Management of Proximal Anterior Cerebral Artery Aneurysms: Anatomical Variations and Technical Nuances.
The proximal segment of the anterior cerebral artery (A1) is among the most uncommon locations for occurrence of an intracranial aneurysm. These aneurysms may be missed if small or misinterpreted when they are near the internal cerebral artery bifurcation or Anterior Communicating Artery region. The association with congenital vascular anomalies and multiplicity makes them unique. Seventeen A1 aneurysms were diagnosed in sixteen patients between January 2000 and October 2014 in our institution. A retrospective review of the clinical, radiological, and management (microsurgical and endovascular) details of these patients was conducted. The incidence of A1 aneurysm was 1.71% of all patients harboring aneurysms and 1.19% of all aneurysms. Half of these patients exhibited subarachnoid hemorrhage. Fourteen aneurysms underwent microsurgical or endovascular intervention. All patients recovered well, except for one patient who died in the postoperative period. A1 aneurysms are rare, with wide anatomic variations. In this article, we discuss those variations in detail with illustrative cases and pictures. We also discussed the microsurgical and endovascular strategies to encounter them highlighting the technical challenges.


Combined amendment improves soil health and Brown rice quality in paddy soils moderately and highly Co-contaminated with Cd and As.
In situ remediation technology applied aims to not only decrease cadmium (Cd) and arsenic (As) uptake by rice but also improve soil health and rice quality in contaminated paddy soils. Here the effects of a combined amendment, consisting of limestone, iron powder, silicon fertilizer, and calcium-magnesium-phosphate fertilizer, with three application rates (0, 450, and 900 g m-2) on soil health, rice root system, and brown rice quality were compared in moderately versus highly Cd and As co-contaminated paddy fields. After the amendment application, soil pH, cation exchange capacity, four kinds of soil enzyme activities increased (sucrase, urease, acid phosphatase, and catalase), and concentrations of leached Cd/As decreased, as measured by the DTPA (diethylene triamine pentaacetic acid) and TCLP (toxicity characteristic leaching procedure). Changes in the above soil indicators promoted soil health. In both fields, the dithionite-citrate-bicarbonate (DCB)-Fe and DCB-Mn concentration in iron plaque increased and root length became longer. Changes in the above root system indicators reduced the root system's absorption of Cd and As but increased that of nutrients. Under 900 g m-2 treatment, the Cd concentration in brown rice of two sites decreased by 55.8% and 28.9%, likewise inorganic As (iAs) decreased by 50.0% and 21.1%, whereas essential amino acids increased by 20.4% and 20.0%, respectively. Furthermore, the Cd and iAs concentrations in brown rice were <0.2 mg kg-1 (maximum contaminant level of Cd and iAs in the Chinese National Food Safety Standards GB2762-2017 for brown rice) under the 900 g m-2 in the moderately contaminated field. These results suggest the combined amendment can improve soil health and brown rice quality in the moderately and highly Cd- and As-co-contaminated paddy soils, offering potential eco-friendly and efficient remediation material for applications in such polluted paddy soils.


γδT cells are prevalent in the proximal aorta and drive nascent atherosclerotic lesion progression and neutrophilia in hypercholesterolemic mice.
Unique innate immunity-linked γδT cells have been seen in early human artery lesions, but their role in lesion development has received little attention. Here we investigated whether γδT cells modulate atherogenesis in apolipoprotein E-deficient (ApoE KO) mice. We found that γδT cell numbers were markedly increased in the proximal aorta of ApoE-deficient vs. wild-type mice during early atherogenesis, particularly in the aortic root and arch, where they comprised most of the T cells and lesion progression is most rapid. γδT cells infiltrated intimal lesions in ApoE KO mice, but only the adventitia in wild-type mice, and were more prevalent than CD4+ T cells in early nascent lesions, as evaluated by en face confocal microscopy. These aortic γδT cells produced IL-17, but not IFN-γ, analyzed by ex vivo FACS. Furthermore, aortic arch lipid accumulation correlated strongly with abundance of IL-17-expressing splenic γδT cells in individual ApoE KO mice. To investigate the role of these γδT cells in early atherogenesis, we analyzed ApoE/γδT double knockout (DKO) compared to ApoE KO mice. We observed reduced early intimal lipid accumulation at sites of nascent lesion formation, both in chow-fed (by 40%) and Western diet-fed (by 44%) ApoE/γδT DKO mice. In addition, circulating neutrophils were drastically reduced in these DKO mice on Western diet, while expansion of inflammatory monocytes and splenic Th1 or Th17 lymphocytes was not affected. These data reveal, for the first time, a pathogenic role of γδT cells in early atherogenesis in ApoE KO mice, by mechanisms likely to involve their IL-17 production and induction of neutrophilia. Targeting γδT cells thus might offer therapeutic benefit in atherosclerosis or other inflammatory vascular diseases.


[Safety analysis of application of medical anti-adhesion modified chitosan in cardiac surgery].
To verify the application safety of medical anti-adhesion modified chitosan (Baifeimi) in cardiac surgery. From August to December 2010, 42 patients undergoing surgery for congenital heart disease, valvular heart disease or ischemic heart disease were selected and divided into testing (n = 22) and control (n = 20) groups. After complete intraoperative hemostasis, two sheets of anti-adhesion modified chitosan (Baifeimi) were placed on the surface of heart and vessels in the testing group and then chest was closed. And the control group underwent routine chest closing without an application of Baifeimi. The systemic and local reactions and drainage fluid were observed. The postoperative drainage fluid was subject to bacteria culture. Blood routines and laboratory tests at preoperation and Day 1 and Week 1 postoperation were performed to evaluate the changes of chemical, biological and immunological parameters. There was no occurrence of systemic reaction, local inflammation or exudation.Wounds were healed at Phase I. The drainage fluid of pericardium and mediastina had no significant intergroup difference. Drainage was unobstructed in the testing group. A comparison of two groups revealed that the differences of aspartate aminotransferase ( (24 ± 17) vs (40 ± 22) U/L), preoperative and postoperative immunoglobulin A( (1.9 ± 0.7) vs (2.9 ± 1.4) g/L, (2.3 ± 0.9) vs (3.3 ± 1.5) g/L) were statistically significant (all P < 0.05). But the average values of both group stayed within a normal range without clinical significance while other indices had no significant difference. The bacteria cultures of all patients in the control group were negative. Anti-adhesion modified chitosan is both convenient and safe for clinical application. The duration of cardiac surgery is not extended.No systemic or local adverse event is reported. There is no interference of hepatic, renal or immune functions.


Differentiation and characterization of human facial subcutaneous adipocytes.
Aging is associated with the loss of facial subcutaneous fat and with increased abdominal subcutaneous fat. Site specific differences in adipocyte phenotype and/or gene expression may play a role in these age-related changes. In this study, we isolated and characterized human facial preadipocytes and investigated distinct metabolic properties such as a differentiation pattern in relation to abdominal preadipocytes. Subcutaneous preadipocytes were isolated from human facial and abdominal skin and cultured in the presence of differentiation factors including rosiglitazone, a known peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, isobutyl-methyl xanthine (IBMX) and insulin. Differentiation was characterized microscopically and by quantitative real-time PCR. Unexpected superior adipogenic capacity of facial preadipocytes was observed; more facial preadipocytes differentiated in response to rosiglitazone than abdominal preadipocytes and facial preadipocytes retained their ability to differentiate through passage 11 compared with passage 5 for abdominal preadipocytes. Experiments confirmed a reduced lipolysis response in facial versus abdominal adipocytes after exposure to isoproterenol, which was consistent with the reduced β2-adrenergic receptor expression by 60% in the facial cells. The expression of other lipid metabolic gene markers was similar in both facial and abdominal adipocytes with the exception of β3-adrenergic receptor which was only found in abdominal adipose tissue. Gene profiling, by microarray analysis, identified that several HOX genes are robustly reduced in facial adipocytes compared to abdominal adipocytes, suggesting different characteristics between the 2 fat depots. These differences may have implications for development of treatments for facial fat loss during aging.


Dietary Adherence of Saudi Males to the Saudi Dietary Guidelines and Its Relation to Cardiovascular Diseases: A Preliminary Cross-Sectional Study.
Cardiovascular disease (CVD) is a major public health problem in Saudi Arabia. Dietary intake plays a major role in CVD incidence; however, the dietary intake status in Saudi nationals with CVD is unknown. We aimed to investigate whether the dietary patterns of Saudi males, using the Saudi dietary guidelines adherence score, in parallel with the measurement of a selective number of cardiovascular disease-related biomarkers, are contributing factors to CVD risk. Demographics, dietary adherence score, and blood biomarker levels were collected for 40 CVD patients and forty non-CVD patients. Fasting blood glucose (p = 0.006) and high-density lipoprotein levels (p = 0.03) were significantly higher in CVD patients. The adherence score to the Saudi dietary guidelines was not significantly different between the CVD and non-CVD patients; however, the specific adherence scores of fruit (p = 0.02), olive oil (p = 0.01), and non-alcoholic beer (p = 0.02) were significantly higher in the non-CVD patients. The differences in CVD family history (p = 0.02) and adherence scores to specific groups/foods between the CVD and non-CVD patients may contribute to CVD risk in Saudi males. However, as the sample size of this study was small, further research is required to validate these findings.


Multimodal imaging enables early detection and characterization of changes in tumor permeability of brain metastases.
Our goal was to develop strategies to quantify the accumulation of model therapeutics in small brain metastases using multimodal imaging, in order to enhance the potential for successful treatment. Human melanoma cells were injected into the left cardiac ventricle of immunodeficient mice. Bioluminescent, MR and PET imaging were applied to evaluate the limits of detection and potential for contrast agent extravasation in small brain metastases. A pharmacokinetic model was applied to estimate vascular permeability. Bioluminescent imaging after injecting d-luciferin (molecular weight (MW) 320 D) suggested that tumor cell extravasation had already occurred at week 1, which was confirmed by histology. 7T T1w MRI at week 4 was able to detect non-leaky 100 μm sized lesions and leaky tumors with diameters down to 200 μm after contrast injection at week 5. PET imaging showed that (18)F-FLT (MW 244 Da) accumulated in the brain at week 4. Gadolinium-based MRI tracers (MW 559 Da and 2.066 kDa) extravasated after 5 weeks (tumor diameter 600 μm), and the lower MW agent cleared more rapidly from the tumor (mean apparent permeabilities 2.27 × 10(-5)cm/s versus 1.12 × 10(-5)cm/s). PET imaging further demonstrated tumor permeability to (64)Cu-BSA (MW 65.55 kDa) at week 6 (tumor diameter 700 μm). In conclusion, high field T1w MRI without contrast may improve the detection limit of small brain metastases, allowing for earlier diagnosis of patients, although the smallest lesions detected with T1w MRI were permeable only to d-luciferin and the amphipathic small molecule (18)F-FLT. Different-sized MR and PET contrast agents demonstrated the gradual increase in leakiness of the blood tumor barrier during metastatic progression, which could guide clinicians in choosing tailored treatment strategies.


