Integrated Transcriptome Analyses Revealed Key Target Genes in Mouse Models of Autism.
Genetic mutations are the major pathogenic factor of Autism Spectrum Disorder (ASD). In recent years, more and more ASD risk genes have been revealed, among which there are a group of transcriptional regulators. Considering the similarity of the core clinical phenotypes, it is possible that these different factors may regulate the expression levels of certain key targets. Identification of these targets could facilitate the understanding of the etiology and developing of novel diagnostic and therapeutic methods. Therefore, we performed integrated transcriptome analyses of RNA-Seq and microarray data in multiple ASD mouse models and identified a number of common downstream genes in various brain regions, many of which are related to the structure and function of the synapse components or drug addiction. We then established protein-protein interaction networks of the overlapped targets and isolated the hub genes by 11 algorithms based on the topological structure of the networks, including Sdc4, Vegfa, and Cp in the Cortex-Adult subgroup, Gria1 in the Cortex-Juvenile subgroup, and Kdr, S1pr1, Ubc, Grm2, Grin2b, Nrxn1, Pdyn, Grin3a, Itgam, Grin2a, Gabra2, and Camk4 in the Hippocampus-Adult subgroup, many of which have been associated with ASD in previous studies. Finally, we cross compared our results with human brain transcriptional data sets and verified several key candidates, which may play important role in the pathology process of ASD, including SDC4, CP, S1PR1, UBC, PDYN, GRIN2A, GABRA2, and CAMK4. In summary, by integrated bioinformatics analysis, we have identified a series of potentially important molecules for future ASD research. Autism Res 2020, 13: 352-368. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Abnormal transcriptional regulation accounts for a significant portion of Autism Spectrum Disorder. In this study, we performed transcriptome analyses of mouse models to identify common downstream targets of transcriptional regulators involved in ASD. We identified several recurrent target genes that are close related to the common pathological process of ASD, including SDC4, CP, S1PR1, UBC, PDYN, GRM2, NRXN1, GRIN3A, ITGAM, GRIN2A, GABRA2, and CAMK4. These results provide potentially important targets for understanding the molecular mechanism of ASD.


Epidermal growth factor inhibits thyrotropin-mediated synthesis of tissue-specific proteins in cultured ovine thyroid cells.
Primary cultures of ovine thyroid cells were induced to differentiate by addition of thyrotropin (TSH). This was demonstrated as an accumulation of 2 thyroid-specific proteins, thyroglobulin and thyroid peroxidase, using immunofluorescent staining methods and immunoprecipitation of biosynthetically labeled cultures. As an additional measure of differentiation, cells exhibited a morphological response to TSH and regained the ability to incorporate radioactive iodide. Epidermal growth factor (EGF) markedly inhibited differentiation when added together with TSH. Thyroglobulin synthesis was reduced to low levels and peroxidase synthesis was reduced to levels that were undetectable by the methods used. Morphological changes in response to TSH were also diminished by EGF. The antagonistic interaction between TSH and EGF in regulating differentiation in cultured thyroid cells may reflect the type of control that exists in vivo.


Differentiation and identification of Enterococcus durans, E. hirae and E. villorum.
To compare different tests in the identification of Enterococcus durans, E. hirae and E. villorum strains. These bacteria belong to the E. faecium species group and are phylogenetically closely related, as evidenced by 16S rRNA sequence homologies of over 98.8%. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis of whole-cell protein, tRNA interpacer polymerase chain reaction (PCR) and arbitrarily-primed (D11344-primed AP) -PCR analysis correctly identified all three species in a collection of strains from very diverse origins. In contrast, biochemical reactions only allowed the unequivocal differentiation of the three species as a group from the other enterococci. Within this group, D-xylose acidification can be used to differentiate E. villorum, but exceptions occur. Strains highly susceptible to clindamycin can be identified as E. durans, but many strains of this species cannot be differentiated from E. hirae and E. villorum due to acquired resistance. Despite their close relationship, E. durans, E. hirae and E. villorum can be differentiated by genomic methods and by whole-cell protein analysis. Only a minority of strains of these three enterococcal species can be identified reliably by the currently available and commonly applied phenotypic tests.


Family studies of red-cell metabolism of pyridoxine in beta-thalassaemia.
Red-cell conversion of pyridoxine to pyridoxal phosphate was measured in 12 families with thalassaemia and 2 normal families. A strong familial pattern was demonstrated and the evidence suggested that the rate of red-cell conversion of pyridoxine is an independently inherited characteristic.


Regional estimation of current and future forest biomass.
The 90,674 wildland fires that burned 2.9 million ha at an estimated suppression cost of $1.6 billion in the United States during the 2000 fire season demonstrated that forest fuel loading has become a hazard to life, property, and ecosystem health as a result of past fire exclusion policies and practices. The fire regime at any given location in these regions is a result of complex interactions between forest biomass, topography, ignitions, and weather. Forest structure and biomass are important aspects in determining current and future fire regimes. Efforts to quantify live and dead forest biomass at the local to regional scale has been hindered by the uncertainty surrounding the measurement and modeling of forest ecosystem processes and fluxes. The interaction of elevated CO2 with climate, soil nutrients, and other forest management factors that affect forest growth and fuel loading will play a major role in determining future forest stand growth and the distribution of species across the southern United States. The use of satellite image analysis has been tested for timely and accurate measurement of spatially explicit land use change and is well suited for use in inventory and monitoring of forest carbon. The incorporation of Landsat Thematic Mapper data coupled with a physiologically based productivity model (PnET), soil water holding capacity, and historic and projected climatic data provides an opportunity to enhance field plot based forest inventory and monitoring methodologies. We use periodic forest inventory data from the USDA Forest Service's Forest Inventory and Analysis (FIA) project to obtain estimates of forest area and type to generate estimates of carbon storage for evergreen, deciduous, and mixed forest classes for use in an assessment of remotely sensed forest cover at the regional scale for the southern United States. The displays of net primary productivity (NPP) generated from the PnET model show areas of high and low forest carbon storage potential and their spatial relationship to other landscape features for the southern United States. At the regional scale, predicted annual NPP in 1992 ranged from 836 to 2181 g/m2/year for evergreen forests and 769-2634 g/m2/year for deciduous forests with a regional mean for all forest land of 1448 g/m2/year. Prediction of annual NPP in 2050 ranged from 913 to 2076 g/m2/year for evergreen forest types to 1214-2376 g/m2/year for deciduous forest types with a regional mean for all forest land of 1659 g/m2/year. The changes in forest productivity from 1992 to 2050 are shown to display potential areas of increased or decreased forest biomass. This methodology addresses the need for spatially quantifying forest carbon in the terrestrial biosphere to assess forest productivity and wildland fire fuels.


Gender Differences in Wear Rates for 28- vs 32-mm Ceramic Femoral Heads on Modern Highly Cross-linked Polyethylene at Midterm Follow-Up in Young Patients Undergoing Total Hip Arthroplasty.
We report on the midterm linear and volumetric wear of highly cross-linked polyethylene (HXLPE) and survivorship of 2 prospective young total hip arthroplasty (THA) cohorts that differed by the size of ceramic femoral head used: 28 vs 32 mm. We prospectively analyzed 220 consecutive primary THAs in patients aged ≤50 years who received a cementless THA with a ceramic femoral head on HXLPE liner (C-HXLPE). There were 101 patients (46%) with 28-mm heads and 119 patients (54%) who received 32-mm heads at a mean follow-up of 5.5 years (range, 60-109 months). Wear was calculated using Martell Software. The 28-mm C-HXLPE cohort demonstrated average linear and volumetric wear of 0.020 mm/y (standard deviation [SD], 0.074; 95% CI, 0.003-0.037) and 18.775 mm(3)/y (SD, 21.743; 95% CI, 13.773-23.778) compared with 0.032 mm/y (SD, 0.087; 95% CI, 0.013-0.050]) and 29.847 mm(3)/y (SD, 35.441; 95% CI, 22.294-37.401) in the 32-mm C-HXLPE group. Subgroup analysis by gender and head size discovered significantly greater wear in females with 32-mm heads compared with 28-mm heads in both linear (0.01, 95% CI = -0.014 to 0.033 vs 0.048, 95% CI = 0.022-0.074 mm/y, P = .004) and volumetric wear (14.11, 95% CI = 8.957-19.271] vs 29.71, 95% CI = 17.584-41.840] mm(3)/y, P = .009). We found a 96% (95% CI = 92.30%-97.94%]) survivorship by Kaplan-Meier analysis at minimum 5 years with no failures because of osteolysis. Ceramic on HXLPE demonstrates extremely low wear properties in young patients at midterm follow-up. We identified a gender-dependent difference in wear based on head size, with 32-mm heads being associated with increased wear in females.


