Retigabine-induced population primary afferent hyperpolarisation in vitro.
Retigabine is a compound of potential interest in analgesia which acts as an M-channel opener to depress neuronal excitability. Here we study the effects of retigabine and its antagonist XE-991 on populations of primary afferents. Experiments were performed using a hemisected spinal cord preparation from rat pups maintained under in vitro conditions. Recording from dorsal roots were performed using tight fitting suction electrodes coupled to AC and DC amplifiers. The adjacent dorsal root was electrically stimulated at regular intervals. The effects of the modulators on basal potential, spontaneous potentials and dorsal root-dorsal root responses were studied. Superfusion of retigabine (10 microM) produced long lasting and robust hyperpolarisation of primary afferents which persisted during superfusion of picrotoxin (20 microM) and tetrodotoxin (0.5 microM). Other effects of retigabine were (1) increase in stimulation threshold; (2) increase in size of responses to suprathreshold stimuli; and (3) increase in amplitude and decrease in frequency of spontaneous dorsal root potentials. Superfusion of XE-991 had little effect on its own but blocked all the effects of retigabine. These results indicate the presence of functional M-currents in central terminals of primary afferents and in the interneurones that mediate dorsal root potentials. The depressant effects of retigabine on the excitability of these structures may contribute to its analgesic effects after pain-inducing treatments.


Protein complex structure prediction powered by multiple sequence alignments of interologs from multiple taxonomic ranks and AlphaFold2.
AlphaFold2 can predict protein complex structures as long as a multiple sequence alignment (MSA) of the interologs of the target protein-protein interaction (PPI) can be provided. In this study, a simplified phylogeny-based approach was applied to generate the MSA of interologs, which was then used as the input to AlphaFold2 for protein complex structure prediction. In this extensively benchmarked protocol on nonredundant PPI dataset, including 107 bacterial PPIs and 442 eukaryotic PPIs, we show complex structures of 79.5% of the bacterial PPIs and 49.8% of the eukaryotic PPIs can be successfully predicted, which yielded significantly better performance than the application of MSA of interologs prepared by two existing approaches. Considering PPIs may not be conserved in species with long evolutionary distances, we further restricted interologs in the MSA to different taxonomic ranks of the species of the target PPI in protein complex structure prediction. We found that the success rates can be increased to 87.9% for the bacterial PPIs and 56.3% for the eukaryotic PPIs if interologs in the MSA are restricted to a specific taxonomic rank of the species of each target PPI. Finally, we show that the optimal taxonomic ranks for protein complex structure prediction can be selected with the application of the predicted template modeling (TM) scores of the output models.


Intraoperative localization of malignant pheochromocytoma by 123-I-metaiodobenzylguanidine single probe measurement.
Metaiodobenzylguanidine (MIBG) imaging is a well-established method for locating intra- and extraadrenal pheochromocytomas. We investigated whether preoperative injection of 123-I-MIBG might be useful for intraoperative staging of chromaffine tumor cells. This was performed in a 46-year-old patient in whom the diagnosis of a malignant pheochromocytoma had been established by 123-I-MIBG imaging and enhanced catecholamine secretion. The rationale for intraoperative staging in this patient was a discrepancy between computed tomography (CI) of the abdomen and the radionuclide imaging, because scintigraphy revealed a mass with MIBG uptake in the right lower abdomen that could not be visualized by CT. We thus applied a preoperative dose of 4 mCi 123-I-MIBG and determined tissue activity by direct organ measurement. A right abdominal mass was thus identified with an activity of 10 x 10(4) impulses/s as compared to normal tissue (15 x 10(2)). The left-sided tumor was found to be identified correctly by prior CT and MIBG imaging. We thus conclude that intraoperative application of this single probe measurement might help to identify chromaffine tumor cells that have not been located fully by CT.


[Synthesis and antibacterial activity of (S) -5-acetylaminomethyl-3-[(4-substituted-aminomethyl) phenyl] -2-oxazolindinone derivatives].
To synthesize oxazolindinone derivatives and test their antibacterial activities. 3-Halo-4-methylaniline was acylated with benzyl chloroformate, followed by cyclization with (R)-glycidyl butyrate, acylation with methanesulfonyl chloride, substitution with NaN3, reduction with H2 + Pd/C or P(OMe)3 + HCl, acylation with Ac2O, and bromination with NBS to form bromides VIIIa and VIIIb, Substitution of the bromides with various amines including aliphatic amine and aromatic amine provided the target compounds IXa and IXb. The in vitro antibacterial activity of the target compounds was tested. Fifty one new compounds were designed and synthesized. And their structures were confirmed by 1H NMR and elemental analyses or MS. Some physical constants such as [alpha]D25 were reported also. Compounds VIIb, IXa1, IXa2, IXa7, IXb1, IXb3, IXb10, IXb16 and IXb23 had moderate in vitro antibacterial activity against G+ bacteria but they were less active than linezolid or norfloxacin. Insertion of methylene group between 4-position of phenyl and morpholinyl group in linezolid derivatives can not increase the antibacterial activity.


Time course of incorporation of 20-carbon polyunsaturated fatty acids in a human keratinocyte cell line.
Human keratinocytes (NCTC 2544) in culture were labeled with equal amounts of either 14C-arachidonic acid, 14C-dihomo-gamma-linolenic acid or 14C-eicosapentaenoic acid. At various time points, the incubations were stopped and the distribution of the 14C-fatty acids was analyzed. All these eicosanoid precursor fatty acids were effectively incorporated into the cellular lipids of the keratinocytes, and the major radiolabeled individual lipid fraction was phosphatidylethanolamine. The distributions of arachidonic acid and dihomo-gamma-linolenic acid within cellular lipids were rather the same. However, less eicosapentaenoic acid than either arachidonic acid or dihomo-gamma-linolenic acid was incorporated into the phospholipids and, correspondingly, more eicosapentaenoic acid was incorporated into the nonphosphorus lipids. In the phosphatidylinositol + phosphatidylserine fraction, there was significantly less eicosapentaenoic acid than either arachidonic acid or dihomo-gamma-linolenic acid. The present study suggests that these eicosanoid precursor fatty acids are effectively incorporated into the human keratinocytes and that the pattern of incorporation and distribution of eicosapentaenoic acid appears to differ slightly from that of either arachidonic acid or dihomo-gamma-linolenic acid.


QTLs for low nitrogen tolerance at seedling stage identified using a recombinant inbred line population derived from an elite rice hybrid.
Tolerance to low nitrogen conditions is a highly desired characteristic for sustainable crop production. In this study, we analyzed the genetic components associated with low N tolerance in rice at seedling stage, including main effects, epistatic effects of the quantitative trait locus (QTLs), and QTL by environment interactions (QEs), using a population of 239 recombinant inbred lines (RILs) from a cross between Zhenshan 97 and Minghui 63, the parents of an elite hybrid. A genetic linkage map with 253 DNA maker loci was constructed. Seedlings of RILs were cultivated in low N and normal N solutions. Root, shoot and plant weight in the two N treatments were measured and the relative weight of the two treatments for each trait was considered as measurements for low N tolerance. Four to eight QTLs with main effects were detected for each of the nine traits. Very few QTLs were detected in both low and normal N conditions, and most QTLs for the relative measurements were different from those for traits under the two N treatments, indicating very little commonality in the genetic basis of the traits and their relative performance under low and normal N conditions. A total of 103 digenic interactions were detected for the nine traits. While the epistatic effects collectively accounted for large proportions of the variation for several traits, the effects of QEs appeared to be trivial. It was concluded that low N tolerance of rice seedling had complex genetic basis that requires extensive studies for full characterization.


Assessing the Underwater Ship Noise Levels in the North Tyrrhenian Sea.
The purpose of this research was to assess the anthropic underwater noise caused by ships within the Cetacean Sanctuary, a wide area in the North Tyrrhenian Sea. Noise from low-frequency continuous sounds has been investigated within the 1/3-octave bands centered at 63 and 125 Hz. All the information about noise sources and sound attenuation have been organized in a database; a tool automatically extracts useful information from it and feeds a ray-tracing model to estimate noise levels. The results show average levels generally over the 100 dB re 1 μPa value.


Medical errors: physician and institutional responsibilities.
When it comes to medical errors, honesty is always the best practice for your practice.


Resilience, post-traumatic growth, and work engagement among health care professionals after the Great East Japan Earthquake: A 4-year prospective follow-up study.
Although attention has been paid to post-traumatic stress disorder (PTSD) among health care professionals after disasters, the impact of traumatic events on their work has not been elucidated. The aim of this study was to examine whether disaster-related distress, resilience, and post-traumatic growth (PTG) affect work engagement among health care professionals who had been deployed to the areas affected by the Great East Japan Earthquake that occurred on March 11, 2011. We recruited disaster medical assistance team members who were engaged in rescue activities after the earthquake. The short version of the Resilience Scale (RS-14) and Peritraumatic Distress Inventory (PDI) were administered one month after the earthquake, and the short form of Posttraumatic Growth Inventory (SF-PTGI) and Utrecht Work Engagement Scale (UWES) were administered four years after the earthquake. Work engagement is composed of vigor, dedication, and absorption. Regression analyses were used to examine the relationship of UWES with RS-14, PDI, and SF-PTGI. We obtained baseline data of 254 participants in April 2011, and 191 (75.2%) completed the follow-up assessment between December 2014 and March 2015. The results showed that RS-14 predicted vigor, dedication, and absorption; in addition, SF-PTGI was positively related with these three parameters (p<0.01 for all). Resilience at baseline and PTG after rescue activities may increase work engagement among health care professionals after disasters. These findings could be useful for establishing a support system after rescue activities during a large-scale disaster and for managing work-related stress among health care professionals.


Factors associated with risk of burnout in neurosurgeons: current status and risk factors.
The study aimed to evaluate burnout and associated risk factors in neurosurgical residents and faculty members. Burnout is an occupational risk of emotional exhaustion, depersonalization, and reduced perception of personal accomplishment secondary to work stress. It burdens the individual with immense mental stress causing compromised professional performance. Healthcare workers, particularly surgeons, have been documented to be at high risk of developing burnout, considering the stressful routine and serious impact of their profession. The modified Maslach Burnout Inventory was filled by fellow neurosurgical residents or consultants. The respondents were classified into burnout and non-burnout groups and then analyzed for the associated risk factors. The data were analyzed using SPSS v26. One hundred and thirty-eight neurosurgical healthcare workers, including 62 residents and 76 consultants, responded to the questionnaire. The burnout and non-burnout groups comprised 83 (60%) and 55 (39.9%) respondents. Female gender and few kids were observed as significant risk factors for the development of burnout (p = 0.013 and p = 0.006, respectively). Regardless of its year, residency was a risk factor for overall burnout, as well as in each subsection of the Maslach Inventory (p = 0.002). In consultants, recent qualifications and a high number of weekly calls were also associated with a significant risk of burnout (p = 0.012 and p = 0 .027, respectively). Marital status and national economic status did not reveal any influence on the status of burnout in neurosurgical healthcare workers. Burnout syndrome is a prevalent and serious, yet overlooked, condition among neurosurgeons. Adequate assessment and steps should be encouraged to ensure physician and patient safety.