Regioselective Ru(II)/Pd(0) Dual Catalysis: One-Pot C-H Diarylation of Five-Membered Heterocyclic Derivatives.
Herein, we report a one-pot site-selective dual metal catalyzed C-H diarylation reaction for the synthesis of multiarylated thiophene and furan derivatives in yields up to 92%. The regioselectivity of the developed methodology was achieved with the sequential use of two metal catalysts within a single vessel, starting with a Ru(II)-catalyzed C3 arylation assisted by an azine directing group, followed by a Pd(0)-catalyzed C-H functionalization on the C5-position of the five-membered heterocycle. Furthermore, the kinetic studies support that the position of the nitrogen atom within the azine moiety exhibits an evident effect on the efficiency of the ruthenium-catalyzed arylation step.


Specific detection of chikungunya virus using a RT-PCR/nested PCR combination.
Chikungunya (CHIK) virus is enzootic in many countries in Asia and throughout tropical Africa. In Asia the virus is transmitted from primates to humans almost exclusively by Aedes aegypti, while various aedine mosquito species are responsible for human infections in Africa. The clinical picture is characterized by a sudden onset of fever, rash and severe pain in the joints which may persist in a small proportion of cases. Although not listed as a haemorrhagic fever virus, illness caused by CHIK virus can be confused with diseases such as dengue or yellow fever, based on the similarity of the symptoms. Thus, laboratory confirmation of suspected cases is required to launch control measures during an epidemic. CHIK virus diagnosis based on virus isolation is very sensitive, yet requires at least a week in conjunction with virus identification using monovalent sera. We developed a reverse transcription-polymerase chain reaction (RT-PCR) assay which amplifies a 427-bp fragment of the E2 gene. Specificity was confirmed by testing representative strains of all known alphavirus species. To verify further the viral origin of the amplicon and to enhance sensitivity, a nested PCR was performed subsequently. This RT-PCR/nested PCR combination was able to amplify a CHIK virus-specific 172-bp amplicon from a sample containing as few as 10 genome equivalents. This assay was successfully applied to four CHIK virus isolates from Asia and Africa as well as to a vaccine strain developed by USAMRIID. Our method can be completed in less than two working days and may serve as a sensitive alternative in CHIK virus diagnosis.


Presentation and characteristics of breast cancer in young women under age 40.
Although uncommon, breast cancer is the leading cause of cancer death in young women. There are limited studies on the presentation and characteristics of breast cancer in women under age 40. This is a retrospective study investigating patient demographics, clinical presentations, imaging findings, and cancer characteristics of a cohort of 145 women under age 40 with breast cancer. Our cohort had more aggressive cancer subtypes than reported in older women; 33.1% triple negative, 80% high Ki-67, and 21.3% with stage 3+ disease. Most were referred from primary care or obstetrician/gynecologist, though 5.5% initially presented from the emergency department and another 2.1% were incidental findings. 16.6% of patients presented while pregnant or breastfeeding. Most patients presented with breast related symptoms. Of the 9.1% of patients diagnosed through our high-risk screening program, 84.6% of the cancers were identified on mammography or simultaneously with mammography and MRI. Most breast cancers presented with typically worrisome imaging (82.6%), though several cancers presented with findings that were typically benign. We recommend prompt breast imaging for young women presenting with breast-related symptoms or an incidental breast finding, as younger patients have more aggressive cancer subtypes and are of a higher grade at presentation compared to older women. We also recommend vigilance when distinguishing suspicious symptoms from pregnancy-related breast changes to minimize delays in diagnosis. Additionally, it is important to identify patients who qualify for high risk screening, since cancers in screening patients were found at a lower grade than those presenting with symptoms.


Activity of oral and intravenous 9-aminocamptothecin in SCID mice engrafted with human leukemia.
The intravenous (i.v.) injection of the human acute myelogenous leukemia cell line KBM-3 into severe combined immune deficient (SCID) mice results in disseminated multi-organ human disease involvement in these animals which leads to their death over a defined period of time. We utilized this model of human leukemia to investigate the in vivo therapeutic efficacy of the topoisomerase I inhibitor 9-aminocamptothecin (9-AC) given by two different routes. Mice injected with KBM-3 were divided into five groups. Group 1 received only diluent and served as control. The four remaining groups were treated with 9-AC four days a week for three consecutive weeks as follows: group 2 received 1.33 mg/kg/dose, i.v.; group 3, 1.33 mg/kg/dose, orally (p.o.); group 4, 2.0 mg/kg/dose i.v. and group 5, 2.0 mg/kg/dose p.o.. All animals in the control group died from disseminated human leukemia by day 64 from grafting, with a median survival of 59 days. Eleven out of 20 treated mice survived with no evidence of disease and were sacrificed at the termination of the experiment on day 128. PCR-assisted tissue analysis for the presence of human DNA showed no evidence of human leukemia. In conclusion, 9-AC is an active agent in SCID mice engrafted with human myelogenous leukemia and should be explored in phase I-II trials. Oral and intravenous routes are equally effective.


Engineering multiferroism in CaMnO3.
Structural instabilities of CaMnO3 are investigated from first principles. We point out that, on top of a strong antiferrodistortive instability responsible for its orthorhombic ground state, the cubic perovskite structure of CaMnO3 also exhibits a weak ferroelectric instability. Although ferroelectricity is suppressed by antiferrodistortive motions, we show that it can be favored using strain or chemical engineering in order to make CaMnO3 multiferroic. We finally highlight that the ferroelectric instability of CaMnO3 is Mn-dominated. This illustrates that, contrary to common belief, ferroelectricity and magnetism are not necessarily exclusive but can be driven by the same cation.


Reactions of lead cluster ions with acetone.
Reactions of lead cluster cations and anions with acetone have been studied using a homemade reflectron time-of-flight mass spectrometer. Association with acetone to form Pb(k)(CH(3)COCH(3))(n)(+), high-energy pathway reactions forming Pb(k)CH(3)(+), and intraheterocluster reaction of Pb(k)(CH(3)COCH(3))(n+1)(+) to give Pb(k)CH(3)(CH(3)COCH(3))(n)(+) were the main reaction pathways for lead cluster cations with acetone. Decomposition of acetone by Pb(k)(-) to give Pb(k)C(m)(-) ions and their further association with acetone, Pb(k)C(m)(CH(3)COCH(3))(-), were the dominant reactions of lead cluster anions with acetone. Pb(7)(-), Pb(10)(-), and Pb(k)C(5)(-) were 'magic numbers' with special structural stabilityin Pb(k)(-) and Pb(k)C(m)(-), respectively. In addition, Pb(k)H(-), CH(2)COCH(3)(CH(3)COCH(3))(n)(-) and Pb(k)CH(2)COCH(3)(CH(3)COCH(3))(n)(-) were also observed in the reaction of lead cluster anions. Some reaction mechanisms are proposed for these reactions. To investigate the isotope effect for the reaction of lead cluster cations and anions with acetone and to verify the structural assignments of the observed ions, reactions of lead cluster cations and anions with deuterated acetone-d(6) were also performed.


[Is breast cancer prevention by tamoxifen possible?].
Breast cancer is a frequent disease especially in the Western world with an incidence that increases by 1% each year. Distressingly, even nowadays, 40% of patients with breast cancer will die of their disease. Postoperative adjuvant therapy and detection of non-palpable cancers by mass screening of women have improved patient survival but have not impinged upon the steady increase in incidence. Treatment before radiological detection could improve the chances of survival and even prevent the full-blown expression of the disease. The probability that a woman will develop breast cancer during her life-time is high but not evenly distributed. Knowledge of predisposing factors can help to identify those women subject to greater risk than the general population. The most important known risk factors are age, family history, factors related to ob-gyn antecedents, lifestyle, benign hyperplastic breast disease with or without atypia. These various risks, are often associated and cumulative. A woman who has already had breast cancer has a 3 to 5 times greater probability of developing cancer of the contralateral breast than the average woman. The second breast is therefore at risk in the same way as are the women with predisposing factors. Many clinical studies have demonstrated the benefits of postoperative adjuvant tamoxifen (TAM) in improving the disease-free interval and survival of patients. An analysis of the site of relapse has interestingly brought to light a marked decrease in the percentage of cancers of the contralateral breast. In order to establish whether TAM could prevent or delay the onset of high-risk women without detectable signs of illness into groups receiving either TAM or placebo. Is this ethically acceptable? The answer to this question rests heavily on an objective evaluation of the unwanted and beneficial side-effects of TAM in order to weigh up all pros and cons before initiating a trial.


Principles and results of corrective lower limb osteotomies for patients with vitamin D-resistant hypophosphatemic rickets.
Forty-four lower limb osteotomies were performed in ten patients with vitamin D-resistant hypophosphatemic rickets. The average follow-up period was 51 months. Osteotomies were combined with shortening and compression plating. This allowed corrections of angular deformities in the sagittal plane as large as 70 degrees and in the coronal plane as large as 78 degrees. There was one complication, a compartment syndrome that resolved completely following prompt fasciotomy. Recurrence of deformity occurred in 27% of the cases. While osteotomies were safe and provided dramatic improvement to limb deformity, postoperative control of vitamin D metabolism was the one constant factor for maintenance of correction.


Does the Somatosensory Temporal Discrimination Threshold Change over Time in Focal Dystonia?
The somatosensory temporal discrimination threshold (STDT) is defined as the shortest interval at which an individual recognizes two stimuli as asynchronous. Some evidence suggests that STDT depends on cortical inhibitory interneurons in the basal ganglia and in primary somatosensory cortex. Several studies have reported that the STDT in patients with dystonia is abnormal. No longitudinal studies have yet investigated whether STDT values in different forms of focal dystonia change during the course of the disease. We designed a follow-up study on 25 patients with dystonia (15 with blepharospasm and 10 with cervical dystonia) who were tested twice: upon enrolment and 8 years later. STDT values from dystonic patients at the baseline were also compared with those from a group of 30 age-matched healthy subjects. Our findings show that the abnormally high STDT values observed in patients with focal dystonia remained unchanged at the 8-year follow-up assessment whereas disease severity worsened. Our observation that STDT abnormalities in dystonia remain unmodified during the course of the disease suggests that the altered activity of inhibitory interneurons-either at cortical or at subcortical level-responsible for the increased STDT does not deteriorate as the disease progresses.