IKK-i signals through IRF3 and NFkappaB to mediate the production of inflammatory cytokines.
IKK-i and TBK1 were recently identified as IKK-related kinases that are activated by toll-like receptors TLR3 and TLR4. These kinases were identified as essential components of the virus-activated as well as LPS-MyD88 independent kinase complex that phosphorylates IRF3 and results in the production of cytokines involved in innate immunity. Both IKK-i and TBK1 have also been implicated in the activation of the NFkappaB pathway but the precise mechanism is not clear. Although the literature to date suggests that IKK-i and TBK1 play redundant roles in TLR3 and TLR4 signaling, recent data suggest that there may be subtle differences in the signaling pathways affected by these kinases. We have generated tetracycline-inducible stable cell lines that express a wild type or kinase-inactive mutant form of IKK-i. Our data suggest that expression of IKK-i can activate both NFkappaB and IRF3, leading to the production of several cytokines including interferon beta. IKK-i most likely acts upstream of IKK2 to activate NFkappaB in these cells since expression of the kinase-inactive version of IKK-i did not inhibit TNFalpha mediated production of inflammatory cytokines. The data suggest that IKK-i is not involved in TNF-alpha mediated signaling but instead could likely play a role in activating IKK2 downstream of Toll-like receptor signaling. We also identified STAT1, Tyk2, and JAK1 as secondary mediators of IKK-i signaling as a result of interferon beta production in these cells.


Relating health policy to women's health outcomes.
Individuals' social and economic circumstances, including socioeconomic status and medical care availability, are central to health outcomes, particularly for women. These factors are often mediated by governmental policies. This exploratory study found associations between women's health outcomes and state-level policies related to women's health. Outcomes were mortality rates for four leading causes of death for women in the US (heart disease, stroke, lung cancer, and breast cancer), infant mortality, and a mental health outcome variable. State policies on key women's health issues were evaluated on the degree to which they adequately protected women's health. Our regression models accounted for significant variance in mortality rates and substantial variance in the mental health outcome. Policies affecting access to care (Medicaid eligibility and efforts to expand Medicaid) and community (environmental health tracking and violence against women) were significantly associated with mortality outcomes. State health policies should be examined further for their relationship to health outcomes.


Exaggerated amygdala activation to ambiguous facial expressions is a familial vulnerability factor for posttraumatic stress disorder.
Previous research has reported hyperresponsivity in the amygdala and hyporesponsivity in ventral portions of the medial prefrontal cortex to threat-related stimuli in posttraumatic stress disorder (PTSD). Whether such findings generalize to more ambiguous stimuli and whether such brain activation abnormalities reflect familial vulnerabilities, trauma-exposure, or acquired characteristics of PTSD remain unclear. In this study, we measured brain responses to emotionally ambiguous stimuli (i.e., surprised facial expressions) in identical twin pairs discordant for trauma exposure to elucidate the origin of brain activation abnormalities. Participants with PTSD (n = 12) and their trauma-unexposed identical cotwins (n = 12), as well as trauma-exposed participants without PTSD (n = 15) and their trauma-unexposed identical cotwins (n = 15), passively viewed surprised and neutral facial expressions during functional magnetic resonance imaging (fMRI). Afterward, participants labeled and rated each facial expression on valence and arousal. Amygdala activation to Surprised and Neutral facial expressions (versus Fixation) was greater in the participants with PTSD and their trauma-unexposed identical cotwins without PTSD, compared to the control twin pairs. In contrast, medial frontal gyrus (MFG) activation to Surprised facial expressions (versus Fixation) was diminished in the PTSD group relative to the other three groups. Amygdala hyperresponsivity to emotionally ambiguous facial expressions may be a familial vulnerability factor that increases the likelihood of developing PTSD after experiencing a traumatic event. In contrast, MFG hyporesponsivity may be an acquired characteristic of the disorder.


Peripheral neuropathy associated with leflunomide: is there a risk patient profile?
(i) To monitor the potential clinical neurotoxic symptoms in patients treated with leflunomide in daily practice and (ii) to describe the characteristics of patients presenting with this peripheral nervous system symptoms. All patients treated with leflunomide between May 2000 and April 2003 and followed in the rheumatology department of the University Hospital participated in the study. Data concerning treatment patterns with leflunomide, demographic and disease characteristics were obtained from clinical charts. Neuropathy was diagnosed with nerve conduction study (NCS). Cases of neuropathy were described and then compared to other patients using univariate analyses. One hundred and thirteen patients were included in the study. M/F sex ratio was 0.45. Mean age at start of treatment was 55.6 years (range = 27-81). During the study period, eight incident cases of peripheral neuropathy and two cases of worsening of preexisting neuropathy were reported (incidence: 9.8%). Compared with other patients, neuropathy cases were older (69 vs. 54 years, p = 0.0006), more often diabetic (30% vs. 2.9%, p = 0.009) and more often treated with potentially neurotoxic drugs (20% vs. 1.9%, p = 0.039). At least one risk factor (potentially neurotoxic drug or diabetes) was found in 50% of patients with neuropathy versus 4% of patients without neuropathy (56% PPV, 96% NPV). Cases of toxic neuropathy have been observed during treatment of rheumatoid arthritis with leflunomide. Their occurrence seems to be associated with known risk factors. Careful monitoring of the patient's neurological status during leflunomide treatment is therefore mandatory.


[Special care units for the treatment of acutely ill, cognitively impaired geriatric patients in Germany].
During recent years, specialized wards have been established in geriatric hospital departments as a consequence of the growing need of special care for acutely ill older patients, who are also cognitively impaired. However, there are neither established standards nor any commonly agreed concept of care. A written survey among 12 specialized wards in Germany revealed some characteristics of these wards: extended geriatric assessment, special education of staff including validation and gerontopsychiatric issues, and particular equipment/architecture, such as hidden doors and group rooms, and in some cases loop tracks for walking, therapeutic facilities, and 'living rooms' on the wards. There is a wide variability with respect to the designation of these wards, the number of beds, length of stay, and admission criteria. It appears from this survey that there should be an exchange of empirical experience made on these wards, and there is a need of collaborative research on its usefulness.


Cavitation in large multinodular pulmonary disease a rare manifestation of sarcoidosis.
Multiple large pulmonary nodules are an uncommon manifestation of sarcoidosis. Cavitation of these nodules has not previously been reported. An asymptomatic young white man had this unusual roentgenographic finding. Open-lung biopsy for diagnosis revealed noncaseating granulomata but did not elucidate the pathogenesis of the cavitation.


Mechanical parameter assessment of fresh human cancellous bone of the femoral head in atraumatic femoral head necrosis and primary coxarthrosis.
Atraumatic femoral head necrosis is a rare pathological change of the femoral head. It is characterized by local necrosis of the cancellous bone as a result of reduced blood supply to the bone. Even today it remains unclear how to assess the hardness of the necrosis, whether it is soft tissue that is easily removed, or hard tissue that is difficult to resect. Femoral heads with primary coxarthrosis were selected as a comparison group. For this purpose, 49 femoral heads obtained during total hip arthroplasty surgery with either condition (23 femoral head necrosis, 26 coxarthrosis) were transferred to the testing laboratory in fresh condition. Cylindrical specimens were obtained using a tenon cutter along the main trabecular load direction in the subchondral region of the femoral head. Additionally, thin bone slices were extracted proximal and distal to the specimens for density measurements. Brass plates were glued to the circular surfaces of the specimens. After curing of the adhesive, the specimens were mounted in the testing machine and destructive uniaxial compression tests were conducted. The recorded mean compressive strengths and elastic moduli were almost identical for both groups, but the necrosis group showed significantly higher data scattering and range regarding the elastic modulus. The mean density of the coxarthrosis specimens was significantly higher than that of the necrotic specimens. The mechanical properties of cancellous bone vary considerably in the presence of femoral head necrosis. The existence of hard necrosis implies a potential challenge regarding the clinical resection of these tissues.