Electrically evoked contractions of the triceps surae during and following 21 days of voluntary leg immobilization.
The effects of 21 days voluntary leg (plaster) immobilization on the mechanical properties of the triceps surae have been studied in 11 young female subjects, mean age 19.4 years. The results show that during the period of immobilization the mean time to peak tension (TPT) and half relaxation time (1/2RT) and tension (Pt) of the maximal twitch increased significantly (p less than 0.001) but the effects were short lived. Maximal tension and contraction times of the twitch recovered within 2-14 days following the removal of the plaster cast. The electrically evoked tetanic tensions at 10 Hz and 20 Hz did not change significantly (P greater than 0.1) during immobilization, but the 50 Hz tetanic tension (Po50) and maximal voluntary contraction (MVC) were reduced (p less than 0.05). The fall in Po50 and MVC was associated with 10% decrease in the estimated muscle (plus bone) cross-sectional area. The relative (%) change in Po50 and MVC following immobilization was related to the initial physiological status (as indicated by the response of the triceps surae to a standard fatigue test prior to immobilization) of the muscle. The rate of rise and recovery fall of the tetanus were slightly but significantly (p less than 0.01) reduced on day 7 of immobilization, but thereafter remained constant. The isokinetic properties of the triceps surae as reflected in the measured torque/velocity relation of the muscle in 4 subjects did not change significantly if account was taken of the slight degree of atrophy present following immobilization.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of atropine on the central mechanism of deglutition in anesthetized sheep.
The role of acetylcholine in the central mechanism of swallowing remains a matter of debate. The aim of this work, conducted in sheep, was to assess the effects of anti-muscarinic drugs (mainly atropine) on the activity of peripheral muscles involved in the oropharyngeal and esophageal phases of swallowing, and on that of dorsal medulla interneurons which program swallow-induced esophageal contractions and therefore belong to the so-called central pattern generator. Our results were obtained in anesthetized animals by means of electromyographic and manometric recordings of peripheral muscle contractions associated with microelectrode recordings of medullary interneuron discharge. They show that both interneuron discharge and primary esophageal contractions that follow the oropharyngeal component of swallowing were suppressed under atropine (0.1--0.5 mg/kg). In contrast, atropine did not impede the swallowing oropharyngeal component, the secondary peristalsis and the "deglutitive inhibition," which affects the esophageal motility during the oropharyngeal phase of swallowing. In conclusion, muscarinic receptors (probably not those of M(1)type) appear to control the primary peristalsis, but neither the secondary peristalsis nor the deglutitive inhibition.


Non-invasive evaluation of hepatic macrosteatosis in deceased donors.
Liver allocation changes have led to increased travel and expenditures, highlighting the need to efficiently identify marginal livers suitable for transplant. We evaluated the validity of existing non-invasive liver quality tests and a novel machine learning-based model at predicting deceased donor macrosteatosis >30%. We compared previously-validated non-invasive tests and a novel machine learning-based model to biopsies in predicting macrosteatosis >30%. We also tested them in populations enriched for macrosteatosis. The Hepatic Steatosis Index area-under-the-curve (AUC) was 0.56. At the threshold identified by Youden's J statistic, sensitivity, specificity, positive, and negative predictive values were 49.6%, 58.9%, 14.0%, and 89.7%. Other tests demonstrated comparable results. Machine learning produced the highest AUC (0.71). Even in populations enriched for macrosteatosis, no test was sufficiently predictive. Commonly used clinical scoring systems and a novel machine learning-based model were not clinically useful, highlighting the importance of pre-procurement biopsies to facilitate allocation.


Instructions and experiential learning have similar impacts on pain and pain-related brain responses but produce dissociations in value-based reversal learning.
Recent data suggest that interactions between systems involved in higher order knowledge and associative learning drive responses during value-based learning. However, it is unknown how these systems impact subjective responses, such as pain. We tested how instructions and reversal learning influence pain and pain-evoked brain activation. Healthy volunteers (n=40) were either instructed about contingencies between cues and aversive outcomes or learned through experience in a paradigm where contingencies reversed three times. We measured predictive cue effects on pain and heat-evoked brain responses using functional magnetic resonance imaging. Predictive cues dynamically modulated pain perception as contingencies changed, regardless of whether participants received contingency instructions. Heat-evoked responses in the insula, anterior cingulate, and other regions updated as contingencies changed, and responses in the prefrontal cortex mediated dynamic cue effects on pain, whereas responses in the brainstem's rostroventral medulla (RVM) were shaped by initial contingencies throughout the task. Quantitative modeling revealed that expected value was shaped purely by instructions in the Instructed Group, whereas expected value updated dynamically in the Uninstructed Group as a function of error-based learning. These differences were accompanied by dissociations in the neural correlates of value-based learning in the rostral anterior cingulate, thalamus, and posterior insula, among other regions. These results show how predictions dynamically impact subjective pain. Moreover, imaging data delineate three types of networks involved in pain generation and value-based learning: those that respond to initial contingencies, those that update dynamically during feedback-driven learning as contingencies change, and those that are sensitive to instruction. Together, these findings provide multiple points of entry for therapies designs to impact pain.


Management of massive air embolism during open-heart surgery with retrograde perfusion of the cerebral vessels and hyperbaric oxygenation.
Retrograde perfusion through the superior vena cava was used in 2 patients who were injured by massive air embolism occurring during open-heart surgery. They underwent hyperbaric treatment immediately following completion of the intracardiac repair. Both patients made complete recovery and were discharged, with no defects attributable to the incident.


Balneotherapy for chronic low back pain: a randomized, controlled study.
A large number of treatments were used for patients with chronic low back pain. Frequent episodes have been reported very high. Although balneotherapy was found effective in this disease, there are not well-designed studies. We aimed to determine the effectiveness of balneotherapy versus physical therapy in patients with chronic low back pain. Exercise was added to both treatment programs. Sixty patients with chronic low back pain were randomly divided into two groups. Physical modalities plus exercise were applied to group 1, and group 2 was received balneotherapy plus exercise for ten sessions. The following parameters were measured: visual analogue scale at rest and movement for pain, paracetamol dose, manual muscle test for lumber muscles, modified Schoeber' test, Oswestry disability index, and Short-Form 36 at the beginning and end of the therapies and at the 3 months follow-up. The statistical analyses were performed using the SPSS 10.0 program. Both groups achieved significant improvements within themselves. But balneotherapy groups were improved at back extensor muscle test (P < 0.05), modified Schoeber's test (P < 0.03), Oswestry disability index, and the some scores of SF 36 (energy vitality, social function, role limitations related to physical problems, and general health P < 0.05). Balneotherapy combined with exercise therapy had advantages than therapy with physical modalities plus exercise in improving quality of life and flexibility of patients with chronic low back pain.


Simultaneous blockade of TIGIT and HIF-1α induces synergistic anti-tumor effect and decreases the growth and development of cancer cells.
T-cell immunoglobulin and ITIM domain (TIGIT) is an immune checkpoint that is overexpressed on both immune cells and some cancer cells. TIGIT can alter the anti-tumor responses inside the tumor microenvironment. Hypoxia-inducible factor 1-alpha (HIF-1α) plays a significant role in the TME and involves suppressing the anti-tumor responses. Under hypoxic conditions, HIF-1α can enhance the expression of different immune checkpoints. Accordingly, hypoxic TME and TIGIT overexpression cause cancer development. Thus, we decided to inhibit tumor cell expansion by inhibiting TIGIT and HIF-1α molecules and discovering the relationship between TIGIT and HIF-1α. In this research, we utilized superparamagnetic iron oxide-based NPs (SPIONs) combined with chitosan lactate (CL) and folic acid (FA) nanoparticles (NPs) loaded with TIGIT-siRNA and HIF-1α- siRNA for suppressing TIGIT and HIF-1α in tumor cells and evaluated the consequences of this treatment strategy on tumor growth, apoptosis, and metastasis. The results showed that cancer cells treated with TIGIT and HIF-1α siRNA-loaded SPIONs-CL-FA NPs, strongly suppressed the TIGIT and HIF-1α expression, colony formation ability, angiogenesis, and the growth rate of cancer cells. Present data suggest the combination treatment of TIGIT and HIF-1α as a novel treatment strategy against colorectal and breast cancer, but more researches are required to realize the complete role of TIGIT and HIF-1α inside the TME.


Angiotensin II receptor blockers versus angiotensin-converting enzyme inhibitors in patients with stable coronary artery disease: Prevalence, correlates, and prognostic impact (from the CORONOR study).
In international guidelines for patients with stable coronary artery disease (CAD), angiotensin-converting enzyme inhibitors (ACE-I) are recommended while angiotensin II receptor blockers (ARB) are proposed as an alternative in case of intolerance. There are no real-life data on the frequency and correlates of ARB use in this setting. We studied 3363 outpatients included in a prospective registry on stable CAD (the CORONOR study) and receiving an ARB or an ACE-I at inclusion. Altogether, 944 patients received an ARB (28.1%). Factors positively and independently associated with ARB use versus ACE-I use were a history of hypertension, the absence of prior myocardial infarction, age, female gender, estimated glomerular filtration rate <60ml/min/m2, and left ventricular ejection fraction ≥40%. In the whole study population, the hazard ratio (HR) for the combined endpoint (cardiovascular death, myocardial infarction, stroke) of patients with ARB use was 0.95 (0.69-1.31) (p=0.765) (patients with ACE-I use as reference). Similar results were observed when the analysis was restricted to a propensity-matched cohort: HR=0.91 (0.62-1.34) (p=0.632). Our study shows that a significant proportion of stable CAD patients are treated with ARB rather than with ACE-I in modern practice. Several correlates of ARB prescription were identified. Our results suggest that patients receiving ARB have similar outcome than patients receiving ACE-I.