The poly(ADP-ribose) polymerase 1 interacts with Sry and modulates its biological functions.
Sry encodes a putative transcription factor that switches on testis differentiation during embryogenesis. Currently, the mechanism(s) by which Sry mediates such developmental process is still uncertain. To understand its gene regulation mechanism, we have utilized an in vitro affinity chromatography and proteomic strategy to identify and characterize Sry binding proteins from the mouse testis potentially involved in the formation of an Sry transcriptional complex(es). Our study has consistently identified the poly(ADP-ribose) polymerase 1 (PARP-1) as an Sry interactive protein. PARP-1 is expressed in mouse fetal gonads at the time of sex determination and co-localized with Sry in the nuclei of pre-Sertoli cells. PARP-1 could be co-immunoprecipitated with Sry in cultured cells. The interactive domains have been mapped to the HMG box of Sry and the zinc fingers of the PARP-1 protein, respectively. The Sry-PARP-1 interaction is evolutionarily conserved and it interferes with the ability of Sry in binding to its consensus sequence. In the presence of its substrate, PARP-1 poly(ADP-ribosyl)ates Sry and minimizes severely its DNA-binding activities. PARP-1 represses Sry-mediated transactivation of a reporter gene in cultured cells. Hence, PARP-1 could modulate the regulatory function(s) of Sry on its target genes in this developmental pathway.


Usability of the revised NIOSH lifting equation.
Following the revision of the 1981 National Institute for Occupational Safety and Health (NIOSH) lifting equation, research needs related to the new equation were outlined. Aside from epidemiological studies, the need to evaluate the usability of the 1991 NIOSH equation in realistic work environments was expressed. This paper reports on extensive experiences with training users and application of the equation in varied work settings. Qualitative results from training sessions indicated that frequency, asymmetry and duration were the parameters that required relatively longer instruction periods and resulted in the most questions. Field applications indicated that the variable nature of lifting/lowering demands found in many jobs resulted in difficulty applying the equation. Approximately 35% of 1103 lifting and lowering tasks had at least one parameter outside of acceptable ranges, while a majority of workers (62.8%) reported other manual handling tasks that are counter to assumptions made in the development of the equation. The practical implications of the findings are discussed.


Dose volume histogram analysis and comparison of different radiobiological models using in-house developed software.
The purpose of this study is to compare Lyman-Kutcher-Burman (LKB) model versus Niemierko model for normal tissue complication probability (NTCP) calculation and Niemierko model versus Poisson-based model for tumor control probability (TCP) calculation in the ranking of different treatment plans for a patient undergoing radiotherapy. The standard normal tissue tolerance data were used to test the NTCP models. LKB model can reproduce the same complication probability data of normal tissue response on radiation, whereas Niemierko model cannot reproduce the same complication probability. Both Poisson-based and Niemierko models equally reproduce the same standard TCP data in testing of TCP. In case of clinical data generated from treatment planning system, NTCP calculated using LKB model was found to be different from that calculated using Niemierko model. When the fractionation effect was considered in LKB model, the calculated values of NTCPs were different but comparable with those of Niemierko model. In case of TCP calculation using these models, Poisson-based model calculated marginally higher control probability as compared to Niemierko model.


Energy-consistent pseudopotentials and correlation consistent basis sets for the 5d elements Hf-Pt.
New relativistic energy-consistent pseudopotentials have been generated for the 5d transition metals Hf-Pt. The adjustment was done in numerical two-component multiconfiguration Hartree-Fock calculations, using atomic valence-energy spectra from four-component multiconfiguration Dirac-Hartree-Fock calculations as reference data. The resulting two-component pseudopotentials replace the [Kr]4d(10)4f(14) cores of the 5d transition metals and can easily be split into a scalar-relativistic and a spin-orbit part. They reproduce the all-electron reference energy data with deviations of approximately 0.01 eV for configurational averages and approximately 0.05 eV for individual relativistic states. Full series of correlation consistent basis sets from double to quintuple-zeta have also been developed in this work for use with the new pseudopotentials. In addition, all-electron triple-zeta quality correlation consistent basis sets are also reported in order to provide calibration for the pseudopotential treatment. The accuracy of both the pseudopotentials and basis sets are assessed in extensive coupled cluster benchmark calculations of atomic ionization potentials, electron affinities, and selected excitation energies of all the 5d metal atoms, including the effects of spin-orbit coupling.


Immunohistochemistry in diagnostic surgical pathology: contributions of protein life-cycle, use of evidence-based methods and data normalization on interpretation of immunohistochemical stains.
Immunohistochemical (IHC) staining of formalin-fixed and paraffin-embedded tissues (FFPE) is widely used in diagnostic surgical pathology. All anatomical and surgical pathologists use IHC to confirm cancer cell type and possible origin of metastatic cancer of unknown primary site. What kinds of improvements in IHC are needed to boost and strengthen the use of IHC in future diagnostic pathology practice? The aim of this perspective is to suggest that continuing reliance on immunohistochemistry in cancer diagnosis, search and validation of biomarkers for predictive and prognostic studies and utility in cancer treatment selection means that minimum IHC data sets including "normalization methods" for IHC scoring, use of relative protein expression levels, use of protein functional pathways and modifications and protein cell type specificity may be needed when markers are proposed for use in diagnostic pathology. Furthermore evidence based methods (EBM), minimum criteria for diagnostic accuracy (STARD), will help in selecting antibodies for use in diagnostic pathology. In the near future, quantitative methods of proteomics, quantitative real-time polymerase chain reaction (qRT-PCR) and the use of high-throughput genomics for diagnosis and predictive decisions may become preferred tools in medicine.


[Progress in isokinetic technology in testing and training for assessment of muscle function].
Isokinetic technology in testing and training is the most advanced practical technique in the evaluation of muscle function. This method is a continuous dynamic test in the full range of the joint motion which has strong pertinence at the aspect of assessing muscle strength, and is an objective and quantitative method for reflecting each point's muscle strength in the range of the joint motion. This article reviews the key concepts, brief history of development and influencing factors of isokinetic technology in testing and training, introduces the progress in the field of rehabilitation medicine and sport science, etc., and discusses the future exploration in forensic science.


Whither health promotion events? A judicial approach to evidence.
This paper reports on a review undertaken for the Health Education Board for Scotland on 'health events'. On the basis of a literature review and interviews with 20 professionals in the UK, it appraised the effectiveness of such activities, assessed their current extent and status, and ultimately considered whether they are useful and relevant within emergent contexts. It suggests that the evidence base for health events is relatively weak, particularly given the scale of such work. At best, all that can be said is that there is some evidence that some of these events have some use within very specific assumptions and values. Consideration is given to possible ways forward. The paper also considers a series of related issues that impinge on the assessment of complex health promotion interventions. From our field interviews, health events are perceived by most to be labour intensive and ineffective. Rather, they are undertaken for a range of pragmatic 'public relations' reasons that exist independent of knowledge, attitudinal or behavioural outcomes. This ambiguity of expectation coupled with a paucity of published high-quality literature led to the use of a judicial approach to evidence appraisal. It considers the ways in which this exercise could be undertaken, ultimately being sceptical of systematic meta-reviews.


Common bacterial infections and their treatment in hospitalized pediatric patients.
Common bacterial infections in pediatric patients that the hospital pharmacist may encounter are reviewed, and guidance on the safe and effective use of antibiotics to treat those infections is provided. Pharmacists play a key role in evaluating and creating antibiotic treatment plans for patients with infections. Bacterial infections are a common reason for hospital admission in pediatric patients, and pharmacists working in hospitals may be consulted to provide treatment and monitoring recommendations. It is important for pharmacists to be aware of similarities and differences in adult and pediatric populations with regard to presenting signs and symptoms of bacterial infections, common causative pathogens, and antibiotic selection, dosing, and monitoring. This article reviews current approaches to treatment of common bacterial infections in pediatric patients and also provides general suggestions for antibiotic use. Pharmacists have an opportunity to positively impact the care of pediatric patients with bacterial infections. Especially at facilities where pediatric patients are not regularly treated, pharmacists can potentially improve care through provision of recommendations for optimal antibiotic selection, dosing, and monitoring.


Visible light-responsive micelles formed from dialkoxyanthracene-containing block copolymers.
A class of dialkoxyanthracene-containing diblock copolymers is synthesized which possesses visible light-responsivity. These copolymers can self-assemble into a micellar structure in water. Green visible light (540 nm) is able to scissor these anthracene species and cleave the diblock copolymer into two fragments, inducing disassembly of the self-assembled micelles.


Thrombus aspiration during primary percutaneous coronary intervention.
The main goal of primary percutaneous coronary intervention (PPCI) is to achieve not only restoration of flow in the epicardial coronary artery, but also reperfusion at the level of myocardial tissue. Distal embolization is a possible complication of PPCI; in these patients, a microvascular injury occurs, which finally leads to a lack of myocardial reperfusion. Thrombus aspiration during PPCI has been proposed to prevent embolization. Several different thrombectomy devices have been demonstrated to be well tolerated and effective in improving surrogate markers of myocardial reperfusion; furthermore, in a few studies, the use of thrombectomy was associated with an improvement of clinical outcome. Because study results appeared largely inconsistent, especially about clinical outcome data, several meta-analyses have been carried out, showing that thrombectomy is able to improve markers of myocardial reperfusion and that manual thrombectomy is associated with better results in terms of myocardial reperfusion and clinical outcome, compared with embolic protection or mechanical thrombectomy devices, probably due to its easy and time-sparing use with low rate of complication. Literature data, based mainly on the Thrombus Aspiration During Primary Percutaneous Coronary Intervention (TAPAS) trial, indicate a favourable effect on outcome of routine manual thrombectomy strategy and the recent European Society of Cardiology (ESC) and European Association for Cardio-Thoracic Surgery (EACTS) guidelines on myocardial revascularization recommend thrombus aspiration during PPCI. However, data on long-term clinical outcome are still inconsistent and no trials have been, at the present time, designed to assess hard endpoint. In this review, we have carefully analysed literature data on thrombectomy during PPCI, taking into account the most recent studies and the last meta-analyses; study results have been compared to verify if either a routine or a selective use of thrombectomy should be adopted and to assess whether the use of thrombectomy may finally improve clinical outcome.