Cytotoxicity towards human endothelial cells, induced by neutrophil myeloperoxidase: protection by ceftazidime.
We investigated the effects of the antibiotic ceftazidime (CAZ) on the cytolytic action of the neutrophil myeloperoxidase-hydrogen peroxide-chloride anion system (MPO/H(2)O(2)/Cl(-)). In this system, myeloperoxidase catalyses the conversion of H(2)O(2) and CI(-) to the cytotoxic agent HOCl. Stimulated neutrophils can release MPO into the extracellular environment and then may cause tissue injury through direct endothelial cells lysis. We showed that human umbilical vein endothelial cells (HUVEC) were capable of taking up active MPO. In presence of H(2)O(2) (10(-4) M), this uptake was accompanied by cell lysis. The cytolysis was estimated by the release of (51)Cr from HUVEC and expressed as an index of cytotoxicity (IC). Dose dependent protection was obtained for CAZ concentrations ranging from 10(-5) to 10(-3) M;this can be attributed to inactivation of HOCl by the drug. This protection is comparable to that obtained with methionine and histidine, both of which are known to neutralize HOCl. This protection by CAZ could also be attributed to inactivation of H(2)O(2), but when cytolysis was achieved with H(2)O(2) or O(2) (-) generating enzymatic systems, no protection by CAZ was observed. Moreover, the peroxidation activity of MPO (action on H(2)O(2)) was not affected by CAZ, while CAZ prevented the chlorination activity of MPO (chlorination of monochlorodimedon). So, we concluded that CAZ acts via HOCl inactivation. These antioxidant properties of CAZ may be clinically useful in pathological situations where excessive activation of neutrophils occurs, such as in sepsis.


Rupture of a pulmonary artery mycotic aneurysm associated with candidal endocarditis.
Candidal endocarditis can develop if candidemia occurs during Swan-Ganz catheterization. Candida endocarditis may persist for many months and is fatal unless the infected valve is resected. Herein is reported the first case of rupture of a mycotic pulmonary artery aneurysm caused by chronic candidal endocarditis. The endocarditis followed Swan-Ganz catheterization and aneurysm progressed despite appropriate medical and surgical therapy.


Sensitivity enhancement in NMR of macromolecules by application of optimal control theory.
NMR of macromolecules is limited by large transverse relaxation rates. In practice, this results in low efficiency of coherence transfer steps in multidimensional NMR experiments, leading to poor sensitivity and long acquisition times. The efficiency of coherence transfer can be maximized by design of relaxation optimized pulse sequences using tools from optimal control theory. In this paper, we demonstrate that this approach can be adopted for studies of large biological systems, such as the 800 kDa chaperone GroEL. For this system, the 1H-15N coherence transfer module presented here yields an average sensitivity enhancement of 20-25% for cross-correlated relaxation induced polarization transfer (CRIPT) experiments.


Simultaneous determination of inorganic nitrogen species by microcolumn ion chromatography.
Inorganic nitrogen species (nitrate, nitrite and ammonium ions) were simultaneously determined by microcolumn ion chromatography. Nitrate and nitrite were determined by UV detection at 206 nm, whereas ammonium ion was determined by fluorescence detection at excitation 410 nm and emission 470 nm. The latter fluorescence detection is based on the postcolumn reaction of ammonium ion with o-phthalaldehyde in the presence of 2-mercaptoethanol. Effects of the reagent concentration, pH, and other reaction conditions on the signal intensity were examined, and the optimum condition was explored. The present method allowed simultaneous determination of nitrate, nitrite and ammonium ions in river water.


Quantitation of cucurbit yellow stunting disorder virus in Bemisia tabaci (Genn.) using digoxigenin-labelled hybridisation probes.
A cost-efficient hybridisation assay was developed to estimate the amount of cucurbit yellow stunting disorder virus (CYSDV) in Bemisia tabaci (Gennadius) whiteflies infesting protected cucumber crops. cDNA from the coat protein (cp) gene and the hsp70 homologue protein gene from CYSDV were obtained by reverse transcriptase-PCR from viruliferous whiteflies and cloned into plasmids. Digoxigenin (DIG)-labelled cDNA probes reacted with extracts from these whiteflies applied on nylon membranes. Precision and linear ranges were established in a hybridisation analysis using known concentrations of unlabelled homologue cDNA. Extracts from non-viruliferous B. tabaci showed a concentration-dependent effect on the assay with cp-specific probes but not with hsp70-specific probes. The hsp70 probe was used to evaluate natural B. tabaci populations in commercial cucumber crops, and the estimated amounts of CYSDV per whitefly were found ranging from 5.6 fg to approximately 2.5 pg of corresponding hsp70-cDNA.


The national health system: future possibilities for the clinical laboratory.
The heavy burden of the costs of medical care has brought changes in the public health policy. The changes are partly related to the health management factors, but several cultural, social and environmental factors have also had a significant impact on healthcare. The role of the laboratory is now considered amidst changes that have occurred in the American health model (free-trader) and in the European-Canadian model (universalistic). Moreover, costs and clinical decision-making in laboratories in Italy have also changed in response to the new focus on the pre- and post-analytical phases of the testing process. In the present study, we used the Laboratory Information System (LIS) to evaluate whether the time involved in stages in the turnaround time (TAT) (admission, performance of tests, validation and decision-making for treatment) were reduced following improvements made to the laboratory organization and management of the pre-analytical and post-analytical phases. In particular, an analysis was made of laboratory testing for myocardial markers in patients with acute coronary syndrome. TAT for myocardial markers in an emergency setting was reduced by 30% following changes made in the laboratory organization and in the management of the pre-analytical and post-analytical phases of the testing process. Thanks to changes in healthcare service/system in Italy, laboratory services will now play a crucial role in cultural and socioeconomic changes, particularly where testing processes and techniques are concerned.


Pediatric liver transplantation: comparison between results from deceased and living related transplantation.
Timely access to a living donor has reduced pretransplant mortality in pediatric liver transplantation. We hypothesized that this strategy may provide better posttransplant outcomes, due to shorter waiting times on the transplant list. A extensive search in the medical literature from the last 10 years showed clear evidence of the benefits of living donors, namely, decreased dropout rates as well as the chance to transplant the patients in better clinical situation. However, a negative impact was related to the higher morbidity rates when compared to whole grafts from deceased donors.


Generation of auditory brain stem responses (ABRs). I. Effects of injection of a local anesthetic (procaine HCI) into the trapezoid body of guinea pigs and cat.
Auditory brain stem potentials were recorded between the skull and a non-cephalic reference electrode in anesthetized guinea pigs before and after the injection of a local anesthetic agent (procaine HCI) into the trapezoid body from a ventral approach. All components except P1, N1 and P2 were affected; N2 was delayed; P3 and N3 were lost; P4 was both broadened in duration and shortened in latency; N4 was attenuated in amplitude. All of these changes were temporary and recovery of the components occurred. Identification of the altered components was aided by their latency and amplitude changes as a function of both stimulus intensity and rate. This study implicates the trapezoid body as contributing to the generation of auditory brain stem components beginning with N2.