Is prophylactic para-aortic irradiation worthwhile in the treatment of advanced cervical carcinoma? Results of a controlled clinical trial of the EORTC radiotherapy group.
From November 1977 to July 1981, 441 patients with cervical carcinoma were randomized between pelvic irradiation and pelvic and para-aortic irradiation. Included were patients with stage I and IIB with proximal vaginal and/or parametrial involvement with positive pelvic lymph nodes either on lymphangiogram or at surgery, and stage IIB with distal vaginal and/or parametrial involvement and III regardless of pelvic node status on lymphangiogram. Patients with clinically or surgically involved para-aortic nodes were not included. The external beam dose to the para-aortic area was fixed at 45 Gy. There was no statistically significant difference between the two treatment arms in terms of local control, overall distant metastases and survival with no evidence of disease (NED), although the incidence of para-aortic metastases and distant metastases without tumor at pelvic sites was significantly higher in patients receiving pelvic irradiation alone (pelvic group). The 4-year NED survival rate was 51%. The incidence of severe digestive complications was significantly higher in patients receiving para-aortic irradiation (para-aortic group). Routine para-aortic irradiation for all high risk patients with cervical carcinoma is of limited value, but patients with a high probability of local control can benefit from extended field irradiation, despite an increase in severe digestive complications.


'Everything's neatly tucked away': young women's views on desirable vulval anatomy.
In the context of rapidly increasing requests for female genital cosmetic surgery (FGCS) and a lack of published research in this area, we explored young women's knowledge of vulval anatomy and sources of anatomical information. We conducted 21 semi-structured interviews with young women aged 18-28 years at an Australian tertiary institution. Interviews explored participants' knowledge of 'normal' and 'ideal' genital anatomy and how these perceptions were formed. Interviews were recorded, transcribed and analysis identified 6 major themes and 30 sub-themes. We found that many women were unsure what constitutes normal genital anatomy. Few women knew to which parts the word vulva refers. All participants identified a photograph of hairless female genitals with no visible labia minora as the societal 'ideal', and all strongly agreed on the need for appropriate educational resources. Young women would benefit from access to resources showing the normal range of genital anatomy. Results suggest that doctors receiving requests for FGCS should explore women's understanding of their anatomy and what they believe the surgery will achieve. Some young women may simply need reassurance of their normality. Findings from this study may contribute to educational material for both health professionals and young people.


Excellent acceleration of the Diels-Alder reaction by microwave irradiation for the synthesis of new fluorine-substituted ligands of NMDA receptor.
A series of 6,11-ethanobenzo[b]quinolizinium derivatives was synthesized through the Diels-Alder reaction between azoniaanthracne and the corresponding 1,1-disubstituted olefin. After a systematic investigation for achieving rapid synthesis, it was found that the reaction is accelerated in polar media such as H2O and trifluoroethanol. In particular, excellent acceleration was effected by microwave irradiation. The new fluorine-substituted ligands thus obtained exhibited potential affinity toward NMDA receptors.


Fusobacterium nucleatum and its associated systemic diseases: epidemiologic studies and possible mechanisms.
Fusobacterium nucleatum (F. nucleatum) is an anaerobic oral commensal and the major coaggregation bridge organism linking early and late colonisers. In recent years, a large number of studies suggest that F. nucleatum is closely related to the development of various systemic diseases, such as cardiovascular diseases, adverse pregnancy outcomes, inflammatory bowel diseases, cancer, Alzheimer's disease, respiratory infection, rheumatoid arthritis, etc. To review the effect of F. nucleatum on systemic diseases and its possible pathogenesis and to open new avenues for prevention and treatment of F. nucleatum-associated systemic diseases. The research included every article published up to July 2022 featuring the keywords 'Systemic diseases' OR 'Atherosclerotic cardiovascular diseases' OR 'Atherosclerosis' OR 'Adverse pregnancy outcomes' OR 'Inflammatory bowel disease' OR 'Ulcerative colitis' OR 'Crohn's disease' OR 'Cancers' OR 'Oral squamous cell carcinomas' OR 'Gastrointestinal cancers' OR 'Colorectal cancer' OR 'Breast cancer' OR 'Genitourinary cancers' OR 'Alzheimer's disease ' OR 'Rheumatoid arthritis' OR 'Respiratory diseases' AND 'Fusobacterium nucleatum' OR 'Periodontal pathogen' OR 'Oral microbiota' OR 'Porphyromonas gingivalis' and was conducted in the major medical databases. F. nucleatum can induce immune response and inflammation in the body through direct or indirect pathways, and thus affect the occurrence and development of systemic diseases. Only by continuing to investigate the pathogenic lifestyles of F. nucleatum will we discover the divergent pathways that may be leveraged for diagnostic, preventive and therapeutic purposes.


Diffusive Gradients in Thin-films technique for uranium monitoring along a salinity gradient: A comparative study on the performance of Chelex-100, Dow-PIWBA, Diphonix, and Lewatit FO 36 resin gels in the Scheldt estuary.
Monitoring of uranium in the environment using the Diffusive Gradients in Thin-films (DGT) technique gains in importance as it can provide unique information about the bioavailability of the element and allows its long-term in-situ measurement. Hence, in this study, four DGT binding phases (Chelex-100, Dow-PIWBA, Diphonix, and Lewatit FO 36 resins) were evaluated for uranium monitoring to assess the robustness of their performance in estuarine and marine environments. These DGTs were deployed along the Scheldt estuary (Belgium and the Netherlands) over four campaigns between 2014 and 2021. The DGT performance (ratio of the DGT-determined vs. dissolved U concentration in grab water sample) varied with the water salinity. The Chelex-100 DGTs generally provided good performance in freshwater (median ratios close to 1.0), but an inverse correlation with the increasing salinity was observed (median ratios 0.7 at the stations with salinity >5). The Lewatit FO 36 DGTs provided good performance in the salinity range 0-18 (median ratios 1.0). However, a strong negative influence was observed at stations with high salinity levels (>18, ratio 0.6) and during the long-term deployment in seawater (ratios <0.5 over deployment periods ≥2 days). The Dow-PIWBA and Diphonix DGTs provided overall similar results with excellent performances along the whole salinity gradient (median ratios 1.1 and 1.0, respectively). Nevertheless, the long-term deployment trial in seawater (salinity ∼27) revealed the robustness of Diphonix DGTs that provided outstanding results even after 28 days of deployment (ratio 1.0). The differences in the performance of tested DGT resins were mostly given by the changes of U speciation along the salinity gradient. The speciation modelling of U showed that calcium uranyl carbonate complexes dominate along the Scheldt estuary (from 97 to 86% seawards) with increasing fraction of UO2(CO3)34- (from 2 to 14%) towards the mouth.


Translating medical image to radiological report: Adaptive multilevel multi-attention approach.
Medical imaging techniques are widely employed in disease diagnosis and treatment. A readily available medical report can be a useful tool in assisting an expert for investigating the patient's health. A radiologist can benefit from an automatic medical image to radiological report translation system while preparing a final report. Previous attempts on automatic medical report generation task includes image captioning algorithms without taking domain-specific visual and textual contents into account, thus arises the question about credibility of generated report. In this work, a novel Adaptive Multilevel Multi-Attention (AMLMA) approach is proposed by offering domain-specific visual-textual knowledge to generate a thorough and believable radiological report for any view of a human chest X-ray image. The proposed approach leverages the encoder-decoder framework incorporated with multiple adaptive attention mechanisms. The potential of a convolutional neural network (CNN) with residual attention module (RAM) is demonstrated as a strong visual encoder for multi-label abnormality detection. The multilevel visual features (local and global) are extracted from proposed visual encoder to retrieve regional-level and abstract-level radiology-based semantic information. The Word2Vec and FastText word embeddings are trained on medical reports to acquire radiological knowledge and further used as textual encoders, feeding as input to Bi-directional Long Short Term Memory (Bi-LSTM) network to learn the co-relationship between medical terminologies in radiological reports. The AMLMA employs a weighted multilevel association of adaptive visual-semantic attention and visual-based linguistic attention mechanisms. This association of adaptive attention is exploited as a decoder and produces significant improvements in the report generation task. The proposed approach is evaluated on a publicly available Indiana University chest X-ray (IU-CXR) dataset. The CNN with RAM shows the significant improvement in recall (0.4423), precision (0.1803) and F1-score (0.2551) for prediction of multiple abnormalities in X-ray image. The results of language generation metrics for proposed variants were acquired using the COCO-caption evaluation Application Program Interface (API). The trained embeddings with AMLMA model generates the convincing radiology report and outperform state-of-the-art (SOTA) approaches with high evaluation metrics scores for Bleu-4 (0.172), Meteor (0.247), Rouge_L (0.376) and CIDEr (0.381). In addition, a new "Unique Index" (UI) statistic is introduced to highlight the model's ability for generating unique reports. The overall architecture aids to the understanding of various X-ray image views and generating the relevant normal and abnormal radiography statements. The proposed model is emphasized on multi-level visual-textual knowledge with adaptive attention mechanism to balance visual and linguistic information for the generation of admissible radiology report.


Expression and function of small heat shock protein genes during Xenopus development.
The hsp30 small heat shock protein family is a stress-inducible group of molecular chaperones in the frog, Xenopus laevis. Hsp30 genes are intronless and present in clusters. Expression of these genes are developmentally regulated likely at the level of chromatin structure. Also heat-induced hsp30 transcripts and protein are enriched in selected embryonic tissues. In vitro studies revealed that multimeric hsp30 binds to heat denatured target protein, inhibits their aggregation and maintains them in a folding-competent state until reactivated by other cellular chaperones. Finally optimal chaperone activity and secondary structure of hsp30 can be inhibited by phosphorylation or mutagenesis of the C-terminal end.


The Role of Neutrophil to Lymphocyte Ratio and its Common Clinical Outcomes Among Patients with Non-ST Elevation Acute Coronary Syndrome.
To evaluate the admission neutrophil-to-lymphocyte ratio (NLR) for risk stratification for in-hospital outcomes and complications in non-ST-elevation acute coronary syndrome (non-ST-ACS) patients. We recruited consecutive patients with non-ST-ACS. The NLR was obtained and stratified as low, intermediate, and high-risk based on <3.0, 3.0-6.0, and >6.0, respectively. The new ST-T changes, arrhythmias, contrast-induced nephropathy (CIN), and mortality were recorded. Median NLR was 3 [2.1-5.3] for 346 patients with 19.9% and 30.6% in high- and intermediate-risk group. New ST-T changes were observed in 3.5% (12) out of which 8, 3, and 1 patient in low, intermediate, and high-risk group (p = 0.424), respectively. Arrhythmias were observed in 5.8% (20) with 7, 5, and 8 patients in low, intermediate, and high-risk group (p = 0.067), respectively. CIN was observed in 4.9% (17) with 5, 5, and 7 in low, intermediate, and high-risk group (p = 0.064), respectively. In-hospital mortality was recorded in 1.4% (5) with 2 and 3 patients in high and low-risk group (p = 0.260), respectively. A significant number of non-ST-ACS patients fall in the high-risk category of NLR. Although, the association between NLR and in-hospital mortality and adverse events was not statistically significant but relatively higher rates of events were observed in high risk group.