A Non-Invasive Soil Moisture Sensing System Electronic Architecture: A Real Environment Assessment.
This paper will show the electronic architecture of a portable and non-invasive soil moisture system based on an open rectangular waveguide. The spectral information, measured in the range of 1.5-2.7 GHz, is elaborated on by an embedded predictive model, based on a partial least squares (PLS) regression tool, for the estimation of the soil moisture (%) in a real environment. The proposed system is composed of a waveguide, containing Tx and Rx antennas, and an electronic circuit driven by a microcontroller (MCU). It will be shown how the system provides a useful and fast estimation of moisture on a silty clay loam soil characterized by a moisture range of about 9% to 32% and a soil temperature ranging from about 8 °C and 18 °C. Using the PLS approach, the moisture content can be predicted with an R2 value of 0.892, a root mean square error (RMSE) of 1.0%, and a residual prediction deviation (RPD) of 4.3. The results prove that it is possible to make accurate and rapid moisture assessments without the use of invasive electrodes, as currently employed by state-of-the-art approaches.


The effect of breastfeeding on childhood overweight and obesity: a systematic review of the literature.
Childhood obesity has reached epidemic proportions. There is increasing attention to the topic of prevention and continued debate as to whether breastfeeding (BF) is protective against childhood obesity. Previous systematic reviews on this topic were done in 2005 showing that BF was protective against childhood obesity but, because of confounding variables, the evidence was weak. To explore the current evidence of the effect of BF on childhood obesity and provide recommendations for the nurse practitioner (NP) as a primary care provider. A systematic review of the literature from 1/2005 to 3/2012 was done to assess the evidence on the relationship between BF and childhood obesity. The majority of studies identified in this article showed a relationship between BF and obesity prevention, but because of confounding maternal, child, cultural, genetic, and environmental variables, the relationship remains unclear. While it is possible that there are protective benefits of BF on childhood obesity, it is difficult to prove because of confounding variables. However, because of other benefits for the mother and child, BF should be encouraged. Whether obesity in childhood can be prevented by BF remains unclear. Further research controlling for confounding variables is needed to provide concrete evidence.


Flaxseed Oil Containing α -Linolenic Acid Ester of Plant Sterol Improved Atherosclerosis in ApoE Deficient Mice.
Plant sterols (PS) have potential preventive function in atherosclerosis due to their cholesterol-lowering ability. Dietary α-linolenic acid in flaxseed oil is associated with a reduction in cardiovascular events through its hypolipidemic and anti-inflammation properties. This study was designed to evaluate the effects of flaxseed oil containing α-linolenic acid ester of PS (ALA-PS) on atherosclerosis and investigate the underlying mechanisms. C57BL/6 mice were administered a regular diet and apoE knockout (apoE-KO) mice were given a high fat diet alone or supplemented with 5% flaxseed oil with or without 3.3% ALA-PS for 18 weeks. Results demonstrated that flaxseed oil containing ALA-PS was synergistically interaction in ameliorating atherosclerosis as well as optimizing overall lipid levels, inhibiting inflammation and reducing oxidative stress. These data were associated with the modification effects on expression levels of genes involved in lipid metabolism (PPARα, HMGCR, and SREBPs), inflammation (IL-6, TNF, MCP-1, and VCAM-1), and oxidative stress (NADPH oxidase).


In vitro cow's milk protein-specific inflammatory and regulatory cytokine responses in preterm infants with necrotizing enterocolitis and sepsis.
Enteral feeding with cow's milk formula is associated with neonatal necrotizing enterocolitis (NEC) and sepsis. Dietary antigen sensitization may play a role in promoting and/or sustaining inflammation in both conditions. Aiming at investigating cow's milk protein (CMP)-specific cytokine responses in preterm infants with NEC and sepsis, 14 babies with NEC, 14 matched healthy controls, and 10 septic controls were recruited. Unstimulated and stimulated peripheral blood mononuclear cells (PBMCs) secreting IFN-γ, IL-4, IL-10, and TGF-β1 were counted by the single-cell enzyme-linked immunospot (ELISPOT) assay. During the acute phase of NEC, patients showed a general pattern of a high level of cytokine secretion both when unstimulated and stimulated by mitogen [phytohaemagglutinin (PHA)] and CMPs: beta-lactoglobulin (β-lg) and casein. These responses were more marked to β-lg for IFN-γ, IL-4, and IL-10 than TGF-β1. Cytokine responses in sepsis were lower than in NEC (lowest in healthy controls, with a minimal TGF-β1 response). At term, lower frequencies of cytokine-secreting cells were elicited than during the acute phase, except for TGF-β1 secreting cells, which increased at term (in response to PHA and CMPs) particularly following not only NEC but also sepsis.


Biotransformation and excretion of lorazepam in patients with chronic renal failure.
To evaluate the effect of end-stage renal insufficiency and haemodialysis on the elimination of lorazepam, single oral doses of the drug (2.5 mg) were administered to normal subjects and patients with chronic renal failure (CC(r) : less than 2 ml/min) in the interdialysis period and during haemodialysis. The concentration of lorazepam and its major metabolite, lorazepam-glucuronide, were assayed using electron capture g.l.c. Plasma half-life (T1/2) of unchanged lorazepam in the patient group (11.3 +/- 0.6 h) was not different from that obtained in normals (11.1 +/- 0.9 h). Only minor quantities of the unchanged drug could be recovered in the 24 h urine in both groups: 0.3% of the ingested dose in normals and trace amounts in the patient group. No unchanged lorazepam could be detected in the ultrafiltrate from the coil kidney. Since the lower sensitivity of the method is about 5 ng/ml, this would indicate the in vivo binding of the active drug to plasma proteins to be at least 70%. The effect of haemodialysis on lorazepam plasma T1/2 was also insignificant (9.4 +/- 1.0 h). Urinary excretion of lorazepam-glucuronide was found to be considerably decreased in chronic renal failure associated with accumulation of high concentrations of this conjugate in plasma during days after a single oral dose. The plasma T1/2 of this conjugate in normals was 20.7 +/- 2.1 h. Roughly 35% of this main metabolite's concentration in plasma was detected in the ultrafiltrate from the coil kidney indicating the dialyzability of this conjugate and that the extent of plasma protein binding of lorazepam-glucuronide in vivo was approximately 65%. The above results indicate that after a single oral dose (2.5 mg) the biotransformation of lorazepam to its glucuronide conjugate remains unaltered and that high concentrations of this metabolite accumulate in plasma in the presence of severe renal function impairment.


Prevalence and Risk Factors of QTc Prolongation During Pregnancy.
Prolonged QT intervals have been observed in pregnant women, which predispose them to a higher risk of potentially lethal ventricular arrhythmias. This study was designed to evaluate the prevalence of QTc prolongation in Chinese hospitalized parturient women with single and twin pregnancies, and to explore potential risk factors associated with QTc prolongation. This retrospective study included 1,218 patients from a large Chinese population between January 2014 and October 2020. Data from parturient women with single and twin pregnancies without pre-pregnancy cardiac diseases were collected. QTc was corrected by the Fridericia formula [QTc = QT/RR(1/3)], and QTc ≥ 460 ms for females was defined as prolonged QTc, QTc ≥ 500 ms was defined as severely prolonged QTc. The prevalence and common risk factors of QTc prolongation during pregnancy were analyzed in this cohort. Uni- and multivariable logistic regression analysis were performed to identify clinical parameters associated with QTc prolongation in this population. The prevalence of QTc prolongation was 48.19% among this population, 10.56% in single pregnancy, 89.44% in twin pregnancies. The prevalence of severely prolonged QTc was 23.48% among the total cohort, 0.49% in single pregnancy, and 46.47% in twin pregnancies. The mean QTc interval was significantly longer in twin pregnancies than in single pregnancy (498.65 ± 38.24 vs. 424.96 ± 27.67 ms, P < 0.001). Systolic blood pressure, diastolic blood pressure, total cholesterol, serum uric acid, gestational hypertension and twin pregnancies were associated with QTc prolongation in parturient women. This is the first study to assess the prevalence and risk factors of QTc prolongation between single and twin pregnancies. QTc prolongation is more prevalent, and QTc intervals are significantly longer in twin pregnancies as compared to single pregnancy.


Biocompatibility and biomechanical characteristics of loofah based scaffolds combined with hydroxyapatite, cellulose, poly-l-lactic acid with chondrocyte-like cells.
The current study reports the biocompatibility and biomechanical characteristics of loofah-based scaffolds combined with hydroxyapatite (HA), cellulose, poly-l-lactic acid (PLLA) with chondrocytes-like cells. Scanning electron microscope (SEM) micrographs of the scaffolds showed that the addition of PLLA usually resulted in an increase in cell's attachment on scaffolds. Mechanical and elemental analyzes were assessed using tensile test and Energy Dispersive X-ray spectrometry (EDS), respectively. In summary, we showed that the loofah+PLLA+HA scaffolds perform significantly better than other loofah-based scaffolds employed in terms of increasing a diversity of mechanical properties including tensile strength and Young's modulus. Based on the analysis of the differential scanning calorimetry (DSC) thermograms and EDS spectrums that give an idea about the calcium phosphate (CaP) ratios, the improvement in the mechanical properties could principally be recognized to the strong interaction formed between loofah, PLLA and HA. The viability of chondrocytes on loofah-based scaffolds was analyzed by XTT tests. However, none of the scaffolds have proved to be toxic in metabolic activity. The histological evaluation obtained by hematoxylin and eosin (H&E), Masson trichrome, toluidine blue and immunohistochemistry methods showed that cells in all scaffolds produced extracellular matrix that defined proteoglycan and type I-II collagens. The results of this study suggest that the loofah-based scaffold with desirable properties can be considered as an ideal candidate for cartilage tissue engineering applications.


Practical Approach to the Evaluation and Management of Rheumatoid Arthritis-Interstitial Lung Disease Based on its Proven and Hypothetical Mechanisms.
The prevalence of interstitial lung disease in patients with rheumatoid arthritis varies from 10 to 42%. Rheumatoid arthritis patients with interstitial lung disease have three times the risk of death compared with those without the disease. Prognosis seems to be related to the high-resolution computed tomography pattern. Usual interstitial pneumonia pattern, resembling idiopathic pulmonary fibrosis, carries a worse prognosis. Validated strategies to identify different phenotypes and assess the disease activity in rheumatoid arthritis interstitial lung disease are lacking. However, the utilization of high-resolution computed tomography, composed disease activity scores, and anti-citrullinated peptide antibodies titers can help to guide decisions in clinical practice. Mechanisms involved in lung disease may be different from those implicated in joint involvement. This could explain why in a significant proportion of cases, interstitial lung disease does not improve or even worsens with standard therapies used successfully to treat the joint component (e.g. anti- umor necrosis factor agents). In this scenario, a group of drugs that targets the adaptive immune response (e.g. rituximab or abatacept) seems to target more specifically the process that takes place in the lungs. Moreover, the recent emergence of anti-fibrotic drugs, which have already proven effective in idiopathic pulmonary fibrosis, may provide an alternative treatment strategy in rheumatoid arthritis-usual interstitial pneumonia. In this review, we propose a practical approach to the evaluation and therapy of rheumatoid arthritis interstitial lung disease. Validation of strategies directed to assess the activity of lung disease and identify the underlying mechanisms are needed. Clinical trials evaluating a therapeutic approach with specific targets based on the disease phenotype are warranted.


