GM-CSF) could improve response to standard 23-valent polysaccharide pneumococcal vaccine (PPV) in patients with chronic lymphocytic leukemia (CLL). Patients were allocated randomly to receive PPV either alone or with 3 doses of GM-CSF (250 microg) given before or after vaccination. Serum was obtained before, 4 weeks after, and 12 weeks after vaccination for antibody determination. Thirty-two patients with CLL were given PPV. They were randomized to receive 3 doses of GM-CSF either before or after vaccination or to receive no GM-CSF. A 4-fold rise in immunoglobulin G (IgG) to capsular polysaccharides from Streptococcus pneumoniae types 4, 6B, 9V, 14, 19F, and 23F occurred in <10% of patients in each of the 3 groups. There were no differences in geometric mean IgG levels in any of the 3 groups 4 weeks or 12 weeks after vaccination. In patients with CLL, the response to pure polysaccharide pneumococcal vaccine was low despite immune enhancement with multiple doses of GM-CSF. In all patients, reactogenicity was minor.


Receptor-mediated activation of electropermeabilized neutrophils. Evidence for a Ca2+- and protein kinase C-independent signaling pathway.
Electrically permeabilized neutrophils were used to study the mechanism of activation of the respiratory burst by the chemotactic agent formyl-methionyl-leucyl-phenylalanine (fMLP). Permeabilization was assessed by flow cytometry, radioisotope trapping, and by the requirement for exogenous NADPH for oxygen consumption. A respiratory burst could be elicited by fMLP, phorbol ester, or diacylglycerol in permeabilized cells suspended in EGTA-buffered medium with 100 nM free Ca2+. The fMLP response persisted even in cells depleted of intracellular Ca2+ stores by pretreatment with ionomycin. Therefore, a change in cytosolic free Ca2+ ([Ca2+]i) is not required for receptor-mediated stimulation of the respiratory burst. The responses induced by phorbol ester and diacylglycerol were largely inhibited by H7, a protein kinase C antagonist. In contrast, the stimulation of oxygen consumption by fMLP was unaffected by H7. These results suggest that a third signaling pathway, distinct from changes in [Ca2+]i and activation of protein kinase C, is involved in the response of neutrophils to chemoattractants.


DNA Extraction: Organic and Solid-Phase.
DNA extraction remains a critical step in DNA profiling of biological material recovered from scenes of crime. In the forensic community several methods have gained popularity, including Chelex(®), organic extraction, and solid-phase extraction. While some laboratories streamlined their processes and only use one method we have retained several methods and continue to use these for different sample types. In this chapter we present three methods that have been used for several years in our laboratory.


A nonelemental versus an elemental diet for early postoperative enteral feeding by needle catheter jejunostomy.
In a prospective randomised study the use of an elemental versus a nonelemental diet for early postoperative enteral feeding by needle catheter jejunostomy was investigated. After extensive gastrointestinal surgery, 25 patients received an elemental and 24 patients a nonelemental diet. The incidence of diarrhoea, the effects of the feeding and the costs were evaluated. The occurrence of diarrhoea was observed more frequently in the elemental diet group (14 25 ) compared to the nonelemental diet group (7 24 ), although this difference was statistically not significant (p > 0.05). No difference was found between the two groups in postoperative restoration of total protein and serum albumin levels and the extent of the postoperative weight loss. The costs showed a clear difference: the nonelemental diet was three times cheaper than the elemental diet. For early postoperative enteral feeding by needle catheter jejunostomy we therefore recommend the use of a nonelemental diet.