Mechanical Properties and Atomic Explanation of Plastic Deformation for Diamond-Like BC₂.
Motivated by a recently predicted structure of diamond-like BC₂ with a high claimed hardness of 56 GPa (J. Phys. Chem. C2010, 114, 22688-22690), we focus on whether this tetragonal BC₂ (t-BC₂) is superhard or not in spite of such an ultrahigh theoretical hardness. The mechanical properties of t-BC₂ were thus further extended by using the first principles in the framework of density functional theory. Our results suggest that the Young's and shear moduli of t-BC₂ exhibit a high degree of anisotropy. For the weakest shear direction, t-BC₂ undergoes an electronic instability and structural collapse upon a shear strain of about 0.11, with its theoretically ideal strength of only 36.2 GPa. Specifically, the plastic deformation under shear strain along the (110)[001] direction can be attributed to the breaking of d1 B-C bonds.


Water-borne oculoglandular tularemia: Two complicated cases and a review of the literature.
In this study, we presented two cases of late diagnosed complicated oculoglandular tularemia and reviewed the clinical features of oculoglandular tularemia in cases reported in the last ten years. Tularemia was diagnosed when serum microagglutination test (MAT) was ≥ 1/160 titer or when there was at least a four-fold increase in MAT titers measured over a two-week interval. We searched the oculoglandular tularemia cases reported in the last 10 years in the PubMed and Google Academic engines. Case 1 (19 M) and case 2 (15 M) had complaints of fever and burning in the eye. In both cases, the diagnosis of tularemia was delayed. Lymph node suppuration developed in both cases. A total of 19 cases of tularemia were found within the search. In the cases of oculoglandular tularemia reported in the last 10 years, submandibular and preauricular lymphadenopathy were most common after ocular findings and fever. The mean time to diagnosis was 41 ± 94 days, and the complication rate was 31.5%. Tularemia should definitely be considered in cases of fever and ocular findings, especially in endemic areas. In non-endemic areas, a good anamnesis and clinical suspicion can help diagnose the disease early and reduce the complication rate.


Generation and characterization of reduced virulence Fusarium oxysporum f. sp. lycopersici mutants through plasmid-vector insertion.
Pathogenicity-impaired mutants, B02 and H15, of Fusarium oxysporum f. sp. lycorpersici (FOL) were obtained using restriction enzyme-mediated integration. Disease severities of Fusarium wilt caused by these mutants were significantly reduced, and their disease development rates were correlated with their colonization rates in tomato vessels. Both B02 and H15 produced significantly smaller amounts of extracellular proteins as well as fusaric acid than the wild-type. Southern blot analyses suggested that B02 and H15 likely contain a single and three copies of transformation vector, respectively. These mutants may thus be useful in isolating genes involved in pathogenicity of FOL.


Mindfulness-based stress reduction and cognitive function among breast cancer survivors: A randomized controlled trial.
Breast cancer (BC) survivors frequently report changes in cognition after chemotherapy. Mindfulness may benefit survivors by mitigating cancer-related cognitive impairment. As part of a larger study investigating the effects of mindfulness-based stress reduction (MBSR) for BC survivors living with neuropathic pain, the authors assessed whether MBSR would have an effect on cognitive outcomes. Participants were randomized to an MBSR intervention group (n = 30) or a waitlist control group (n = 30). Cognitive assessments were administered at 3 time points: at baseline, 2 weeks, and 3 months post-MBSR in the intervention group and at equivalent time intervals for the control group. Multilevel models were used to assess whether MBSR significantly improved task performance at each time point. MBSR participants showed a significantly greater reduction in prospective and retrospective memory failures at 2 weeks postintervention. No effects of MBSR were noted for objective assessments. These results suggest that MBSR training reduces subjective (but not objective) memory-related impairments in BC survivors who receive treatment with chemotherapy. This study provides insight into a noninvasive intervention to ameliorate memory difficulties in BC survivors.


Comparison between mefenamic acid and danazol in the treatment of established menorrhagia.
Forty women with established menorrhagia were treated with either mefenamic acid (500 mg thrice daily for 3-5 days in two cycles) or danazol (100 mg twice daily for 60 days) in an open parallel group randomized study. Mefenamic acid reduced mean menstrual blood loss from 160 ml to 127 ml (20%, P less than 0.01). Danazol reduced mean menstrual loss from 163 ml to 65 ml (60%, P less than 0.001). The percentage reduction in menstrual blood loss was significantly greater in the danazol group than in the mefenamic acid group, but the adverse side-effects occurred significantly more often in the danazol group (75%) than in the mefenamic acid group (30%, P less than 0.005). Overall, approximately half the women in each group were prepared to continue with the treatment they received to reduce their menstrual bleeding.


Spinal multiparametric MRI and DEXA changes over time in men with prostate cancer treated with androgen deprivation therapy: a potential imaging biomarker of treatment toxicity.
To explore changes in bone mineral density (BMD) measured by DEXA and MRS fat fraction (FF), Dixon FF, and ADC in lower spinal vertebral bodies in men with prostate cancer treated with androgen deprivation therapy (ADT). Twenty-eight men were enrolled onto a clinical trial. All received ADT. DEXA imaging was performed at baseline and 12 months. L-spine MRI was done at baseline and 6 months. The number of patients who underwent DEXA, Dixon, ADC, and MRS at baseline/follow-up were 28/27, 28/26, 28/26, and 22/20. An increase in FF was observed from T11 to S2 (average 1 %/vertebra). There was a positive correlation between baseline MRS FF and Dixon FF (r = 0.85, p < 0.0001) and a negative correlation between MRS FF and ADC (r = -0.56, p = 0.036). Over 6 months, MRS FF increased by a median of 25 % in relative values (p = 0.0003), Dixon FF increased (p < 0.0001) and ADC values decreased (p = 0.0014). Men with >5 % BMD loss after 1 year had triple the percentage increase in MRS FF at 6 months (61.1 % vs. 20.9 %, p = 0.19). Changes are observed on L-spine MRI after 6 months of ADT. Further investigation is warranted of MRS change as a potential predictive biomarker for later BMD loss. • Spinal marrow fat fraction increases after 6 months of androgen deprivation therapy. • More inferior vertebral bodies tend to have higher fat fractions. • MRS fat fraction changes were associated with later changes in DEXA BMD.


Teratogenicity and antiepileptic drugs: potential mechanisms.
Congenital malformations often the most concerning risk of taking antiepileptic drugs (AEDs) during pregnancy for both the patient and the physician. This chapter reviews aspects of the association between AEDs and congenital malformations, including a historical perspective, type and patterns of congenital malformations, possible confounding factors, and potential mechanisms of teratogenicity. The role of folic acid in preventing birth defects in the general population and in setting of taking AEDs is also presented. One of the most serious congenital malformations, spina bifida (SB), and its association with intrauterine valproate exposure, is discussed in depth.


Nitric oxide scavenging by red blood cells as a function of hematocrit and oxygenation.
The reaction rate between nitric oxide and intraerythrocytic hemoglobin plays a major role in nitric oxide bioavailability and modulates homeostatic vascular function. It has previously been demonstrated that the encapsulation of hemoglobin in red blood cells restricts its ability to scavenge nitric oxide. This effect has been attributed to either factors intrinsic to the red blood cell such as a physical membrane barrier or factors external to the red blood cell such as the formation of an unstirred layer around the cell. We have performed measurements of the uptake rate of nitric oxide by red blood cells under oxygenated and deoxygenated conditions at different hematocrit percentages. Our studies include stopped-flow measurements where both the unstirred layer and physical barrier potentially participate, as well as competition experiments where the potential contribution of the unstirred layer is limited. We find that deoxygenated erythrocytes scavenge nitric oxide faster than oxygenated cells and that the rate of nitric oxide scavenging for oxygenated red blood cells increases as the hematocrit is raised from 15% to 50%. Our results 1) confirm the critical biological phenomenon that hemoglobin compartmentalization within the erythrocyte reduces reaction rates with nitric oxide, 2) show that extra-erythocytic diffusional barriers mediate most of this effect, and 3) provide novel evidence that an oxygen-dependent intrinsic property of the red blood cell contributes to this barrier activity, albeit to a lesser extent. These observations may have important physiological implications within the microvasculature and for pathophysiological disruption of nitric oxide homeostasis in diseases.


Role of cell free microRNA-19a and microRNA-19b in gestational diabetes mellitus patients.
Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes in pregnant women and it's prevalence is increasing worldwide. A total 100 cases of GDM and 100 healthy controls were included in a study and blood samples were collected in plain vials from all study participant. Difference among several variables which included BMI, glycemia, insulinaemia, HbA1c, total cholesterol, triglycerides, urinary albumin were compared between GDM cases and controls and were found to be statistically significant (p < 0.0001). Additionally, GDM cases showed 4.0 fold increase in miRNA-19a and 4.7 mean increase in miRNA-19b expression compared to healthy control individuals. A positive correlation was observed between miRNA-19a and miRNA-19b among GDM cases. However the correlation coefficient was 0.13 between miRNA-19a and miRNA-19b. This suggested that with the increase in miRNA-19a, miRNA-19b also increased. The findings of this study concludes that an increase in microRNA-19a and microRNA-19b is observed in GDM cases and could be linked with increased risk factor for worsening of the disease. MicroRNA-19a and 19b have been linked to alcoholism and smoking and could also be the factors in GDM.


Pediatric dermatology.
Physicians who treat children will encounter dermatologic conditions in their daily practice. A general approach to the diagnosis and management of pediatric skin disease is discussed in this article, and specific common entities are summarized, with emphasis on diagnosis and treatment.