Effect of total enteral nutrition on the short-term outcome of severely malnourished cirrhotics. A randomized controlled trial.
Thirty-five severely malnourished cirrhotic patients were randomized to receive either enteral-tube feeding as the sole nutritional support (n = 16) or an isocaloric, isonitrogenous, low-sodium standard oral diet (n = 19). Both groups were homogeneous regarding age, sex distribution, etiology of liver cirrhosis, history of previous complications, clinical status, liver and renal function, modified Child's score, and nutritional status at admission. The enteral formula diet was energy dense, containing 40 mmol Na/day, whole protein plus branched-chain amino acids, medium- and long-chain triglycerides, and maltodextrin. It supplied 2115 kcal/day. The amount of vitamins and trace elements was at the upper limit of the recommended dietary allowances. The orally fed patients were encouraged to eat all meals served. Total enteral nutrition was well tolerated without major complications. Serum albumin and Child's score improved in the enterally fed patients but not in controls. Mortality rate while in the hospital was lower in patients on enteral feeding than in controls (12% vs 47%). These results show that total enteral nutrition is safe and effective in improving the short-term clinical outcome in severely malnourished cirrhotics.


The nomenclature and conformational analysis of lipids and lipid analogues.
Lipids form an essential part of the biomembrane and it is of paramount importance to study their conformational aspects. It is found that the present methods of nomenclature for lipids are totally inadequate for describing these diverse amphipathic molecules. Further the existing methods are incompatible in terms of assignment of the absolute configuration. A systematic method for the naming of lipids which is rationally extendible to a wide class of amphipaths is described. The conformational features of the natural glycerolipids as well as a synthetic amphipath containing a glutamic acid moiety known to undergo interesting phase transitions, have been examined in detail using the framework of the current nomenclature system. The implications of the conformational flexibility of these molecules on assemblies of these systems is touched upon.


Assessment of joystick and wrist control in hand-held articulated laparoscopic prototypes.
Various steerable instruments with flexible distal tip have been developed for laparoscopic surgery. The problem of steering such instruments, however, remains a challenge, because no study investigated which control method is the most suitable. This study was designed to examine whether thumb (joystick) or wrist control method is designated for prototypes of steerable instruments by means of motion analysis. Five experts and 12 novices participated. Each participant performed a needle-driving task in three directions (right → left, up → down, and down → up) with two prototypes (wrist and thumb) and a conventional instrument. Novices performed the tasks in three sessions, whereas experts performed one session only. The order of performing the tasks was determined by Latin squares design. Assessment of performance was done by means of five motion analysis parameters, a newly developed matrix for assigning penalty points, and a questionnaire. The thumb-controlled prototype outperformed the wrist-controlled prototype. Comparison of the results obtained in each task showed that regarding penalty points, the up → down task was the most difficult to perform. The thumb control is more suitable for steerable instruments than the wrist control. To avoid uncontrolled movements and difficulties with applying forces to the tissue while keeping the tip of the instrument at the constant angle, adding a "locking" feature is necessary. It is advisable not to perform the needle driving task in the up → down direction.


Secondary care usage and characteristics of hospital inpatients referred to a UK homeless health team: a retrospective service evaluation.
UK "Pathway" teams offer specialist hospital care coordination for people experiencing homelessness. Emergency healthcare use is high among homeless people, yet "homelessness" is not routinely coded in National Health Service (NHS) data. Pathway team records provide an opportunity to assess patterns in admissions and outcomes for inpatients identified as homeless. Retrospective analysis of patients referred to "Pathway" homelessness teams in seven UK hospitals to explore the patterns of hospital admission, morbidity, secondary healthcare utilisation and housing status. Each patient was individually identified as experiencing homelessness. Within a six-month period, demographic data, reason for admission, morbidity, mortality and secondary care hospital usage 120-days before and 120-days after the index admission was collected. A total of 1009 patients were referred, resulting in 1135 admissions. Most admissions had an acute physical health need (94.9%). Co-morbid mental illness and/or substance misuse was common (55.7%). Reasons for admission included mental and behavioral disorders (overdose, alcohol withdrawal or depression, 28.3%), external causes of morbidity and mortality (assault or trauma, 18.7%), and injury, poisoning and external causes (head injury, falls and fractures, 12.4%). Unplanned Emergency Department attendances reduced after index admission and unplanned hospital admissions increased slightly. Planned admissions doubled and total bed days increased. Housing status was maintained or improved for over 60% of inpatients upon discharge. Within 12 months of index admission, 50 patients (5%) died, 15 deaths (30%) occurred during the index admission. Disengagement with health services is common among homeless people. Many deaths are due to treatable medical conditions (heart disease, pneumonia, cancer). Observed increases in planned admissions suggests intervention from Pathway teams facilitates necessary investigations and treatment for homeless people. Equity, parity of care, and value should be inbuilt interventions for inclusion health groups and evaluations need to move beyond simply seeking cost reductions.


Specific interaction of insulin receptor and GLP-1 receptor mediates crosstalk between their signaling.
Both GLP-1 receptor (GLP-1R) and insulin receptor (IR) transmit signals for insulin release and/or cellular metabolism although using distinct sets of transducing molecules and separate pathways. We proposed a possible association of IR and GLP-1R, since they are coexpressed in diverse tissues including the pancreatic β-cells and crosstalk between their signaling was frequently reported. We showed a specific interaction between GLP-1R and IR which was independent of intracellular receptor domains and not responsive to ligand binding. In signaling, the IRS-1 was coupled more to GLP-1R and less to IR in the receptor complex at IR activation, with subsequent IRS-1 degradation suppressed rather than its activation inhibited. The Gsα recruitment to the activated GLP-1R was inhibited in the GLP-1R/IR complex, with the signaling in cAMP pathway suppressed at IR activation. Therefore, the identified GLP-1R/IR complex recruits their signaling molecules which are differentially modified, leading to a crosstalk between their signaling.


Testing the compensatory and immunity models of children's adaptive behaviors: the role of appraisal.
The present article examines the relations of negatively appraised and total life events and potential protective factors with adaptive behavior in 432 children (ages 8-12). Appraisal and protective factors were hypothesized to moderate the relation between stress exposure and adaptive behavior. Several significant interactions emerged between events rated as negative and variables reflecting social support, positive family environment, and intelligence level on adaptive behavior. Contrary to past research, the buffering role of protective factors was optimized only when the appraisal of the event was considered.


Assay of ephedrine hydrochloride and theophylline in pharmaceutical formulations by differential-derivative spectroscopy.
Rapid and accurate binary mixture resolution of ephedrine hydrochloride and theophylline was performed. Differential-derivative spectrophotometry with a zero-crossing measurement technique was used for the quantitative determination of ephedrine hydrochloride and theophylline in pharmaceuticals. Neither sample pretreatment nor separation were required. Linear calibration graphs of differential first derivative values (at 262.4 and 256.3 nm for theophylline and ephedrine hydrochloride, respectively) versus concentration (in the ranges 6.0-40.0 and 100.0-1000.0 microg ml(-1) for theophylline and ephedrine hydrochloride, respectively) were obtained with negligible intercepts. Vierordt's method was also developed for a comparison method. Commercial tablet and laboratory-prepared mixtures containing both drugs were assayed using the developed methods. Both methods showed good linearity, precision and reproducibility.


Do plant secondary compounds determine feeding preferences of snowshoe hares?
We investigated the food preferences of captive snowshoc hares (Lepus americanus) in winter to test three hypotheses proposed to explain food choices by hares: (1) that food choice is related to the protein content of twigs; 92) that defensive chemicals present in twigs are negatively correlated with hare food preferences; and (3) that hares eat less-preferred but protein-rich twigs when their diet is buffered by large amounts of palatable food. Hares exhibited striking and consistent preferences for different species and, in general, preferred mature twigs to juvenile growth stages. Preferences across species among mature twigs were not, however, the same as preferences for juvenile growth stages across species. None of the three hypotheses adequately explained food choice by hares. Hares did not (1) select twigs that were high in protein content. They also did not (2) consistently select twigs that were low in resins or phenols. Finally (3), hares generally ate less, not more of non-preferred twigs in the presence of a protein and energy rich alternative food, commercial rabbit chow. Food preferences of hares must presumably have some chemical basis, but no simple theory has yet explained what this is. We suggest that hares may not be under severe dietary constraints imposed by chemical defenses in winter.