Trajectories of parenting and child negative emotionality during infancy and toddlerhood: a longitudinal analysis.
The current longitudinal study examined trajectories of child negative emotionality, parenting efficacy, and overreactive parenting among 382 adoptive families during infancy and toddlerhood. Data were collected from adoptive parents when the children were 9-, 18-, and 27-month-old. Latent growth curve modeling indicated age-related increases in child negative emotionality and overreactive parenting for adoptive fathers and adoptive mothers (AM), and decreases in parent efficacy among AM. Increases in child negative emotionality were also associated with increases in parent overreactivity and decreases in maternal efficacy. Mothers' and fathers' developmental patterns were linked within but not across parenting domains. Limitations and directions for future research are discussed.


Relationship between respiration, end-tidal CO2, and BOLD signals in resting-state fMRI.
A significant component of BOLD fMRI physiological noise is caused by variations in the depth and rate of respiration. It has previously been demonstrated that a breath-to-breath metric of respiratory variation (respiratory volume per time; RVT), computed from pneumatic belt measurements of chest expansion, has a strong linear relationship with resting-state BOLD signals across the brain. RVT is believed to capture breathing-induced changes in arterial CO(2), which is a cerebral vasodilator; indeed, separate studies have found that spontaneous fluctuations in end-tidal CO(2) (PETCO(2)) are correlated with BOLD signal time series. The present study quantifies the degree to which RVT and PETCO(2) measurements relate to one another and explain common aspects of the resting-state BOLD signal. It is found that RVT (particularly when convolved with a particular impulse response, the "respiration response function") is highly correlated with PETCO(2), and that both explain remarkably similar spatial and temporal BOLD signal variance across the brain. In addition, end-tidal O(2) is shown to be largely redundant with PETCO(2). Finally, the latency at which PETCO(2) and respiration belt measures are correlated with the time series of individual voxels is found to vary across the brain and may reveal properties of intrinsic vascular response delays.


The effect of low and high doses of beta-carotene and exposure to cigarette smoke on the lungs of ferrets.
When the diets of ferrets were supplemented with large (pharmacologic) daily doses of beta-carotene (BC) for 6 months, the levels of retinoic acid and the retinoic acid receptor beta declined significantly in lung tissues. Indicators of cell proliferation (c-jun and c-fos proteins and others) increased. Histologic observations showed that feeding high doses of BC resulted in keratinized squamous metaplasia in the lung tissues. When high-doses of BC were combined with daily exposure to cigarette smoke, the BC effects were greatly accentuated. These results may lead to an explanation of the increased incidence of lung cancer in two large independent epidemiologic studies of smokers in which pharmacologic doses of BC were given.


Characterisation of flower colouration in 30 Rhododendron species via anthocyanin and flavonol identification and quantitative traits.
Floral colour is a key reproductive character, often associated with environmental adaptation, and subject to human intervention. A large number of Rhododendron species differ widely in flower colour, providing a good model for flower colouration. The chromatic features and anthocyanin compositions of 30 species from seven subgenera were systematically analysed. The Royal Horticultural Society Colour Chart and CIE L*a*b* system were employed to describe and investigate flower colours. The UPLC-PDA/ESI-MSn system was used to identify and quantify anthocyanins in petal extracts. The flower colours of 30 Rhododendron species were categorised into four groups - red, purplish pink, purple and white. Seven anthocyanins were identified and quantified in petals: delphinidin, cyanidin and malvidin 3-O-arabinoside-5-O-glucosides, cyanidin 3,5-di-O-glucoside, 3-O-galactoside and 3-O-arabinoside, and delphinidin 3-O-glucoside. The red-flowered species mainly contained cyanidin monoglycosides and had much higher total anthocyanin content than purplish pink- and purple-flowered species. Purplish pink- and purple-flowered species had similar anthocyanin types and content. The chromatic differences were significant among groups, except the purplish pink and purple groups. Statistical analysis showed that Cy3Gal and Cy3Arb are characteristic for red-flowered species, and Mv3Arb5G and Dp3Arb5G play important roles in purple colouration; their contents were major components that greatly affected the chromatic parameters. In total, 21 flavonol derivates were identified. However, total flavonol content and co-pigmentation index showed no significant difference or correlation among/with colour groups, suggesting that flavonols might not play a major role in colouration. These results enhance our knowledge of the biochemical basis of flower colouration in Rhododendron species, and provide a foundation for genetic variation studies and aid in breeding cultivars with novel flower colours.


Multipoint gene mapping using seriation. I. General methods.
Initial and accurate inference of locus order and estimates of interlocus distances and interference can be obtained using seriation techniques. The analysis requires a matrix of recombination values that can be estimated by standard pairwise linkage analysis. This allows combination of results from individual investigators without reanalysis of basic pedigree material. Seriation can be performed without the use of a computer.


Reproducibility of the mean, fluctuation, and IOP peak in the diurnal tension curve.
To verify the reproducibility of the mean, peak, and fluctuation of intraocular pressure (IOP) observed during modified diurnal tension curves (mDTC) performed on ocular hypertensive and primary open-angle glaucoma patients. Prospective analysis of 88 eyes from 88 ocular hypertensive and primary open-angle glaucoma patients subjected to 2 consecutive mDTCs (IOP measurements obtained at 8:00 AM, 11:00 AM, 2:00 PM, and 4:00 PM) on 2 consecutive days. Mean IOP was calculated as the average of all IOP measurements obtained during each mDTC. Peak and minimum IOP levels were considered as the highest and lowest IOP level during each mDTC, respectively. IOP fluctuation was calculated using 2 different approaches: the difference between IOP peak and minimum IOP detected during each mDTC and as the SD of all mDTC measurements. Reproducibility was assessed using the intraclass correlation coefficient (ICC). IOP fluctuation between 2 days in the modified diurnal curve, calculated as the difference between peak IOP and minimum IOP and as the SD of all mDTC measurements, was less reproducible than the mean IOP and peak IOP (ICC values 0.60, 0.62, 0.91, and 0.85, respectively; all ICC values, P<0.001). Mean IOP and peak IOP observed during the mDTC had good reproducibility, whereas the reproducibility of IOP fluctuation was only fair.


Neuroblastoma and venous sinus thrombosis in an adult patient.
A 35-year-old woman developed symptoms consistent with intracranial venous sinus occlusions that were demonstrated by MR angiography. After a few weeks of anticoagulant therapy, she became paraplegic due to haemorrhages in the caudal spinal canal. A decompressive laminectomy did not improve her neurological deficits. Up to this point, we assumed her condition to be caused solely by the intracranial venous thrombosis and complications of the treatment. A tumour diagnosis had so far not been considered. A few months later she became tetraplegic. MRI revealed fresh bleeding in the upper spinal cord and a dissemination of tumour along the entire craniospinal axis. Biopsy specimens obtained from the spinal canal contained tumour cells with the characteristics of neuroblastoma.


[Chinese expert consensus on clinical diagnosis and treatment of immune-related peripheral keratopathy (2022)].
Immune-related keratopathy is a type of corneal disease caused by systemic or ocular immune disorders, with abnormal immune response to normal or degenerated corneal tissue, leading to the damage to ocular structure and function and the visual impairment. It mainly includes Mooren's ulcer, blepharokeratoconjunctivitis, and peripheral corneal ulcer associated with rheumatoid arthritis or other systemic immune diseases. Due to the diverse clinical manifestations, repeated and prolonged disease course, and high misdiagnosis and missed diagnosis rates, immune-related peripheral keratopathy often has a poor prognosis. The Cornea Group of Ophthalmology Branch of Chinese Medical Association has convened experts to discuss and reach the current consensus, focusing on the principle of diagnosis, differential diagnosis, and treatment of immune-related peripheral keratopathy, which would play an important clinical guiding role in the early detection, timely intervention, and proper treatment of the disease.


Associations Between Acute Conflict and Maternal Care Usage in Egypt: An Uncontrolled Before-and-After Study Using Demographic and Health Survey Data.
United Nations' (UN) data indicate that conflict-affected low- and middle-income countries (LMICs) contribute considerably to global maternal deaths. Maternal care usage patterns during conflict have not been rigorously quantitatively examined for policy insights. This study analysed associations between acute conflict and maternal services usage and quality in Egypt using reliable secondary data (as conflict-affected settings generally lack reliable primary data). An uncontrolled before-and-after study used data from the 2014 Egypt Demographic and Health Survey (EDHS). The 'pre-conflict sample' included births occurring from January 2009 to January 2011. The 'peri-conflict sample' included births from February 2011 to December 2012. The hierarchical nature of demographic and household survey (DHS) data was addressed using multi-level modelling (MLM). In total, 2569 pre-conflict and 4641 peri-conflict births were reported. After adjusting for socioeconomic variables, conflict did not significantly affect antenatal service usage. Compared to the pre-conflict period, periconflict births had slightly lower odds of delivery in public institutions (odds ratio [OR]: 0.987; 95% CI: 0.975-0.998; P<.05), institutional postnatal care (OR: 0.995; 95% CI: 0.98-1.00; P=.05), and at least 24 hours post-delivery stay (OR: 0.921; 95% CI: 0.906-0.935; P<.01). Peri-conflict births had relatively higher odds of doctor-assisted deliveries (OR: 1.021; 95% CI: 1.004-1.035; P<.05), institutional deliveries (OR: 1.022; 95% CI: 1.00-1.04; P<.05), private institutional deliveries (OR: 1.035; 95% CI: 1.017-1.05; P<.001), and doctor-assisted postnatal care (OR: 1.015; 95% CI: 1.003-1.027; P<.05). Sensitivity analysis did not change results significantly. Maternal care showed limited associations with the acute conflict, generally reflecting pre-conflict usage patterns. Further qualitative and quantitative research could identify the effects of larger conflicts on maternal careseeking and usage, and inform approaches to building health system resilience.