Reversible cerebral vasoconstriction syndrome associated with brain parenchymal hemorrhage.
We described a 7-year-old girl with reversible cerebral vasoconstriction syndrome associated with brain parenchymal hemorrhage. She initially presented with high fever and pancytopenia, leading to a diagnosis of most severe type aplastic anemia. We treated her with cyclosporine, methylprednisolone and anti-thymocyte globulin. Thereafter she recurrently complained of a very severe headache called as thunderclap, and finally exhibited loss of consciousness. Brain imaging revealed massive parenchymal hemorrhage between the left occipital and parietal lobes on computed tomography, and diffuse cerebral vasoconstriction on magnetic resonance angiography. The cerebral vasoconstriction resolved within two months, and thus we diagnosed her as having reversible cerebral vasoconstriction syndrome associated with brain parenchymal hemorrhage. This syndrome has been frequently reported in adult females, but rarely in children. However, even in children, a so called thunderclap headache may become a clue for the diagnosis of reversible cerebral vasoconstriction syndrome, especially in cases taking immunosuppressive agents. Immediate magnetic resonance angiography is essential to diagnose this syndrome, and a prompt application of calcium channel inhibitors should be considered to resolve constriction of the vessels and to prevent subsequent brain damage.


Albumycin, a new isoindolequinone from Streptomyces albus J1074 harboring the fluostatin biosynthetic gene cluster.
Heterologous expression of the fluostatin biosynthetic gene cluster from the marine-derived Micromonospora rosaria SCSIO N160 in Streptomyces albus J1074 led to the isolation of a novel isoindolequinone albumycin (1) and a known isoquinolinequinone mansouramycin A (2). The structure of 1 was elucidated on the basis of detailed 1D and 2D NMR spectroscopic analysis. Mansouramycin A (2) is active against methicillin-resistant Staphylococcus aureus ATCC 43300, with a MIC of 8 μg ml-1, while albumycin (1) displayed negligible antibacterial activities. This study represents another example of activation of secondary metabolites that are non-relevant to the heterologously introduced biosynthetic gene cluster in a bacterial host.


Expression of vascular endothelial growth factor and basic fibroblast growth factor in sporadic vestibular schwannomas correlates to growth characteristics.
Expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) may have an impact on the growth characteristics of sporadic vestibular schwannomas (VSs). Vestibular schwannoma is a benign, slow-growing neoplasm that accounts for 6% of all intracranial tumors. The biological backgrounds for neoplastic growth and especially for the various growth patterns of VS remain largely unknown. Because several angiogenic and cytotrophic factors have been described to be involved in the growth of malignant tumors, we initiated this study to examine 2 major representatives of such growth factors in VS and their possible correlation to the growth characteristics of sporadic VSs. Surgical specimens from 17 patients with sporadic VS were examined, and the expression of 2 major angiogenic and neurotrophic factors, bFGF and VEGF, was quantitatively analyzed at the mRNA and protein levels. The microvessel density (MVD) was defined by CD31 staining. All tumors showed expression of bFGF and VEGF at both the mRNA and protein levels. The mRNA expression and the protein expression of both growth factors correlated positive to tumor volume, to tumor growth index, and to MVD. The bFGF and VEGF mRNA expression and the bFGF and VEGF protein expression in sporadic VS correlates to the tumour volume, to the tumor growth index, and to the MVD. This might indicate an angiogenic and neurotrophic influence of these factors and a possible involvement in the growth of sporadic VS.


Mental health and well-being trends among children and young people in the UK, 1995-2014: analysis of repeated cross-sectional national health surveys.
There is a growing concern about the mental health of children and young people (CYP) in the UK, with increasing demand for counselling services, admissions for self-harm and referrals to mental health services. We investigated whether there have been similar recent trends in selected mental health outcomes among CYP in national health surveys from England, Scotland and Wales. Data were analysed from 140 830 participants (4-24 years, stratified into 4-12, 13-15, 16-24 years) in 36 national surveys in England, Scotland and Wales, 1995-2014. Regression models were used to examine time trends in seven parent/self-reported variables: general health, any long-standing health condition, long-standing mental health condition; Warwick-Edinburgh Mental Wellbeing Score (WEMWBS), above-threshold Strengths and Difficulties Questionnaire Total (SDQT) score, SDQ Emotion (SDQE) score, General Health Questionnaire (GHQ) score. Across all participants aged 4-24, long-standing mental health conditions increased in England (0.8-4.8% over 19 years), Scotland (2.3-6.0%, 11 years) and Wales (2.6-4.1%, 7 years) (all p < 0.001). Among young children (4-12 years), the proportion reporting high SDQT and SDQE scores decreased significantly among both boys and girls in England [SDQE: odds ratio (OR) 0.97 (0.96-0.98), p < 0.001] and girls in Scotland [SDQE: OR 0.96 (0.93-0.99), p = 0.005]. The proportion with high SDQE scores (13-15 years) decreased in England [OR 0.98 (0.96-0.99), p = 0.006] but increased in Wales [OR 1.07 (1.03-1.10), p < 0.001]. The proportion with high GHQ scores decreased among English women (16-24 years) [OR 0.98 (0.98-0.99), p = 0.002]. Despite a striking increase in the reported prevalence of long-standing mental health conditions among UK CYP, there was relatively little change in questionnaire scores reflecting psychological distress and emotional well-being.


Sarcolipin Signaling Promotes Mitochondrial Biogenesis and Oxidative Metabolism in Skeletal Muscle.
The major objective of this study was to understand the molecular basis of how sarcolipin uncoupling of SERCA regulates muscle oxidative metabolism. Using genetically engineered sarcolipin (SLN) mouse models and primary muscle cells, we demonstrate that SLN plays a crucial role in mitochondrial biogenesis and oxidative metabolism in muscle. Loss of SLN severely compromised muscle oxidative capacity without affecting fiber-type composition. Mice overexpressing SLN in fast-twitch glycolytic muscle reprogrammed mitochondrial phenotype, increasing fat utilization and protecting against high-fat diet-induced lipotoxicity. We show that SLN affects cytosolic Ca2+ transients and activates the Ca2+/calmodulin-dependent protein kinase II (CamKII) and PGC1α axis to increase mitochondrial biogenesis and oxidative metabolism. These studies provide a fundamental framework for understanding the role of sarcoplasmic reticulum (SR)-Ca2+ cycling as an important factor in mitochondrial health and muscle metabolism. We propose that SLN can be targeted to enhance energy expenditure in muscle and prevent metabolic disease.


Dimethylsulphoxide as a tool to increase functional expression of heterologously produced GPCRs in mammalian cells.
High-level overexpression of G protein-coupled receptors GPCRs in mammalian cells remains a difficult task inspite of newly developed virus based expression systems. Here, we show that the functional expression level of the recombinant bradykinin receptor (B(2)R) in mammalian cells can be increased up to sixfold just by the addition of dimethylsulphoxide in the culture medium. Total expression level, cellular localization and binding affinity of the recombinant receptor for its endogenous ligand remains unaltered. The strategy presented here, with recombinant B(2)R as a case example, is applicable to other GPCRs and provides a generic tool to improve the functional expression level of recombinant GPCRs in mammalian cells.


[Comparison of cases of isolated pulmonary tuberculosis with cases of other localizations of tuberculosis in the course of an active surveillance (Gironde, 1995-1996)].
Data collected during the years 1995 and 1996 in the course of an epidemiological survey of tuberculosis in Gironde allowed comparison of pulmonary tuberculosis with extrapulmonary localizations, evaluation of the importance of each localization and highlighting of potential risk factors. Patients living in Gironde who had evidence of either clinical, radiological or bacteriological expression of tuberculosis were included in the survey. Statistical comparisons were done using either Pearson's Chi 2 or Fisher's exact test. The survey included 292 cases subdivided into 183 cases of pulmonary tuberculosis (63%) and 109 cases in which another localization had been diagnosed (37%). Extrapulmonary localizations that were the most often encountered either alone or in association with pulmonary localization were the following: lymphadenopathy (32%), pleural (28%), genito-urinary (12%) and osteo-articular localizations (7%). The survey showed that patients in whom tuberculosis localization was extra-pulmonary were more frequently under 20 years of age or over 60 years of age (P < 0.04). These patients also presented more often with HIV-infection (P < 0.02). Extrapulmonary localizations of tuberculosis should be systematically investigated in young and elderly patients as well as in HIV-infected patients.


Lymphocyte mitogenesis induced by monoclonal antibodies to the T3 complex. Differential modulation by human IgG.
Murine monoclonal antibodies OKT3 (IgG2), 64.1 (IgG2), and Leu 4 (IgG1) react with a common membrane antigen on human T cells and induce potent mitogenesis at concentrations of 1 ng/ml, 10 ng/ml, and 100 ng/ml, respectively. Human serum inhibits the mitogenic effect of antibodies OKT3 and 64.1, but not that of Leu 4. The inhibitor in serum has been identified as immunoglobulin G (IgG) as evidenced by the ability of anti-human IgG-Sepharose affinity columns to retain the inhibitory activity. Various immunoglobulin classes and subclasses obtained from human myelomas differ in their ability to inhibit the OKT3-induced activation. The best inhibition is obtained with the IgG subclasses IgG1 and IgG3, followed by IgG2; IgG4, IgM, and IgA have little if any effect. None of the IgG subclasses inhibit the Leu 4-induced mitogenesis. Indomethacin as well as supernatants containing interleukin 2 (IL-2) can reverse the inhibitory effects of IgG. Prostaglandins (PGE1 and PGE2) inhibit both the OKT3- and Leu 4-induced mitogenesis, thus lacking the selectivity seen with IgG. Since stimulation by the monoclonal antibodies requires the participation of monocytes, an interpretation consistent with the present data is that IgG stimulates monocytes via its Fc portion to release prostaglandins and/or other suppressor factors via an indomethacin-sensitive pathway. The inability of IgG to inhibit Leu 4-induced mitogenesis may therefore relate to an inability of the monocyte subpopulation, which mediates the Leu 4 response, to secrete suppressor factors. These data suggest a potential value of the mitogenic monoclonal antibodies as probes in studying monocyte heterogeneity and T-cell-monocyte interactions.


Interaction of formin FH2 with skeletal muscle actin. EPR and DSC studies.
Formins are highly conserved proteins that are essential in the formation and regulation of the actin cytoskeleton. The formin homology 2 (FH2) domain is responsible for actin binding and acts as an important nucleating factor in eukaryotic cells. In this work EPR and DSC were used to investigate the properties of the mDia1-FH2 formin fragment and its interaction with actin. MDia1-FH2 was labeled with a maleimide spin probe (MSL). EPR results suggested that the MSL was attached to a single SH group in the FH2. In DSC and temperature-dependent EPR experiments we observed that mDia1-FH2 has a flexible structure and observed a major temperature-induced conformational change at 41 °C. The results also confirmed the previous observation obtained by fluorescence methods that formin binding can destabilize the structure of actin filaments. In the EPR experiments the intermolecular connection between the monomers of formin dimers proved to be flexible. Considering the complex molecular mechanisms underlying the cellular roles of formins this internal flexibility of the dimers is probably important for manifestation of their biological functions.