Lasers in medicine: treatment of retinopathy of prematurity.
Lasers are a unique surgical tool, but what actually are they? This article answers that question and describes how lasers work and how they are being used in medicine. Retinopathy of prematurity (ROP) then is defined. Cryotherapy, a surgical procedure often performed on ROP patients, is reviewed and compared to photocoagulation, a form of laser therapy. Photocoagulation and its complications are then discussed.


Transhepatic intravascular ultrasound for evaluation of portal venous involvement in patients with cancer of the pancreatic head region.
The aim of this study was to evaluate the ability of intravascular ultrasound to diagnose tumor involvement of the portal and the superior mesenteric veins using the preoperative percutaneous, transhepatic approach, and to compare the findings with those made at concomitant direct portography, surgery, and histopathological examination. Ten patients with a preoperative diagnosis of a resectable tumor in the pancreatic head region were examined with percutaneous transhepatic portography (PTP) and intravascular ultrasound (IVUS). The surgeon's intraoperative evaluation and the histopathological examination in combination revealed tumor involvement of the portal or superior mesenteric veins in six of the ten patients. Percutaneous transhepatic portography suggested tumor involvement of the veins in six patients but two of the examinations were false positive and another two were false negative. Intravascular ultrasound showed signs of tumor involvement in eight patients. The examination was, however, false positive in two patients, but there were no false negatives. Complications of the percutaneous transhepatic procedure occurred in six patients including severe pain, bleeding, and related death. Percutaneous transhepatic IVUS of the portal vein may be a useful tool in the preoperative selection of the subgroup of patients with tumor of the pancreatic head region that could benefit from surgery. There is a need for technical improvement as well as studies with larger patient series to definitely decide the role of the technique.


Chick growth and prey quality in the European Bee-eater (Merops apiaster).
1. In each of four replicate experiments we fed three groups of bee-eater chicks for 24 h on different diets: bees, dragonflies, and a mixture of the two. 2. Dry weight assimilation efficiency did not differ between treatments and was in the region of 40-50%. Caloric assimilation efficiency was about 60% and did not differ significantly between diets. 3. Mean Growth efficiency (wt. gain/intake) was highest in all four replicates in chicks fed on the mixed diet. 4. When metabolic requirements are taken into account, growth efficiency on the mixed diet varies less with variation in intake than on the two pure diets. 5. The advantage of feeding chicks on a mixed diet may partly explain why parents do not show exclusive preferences for energy-maximising prey types.


A comparative study of differences in the referral behaviour patterns of men and women who have experienced cardiac-related chest pain.
Survival and long-term prognosis after a myocardial infarction are directly related to the individuals's decision to seek medical help. Early medical intervention is imperative if thrombolytic therapy is to be effective. Emerging research has indicated that women frequently have longer pre-hospital delays than men. Incorporating a comparative descriptive design, this research compared the pre-hospital admission behaviour patterns of women and men, following the onset of acute chest pain. A convenience sample of 12 women and 12 men were selected following admission to a local coronary care unit. Structured interviews and the examination of medical notes/relevant documentation provided the data. Findings were examined and compared through the use of content analysis and descriptive statistics. Severity of symptoms proved to be the strongest influence in shortening pre-hospital delay. Despite this, overall, men were admitted to hospital more quickly than women. Men were more ready than women to believe that they might be having a heart attack and this belief led them to seek treatment promptly. In order to improve female mortality and morbidity following a myocardial infarction, it is recommended that there is an urgent need to target women, through health promotion and media interventions.


Robotic tissue tracking for beating heart mitral valve surgery.
The rapid motion of the heart presents a significant challenge to the surgeon during intracardiac beating heart procedures. We present a 3D ultrasound-guided motion compensation system that assists the surgeon by synchronizing instrument motion with the heart. The system utilizes the fact that certain intracardiac structures, like the mitral valve annulus, have trajectories that are largely constrained to translation along one axis. This allows the development of a real-time 3D ultrasound tissue tracker that we integrate with a 1 degree-of-freedom (DOF) actuated surgical instrument and predictive filter to devise a motion tracking system adapted to mitral valve annuloplasty. In vivo experiments demonstrate that the system provides highly accurate tracking (1.0 mm error) with 70% less error than manual tracking attempts.


Lipid-mediated regulation of the cancer-immune crosstalk.
Besides acting as principle cellular building blocks and energy reservoirs, lipids also carry important signals associated with many fundamental cell biological processes, such as proliferation, differentiation, migration, stress responses and cell demise. Hyperactive lipid metabolism is closely associated with cancer progression and unfavorable outcomes. The underlying mechanisms are being gradually deciphered. In this review, we aim to summarize recent advances on how reprogrammed lipid metabolism and accompanying signaling cascades directly modulate cancer cells, as well as influencing stromal cells and immune cells within the tumor microenvironment. For future studies, special attention should be paid to lipid-mediated crosstalk among cancer cells, their neighboring stromal cells, and immune cells, plus how these multi-level communications determine anti-tumor immunity and bring novel immunotherapeutic opportunities.


A series of robust genetic indicators for definitive identification of cardiomyocytes.
Definitively identifying the cell type of newly generated cells in the heart and defining their origins are central questions in cardiac regenerative medicine. Currently, it is challenging to ascertain the myocardial identity and to track myocardial progeny during heart development and disease due to lack of proper genetic tools. This may lead to many misinterpretations of the findings in cardiac regenerative biology. In this study, we developed a set of novel mouse models by inserting double reporter genes nlacZ/H2B-GFP, mGFP/H2B-mCherry into the start codon of Tnnt2 and Myh6. nlacZ (nuclear lacZ) and mGFP (membrane GFP) are flanked by two LoxP sites in these animals. We found that the reporter genes faithfully recapitulated Tnnt2 and Myh6 cardiac expression from embryonic stage and adulthood. The reporter mice provide unprecedented robustness and fidelity for visualizing and tracing cardiomyocytes with nuclear or cell membrane localization signals. These animal models offer superior genetic tools to meet a critical need in studies of heart development, cardiac stem cell biology and cardiac regenerative medicine.


Insufficient tuberculosis treatment leads to earlier and higher mortality in individuals co-infected with HIV in southern China: a cohort study.
Tuberculosis (TB) and Acquired Immune Deficiency Syndrome (AIDS) are leading causes of death globally. However, little is known about the long-term mortality risk and the timeline of death in those co-infected with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (MTB). This study sought to understand the long-term mortality risk, factors, and the timeline of death in those with HIV-Mycobacterium tuberculosis (MTB) coinfection, particularly in those with insufficient TB treatment. TB-cause specific deaths were classified using a modified 'Coding of Cause of Death in HIV' protocol. A longitudinal cross-registration-system checking approach was used to confirm HIV/MTB co-infection between two observational cohorts. Mortality from the end of TB treatment (6 months) to post-treatment year (PTY) 5 (60 months) was investigated by different TB treatment outcomes. General linear models were used to estimate the mean mortality at each time-point and change between time-points. Cox's proportional hazard regressions measured the mortality hazard risk (HR) at each time-point. The Mantel-Haenszel stratification was used to identify mortality risk factors. Mortality density was calculated by person year of follow-up. At the end point, mortality among patients with HIV/MTB coinfection was 34.7%. From the end of TB treatment to PTY5, mortality and loss of person years among individuals with TB treatment failure, missing, and adverse events (TBFMA) were significantly higher than those who had TB cure (TBC) and TB complete regimen (TBCR). Compared to individuals with TBC and with TBCR, individuals with TBFMA tended to die earlier and their mortality was significantly higher (HRTBFMA-TBC = 3.0, 95% confidence interval: 2.5-3.6, HRTBFMA-TBCR = 2.9, 95% CI: 2.5-3.4, P < 0.0001). Those who were naïve to antiretroviral therapy, were farmers, had lower CD4 counts (≤200 cells/μL) and were ≥ 50 years of age were at the highest risk of mortality. Mortality risk for participants with TBFMA was significantly higher across all stratifications except those with a CD4 count of ≤200 cells/μL. Earlier and long-term mortality among those with HIV/MTB co-infection is a significant problem when TB treatment fails or is inadequate.