SARS-COV-2 Infection in People Living with HIV: Experience from a Tertiary Hospital in Madrid.
Since SAR-COV-2 infection emerged and spread worldwide, little is known about its impact on people living with human immunodeficiency virus (HIV). We performed a single-center retrospective study to describe the potential particularities and risk factors for respiratory failure (RF) in that population. This single-center retrospective study included patients infected with HIV, whose current follow-up is run in this center, above18 years of age, with diagnosis of SARS-CoV-2 infection between March 5, 2020 and April 15, 2021. We collected data regarding HIV immunological and virological status, main epidemiological characteristics, as well as those conditions considered to potentially influence in SARS-CoV-2 evolution; and clinical, microbiological, radiological, respiratory status, and survival concerning coronavirus disease 2019 (COVID-19). We compared all that, for patients with and without RF and performed a logistic regression for suspected risk factors for RF. One hundred seventy-seven HIV patients were diagnosed from COVID-19 (mean age 53.8 years, 81.3% male). At diagnosis, 95.5% were receiving ART and 91.3% had undetectable viral load, with median CD4 count of 569 cells/μL. One hundred thirty-eight patients (78.4%) had symptoms, 44 (25%) developed RF and 53 (31%) developed bilateral pneumonia. The most commonly used treatments were: steroids (26.7%) and hydroxychloroquine (13.1%). When comparing patients with and without RF, we found statistically significant differences for 20 of the analyzed variables such as age (p < .001) and CD4 (p 0.002), and route of HIV transmission by intravenous drug users IVDU (p 0.002) were determined. In multivariate analysis, age [odds ratio (OR) 1.095] and CD4 count less than 350 cells/μL (OR 3.36) emerged as risk factor for RF. People living with HIV whose CD4 count is <350 cells are at higher risk of developing RF when infected by SARS-CoV-2.


Design Principles of Responsive Relaxometric 19F Contrast Agents: Evaluation from the Point of View of Relaxation Theory and Experimental Data.
19F magnetic resonance imaging (MRI) is a promising tool in medical diagnostics. An important class of 19F MRI contrast agents is based on paramagnetic resonance enhancement. This effect allows an improvement in sensitivity by increasing the number of scans per unit of time or facilitates the development of responsive contrast agents that are based on changes in relaxation rates as a detection principle. In this work, Bloch-Redfield-Wangsness relaxation theory was used to predict the relaxation properties of existing lanthanoid and transition metal complexes of fluoroorganic ligands and to evaluate several design strategies for responsive contrast agents. Electron-nucleus dipole-dipole, Curie relaxation, and contact interactions were included in the model. Potential significance of chemical shift anisotropy-anisotropic dipolar shielding cross-correlation was discussed. The calculated and experimental results were well aligned. The presented model, along with the optimized field-dependent values of electronic relaxation times, could be used for the preliminary selection of the optimal metal ion for applications in 19F MRI. The results indicate potential advantages of other metal ions in addition to Gd3+ particularly Cu2+, Mn2+, Ni2+, Fe3+, and other lanthanoids as a part of 19F contrast agents.


Less Invasive Corneal Transepithelial Electrical Resistance Measurement Method.
To evaluate acute corneal permeability changes after instillation of benzalkonium chloride (BAC) using a newly developed in vivo less invasive corneal transepithelial electrical resistance (TER) measurement method in animals and humans. We previously developed an in vivo method for measuring corneal TER using intraocular electrodes in animals. This method can be used to precisely measure the decline of the corneal barrier function after instillation of BAC. To lessen the invasiveness of that procedure, we further refined the method for measuring the corneal TER by developing electrodes that could be placed on the surface of the cornea and in the conjunctival sac instead of inserting them into the anterior chamber. Corneal TER changes before and after exposure to 0.02% BAC were determined in this study using the new device in both rabbits and humans. There was a significant decrease in the corneal TER after exposure of the cornea to 0.02% BAC solution in both rabbits and humans (P<.01). The results of this new less invasive method agreed with those of formerly established anterior chamber methods in rabbit experiments. This new less invasive corneal TER measurement method enables us for the first time to measure TER of the human cornea, allowing safe and reliable investigation of the direct effect of different eye drop treatments on the corneal epithelium.


COVID-19 vaccine hesitancy and health literacy in US Southern states.
COVID-19 vaccination in the United States has stalled, with some of the lowest rates in the South. Vaccine hesitancy is a primary contributor and may be influenced by health literacy (HL). This study assessed the association between HL and COVID-19 vaccine hesitancy in a population residing in 14 Southern states. Cross-sectional study using a web-based survey conducted between February and June 2021. The outcome was vaccine hesitancy, and the main independent variable was HL, assessed as an index score. Descriptive statistical tests were performed, and multivariable logistic regression analysis was conducted, controlling for sociodemographic and other variables. Of the total analytic sample (n = 221), the overall rate of vaccine hesitancy was 23.5%. Vaccine hesitancy was more prevalent in those with low/moderate HL (33.3%) vs those with high HL (22.7%). The association between HL and vaccine hesitancy, however, was not significant. Personal perception of COVID-19 threat was significantly associated with lower odds of vaccine hesitancy compared with those without perception of threat (adjusted odds ratio, 0.15; 95% CI, 0.03-0.73; P = .0189). The association between race/ethnicity and vaccine hesitancy was not statistically significant (P = .1571). HL was not a significant indicator of vaccine hesitancy in the study population, suggesting that general low rates of vaccination in the Southern region may not be due to knowledge about COVID-19. This indicates a critical need for place-based or contextual research on why vaccine hesitancy in the region transcends most sociodemographic differences.