Histone Deacetylases and Cardiometabolic Diseases.
Cardiometabolic disease, emerging as a worldwide epidemic, is a combination of metabolic derangements leading to type 2 diabetes mellitus and cardiovascular disease. Genetic and environmental factors are linked through epigenetic mechanisms to the pathogenesis of cardiometabolic disease. Post-translational modifications of histone tails, including acetylation and deacetylation, epigenetically alter chromatin structure and dictate cell-specific gene expression patterns. The histone deacetylase family comprises 18 members that regulate gene expression by altering the acetylation status of nucleosomal histones and by functioning as nuclear transcriptional corepressors. Histone deacetylases regulate key aspects of metabolism, inflammation, and vascular function pertinent to cardiometabolic disease in a cell- and tissue-specific manner. Histone deacetylases also likely play a role in the metabolic memory of diabetes mellitus, an important clinical aspect of the disease. Understanding the molecular, cellular, and physiological functions of histone deacetylases in cardiometabolic disease is expected to provide insight into disease pathogenesis, risk factor control, and therapeutic development.


Growth factor delivery from self-assembling nanofibers to facilitate islet transplantation.
Recent advances in nanotechnology and molecular self-assembly may provide novel solutions to current cell transplantation deficiencies. Heparin-binding peptide amphiphiles (HBPAs) self-assemble from aqueous media into nanofibers that bind growth factors through interactions with the bioactive polymer heparin. In this report, we demonstrate that delivery of vascular endothelial growth factor and fibroblast growth factor-2 from HBPA scaffolds significantly increases blood vessel density in the mouse omentum over control scaffolds without growth factors (P<0.0005) and significantly enhances islet engraftment. Diabetic recipients transplanted with 250 isologous islets and HBPA scaffolds containing vascular endothelial growth factor/fibroblast growth factor-2 achieved normoglycemia at a higher rate (78%) than control animals receiving identical scaffolds without growth factors (30%; P<0.05) or growth factors alone (20%). These data indicate that the enhanced engraftment can be attributed to specific growth factor effects that were made possible by the delivery mechanism of HBPA nanostructures.


Fragility of reward vs antifragility of defense brain systems in drug dependence.
Drug dependence is a debilitating disorder, affecting 30 million people worldwide. In this short review we discuss about the plasticity changes in the reward and defense brain systems induced by early-life psychosocial stressful experiences. Such changes may render persons more vulnerable to illicit drugs use, facilitating behaviors of abuse and development of addiction. We propose that underlying plasticity changes render brain reward system as increasingly fragile because of tolerance and other physiological effects that reduce responsiveness with repeated use. In contrast, we propose that brain defense system makes maintain antifragile mechanisms that generate more robust responses with the prolonged consumption of drugs. Investigating the underlying mechanisms of these brain plasticity changes may advance the development of more efficacious pharmacologic and psychotherapeutic approaches to rehabilitate patients and more efficacious prevention policies to protect children from stressful experiences.


Silicon-assisted propargylic transfer to aldehydes.
A new and efficient method of obtaining homopropargylic alcohols via homopropargylic transfer from the allenic alcohol to various aldehydes in the presence of Lewis acid catalysts is described; stereochemical studies have shown that this process is the first oxonium [3,3]-sigmatropic rearrangement of an allenic alcohol to a homopropargylic alcohol in the presence of aldehydes and Lewis acid.


Control of chiral nanostructures by self-assembly of designed amphiphilic peptides and silica biomineralization.
Peptides, the fundamental building units of biological systems, are chiral in molecular scale as well as in spatial conformation. Shells are exquisite examples of well-defined chiral structures produced by natural biomineralization. However, the fundamental mechanism of chirality expressed in biological organisms remains unclear. Here, we present a system that mimics natural biomineralization and produces enantiopure chiral inorganic materials with controllable helicity. By tuning the hydrophilicity of the amphiphilic peptides, the chiral morphologies and mesostructures can be changed. With decreasing hydrophilicity of the amphiphilic peptides, we observed that the nanostructures changed from twisted nanofibers with a hexagonal mesostructure to twisted nanoribbons with a lamellar mesostructure, and the extent of the helicity decreased. Defining the mechanism of chiral inorganic materials formed from peptides by noncovalent interactions can improve strategies toward the bottom-up synthesis of nanomaterials as well as in the field of bioengineering.


[The stem cell system of hematopoiesis: physiological and pathophysiological concepts].
It is the purpose of this review to describe the physiological as well as the pathophysiological principles of the hematopoietic stem cell system. The concept of hemopoietic stem cells has a long history which is now understood on the basis of its embryogenesis and after collecting extensive experimental and clinical experience using stem-cell transplantations as a means to restore hematopoietic function of the bone marrow after appropriate conditioning. The hemopoietic stem cells cannot be distinguished by light microscopy from "lymphocytes" considered to be a heterogeneous group of mononuclear cells. These stem cells can respond to specific regulatory factors with specific differentiation and proliferation, and are very radiosensitive and resistant to cryopreservation. The system responds to perturbations in a manner characteristic for feed back regulation and is bound in its physiology to an intact stromal matrix.


Molecular insights into mu opioid pharmacology: From the clinic to the bench.
Most of the opioids used in clinical practice exert their effects through mu opioid receptors. Yet, subtle but important pharmacological differences have been observed among the mu opioids. Their potency, effectiveness, and adverse effects can vary unpredictably among patients. These clinical differences among the mu opioids strongly argue against a single receptor mediating their actions. The cloning of the mu opioid receptor has greatly enhanced our understanding of the complexity of this system and has provided possible mechanisms to explain these observations. A single mu opioid receptor gene has been identified, but we now know that it generates a multitude of different mu opioid receptor subtypes through a mechanism commonly used to enhance protein diversity, alternative splicing. Early studies identified a number of splice variants involving the tip of the C-terminus. This region of the receptor is far away from the binding pocket, explaining why these variants still exhibit the same selectivity for mu opioids. However, the differences in structure at the C-terminus influence the activation patterns of the mu opioids. In addition, a second series of variants has been isolated that involves alternative splicing at the N-terminus. Together, these sets of mu opioid receptor splice variants may help explain the clinical variability of the mu drugs among patients and provide insights into why it is so important to individualize therapy for every patient in pain.


Outbreak of CTX-M-15 Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae ST394 in a French Intensive Care Unit Dedicated to COVID-19.
Infections caused by extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-KP) are constantly rising worldwide and are often reported as causative agent of outbreaks in intensive care units (ICUs). During the first wave of the COVID-19 pandemic, bacterial cross-transmission was thought unlikely to occur due to the reinforcement of hygiene measures and prevention control. However, we report here an ESBL-producing K. pneumoniae (ST394) isolate responsible for a nosocomial outbreak in an ICU dedicated to COVID-19 patients.


Potential Life-Cycle Environmental Impacts of the COVID-19 Nucleic Acid Test.
Massive diagnostic testing has been performed for appropriate screening and identification of COVID-19 cases in the ongoing global pandemic. However, the environmental impacts of COVID-19 diagnostics have been least considered. In this paper, the environmental impacts of the COVID-19 nucleic acid diagnostics were assessed by following a full cradle-to-grave life-cycle approach. The corresponding life-cycle anthology was established to provide quantitative analysis. Moreover, three alternative scenarios, i.e., material substitution, improved waste treatment, and electric vehicle (EV)-based transportation, were further proposed to discuss the potential environmental mitigation and conservation strategies. It was estimated that the life cycle of a single COVID-19 nucleic acid diagnostic test in China would lead to the emission of 612.9 g CO2 equiv global warming potential. Waste treatment, as a step of life cycle, worsen the environmental impacts such as global warming potential, eutrophication, and ecotoxicity. Meanwhile, diesel-driven transportation was considered as the major contributor to particulate air. Even though COVID-19 diagnostics are of the greatest importance to end the pandemic, their environmental impacts should not be ignored. It is suggested that improved approaches for waste treatment, low-carbon transportation, and a reliable pool sampling strategy are critical for the achievement of sustainable and green diagnostics.


Association of Kaposi's sarcoma and prior immunosuppressive therapy: a 5-year material of Kaposi's sarcoma in Norway.
A retrospective study of 53 cases with a histological diagnosis of Kaposi's sarcoma (KS) reported to The Cancer Registry of Norway during a five year period is presented. Four cases were excluded from the material because further information contradicted the diagnosis of KS. Of the remaining 49 cases, information of treatment received before the development of KS was obtained in 41 (83.7%). Six (14.6%) of the 41 patients developed KS during systemic treatment with corticosteroids, two of the 6 cases also used azathioprine. None of the patients had undergone renal transplantation. One additional patient had received radiotherapy for a malignant lymphoma prior to the development of KS. In a control group of 242 consecutive patients hospitalized because of basal cell carcinoma of the skin, none had used systemic corticosteroid or cytotoxic drugs. Case reports of the 7 patients with KS developing after immunopressive therapy are presented.


Involvement of activation of PI3K/Akt pathway in the protective effects of puerarin against MPP+-induced human neuroblastoma SH-SY5Y cell death.
In an attempt to clarify the protective effect of puerarin on toxin-insulted dopaminergic neuronal death, this present study was carried out by using a typical Parkinson's disease (PD) model - 1-methyl-4-phenylpyridinium iodide (MPP(+))-induced dopaminergic SH-SY5Y cellular model. Data are presented, which showed that puerarin up-regulated Akt phosphorylation in both of MPP(+)-treated and non-MPP(+)-treated cells. The presence of PI3K inhibitor LY294002 completely blocked puerarin-induced activation of Akt phosphorylation. Moreover, puerarin decreased MPP(+)-induced cell death, which was blocked by phosphoinositide 3-kinase (PI3K) inhibitor LY294002. We further demonstrated that puerarin protected against MPP(+)-induced p53 nuclear accumulation, Puma (p53-upregulated mediator of apoptosis) and Bax expression and caspase-3-dependent programmed cell death (PCD). This protection was blocked by applying a PI3K/Akt inhibitor. Additionally, it was Pifithrin-α, but not Pifithrin-μ, which blocked MPP(+)-induced Puma and Bax expression, caspase-3 activation and cell death. Collectively, these data suggest that the activation of PI3K/Akt pathway is involved in the protective effect of puerarin against MPP(+)-induced neuroblastoma SH-SY5Y cell death through inhibiting nuclear p53 accumulation and subsequently caspase-3-dependent PCD. Puerarin might be a potential therapeutic agent for PD.