The interaction of oxymyoglobin with hydrogen peroxide: the formation of ferrylmyoglobin at moderate excesses of hydrogen peroxide.
The reaction of oxymyoglobin with H2O2 has been examined at pH 7.2 and 20(+/-2) degrees over a range of [H2O2] up to an initial excess of 25:1. The reaction is characterized by a direct conversion of oxymyoglobin to ferrylmyoglobin without the intermediacy of the ferri derivative. The initial rate of loss of oxymyoglobin is first-order with respect to [oxymyoglobin], and exhibits saturation kinetics with increasing [H2O2]. In addition, the stoichiometric relationship between the reactants varies as [H2O2] increases. A complex non-Michaelis-Menten mechanism is proposed in which an intermediate, produced upon the initial interaction of the reactants, regenerates oxymyoglobin by reaction with further H2O2, in competition with the formation of the ferryl derivative. In this way, oxymyoglobin catalytically decomposes excess H2O2. Deoxygenated ferromyoglobin is substantially more reactive with H2O2 in producing the transient intermediate than the oxy analog. Some fundamental similarity is noted between the catalytic mechanism and that of catalase activity. From a detailed examination of the probable nature of the intermediate, conventional Fenton reactivity is rejected for the reaction of H2O2 with oxymyoglobin.


[Method of evaluating the clinical status of patients during rehabilitation from the sequelae of stroke].
The authors propose the methodology of the comprehensive assessment of the status of patients with cerebral stroke consequences which is based on the total score evaluation of the most informative clinical signs with due regard to their relative significance.


AntagomiR-27a targets FOXO3a in glioblastoma and suppresses U87 cell growth in vitro and in vivo.
To study the effect of the antagomiR-27a inhibitor on glioblastoma cells. The miR- 27a expression level in specimens of human glioblastoma and normal human brain tissues excised during decompression for traumatic brain injury was assessed using qRT-PCR; The predicted target gene of miR-27a was screened out through bioinformatics databases, and the predicted gene was verified using genetic report assays; the effect of antagomiR-27a on the invasion and proliferation of glioma cells was analyzed using MTT assays and 5-ethynyl-2'-deoxyuridine (EdU) labeling. A xenograft glioblastoma model in BALB-c nude mice was established to detect the effect of antagomiR-27a on tumour growth. qRT-PCR results showed that miR-27a significantly increased in specimens from glioblastoma comparing with normal human brain tissues. Th miR-27a inhibitor significantly suppressed invasion and proliferation of glioblastoma cells. FOXO3a was verified as a new target of miR-27a by Western blotting and reporter analyzes. Tumor growth in vivo was suppressed by administration of the miR-27a inhibitor. MiR-27a may be up-regulated in human glioblastoma, and antagomiR-27a could inhibit the proliferation and invasion ability of glioblastoma cells.


How Will the Transition to ICD-10 Affect Urology Coding? An Analysis of ICD-9 Code Use from a Large Group Practice.
On October 1, 2015 the ICD (International Classification of Diseases)-10-CM (10th Revision, Clinical Modification) code set replaced ICD-9 (9th Revision) for coding medical encounters in the United States. The introduction of this unique, expanded code set will change the way medical encounters are coded, and may affect specialties and subspecialists to different degrees. A retrospective review was performed evaluating ICD-9 codes used at a large urology group. The most commonly used codes were evaluated in the office and hospital settings, and also from 3 individual subspecialists including a men's health/infertility subspecialist, a pelvic floor/reconstruction subspecialist and a pediatric subspecialist. The top 30 ICD-9 codes comprised 82.5% and 80.7% of the codes chosen in the office and hospital settings, with a 1:1 conversion from ICD-10 in 60% (18 of 30) and 36.7% (11 of 30), respectively. The top 25 codes from the 3 subspecialists (men's health/infertility, pelvic floor/reconstruction and pediatric) comprised 86.8%, 88.7% and 88.1% of the ICD-9 codes chosen, with a 1:1 correlation in 48% (12 of the top 25), 56% (14 of 25) and 40% (10 of 25), respectively. A significant number of unspecified codes was used across all of the aspects of practice. Urologists need to be aware of their practice patterns when converting from ICD-9 to ICD-10. The high percentage of codes concentrated in the top 25 of a practice may allow urologists to focus on their individual needs. Improved documentation and coding education may decrease the number of unspecified codes chosen, leading to improved coding accuracy.


Pharmacotherapeutic strategies for epithelioid sarcoma: are we any closer to a non-surgical cure?
Epithelioid sarcoma (ES) is a rare soft tissue sarcoma subtype, predominantly occurring in children and young adults. Despite optimal management of localized disease, approximately 50% of patients develop advanced disease. The management of advanced ES remains challenging due to limited response to conventional chemotherapy and despite novel oral EZH2 inhibitors that have better tolerability but similar efficacy to chemotherapy. We performed a literature review using the PubMed (MEDLINE) and Web of Science databases. We have focused on the role of chemotherapy, targeted agents such as EZH2 inhibitors, potential new targets and immune checkpoint inhibitors and combinations of therapies currently undergoing clinical investigation. ES is a soft tissue sarcoma with a heterogeneous pathological, clinical, and molecular presentation. In the current era of precision medicine, more trials with targeted therapies and a combination of chemotherapy or immunotherapy with targeted therapies are required to establish optimal treatment for ES.


Perovskite-type CaMnO3 anode material for highly efficient and stable lithium ion storage.
Lithium ion batteries are attracting ever increasing attention due to their advantages of high energy/ power density, environmental friendly, lifetime and low cost. As a star in the field of materials and energy, perovskites have received extensive attention due to their attracting physical and chemical properties. Herein, CaMnO3, one material from the perovskite family is introduced as a novel anode material for lithium ion batteries, and its electrochemical performance at different temperatures is systematically investigated. CaMnO3 has been synthesized using a liquid phase synthesis method followed by high temperature calcination. The as-obtained CaMnO3 exhibits an initial high discharge capacity of 708.4 mAh g-1, superior rate capability and stable cycling performance at room temperature, the specific capacity is 102.5 mAh g-1 after 500 cycles at a current density of 0.1 A g-1. Additionally, at an extreme temperature of 0 °C, the discapacity can reach 138.2 mAh g-1 at a current density of 0.05 A g-1. At high temperature of 50 °C, the reversible discharge capacity is up to 216.5 mAh g-1under the same condition. It is believed that this contribution may lay the foundation for the application of perovskites in other rechargeable batteries and energy storage devices.


The remains of the day: neuropsychological findings in postacute transient global amnesia.
Current clinical diagnostic criteria of transient global amnesia (TGA) require the episode to completely resolve within 24 h. Small case series investigating the neuropsychological profiles obtained during the first days after TGA are inconclusive, with some suggesting the persistence of memory deficits. In this retrospective observational study, neuropsychological data of 185 TGA patients obtained during the first days following an attack were analysed. Data of cognitive functions assessed in at least 50 patients were evaluated and dichotomised according to z-values as "impaired" or "unimpaired". Moreover, the results of magnetic resonance imaging (MRI) were collected. Neuropsychological assessment was performed within the first 3 days after TGA in 158 (85.4%) of all patients. The majority of patients showed no significant neuropsychological sequelae in the postacute phase of TGA. However, Mini-Mental Status Examination showed impairment in 22.6% of 159 patients, and we found subtle reductions of patients' performance in tests of verbal long-term memory and executive function in 16.3-24.6% of patients. Patients with hippocampal diffusion-weighted imaging (DWI) lesions performed significantly worse in a verbal recognition task than those without DWI lesions. Our findings reflect subtle performance reductions in different cognitive domains in a small subgroup of TGA patients. This implies that the gradual resolution of subclinical symptoms may take longer than the 24 h required as maximum episode duration by current diagnostic criteria.