Synthesis of non-anomeric C-glycosyl pyrazolidinone derivatives via visible-light photoredox catalysis.
C-Glycosyl compounds have gained considerable attention over the last few decades due to their high chemical stability and promising applications in drug discovery. Herein we disclose an operationally simple, metal-free, photocatalytic approach for the glycosylation of azomethine imines using 4-glycosyl-1,4-dihydropyridines (DHPs) as radical precursors. The protocol features mild reaction conditions, scalability, broad substrate scope, and good functional group tolerance. Moreover, the resulting pyrazolidinone moiety can be easily deprotected, acylated or reduced into a glycosyl β-alanine analog.


Removal of chlorine-contaminated groundwater by two-stage ozonation and biostimulation methods.
Trichloroethene (TCE) contamination is a critical environmental hazard, and the substrate options for its biostimulated remediation are limited. This study applied an ozonation-and-biostimulation process to remove TCE from groundwater. The substrate used, denoted as Transferred Energy Element (TEE), was composed of natural organic materials and had a low viscosity (2.914 cP). Ten batch experiments were conducted through the application of micro-nano bubbles (MNBs) and substrates (TEE and EOS® [emulsified oil substrate]). MNBs with an average diameter of 157.5-180.8 nm effectively degraded TCE and dichloroethane within 6 min. Biostimulation using the TEE substrate effectively degraded both TCE and vinyl chloride pollutants and reached a steady state after 25 days. The two-stage dechlorination procedure with MNB treatment as the first stage enhanced TCE removal via biostimulation. MNBs reduced the TCE concentration in the first 20 min, but increased the chloride (Cl-) concentration over the following five days (∼80 mg/L). The procedure with biostimulation as the first stage and 20 min ozonation as the second stage reduced the Cl- concentration by ∼10 mg/L. The Cl- concentrations rebounded after day 25 in the EOS environment. X-ray diffraction revealed that the released Na+ from the TEE settled with Cl- as minerals in the soil. The novel two-stage method for TCE removal was found to be more effective than solo MNB treatment or biostimulation.


The role of mesh technology with tumor prosthesis reconstruction to reconstruct the extensor mechanism of knee joint after resection of proximal tibial tumors.
The aim of this study was to evaluate the role of mesh technique in the reconstruction of the extensor mechanism after resection of proximal tibial tumors. We retrospectively analyzed the cases of 14 patients who were diagnosed with proximal tibial tumors at our center and reconstructed with tumor prosthesis, gastrocnemius muscle, and mesh between 2012 and 2017. The treatment strategies for patellar tendon reconstruction primarily involve gastrocnemius reconstruction to cover the tumor prosthesis and mesh reconstruction for the patellar ligament. Among the 14 patients, the mean was 1.57° (range 0-12°) for active extension versus 105.00° (range 80-120°) for active flexion. The mean for passive extension was 0°. The passive flexion mean was 115.00° (range 90-120°). The extensor lag averaged 1.57° (range 0-12°), and the mean Musculoskeletal Tumor Society score (MSTS) was 23.57 (range 19-27). The average follow-up for all patients was 23.50 months (range 14-37). During the recent follow-up, all patients were able to walk without crutches. Two patients underwent above-the-knee amputation for local recurrence of the tumor, and lung metastasis occurred in three patients after operation. There were no postoperative complications. Extensor lag was remarkably reduced in the surgery group in comparison to previous study reports. Surgical resection is a simple, reliable, and effective method to remove and control the tumor. Mesh reconstruction of patellar ligament is effective to reconstruct the extensor mechanism of the knee after excision of tumor.


A hypothesis about the role of fetal hemoglobin in COVID-19.
COVID-19 infection is less common in children (with higher fetal hemoglobin levels). In our preliminary study, we also observed a low prevalence and fatality of COVID-19 in countries with high rate of hemoglobinopathy carries. Given these two facts, the hemoglobin structure can play a role in the physiopathology of COVID-19 disease. Several drugs are known to increase fetal hemoglobin in adults. Adding these drugs to COVID-19 clinical trials may improve the patients' outcomes.