Preparation and characterization of vanillin-conjugated chitosan-stabilized emulsions via a Schiff-base reaction.
In the current work, vanillin-conjugated chitosan stabilized emulsions (CSVAEs) were successfully prepared and its characterization and antibacterial properties were investigated. Under stirring condition, CSVAEs were produced by a Schiff base reaction between the vanillin aldehyde group and the chitosan active amino group. The CSVAEs were described through Fourier transform infrared spectroscopy, X-ray diffraction, ultraviolet spectrophotometry and thermogravimetric analysis, which demonstrated the generation of Schiff bases between vanillin and chitosan. Furthermore, the CSVAEs displayed differences at different pH values, indicating their potential as pH-responsive materials. By studying their release behavior, pH 4 was a critical point at which the properties of the CSVAEs changed. The antibacterial tests showed that the CSVAEs had good pH-responsive antibacterial abilities against Staphylococcus aureus and Escherichia coli.


Excimer fluorescence of (+)-anti-benzo (a)pyrene diol epoxide covalently bound to poly(dG-dC): structural implications.
Fluorescence of (+)-anti-benzo(a)pyrene diol epoxide [(+)-anti-BPDE] covalently bound to poly(dG-dC) has been studied with steady-state and time-resolved techniques. Extensive formation of excimers is found, even at small (0.008) BPDE/nucleotide ratios. This indicates favored covalent binding to bases close to already modified guanines. Both fluorescence excitation spectra and lifetime measurements reveal two populations of (+)-anti-BPDE adducts: one that can form excimers and one that cannot. Three excimer lifetimes (4.5, 29, and 83 ns) are observed. Differently shifted monomer and excimer excitation spectra are discussed in terms of pyrene-pyrene exciton interactions, consistent with a distance shorter than 7 A between the excimer-forming BPDE chromophores.


What children do while they wait: The role of self-control strategies in delaying gratification.
Self-control plays an essential role in children's emotional and behavioral adjustment. A central behavioral indicator of self-control is the ability to delay gratification. Few studies have focused on understanding the heterogeneity of self-control behaviors that underlie children's ability to delay gratification. Therefore, we examined the role of spontaneous self-control behaviors (fidgeting, vocalizations, and anticipation/attentional focus toward a reward) in relation to 5-year old children's delay ability using Mischel's delay task (N = 144; Mage = 5.4 years, SD = 0.29). Latent mixture modeling was used to derive three distinct classes of self-control behaviors observed during the delay task: (1) Passive (low fidgeting, low vocalizations, but moderate anticipation), (2) Active (moderate fidgeting, moderate vocalizations, but high anticipation), and (3) Disruptive (high fidgeting, high vocalizations, and high anticipation). Children in the Passive class were more likely to delay the full task time compared with children in the Active class (odds ratio = 1.50, 95 % confidence interval = 1.28-1.81). There were no other differences in delay ability by self-control class. Children whose level of fidgeting and vocalizations matched their level of anticipation (i.e., Passive and Disruptive regulators) were able to delay more successfully than children who were mostly driven by anticipation (Active regulators). Some variation in children's delay ability and use of self-control strategies was explained by sociodemographic differences, specifically maternal age. Findings suggest probing processes underlying children's self-control to identify potential targets for intervention.


Human factors affect the quality of cardiopulmonary resuscitation in simulated cardiac arrests.
Cardiopulmonary resuscitation is a team endeavour. There are only limited data on whether team performance during cardiopulmonary resuscitation is influenced by behavioural issues. The aim of the study was to determine whether and how human factors affect the quality of cardiopulmonary resuscitation. 16 teams, each consisting of three health-care workers, were studied in a patient simulator. A scenario of witnessed cardiac arrest due to ventricular fibrillation was used. Ventricular fibrillation could be converted into sinus rhythm by two countershocks administered during the first 2 min or by two countershocks administered during the first 5 min provided that uninterrupted basic life support was started in under 60 s. Teams were rated to be successful if ventricular fibrillation was converted into sinus rhythm. Behavioural rating included leadership, task distribution, information transfer, and conflicts. Only six out of 16 teams were successful. Compared with successful teams, teams that failed exhibited significantly less leadership behaviour (P=0.033) and explicit task distribution (P=0.035). All teams shared among them sufficient theoretical knowledge to successfully treat the simulated cardiac arrest. In a scenario of simulated witnessed cardiac arrest almost two thirds of teams composed of qualified health-care workers failed to provide basic life support and/or defibrillation within an appropriate time window. Absence of leadership behaviour and absence of explicit task distribution were associated with poor team performance. Failure to translate theoretical knowledge into effective team activity appears to be a major problem.


The double J-spring guide wire and its hazards. Partially retained double J-wire: a complication during central venous catheterization. Case report.
A case is presented in which the outer part of a double J-spring guide wire was retained in the patient because of separation of the two parts. Warning against the use of this kind of wire is given.


Measuring indirect transmission-reducing effects in tuberculosis vaccine efficacy trials: why and how?
Tuberculosis is the leading bacterial cause of death globally. In 2021, 10·6 million people developed symptomatic tuberculosis and 1·6 million died. Seven promising vaccine candidates that aim to prevent tuberculosis disease in adolescents and adults are currently in late-stage clinical trials. Conventional phase 3 trials provide information on the direct protection conferred against infection or disease in vaccinated individuals, but they tell us little about possible indirect (ie, transmission-reducing) effects that afford protection to unvaccinated individuals. As a result, proposed phase 3 trial designs will not provide key information about the overall effect of introducing a vaccine programme. Information on the potential for indirect effects can be crucial for policy makers deciding whether and how to introduce tuberculosis vaccines into immunisation programmes. We describe the rationale for measuring indirect effects, in addition to direct effects, of tuberculosis vaccine candidates in pivotal trials and lay out several options for incorporating their measurement into phase 3 trial designs.


The association of significant renal anomalies with Turner's syndrome.
The incidence of significant renal anomalies in 38 patients with Turner's syndrome was 26 per cent (10 of 38 cases). An additional 11 per cent of the patients have insignificant renal abnormalities and 63 per cent apparently have normal excretory urograms. In this series there seemed to be no correlation of the incidence of abnormalities with either the phenotypic or karyotypic expression of Turner's syndrome, that is the 45/XO pattern of the mosaic variants. Therefore, clinicians should be aware that any patient with Turner's syndrome must receive a thorough clinical and radiologic evaluation of the urogenital tract.


Resident dendritic cell density in the lymph node paracortex is preDC-estined.
Dendritic cells (DCs) are relatively short lived, yet DC frequencies in lymph nodes are stable. In this issue of Immunity, Ugur et al. reveal that type 1 conventional DCs (cDC1s) are maintained in the deep paracortex of the lymph node from a supply of preDCs that proliferate in nearby medullary vessels. Transition from preDC to cDC1 is regulated by Flt3L sensing.


Surface plasmon resonance imaging as a multidimensional surface characterization instrument--application to biochip genotyping.
Surface plasmon resonance imaging (SPRI) sensors allow the characterization of a metal/dielectric interface. Providing proper biochemical functionalization and spatial structuration of the functionalized surface, an optical biochip system--label free and real time--can be achieved. We study the impact of the different physical parameters on the quality of the measurements. Such a SPRI system has a great sensitivity to small variations of the physical parameters (layer optical index, thickness, etc.) occurring at the sensor surface. Precision and reliability of the measurements are provided by a multidimensional approach (4D i.e. spatial coordinates x-y, time t, angle of incidence theta) allowing multiple self-calibration procedures. Such apparatus has already been successfully applied in genomics and proteomics, studying DNA:DNA and oligosaccharide:protein interactions. In this article, we illustrate the advantages of the SPRI setup applied to the detection of gene mutations, using as a model the genetic disease Cystic Fibrosis. The results demonstrate that the system is able to monitor and analyse the interaction under investigation, allowing the diagnosis of genetic single nucleotide polymorphisms by exploiting only a part of the multidimensional potential (x, y, t, theta).


Thrombophilic gene polymorphisms in puerperal cerebral veno-sinus thrombosis.
Puerperal cerebral veno-sinus thrombosis (PCVT) is a common form of stroke in young women in India, which is associated with high morbidity and mortality. The frequency of PCVT in India is 10 to 12 times more compared to western population. As yet, the etiology of this condition is unclear. Our aim was to study the prevalence and the role of the common genetic polymorphisms associated with thrombophilia such as factor V Leiden, prothrombin G20210A and methylene tetrahydrofolate reductase (MTHFR) C677T, in aseptic PCVT. We investigated 86 women with PCVT and 86 age-matched women with no post-partum complications. Polymerase chain reaction (PCR)/restriction fragment length polymorphism analysis was used to identify their genotypes. The frequency of the three polymorphisms in cases and controls were: factor V Leiden, 2.3% versus 1.2% (OR 0.49, 95% CI=0.02-7.12, p=1.000) and MTHFR C677T, 16.3% versus 17.4% (OR 0.92, 95% CI=0.39-2.19, p=0.838). The prothrombin G20210A variant was not detected in either patients or controls. The clinical characteristics of the PCVT patients with the polymorphisms did not differ significantly from those without them. In our series of PCVT patients, the risk associated with the established thrombophilic risk factors is insignificant. Exploration of these gene polymorphisms seems to be of limited value in the investigation of PCVT in south Indian women.