Up-regulation of arginine decarboxylase gene expression and accumulation of polyamines in mustard (Brassica juncea)in response to stress.
Arginine decarboxylase (ADC) is a key enzyme involved in the synthesis of polyamines, which have been implicated in a wide range of plant responses, including stress. However, regulation of polyamine levels in relation to ADC in response to stress at the molecular level is not well understood. In an attempt to address this question, we first cloned two cDNAs in mustard (Brassica juncea[L.] Czern & Coss var. Indian Mustard), designated MADC2 and MADC3, encoding predicted ADC. MADC2 and MADC3 encode polypeptides of 692 and 680 amino acid residues, respectively. A comparison of deduced amino acid sequence revealed that both were highly homologous to MADC1 (77%), a mustard ADC, and other plant ADCs (63-84%). Northern analysis revealed that ADC transcripts in mustard were generally more abundant in stem and root but were barely detectable in leaf. However, ADC expression in the leaf was up-regulated differentially in response to stress such as chilling, salt and mannitol and to treatments with exogenous polyamines. While chilling induced expression of all three ADC genes, salt predominantly resulted in increased accumulation of MADC3 transcript. Leaves exhibited a similar response to exogenous putrescine, spermidine and spermine, all of which stimulated accumulation of MADC2 and MADC3 transcripts but not MADC1. Furthermore, exogenous putrescine also increased the endogenous levels of spermidine and spermine, while a higher endogenous putrescine and spermidine content was detected in leaf incubated with exogenous spermine. Leaves also responded to chilling, salt and mannitol by increasing the levels of the cellular polyamine content, in which the level of spermine in free and conjugated forms increased most profoundly.


Reliability of the Woodway Curve(TM) Non-Motorized Treadmill for Assessing Anaerobic Performance.
A curved treadmill offers a practical method of assessing anaerobic power by enabling unrestricted running motion and greater sport specificity. The purpose of this research was to determine reliability of a curved treadmill (cTM) sprint test and to compare performance measures to the traditional Wingate anaerobic power test (WAnT) performed on a cycle ergometer. Thirty-two recreationally active men and women (22.4 ± 2.8 yrs; 1.73 ± 0.08 m; 74. 2 ± 13.2 kg) performed four familiarization trials on cTM, followed by two randomly assigned experimental trials consisting of one 30-second maximum effort on either cTM or WAnT. Each trial was separated by at least 48 hours. Repeated measures analysis of variance (ANOVA), interclass correlations (ICC), standard error of measurement (SEM), and minimal differences (MD) were used to determine reliability of familiarization trials on cTM, and Pearson product moment correlations were calculated to compare cTM and WAnT. ANOVA results showed significant differences (p < 0.05) during the four familiarization trials. Post hoc analysis showed significant differences (p < 0. 05) between the first two trials. Familiarization trials 3 and 4 showed a high reliability for each performance variable (distance: ICC2,1 = 0.969, %SEM = 2.645, p = 0.157; mean velocity: ICC2,1 = 0. 969, %SEM = 2.622, p = 0.173; peak velocity: ICC2,1 = 0.966, %SEM = 3.142, p = 0.033; mean power: ICC2,1 = 0.940, %SEM = 4.140, p = 0.093; and peak power: ICC2,1 = 0.887, %SEM = 11.244, p = 0.669). Participants elicited an average peak power of 1050.4 ± 338.5 Watts on cTM and 1031.4 ± 349.8 Watts on WAnT. Pearson product moment coefficients indicated high correlations between peak power, mean power, and peak velocity (r = 0.75, p < 0.001; r = 0.84, p < 0.001; and r = 0.76, p < 0. 001, respectively) derived from cTM and WAnT. In conclusion, results suggest that after two familiarization trials, cTM is a reliable sprint test for recreationally active men and women. In addition, there are strong relationships between cTM and WAnT in assessing anaerobic performance. Key pointsThe Woodway Curve 3.0(TM) is a non-motorized treadmill utilizing a curved platform which allows individuals to simulate an unrestricted sprint test in a laboratory setting, offering a practical and sport specific method of assessing anaerobic power.The curved treadmill provides a reliable sprint test for recreationally active men and women.There are strong relationships between the curved treadmill and cycle ergometer in assessing anaerobic performance.


Prevention of haemoglobin glycation by acetylsalicylic acid (ASA): A new view on old mechanism.
Diabetic hyperglycemia provokes glycation of haemoglobin (Hb), an abundant protein in red blood cells (RBCs), by increasing its exposure to carbohydrates. Acetylsalicylic acid (ASA; Aspirin) is one of the first agents, which its antiglycation effect was witnessed. Although the precise molecular mechanism of action of ASA on protein glycation is not indisputably perceived, acetylation as its main molecular mechanism has been proposed. This report aims to unravel the meticulous mechanism of action of ASA by using two ASA analogues; benzoic acid (BA) and para-nitrobenzoic acid (NBA), despite their lack of acetyl group. In this regard, the inhibitory effect of these two chemicals in comparison with ASA on Hb fructation is reported. UV-visible spectroscopy, intrinsic advanced glycation end products (AGE) fluorescence spectroscopy, extrinsic thioflavin T (ThT) binding fluorescence spectroscopy, 2,4,6-trinitrobenzenesulfonic acid (TNBSA) assay, and single cell gel electrophoresis (SCGE) were used to explore the effects of BA and NBA in comparison with aforementioned chemicals in the context of protein glycation. In spite of the lack of acetyl substitution, NBA is reported as a novel agent with prominent inhibitory efficacy than ASA on the protein glycation. This fact brings up a possible new mechanism of action of ASA and reconsiders acetylation as the sole mechanism of inhibition of protein glycation.


Assessing water-related risk factors for Buruli ulcer: a case-control study in Ghana.
To assess water-related risk factors of Buruli ulcer, a case-control study of 102 patients (51 cases and 51 controls) was undertaken by matching age group, sex, and bacille Calmette-Guerin (BCG) vaccination history in Ghana. The factors used here for matching have previously been implicated as factors of Buruli ulcer, an emerging infectious disease. This is the first study to delineate a set of previously suspected, water-related risk factors, in a case-control study matching for age group, sex, and BCG vaccination status. The results of both bivariate and multivariate analyses presented a significantly high odds ratio (OR) only for swimming in rivers on a habitual basis (OR = 18.00, P < 0.01) among the major water-related risk factors. Use of water from rivers and ponds for drinking, cooking, bathing, and washing purposes were not significant risk factors. Our data suggest that swimming, or activities on riverbanks associated with it, is a risk factor.


High power density from a miniature microbial fuel cell using Shewanella oneidensis DSP10.
A miniature microbial fuel cell (mini-MFC) is described that demonstrates high output power per device cross-section (2.0 cm2) and volume (1.2 cm3). Shewanella oneidensis DSP10 in growth medium with lactate and buffered ferricyanide solutions were used as the anolyte and catholyte, respectively. Maximum power densities of 24 and 10 mW/m2 were measured using the true surface areas of reticulated vitreous carbon (RVC) and graphite felt (GF) electrodes without the addition of exogenous mediators in the anolyte. Current densities at maximum power were measured as 44 and 20 mA/m2 for RVC and GF, while short circuit current densities reached 32 mA/m2 for GF anodes and 100 mA/m2 for RVC. When the power density for GF was calculated using the cross sectional area of the device or the volume of the anode chamber, we found values (3 W/m2, 500 W/m3) similar to the maxima reported in the literature. The addition of electron mediators resulted in current and power increases of 30-100%. These power densities were surprisingly high considering a pure S. oneidensis culture was used. We found that the short diffusion lengths and high surface-area-to-chamber volume ratio utilized in the mini-MFC enhanced power density when compared to output from similar macroscopic MFCs.


Morphology of the cervical intervertebral disc: implications for McKenzie's model of the disc derangement syndrome.
Studies which have examined the cervical intervertebral disc have demonstrated that it is not morphologically similar to the lumbar intervertebral disc. Yet review of the clinical literature has revealed that clinicians have often based clinical theories on the assumption that the cervical and lumbar discs do have a similar structure. The purpose of this paper is to review the literature regarding the morphology of the cervical intervertebral disc in relation to McKenzie's clinical theories which claim that the nucleus pulposus of the adult cervical intervertebral disc may be repositioned. Discussion of the proposed biological mechanisms underlying examination and treatment techniques is imperative if the basis of these techniques is to be better understood.


Safety and Efficacy of Tranexamic Acid in Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis of Randomized Controlled Trials.
In recent decades, tranexamic acid (TXA) antifibrinolytic therapy before aneurysm clipping or embolization has been widely reported, but its safety and efficacy remain controversial. This meta-analysis evaluated the efficacy and safety of TXA therapy in aneurysmal subarachnoid hemorrhage (aSAH) patients, aiming to improve the evidence-based medical knowledge of treatment options for such patients. Pubmed, Web of Science, and Cochrane Library databases were searched up to 1 March 2021 for randomized controlled trials (RCTs). We extracted safety and efficacy outcomes and performed a meta-analysis using the Review Manager software. We performed two group analyses of TXA duration and daily dose. Ten RCT studies, enrolling a total of 2,810 participants (1,410 with and 1,400 without TXA therapy), matched the selection criteria. In the TXA duration group: TXA did not reduce overall mortality during the follow-up period [RR 1.00 (95% CI 0.81-1.22)]. The overall rebleeding rate in the TXA group was 0.53 times that of the control group, which was statistically significant [RR 0.53 (95% CI 0.39-0.71)]. However, an RR of 0.43 was not statistically significant in the subgroup analysis of short-term therapy [RR 0.43 (95% CI 0.13-1.39)]. The overall incidence of hydrocephalus was significantly higher in the TXA group than in the control group [RR 1.13 (95% CI 1.02-1.24)]. However, the trend was not statistically significant in the subgroup analysis [short-term: RR 1.10 (95% CI 0.99-1.23); long-term: RR 1.22 (95% CI 0.99-1.50)]. Treatment with TXA did not cause significant delayed cerebral ischemia [RR 1.18 (95% CI 0.89-1.56)], and its subgroup analysis showed an opposite and insignificant effect [short-term: RR 0.99 (95% CI 0.79-1.25); long-term: RR 1.38 (95% CI 0.86-2.21)]. Results in the daily dose group were consistent with those in the TXA duration group. Tranexamic acid does not reduce overall mortality in patients with aSAH, nor does it increase the incidence of delayed cerebral ischemia. Tranexamic acid in treating aSAH can reduce the incidence of rebleeding. However, there is no statisticalsignificance in the ultra-early short-term and low daily dose TXA therapy, which may be due to the lack of relevant studies, and more RCT experiments are needed for further study. https://www.crd.york.ac.uk/PROSPERO/display_record.asp? PROSPERO, identifier: 244079.