Do Monkeys and Young Children Understand Exclusive "Or" Relations? A Commentary on Ferrigno et al. (2021).
Ferrigno et al. (2021) claim to provide evidence that monkeys can reason through the disjunctive syllogism (given A or B, not A, therefore B) and conclude that monkeys therefore understand logical "or" relations. Yet their data fail to provide evidence that the baboons they tested understood the exclusive "or" relations in the experimental task. For two mutually exclusive possibilities-A or B-the monkeys appeared to infer that B was true when A was shown to be false, but they failed to infer that B was false when A was shown to be true. In our own research, we recently found an identical response pattern in 2.5- to 4-year-old children, whereas 5-year-olds demonstrated that they could make both inferences. The monkeys' and younger children's responses are instead consistent with an incorrect understanding of A and B as having an inclusive "or" relation. Only the older children provided compelling evidence of representing the exclusive "or" relation between A and B.


The fate of memory: Reconsolidation and the case of Prediction Error.
The ability to make predictions based on stored information is a general coding strategy. A Prediction-Error (PE) is a mismatch between expected and current events. It was proposed as the process by which memories are acquired. But, our memories like ourselves are subject to change. Thus, an acquired memory can become active and update its content or strength by a labilization-reconsolidation process. Within the reconsolidation framework, PE drives the updating of consolidated memories. Moreover, memory features, such as strength and age, are crucial boundary conditions that limit the initiation of the reconsolidation process. In order to disentangle these boundary conditions, we review the role of surprise, classical models of conditioning, and their neural correlates. Several forms of PE were found to be capable of inducing memory labilization-reconsolidation. Notably, many of the PE findings mirror those of memory-reconsolidation, suggesting a strong link between these signals and memory process. Altogether, the aim of the present work is to integrate a psychological and neuroscientific analysis of PE into a general framework for memory-reconsolidation.


Off-label Medication Use: A Double-edged Sword.
Agarwal V. Off-label Medication Use: A Double-edged Sword. Indian J Crit Care Med 2021;25(8):845-846.


Immunological evaluation of repeated administration of erythrocyte-entrapped protein to C3H/HeJ mice.
The immunogenicity of heterologous protein entrapped in autologous erythrocytes was evaluated in a mouse system. Multiple intravenous administrations of an erythrocyte-entrapped bovine beta-glucuronidase preparation resulted in little, if any, immunological response to the entrapped protein or erythrocyte carrier. Erythrocyte entrapment also protected protein from circulating antibody elicited by prior subcutaneous sensitization with unentrapped enzyme in adjuvant. Thus erythrocyte entrapment may protect potentially immunogenic agents from immunological surveillance.


Maximizing signal-to-noise and contrast-to-noise ratios in FLASH imaging.
This paper presents an analysis of signal-to-noise and contrast-to-noise ratios from small tip angle, gradient reversal (FLASH) imaging. Analytic and numerical techniques are used to determine the delay times and tip angles that maximize signal-to-noise per unit time from a single tissue. Similar procedures are used to determine the delay times and tip angles that maximize both T1-induced and T-2*-induced contrast-to-noise per unit time for a pair of tissues as a function of tissue characteristics and pulse sequence sampling times. The advantage of optimized FLASH imaging over optimized spin-echo imaging is quantitated by comparing signal-to-noise and contrast-to-noise ratios per unit time from the two sequences. Images are used to confirm these numerical results, to compare noise levels resulting from gradient reversals versus 180 degrees rephasing pulses and to assess the possible adverse effects of static magnetic field inhomogeneities on FLASH imaging.


Effects of acute hyperglycaemia on anorectal motor and sensory function in diabetes mellitus.
To determine the effects of acute hyperglycaemia on anorectal motor and sensory function in patients with diabetes mellitus. In eight patients with Type 1, and 10 patients with Type 2 diabetes anorectal motility and sensation were evaluated on separate days while the blood glucose concentration was stabilized at either 5 mmol/l or 12 mmol/l using a glucose clamp technique. Eight healthy subjects were studied under euglycaemic conditions. Anorectal motor and sensory function was evaluated using a sleeve/sidehole catheter, incorporating a barostat bag. In diabetic subjects hyperglycaemia was associated with reductions in maximal (P<0.05) and plateau (P<0.05) anal squeeze pressures and the rectal pressure/volume relationship (compliance) during barostat distension (P<0.01). Hyperglycaemia had no effect on the perception of rectal distension. Apart from a reduction in rectal compliance (P<0.01) and a trend (P=0.06) for an increased number of spontaneous anal sphincter relaxations, there were no differences between the patients studied during euglycaemia when compared with healthy subjects. In patients with diabetes, acute hyperglycaemia inhibits external anal sphincter function and decreases rectal compliance, potentially increasing the risk of faecal incontinence.


Complete Genomes of Three Pseudomonas aeruginosa Bacteriophages, Kara-mokiny 1, Kara-mokiny 2, and Kara-mokiny 3.
Here, we present the complete genome sequence of Pseudomonas aeruginosa phages Kara-mokiny 1, Kara-mokiny 2, and Kara-mokiny 3. These phages have lytic capabilities against P. aeruginosa and belong to the myovirus morphotype. The genomes of Kara-mokiny 1 and Kara-mokiny 2 are 67,075 bp while that of Kara-mokiny 3 is 66,019 bp long.


Combining femoral and acetabular parameters in femoroacetabular impingement: the omega surface.
The concept of femoroacetabular impingement (FAI) proposes the development of hip osteoarthritis through motion-induced damage to the acetabular cartilage and labrum. Thus, dynamic interaction of the proximal femur and acetabulum is the crux of FAI. Several types of FAI can be distinguished, but FAI classification is mostly done with separate parameters for acetabular and femoral morphology on planar images, without direct representation of the femoroacetabular interaction. Five main parameters influence impingement between the proximal femur and the acetabular rim: alpha and center edge angles, acetabular and femoral version, and neck-shaft angle. We attempted to integrate these five parameters in order to reflect their interaction and derive a signal comprehensive parameter, the omega surface, to characterize the severity of FAI. The omega surface is a CT-based delineation of the femoral head surface that represents the area for impingement-free motion. The omega surface is determined with dedicated software (Articulis™) and can be determined for various positions of the hip joint. We determined the omega surface in a pilot study for five different hip morphotypes and found the omega surface was smaller in FAI morphotypes than in a normal hip. Furthermore, the omega surface was smaller in symptomatic versus control subjects with FAI morphotypes. The omega surface may therefore help in improved differentiation between symptomatic and asymptomatic FAI hips.


Efficacy of the topical 5% lidocaine medicated plaster in the treatment of chronic post-thoracotomy neuropathic pain.
To assess the efficacy of the topical 5% lidocaine medicated plaster (Versatis®, Grünenthal GmbH, Aachen, Germany) in patients with post-thoracotomy neuropathic pain. Patients were randomized to receive the topical 5% lidocaine medicated plaster (n = 33) or non-medicated placebo plasters (n = 30) for 12 h every day for 8 weeks. Laser-evoked potentials (LEPs) were measured, and various questionnaires/scales completed. Numeric Rating Scale pain scores improved significantly (p < 0.01) more in topical 5% lidocaine medicated plaster than in placebo recipients. The same was true for N2 and P2 LEP latency and amplitude, and other parameters. The study included neurophysiological findings and confirmed the efficacy of the topical 5% lidocaine medicated plaster in patients with chronic post-thoracotomy neuropathic pain.