A prospective observational cohort safety study of 5106 platelet transfusions with components prepared with photochemical pathogen inactivation treatment.
Inactivation of pathogens and white blood cells in platelet (PLT) components with amotosalen and UVA light (INTERCEPT, Cerus Europe BV) has entered clinical practice in European blood centers. A prospective cohort study was implemented to characterize the safety profile of this new PLT component in a broad patient population. Apheresis or buffy-coat PLT components were leukoreduced, suspended in approximately 35 percent plasma and 65 percent PLT additive solution, and treated with the INTERCEPT process. Blood centers were requested to complete a safety data form after each transfusion. Data for 5106 INTERCEPT components administered to 651 patients were monitored. A total of 5051 (98.9%) transfusions and 609 (93.5%) patients had no reported reactions. Fifty-five (1.1%) transfusions were associated with adverse events, and 42 (0.8%) were possibly, probably, or related to the PLT transfusion. Adverse events occurred in 42 (6.4%) patients, but in only 32 (4.9%) patients was a causal relationship to PLT transfusion established. One reaction was serious, and no deaths were related to PLT transfusion. Among the transfusions reactions, the most frequent clinical events in descending frequency were chills, fever, dermatologic reactions, dyspnea, nausea or vomiting, and hypotension. No episodes of transfusion-related acute lung injury were reported. In this cohort study, 99.2 percent of transfusions were without reactions attributed to PLTs. INTERCEPT PLTs exhibited a safety profile similar to that previously reported for conventional PLT components.


Iatrogenic retinal breaks in 20-G versus 23-G pars plana vitrectomy.
The purpose of this study was to compare the incidence of iatrogenic anterior retinal breaks in 20-G vitrectomy (PPV) with transconjunctival 23-G PPV. Retrospective, observational review study involving consecutive patients undergoing PPV in a single center in the UK during a 2-year period. Sclerotomy-related entry-site breaks (ESB) were found in 50/628 (7.9 %) 20-G PPV cases and 5/296 (1.7 %) 23-G PPV eyes (p<0.0001*). Anterior non-sclerotomy iatrogenic breaks (ANSB) were present in 55/628 (8.7 %) 20-G PPV cases and 18/296 (6.1 %) 23-G PPV eyes (p=0.19). The incidence of total anterior iatrogenic breaks (ANSB + ESB) was 105/628 (16.7 %) for 20-G PPV and 23/296 (7.8 %) for 23-G PPV (p=0.002*). Univariate analysis showed that posterior vitreous detachment induction was the only risk factor significantly associated with the development of anterior retinal breaks for both 20-G and 23-G PPV. Multivariate logistic model of risk factors for development of iatrogenic retinal breaks demonstrated that 23-G PPV was the most important factor reducing the risk of anterior breaks (p<0.0001*). We report the largest series of patients undergoing 20-G and 23-G vitrectomy, where 23-G vitrectomy was associated with a significantly lower incidence of anterior iatrogenic retinal breaks.


Impact of a Donor Age >75 Years on the Survival of Liver Transplant Recipients.
An organ shortage is the reason why it is necessary to expand the pool of donors, which can be achieved by using elderly donors. The main goal of this study is to analyze the outcomes of liver transplant (LT) when it is performed with donors older than 75 years. We carried out a retrospective case-control study (N = 212) that included LTs with donors older than 75 years (group A, n = 106 cases) that were performed in our center between the years 2010 and 2020. This cohort has been paired off with a similar control group (group B, n = 106) whose donors were significantly younger. A survival analysis using the Kaplan-Meier model was performed. Average (SD) age of donors in group A was statistically greater than group B (A, 79.1 [3.0] years vs B, 54.4 [15.3], P < .001). There were no differences either in the average age of the recipients or in the Model for End-Stage Liver Disease score of both groups. Indications for LT were distributed equally in both groups: the most common was cellular hepatocarcinoma followed by alcohol-related cirrhosis. Survival rates for group A were 81%, 78%, and 67%, in 1, 3, and 5 years, respectively, while in group B they were 85%, 76%, and 71%, respectively, without differences found between the groups (P = .57). Using elderly liver donors is safe, achieving good outcomes in terms of short- and midterm rates of survival.