Airway management and anesthesia in neonates, infants and children during endolaryngotracheal surgery.
Endolaryngotracheal surgery in neonates, infants and children poses a big challenge for both anesthesiologist and surgeon. The narrowness of the airways and the great variability of the pathological lesions necessitate close collaboration between the surgical and the anesthesia team to provide optimal operating conditions and ensure adequate ventilation and oxygenation. Sixty-two anesthetic records of endolaryngotracheal surgical procedures in neonates, infants and children with ASA physical status 1-3 were analyzed retrospectively. Anesthesia was administered as total intravenous anesthesia; propofol supplemented with remifentanil. Ventilation was performed as supraglottic, superimposed high-frequency jet ventilation via jet laryngoscope with integrated jet nozzles. Age was 58.93 (SD 35.40) months, range 3 weeks to 14 years; body weight 17.83 (SD 8.79) kg, range 2.4-50 kg. The capillary pCO(2) 5 min after the start of the surgical procedure (n = 62) was 40.01 (SD 7.71) mmHg and after 20 min (n = 24) 41.77 (SD 7.12) mmHg. No hypoxemia (oxygen saturation <90%) developed. All patients were hemodynamically stable during jet ventilation. Barotrauma or gas insufflation in the stomach did not occur. No perioperative tracheostomy was necessary. Laryngospasm occurred in one child during emergence from anesthesia. Four infants received postoperative conventional respirator therapy in the ICU overnight. Supraglottic superimposed high-/low-frequency jet ventilation via jet laryngoscopes with integrated jet nozzles is a minimally invasive ventilation technique for neonates, infants and children in endolaryngotracheal surgery, which allows an unimpaired operating field for the surgeon especially in LASER surgery.


[Economic aspects in sIngle-event multilevel orthopedic surgery in patients with cerebral palsy].
This article reports an assessment of direct expenses for surgical treatment of patients with cerebral palsy and secondary orthopedic complications, who have undergone single-event multilevel orthopedic surgeries (SEMLS). It has been demonstrated that modern approach based on SEMLS is substantiated from the medical point of view and at present it is also justified from the point of view of economic assistance for that type of treating activity of a Federal Centre specialized in trauma and orthopaedics. Organization of surgical treatment using multilevel orthopaedic interventions requires selection of implants for specific characteristics and, on expenditure side, not exceeding funding of direct expenses intended for this treating process.


[German Cohort Study of Women's Health--benefits of oral contraceptives. Study protocol].
This publication is about the study protocol of the German Cohort Study on Women's Health. The main objective is to investigate medical benefits of a long-term oral contraceptive use. The design is an analytical cohort study based on inquiries. Additional cases will be recruited to analyse rare events in separate case-control studies. Voluntary participants who signed to participate in a long-term study are included. An annual drop-out rate of 15% is expected. Study variables encompass personal characteristics, lifetime history of diseases, but also disturbances of the state of health, and quality of life. It is anticipated to achieve 400,000 women-years of observation by 2001 (historic and concurrent follow-up). The study started April 1, 1998 and the current financial phase finishes December 31, 2001. 6000 participants were recruited until December 1998 equivalent to about 190,000 observation-years. Until the end of 1999, an additional 70,000 women-years should be included. There have been many suggestions from participants' to include additional issues of women's health into the study.


Acute myocardial infarction in a patient with essential thrombocythemia who underwent successful stenting--a case report.
Essential thrombocythemia (ET) can cause systemic vascular thrombosis, but involvement of coronary arteries in the setting of ET is rare. This report describes a case of acute myocardial infarction (MI) in a patient with ET. A 67-year-old man with ET complained of severe acute chest pain. Emergent coronary angiography revealed subtotal thrombotic occlusion of the left main trunk (LMT) coronary artery. Coronary angioplasty and stenting were performed successfully. Coronary angiography 4 weeks later revealed no significant restenosis. The patient has done well after primary coronary stenting with the use of only an antiplatelet agent to treat the thrombocythemia.


Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes.
This study evaluated the ability of the incretin mimetic exenatide (exendin-4) to improve glycemic control in patients with type 2 diabetes failing maximally effective doses of a sulfonylurea as monotherapy. This was a triple-blind, placebo-controlled, 30-week study conducted at 101 sites in the U.S. After a 4-week, single-blind, placebo lead-in period, 377 subjects were randomized (60% men, age 55 +/- 11 years, BMI 33 +/- 6 kg/m(2), HbA(1c) 8.6 +/- 1.2% [+/-SD]) and began 4 weeks at 5 microg subcutaneous exenatide twice daily (before breakfast and dinner; arms A and B) or placebo. Subsequently, subjects in arm B were escalated to 10 microg b.i.d. exenatide. All subjects continued sulfonylurea therapy. At week 30, HbA(1c) changes from baseline were -0.86 +/- 0.11, -0.46 +/- 0.12, and 0.12 +/- 0.09% (+/-SE) in the 10-microg, 5-microg, and placebo arms, respectively (adjusted P < 0.001). Of evaluable subjects with baseline HbA(1c) > 7% (n = 237), 41% (10 microg), 33% (5 microg), and 9% (placebo) achieved HbA(1c) <or= 7% (P < 0.001). Fasting plasma glucose concentrations decreased in the 10-microg arm compared with placebo (P < 0.05). Subjects in the exenatide arms had dose-dependent progressive weight loss, with an end-of-study loss in the 10-microg exenatide arm of -1.6 +/- 0.3 kg from baseline (P < 0.05 vs. placebo). The most frequent adverse events were generally mild or moderate and gastrointestinal in nature. No severe hypoglycemia was observed. Exenatide significantly reduced HbA(1c) in patients with type 2 diabetes failing maximally effective doses of a sulfonylurea. Exenatide was generally well tolerated and was associated with weight loss.


Teledentistry: protocols for the transmission of digitized radiographs of the temporomandibular joint.
Tomograms of the temporomandibular joint were digitized in three different formats using a PC-based system. The image resolution for various projections was determined at different camera-film distances. Three series of images were transmitted by telephone, and transmission times were measured. The original radiographs, the digitized images, the transmitted images and the transmitted-and-printed images were presented to 10 observers, who were asked to rate image quality. No difference in image quality was found between the initial digitized and the transmitted images. However, transmitted and transmitted-and-printed images were of significantly lower quality than the original radiographs or the digitized images viewed on a computer monitor. Transmission time was reduced significantly (50%) by cropping the images before transmission. The image quality of individual radiographs was better than radiographs formatted as a series.


[Combined assessment of early-stage primary open-angle glaucoma progression].
A total of 92 patients (92 eyes), including 52 patients with early-stage primary open-angle glaucoma and 40 glaucoma suspects, were enrolled in the study and followed up during 25.5 +/- 3.3 months on the average by means of computer perimetry, optical coherence tomography and Heidelberg retinal tomography. The prognoses for POAG progression made on the basis of these tests using both conventional (conservative) and extended (liberal) evaluation criteria demonstrated poor correspondence. It is suggested to consider glaucoma progression confirmed if characteristic changes are registered by at least two of the three methods.


Bayesian modeling of item heterogeneity in dichotomous recognition memory data and prospects for computerized adaptive testing.
Most current models of recognition memory fail to separately model item and person heterogeneity which makes it difficult to assess ability at the latent construct level and prevents the administration of adaptive tests. Here we propose to employ a General Condorcet Model for Recognition (GCMR) in order to estimate ability, response bias and item difficulty in dichotomous recognition memory tasks. Using a Bayesian modeling framework and MCMC inference, we perform 3 separate validation studies comparing GCMR to the Rasch model from IRT and the 2-High-Threshold (2HT) recognition model. First, two simulations demonstrate that recovery of GCMR ability estimates with varying sparsity and test difficulty is more robust and that estimates improve from the two other models under common test scenarios. Then, using a real dataset, face validity is confirmed by replicating previous findings of general and domain-specific age effects (Güsten et al. in Cortex 137:138-148, https://doi.org/10.1016/j.cortex.2020.12.017 , 2021). Using cross-validation we show better out-of-sample prediction for the GCMR as compared to Rasch and 2HT model. In addition, we present a hierarchical extension of the model that is able to estimate age- and domain-specific effects directly, without recurring to a two-stage procedure. Finally, an adaptive test using the GCMR is simulated, showing that the test length necessary to obtain reliable ability estimates can be significantly reduced compared to a non-adaptive procedure. The GCMR allows to model trial-by-trial performance and to increase the efficiency and reliability of recognition memory assessments.


Combining Pickering Emulsion Polymerization with Molecular Imprinting to Prepare Polymer Microspheres for Selective Solid-Phase Extraction of Malachite Green.
Malachite green (MG) is currently posing a carcinogenic threat to the safety of human lives; therefore, it is highly desirable to develop an effective method for fast trace detection of MG. Herein, for the first time, this paper presents a systematic study on polymer microspheres, being prepared by combined Pickering emulsion polymerization and molecular imprinting, to detect and purify MG. The microspheres, molecularly imprinted with MG, show enhanced adsorption selectivity to MG, despite a somewhat lowered adsorption capacity, as compared to the counterpart without molecular imprinting. Structural features and adsorption performance of these microspheres are elucidated by different characterizations and kinetic and thermodynamic analyses. The surface of the molecularly imprinted polymer microspheres (M-PMs) exhibits regular pores of uniform pore size distribution, endowing M-PMs with impressive adsorption selectivity to MG. In contrast, the microspheres without molecular imprinting show a larger average particle diameter and an uneven porous surface (with roughness and a large pore size), causing a lower adsorption selectivity to MG despite a higher adsorption capacity. Various adsorption conditions are investigated, such as pH and initial concentration of the solution with MG, for optimizing the adsorption performance of M-PMs in selectively tackling MG. The adsorption kinetics and thermodynamics are deeply discussed and analyzed, so as to provide a full picture of the adsorption behaviors of the polymer microspheres with and without the molecular imprinting. Significantly, M-PMs show promising solid-phase extraction column applications for recovering MG in a continuous extraction manner.


Inhibition of bone resorption by H+/K(+)-ATPase inhibitors.
We have found that 3-(3-(ethoxycarbonyl)propionyl)-8-methoxy-4-((2- methylphenyl)amino)quinoline (1, CP-113,411), a reversible inhibitor of gastric H+/K(+)-ATPase (IC50 10-20 mM), is also a potent inhibitor of bone resorption by osteoclasts in a bone slice assay at concentrations as low as 10(-7) M, with an IC50 of 2 mM. By contrast, the structurally related H+/K(+)-ATPase inhibitor 2 (3-(ethoxycarbonyl)-8-methoxy-4-((2-methylphenyl)amino)quinoline) disclosed by Robins is slightly more potent as an inhibitor of the gastric enzyme (IC50 3-10 microM in our hands) but less efficacious than 1 as an inhibitor of osteoclasts in the bone slice assay at the lower concentrations (no effect at < or = 10(-6) M, IC50 4 mM). These findings suggest that osteoclasts contain an H+/K(+)-ATPase-like enzyme which differs from the gastric one.