Presence of molecular chaperones, heat shock cognate (Hsc) 70 and heat shock proteins (Hsp) 40, in the postsynaptic structures of rat brain.
The synaptic localization of molecular chaperones, heat shock cognate protein 70 (Hsc70) and Hsp40, was investigated immunohistochemically in the normal rat brain. Postsynaptic density (PSD) fractions contained a constitutive form of HSP70, heat shock cognate protein 70 (Hsc70 or p73) but not inducible form of HSP70 (p72). The immunoreactivities of Hsc70 (p73) were distributed throughout the rat brain, in neuronal somata, dendrites and axons. Their immunoreactivity in neurons was localized in the cytoplasmic matrix, dendrites, and spines at the electron microscopic level. Presynaptic terminals, but less frequently than postsynaptic staining, were also reactive. Postsynaptic areas immediately beneath the synaptic contact or PSDs were immunoreactive for Hsc70. The Hsp40 was highly concentrated in PSD fractions. The staining of Hsp40 immunoreactivity was punctate and distributed widely in the brain. Hsp40 immunoreactivity was localized in dendritic spines, especially in the subsynaptic web, with weak staining of PSDs at the electron microscopic level. Double immunofluorescent staining and confocal microscopy revealed that Hsc70 and Hsp40 were co-localized on somata and neuronal processes of cultured cerebral neurons, on which synaptophysin immunoreactive spots were scattered. These results suggest that Hsp40 and Hsc70 are co-localized at postsynaptic sites and postsynaptic chaperone activity may be mediated by these two heat shock proteins.


An analysis of net energy production and feedstock availability for biobutanol and bioethanol.
In this study, the potential of biobutanol was evaluated as an alternative to bioethanol which is currently the predominant liquid biofuel in the US. Life-cycle assessments (LCAs) suggest that the net energy generated during corn-to-biobutanol conversion is 6.53 MJ/L, which is greater than that of the corn-derived bioethanol (0.40 MJ/L). Additionally, replacing corn with lignocellulosic materials in bioethanol production can further increase the net energy to 15.90 MJ/L. Therefore, it was interesting to study the possibility of using domestically produced switchgrass, hybrid poplar, corn stover, and wheat straw as feedstocks to produce liquid biofuels in the US. By sustainable harvest based on current yields, these materials can be converted to 8.27 billion gallons of biobutanol replacing 7.55 billion gallons of gasoline annually. To further expand the scale, significant crop yield increases and appropriate land use changes are considered two major requirements.


What slaughterhouse workers' attitudes and knowledge reveal about human-pig relationships during pre-slaughter operations: A profile-based approach.
Slaughterhouse workers are strategic capital for the meat industry in terms of operational and animal welfare issues; however, information about the attitudes of workers toward the human-animal relationship is limited. The main aim of our study was to identify the profiles of workers based on their attitudes toward pigs, occupational satisfaction, sociodemographics, and animal handling. The survey included 171 workers in 12 Colombian pig slaughterhouses. A factor analysis and a hierarchical cluster analysis identified four segments or worker profiles. The first comprised workers who relate to animals and their work in a mechanical way, the second comprised professional workers who are emotionally close to animals, the third comprised those committed to animals and their work, and the fourth comprised workers who are apathetic toward animals and work activity. The human-animal relationship at the slaughterhouse level is multifaceted, but is influenced by dependent on work satisfaction and sympathy toward the animals.


Semantic contribution to verbal short-term memory: are pleasant words easier to remember than neutral words in serial recall and serial recognition?
In the four experiments reported here, we examined the role of word pleasantness on immediate serial recall and immediate serial recognition. In Experiment 1, we compared verbal serial recall of pleasant and neutral words, using a limited set of items. In Experiment 2, we replicated Experiment 1 with an open set of words (i.e., new items were used on every trial). In Experiments 3 and 4, we assessed immediate serial recognition of pleasant and neutral words, using item sets from Experiments 1 and 2. Pleasantness was found to have a facilitation effect on both immediate serial recall and immediate serial recognition. This study supplies some new supporting arguments in favor of a semantic contribution to verbal short-term memory performance. The pleasantness effect observed in immediate serial recognition showed that, contrary to a number of earlier findings, performance on this task can also turn out to be dependent on semantic factors. The results are discussed in relation to nonlinguistic and psycholinguistic models of short-term memory.


ASCO Provisional Clinical Opinion: KRAS, Cetuximab, and Panitumumab-Clinical Implications in Colorectal Cancer.
ASCO's Provisional Clinical Opinion alerts oncologists to emerging information from recent clinical trials that can assist them in treatment selection. Evidence suggests that cetuximab and panitumumab are ineffective in patients with KRAS mutations at codon 12 or 13. Thus, patients with colorectal cancer with these mutations should be spared the toxicity and cost of an ineffective therapy.


Engineering bacterial membrane nanovesicles for improved therapies in infectious diseases and cancer.
Research on bacterial membrane vesicles (BMVs) is an emerging topic, and the goal is to address whether BMVs can bring translational tools to improve current therapies. In this review, we provided the updated studies on BMVs including their production, their types, and therapeutic regimens for treating infectious diseases and cancers. We described several platforms of BMVs, such as outer membrane vesicles (OMVs), inner membrane vesicles (IMVs) and double membrane vesicles (DMVs), and those structures were produced from Gram-negative or Gram-positive bacteria. We also discussed how to engineer and formulate new and novel BMVs using chemical, physical, and genetic methods. For therapies, we analyzed current methods for loading drugs in BMVs and discussed their limitations. Finally, we reviewed several therapeutic platforms of BMVs that have been exploited in improving the treatments of infectious diseases and cancers. Although BMVs offer the promising biomedical applications, it is needed to develop rigorous approaches and methods to generate reproducible and scalable drug delivery systems for translation.


Dexamethasone in the era of COVID-19: friend or foe? An essay on the effects of dexamethasone and the potential risks of its inadvertent use in patients with diabetes.
The disclosure in the media of a benefit with the use of dexamethasone in patients with COVID-19 infection sets precedents for self-medication and inappropriate use of corticosteroids. This is a critical interpretive synthesis of the data available in the literature on the effects of the use of corticosteroids and the impact that their indiscriminate use may have on patients with diabetes. Reviews and observational and experimental studies published until June 18, 2020 were selected. Corticosteroids are substances derived from cholesterol metabolism that interfere with multiple aspects of glucose homeostasis. Interactions between corticoid receptors and target genes seem to be among the mechanisms responsible for the critical functions of glucocorticoids for survival and anti-inflammatory effects observed with these medications. Corticosteroids increase hepatic gluconeogenesis, reduce peripheral use of glucose and increase insulin levels. Previous studies have shown that glucocorticoids have a pro-adipogenic function, increasing deposition of abdominal fat, and lead to glucose intolerance and hypertriglyceridemia. In addition, these drugs play a role in controlling liver metabolism and can lead to the development of hepatic steatosis. Glucocorticoids reduce the recruitment of osteoblasts and increase the number of osteoclasts, which results in increased bone resorption and greater bone fragility. Moreover, these medications cause water and sodium retention and increase the response to circulating vasoconstrictors, which results in increased blood pressure levels. Chronic or high-dose use of corticosteroids can, by itself, lead to the onset of diabetes. For those who were already diagnosed with diabetes, studies show that chronic use of corticosteroids leads to a 94% higher risk of hospitalization due to diabetes complications. In addition to the direct effects on glycemic control, the effects on arterial pressure control, lipids and bone metabolism also have a potential for severe consequences in patients with diabetes. Fear and uncertainty toward a potentially serious infection may lead people to self-medication and the inappropriate and abusive use of corticosteroids. More than ever, it is necessary for health professionals to be alert and able to predict damages related to the use of these drugs, which is the first step to minimize the potential damages to come.


Neoproterozoic rifting in the Upper Yangtze Continental Block: Constraints from granites in the Well W117 borehole, South China.
Well W117 in the Sichuan Basin reveals a suite of ~814 Ma quartz monzonites, unconformably overlain by Sinian clastic and carbonate sediments. The quartz monzonites contain no muscovite and amphibole, and are characterized by high SiO2 (72.26-77.93%), total alkali, and TFe2O3/MgO content, and low P2O5 and CaO abundance, with variable A/CNK ratio (0.93-1.19), classified as metaluminous to weakly aluminous highly fractionated I-type granites. They are preserved in the Neoproterozoic rift and exhibit restricted negative εNd(t) values (-7.0 to -5.2) and variable zircon εHf(t) values (-13.9 to 2.3), suggesting their generation via melting of both ancient and juvenile crustal materials in an extensional setting. Their parent magmas were formed in a low-temperature condition (831-650 °C) and finally emplaced at ca. 9-10 km below the surface, indicating that the intrusion underwent exhumation before the deposition of Sinian sag basin. Such geological processes, together with evidence for Neoproterozoic structures in the surrounding area, support that the Upper Yangtze craton experienced two main phases of rifting from 830-635 Ma. The Well W117 granites and its overlying sediments record a geodynamic evolution from orogenic collapse to continental rifting, and to thermal subsidence, probably related to the Rodinia supercontinent breakup.


[Gender-inclusive care of victims of violence : The model project "Gender Gewaltkonzept" at the University Hospital Aachen].
Violence is a topic of great social relevance, frequently causing tremendous health consequences for those affected and high consequential costs for health care and the national economy. The established consulting and assistance services are usually restricted to offers for ambulant supply, mainly from private agencies or societies. As a result, there is no identification and care for patients who have experienced violence and who are treated in hospital. Another deficiency is the identification and care of male victims of violence. Despite wide-ranging offers of assistance, only very few gender-specific consulting and support services have been available to date.Therefore, the model project "Gender Gewaltkonzept" was initiated at Aachen University Hospital to assess the prevalence of violence and the potential consequences of the violence experienced on the patients' health. In addition, we investigated whether males and females are in need of different supply requirements.Based on the results of the project "Gender Gewaltkonzept" so far, and on prevalence estimates proving that there is a high rate of violent experiences in both males and females, this overview is aimed at presenting the aid and protection concepts available for victims of violence, in addition to the existing deficiencies of the care system. We present approaches to resolving these deficiencies to be able to establish all-encompassing gender-appropriate support for victims of violence.


Snapshots reflecting the lives of siblings of children with autism spectrum disorders.
Past research focused on the effects of raising a child with autism spectrum disorder on families. However, most research examined parents' perspectives rather than siblings' perspectives. Therefore, the purpose of this qualitative descriptive design was to use photo elicitation to capture perspectives of siblings living with a child with autism spectrum disorder. Fourteen siblings (nine male) of 13 children with autism spectrum disorder received disposable cameras with 24-27 colour exposures, and were asked to photograph what was important to them within 2 weeks. After developing snapshots, investigators interviewed siblings about their photographs, and used open, axial and selective coding to determine photograph categories and subcategories. Two major categories were found: people (family members, non-family members) and non-people (personal items/objects, animals, buildings, scenery). Interviews about photographs reflected experiences siblings had with people/non-people in the snapshots and their normal everyday activities. Most photographs revealed family life and activities any sibling would experience whether or not they lived in a family raising a child with autism spectrum disorder. Photo elicitation facilitates communication between children and health-care professionals, and provides information about living with a child with autism spectrum disorder from the sibling's perspective. This information contributes to our knowledge base and allows development of specific intervention plans for siblings of these children.


Analgesics in the management of chronic pain. Part Three: Step 2 analgesic drug therapy.
In this, the third article in the series, the role of analgesic drugs appropriate for the treatment of moderate to severe pain is reviewed along with therapies frequently applied in the treatment of poorly responsive neurogenic pain. The article should be read in conjunction with part one outlining general principles in the management of chronic pain.


Identification of genus Acinetobacter: Standardization of in-house PCR and its comparison with conventional phenotypic methods.
Acinetobacter is grouped under nonfermenting Gram-negative bacilli. It is increasingly isolated from pathological samples. The ability of this genus to acquire drug resistance and spread in the hospital settings is posing a grave problem in healthcare. Specific treatment protocols are advocated for Acinetobacter infections. Hence, rapid identification and drug susceptibility profiling are critical in the management of these infections. To standardize an in-house polymerase chain reaction (PCR) for identification of genus Acinetobacter and to compare PCR with two protocols for its phenotypic identification. A total of 96 clinical isolates of Acinetobacter were included in the study. An in-house PCR for genus level identification of Acinetobacter was standardized. All the isolates were phenotypically identified by two protocols. The results of PCR and phenotypic identification protocols were compared. The in-house PCR standardized was highly sensitive and specific for the genus Acinetobacter. There was 100% agreement between the phenotypic and molecular identification of the genus. The preliminary identification tests routinely used in clinical laboratories were also in complete agreement with phenotypic and molecular identification. The in-house PCR for genus level identification is specific and sensitive. However, it may not be essential for routine identification as the preliminary phenotypic identification tests used in the clinical laboratory reliably identify the genus Acinetobacter.


Differences in spine volumetric bone mineral density between grade 1 vertebral fracture and non-fractured participants in the China action on spine and hip status study.
This study evaluated the prevalence of vertebral fractures (VF) in middle-aged and elderly Chinese men and women and explored the differences in lumbar spine volumetric bone mineral density (vBMD) derived from quantitative CT (QCT) between those with a grade 1 vertebral fracture and non-fractured individuals. 3,457 participants were enrolled in the China Action on Spine and Hip Status (CASH) study and had upper abdominal CT examinations. Vertebral fractures were identified by Genant's semi-quantitative method from lateral CT scout views or CT sagittal views. L1-3 vBMD was measured by Mindways QCT Pro v5.0 software. The characteristics of different fracture severity groups were compared using one-way ANOVA, independent-samples t-tests, and Kruskal-Wallis H-tests. 1267 males (aged 62.77 ± 9.20 years) and 2170 females (aged 61.41 ± 9.01 years) were included in the analysis. In men, the prevalence of VF increased from 14.7% at age<50 years to 23.2% at age ≥70 years, and in women from 5.1% at age<50 years to 33.0% at age ≥70 years. Differences in mean age and vBMD were found between the different fracture grade groups. After age stratification, vBMD differences in men aged < 50 years old disappeared (p = 0.162) but remained in the older age bands. There was no significant difference in mean vBMD between those with multiple mild fractures and those with a single mild fracture. In women, the prevalence of VF increased rapidly after age 50, while it grew more slowly in men. In general, with the exception of men <50 years old, participants with a grade 1 VF had lower vBMD than non-fractured individuals. The majority of women younger than 50 with a grade 1 VF had normal bone mass. We recommend that a vertebral height reduction ratio of <25% be diagnosed as a deformity rather than a fracture in people under the age of 50. The presence of multiple mild fractured vertebrae does not imply lower BMD.


Isolation and characterization of Chinese hamster ovary cell mutants deficient in acyl-coenzyme A:cholesterol acyltransferase activity.
A protocol has been developed for isolating cholesterol ester-deficient cells from the Chinese hamster ovary cell clone 25-RA. This cell line previously was shown to be partially resistant to suppression of cholesterogenic enzyme activities by 25-hydroxycholesterol and to accumulate a large amount of intracellular cholesterol ester when grown in medium containing 10% fetal calf serum (Chang, T. Y., and Limanek, J. S. (1980) J. Biol. Chem. 255, 7787-7795). The higher cholesterol ester content of 25-RA is due to an increase in the rate of cholesterol biosynthesis and low density lipoprotein receptor activity compared to wild-type Chinese hamster ovary cells, and not due to an abnormal acyl-CoA:cholesterol acyltransferase enzyme. The procedure to isolate cholesterol ester-deficient mutants utilizes amphotericin B, a polyene antibiotic known to bind to cholesterol and to form pore complexes in membranes. After incubation in cholesterol-free medium plus an inhibitor of endogenous cholesterol biosynthesis, 25-RA cells were found to be 50-500 times more sensitive to amphotericin B killing than were mutant cells containing reduced amounts of cholesterol ester. Twelve amphotericin B-resistant mutants were isolated which retained the 25-hydroxycholesterol-resistant phenotype. These mutants did not exhibit the perinuclear lipid droplets characteristic of 25-RA cells, and lipid analysis revealed a large (up to 40-fold) reduction in cellular cholesterol ester. The acyl-CoA:cholesterol acyltransferase activities of these cholesterol ester-deficient mutants were markedly lower than 25-RA when assayed in intact cells or in an in vitro reconstitution assay. The tightest mutant characterized, AC29, was found to have less than 1% of the parental acyl-CoA:cholesterol acyltransferase activity. These mutants all have reduced rates of sterol synthesis and lower low density lipoprotein receptor activity compared to 25-RA, probably as a consequence of their reduced enzyme activities. Cell fusion experiments revealed that the phenotypes of all the mutants examined are not dominant and that the mutants all belong to the same complementation group. We conclude that these mutants contain a lesion in the gene encoding acyl-CoA:cholesterol acyltransferase or in a gene encoding a factor needed for enzyme production.


Factors Associated With Willingness to Use Preexposure Prophylaxis Among Black Cisgender Women Residing in Rural and Urban Areas: A Cross-Sectional Study.
Black cisgender women (CGW) are disproportionately impacted by the human immunodeficiency virus (HIV) epidemic in the United States. Black women account for 57% of the total new diagnoses among CGW. In addition, Black CGW women are 9 times more likely to be diagnosed with HIV than their White counterparts. We conducted surveys (September 2019-March 2020) and collected information on sociodemographics, HIV/preexposure prophylaxis (PrEP) knowledge, HIV/PrEP stigma, sexual practices, and other factors identified as PrEP barriers among Black CGW (n = 795). This cross-sectional study used logistic regression models to assess intrapersonal, interpersonal, and structural factors among individuals willing to use PrEP versus individuals unwilling or unsure to use PrEP. Our study population had a mean age of 37 years, predominantly lived in urban areas (65%), had stable housing (96.7%), and had private insurance/Medicare (78.2%). Overall, 29.6% reported willingness to use PrEP, 35.6% reported unwillingness to use PrEP, and 34.8% were unsure of PrEP use. The multivariable analysis showed that, compared with individuals reporting unwillingness/unsure to PrEP use, those reporting willingness to PrEP use were younger (adjusted odds ratio [AOR; 95% confidence interval {CI}], 0.97 [0.96-0.99]), had lower odds of intimate partner violence (AOR [95% CI], 0.87 [0.78-0.98), and had higher odds of organizational religiosity (AOR [95% CI], 1.10 [1.01-1.20]), HIV knowledge (AOR [95% CI], 1.08 [1.03-1.13]), and perceived need for PrEP (AOR [95% CI], 6.38 [3.36-12.11]). Preexposure prophylaxis willingness among Black CGW was impacted by individual-level, interpersonal, and structural factors. Improving PrEP willingness and uptake among Black CGW will require multilevel interventions.


Essential fatty acid deficiency and postresection mucosal adaptation in the rat.
The effect of short-term (biochemical) and long-term (clinical) essential fatty acid (EFA) deficiency on mucosal adaptation was studied in a surgical model of short bowel syndrome. Rats fed an EFA-deficient diet for 4 wk had biochemical evidence of EFA deficiency (hepatic and red blood cell triene to tetraene ratios greater than 0.4). Resected animals (70% proximal jejunoileal resection) receiving an EFA-deficient diet had a significantly impaired intestinal mucosal hyperplasia response in all remaining small bowel segments compared with resected controls. The effect of refeeding a control diet to clinically EFA-deficient resected rats was also evaluated. Short-term refeeding (2 wk) of a control diet resulted in a significant return toward normal tissue triene to tetraene ratios. Concomitantly, refed animals had significantly greater mucosal adaptation in the remaining duodenal/jejunal segment compared with resected animals maintained on an EFA-deficient diet postoperatively. These experiments underscore the dynamic nature of tissue EFA status and the importance of fatty acids in the normal compensatory mechanisms of mucosal adaptation after resection.


Pseudohyperkalaemia associated with leukaemic cell lysis during pneumatic tube transport of blood samples.
Pseudohyperkalaemia is relatively uncommon in children, but needs to be considered in cases where extreme hyperkalaemia is associated with normal renal function. A previously well 12 year-old boy presented with new onset T cell acute lymphoblastic leukaemia associated with a high peripheral blood white cell count. Plasma biochemistry tests on a blood sample sent to the laboratory using a pneumatic tube system showed a high plasma potassium level of 16.6 mmol/l, with otherwise normal electrolytes and renal function. A 12-lead electrocardiogram was normal, with no changes suggestive of hyperkalaemia. Pseudohyperkalaemia was suspected, and further samples transported to the laboratory by foot showed normal plasma potassium levels. It was subsequently demonstrated that the pseudohyperkalemia was due to the lysis of leukaemic white cells during the transport of blood samples from the ward to the laboratory within the pneumatic tube system. Paediatricians caring for children with haematological malignancies need to be aware of this cause of pseudohyperkalaemia so that unnecessary treatment, including the commencement of acute dialysis, is avoided. We recommend that blood samples collected from children with high white cell count malignancies are transported to the laboratory by foot rather than in pneumatic tube systems.


Synthesis of (-)-julocrotine and a diversity oriented Ugi-approach to analogues and probes.
An improved total synthesis of (-)-julocrotine in three steps from Cbz-glutamine, in 51% overall yield, is presented. To demonstrate the potential of the heterocyclic moiety for diversity oriented synthesis, a series of (-)-julocrotine analogues was synthesized by employing the heterocyclic precursor as an amino input in Ugi four-component reactions (Ugi-4CR) [1].