Resveratrol regulates the expression of NHE-1 by repressing its promoter activity: critical involvement of intracellular H2O2 and caspases 3 and 6 in the absence of cell death.
Na(+)/H(+) exchanger-1 (NHE-1) overexpression is associated with carcinogenesis and is an attractive target for intervention. We report that the chemopreventive agent resveratrol (RSV) downregulates NHE-1 in a caspase-dependent manner without inducing cell death. Resveratrol triggered early activation of caspase 3 and late activation of caspase 6, which were not inter-dependent. Whereas, caspase 3 activation appeared to be a direct effect of resveratrol, caspase 6 activation was mediated via intracellular hydrogen peroxide production and iron. Moreover, downregulation of NHE-1 expression was a function of resveratrol-induced repression of NHE-1 gene promoter activity. RNAi-mediated silencing of caspase 3 or 6 blocked the effect of resveratrol on NHE-1 expression, however the effect on NHE-1 promoter was observed at different phases of promoter repression with caspase 3 controlling the early phase (4-12 h) and caspase 6 regulating the late phase (12-24 h). Scavenging hydrogen peroxide or iron only reversed the late phase of resveratrol-induced NHE-1 promoter repression. Finally, an AP2 binding region within NHE-1 gene promoter was identified as the target of resveratrol. Collectively, these data could explain the anti-cancer activity of resveratrol in the light of the association of increased NHE-1 expression with carcinogenesis.


Anticonflict effect of MK-801 in rats: time course and chronic treatment studies.
The present study examined the time course and chronic treatment effects of the noncompetitive N-methyl-D aspartate (NMDA) antagonist, MK-801 (dizocilpine), on conflict behavior in the conditioned suppression of drinking (CSD) paradigm, a repeated-measures conflict task. In daily 10-min sessions, water-restricted rats drank from a tube that was occasionally electrified (0.25- or 0.5-mA shocks signaled by a tone). Trained subjects (4 weeks of CSD testing) exhibited stable baselines for both punished responding and unpunished responding. In the first experiment, the effects of MK-801 administered IP were determined in female and male rats following a range of pretreatment intervals (i.e., 0.5-48 h). In female rats, 0.2 mg/kg MK-801 exerted an anticonflict effect at pretreatment intervals of 10-36 h, but not before 10 h or after 36 h. In male rats, qualitatively similar results were obtained; MK-801 (0.4 mg/kg) exerted anticonflict effects following pretreatment intervals of 6-14 h, but not before 6 or after 14 h. In the second experiment, chronic treatment of female rats with 0.04, 0.01, or 0.2 mg/kg MK-801 resulted in a dose-dependent anticonflict effect in CSD paradigm, which remained stable over the course of 5 weeks of chronic treatment. Punished responding returned to pretreatment levels within 2-3 days after discontinuation of chronic treatment with MK-801. These data suggest that MK-801 exerts a delayed anticonflict effect in both female and male rats with a qualitatively similar pattern, and that there is no tolerance to the anticonflict effect of MK-801 with chronic treatment.


tDCS-induced modulation of GABA concentration and dopamine release in the human brain: A combination study of magnetic resonance spectroscopy and positron emission tomography.
Transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex (DLPFC) hypothetically modulates cognitive functions by facilitating or inhibiting neuronal activities chiefly in the cerebral cortex. The effect of tDCS in the deeper brain region, the basal ganglia-cortical circuit, remains unknown. To investigate the interaction between γ-aminobutyric acid (GABA) concentrations and dopamine release following tDCS. This study used a randomized, placebo-controlled, double-blind, crossover design. Seventeen healthy male subjects underwent active and sham tDCS (13 min twice at an interval of 20 min) with the anode placed at the left DLPFC and the cathode at the right DLPFC, followed by examinations with [11C]-raclopride positron emission topography (PET) and GABA-magnetic resonance spectroscopy (MRS). MRS voxels were set in the left DLPFC and bilateral striata. Paired t-tests and regression analyses were performed for PET and MRS parameters. MRS data analyses showed elevations in GABA in the left striatum along with moderate reductions in the right striatum and the left DLPFC after active tDCS. PET data analyses showed that reductions in [11C]-raclopride binding potentials (increase in dopamine release) in the right striatum were inversely correlated with those in the left striatum after active tDCS. GABA reductions in the left DLPFC positively correlated with elevations in GABA in the left striatum and with increases in right striatal dopamine release and negatively correlated with increases in left striatal dopamine release. The present results suggest that tDCS to the DLPFC modulates dopamine-GABA functions in the basal ganglia-cortical circuit.


Synthesis and brush border expression of intrinsic factor-cobalamin receptor from rat renal cortex.
The main objective of the current study was to investigate the factors that affect brush border membrane expression of intrinsic factor-cobalamin receptor (IFCR). Because of high levels of IFCR expression (Seetharam, B., Levine, J. S., Ramasamy, M., and Alpers, D. H. (1988) J. Biol. Chem. 263, 4443-4449) in the rat kidney, we have studied the synthesis and expression of IFCR using rat cortical slices in culture. The IFCR activity in the renal apical brush border was maximum from rats between the age of 20-24 days and about 75% of the activity was lost from the isolated apical surface membranes following culture of cortical slices with nonradioactive intrinsic factor-cobalamin. However, the membrane IFCR activity recovered to 100 or 75%, respectively, when the slices were cultured with intrinsic factor-cobalamin mixed with either leupeptin or chloroquine. When these lysosomotropic agents were added during the metabolic labeling of the cortical slices with trans-35S-label neither the synthesis nor the amount of [35S]IFCR transported to the apical membrane was inhibited. However, with the addition of colchicine, the apical membrane expression of [35S]IFCR was inhibited by 75-80%. Metabolic labeling of cortical slices with trans-35S-label and immunoprecipitation of the Triton X-100 extract from the total, internal, and apical membranes revealed the presence of a 230-kDa band following sodium dodecyl sulfate-polyacrylamide gel electrophoresis. With either continuous or pulse-chase labeling of the cortical slices, the amount of 230-kDa [35S]IFCR recovered in the apical membrane did not exceed 10-15% of the total labeled receptor synthesized. Based on these and our recent studies (Seetharam, S., Dahms, N., Li, N., Ramanujam, K.S., and Seetharam, B. (1991) Biochem. Biophys. Res. Commun. 177, 751-756), we propose that rat renal IFCR is synthesized as a single polypeptide chain of 220 kDa and is transported slowly to the apical membrane during which four or five N-linked oligosaccharides are processed to the complex type. Moreover, the brush border expression of IFCR is regulated by the biosynthetic and not by the endocytic pathway.


Histological localization of methylmercury in mouse brain and kidney by emulsion autoradiography of 203Hg.
Some investigators have abandoned the use of 203Hg emulsion autoradiography in favor of chemical methods of microscopic localization of mercury. However, recent studies indicate that the latter methods identify only inorganic mercury, or some product of inorganic mercury, making them of little or no value for studies of methylmercury toxicity. Doubts about the use of 203Hg for microscopic localization arose because of the high maximum energy of its emissions and the concern that its latent images might be confounded with silver grains produced by chemical reactions between tissue Hg and the silver supplied by photographic emulsions. Examination of the spectrum of emissions from 203Hg demonstrates that its maximum energy emissions are rare. The mean energy of 203Hg emissions is in the 50-ke V range and the modal emissions are close to 0 ke V, indicating sufficient low energy emissions for autoradiography. In preliminary experiments, methylmercury content of mouse brain was shown to be stable through the steps of tissue processing for plastic sections. A direct comparison of autoradiographic grain counts from tissue treated with "cold" or "hot" methylmercury demonstrated that no grains above background were produced in the absence of nuclear emissions--only "hot" samples affected emulsion. In the kidneys of mice killed 24 hr after dosing, grains were most numerous over cortical tubules and significantly less numerous over glomeruli. In the cerebellum, the molecular layer was significantly more heavily labeled than the granular layer. The number of grains was greatly increased in every region by increasing the specific activity of the methylmercury dosing solution while holding the dose of methylmercury constant. Like the differential effect of "hot" vs "cold" tissue, the differential effect of low vs high specific activity confirms that the grain counts reflect nuclear emissions from the sample tissues, rather than a chemical effect dependent only on mercury content. Grain counts provided a measure of methylmercury content that matched the content measured by atomic absorption (AA). For example, the ratio of kidney/brain content was 32 by AA and 31 by grain counts in one experiment. Thus, 203Hg emulsion autoradiography appears to be a useful approach to localization of methylmercury in tissue sections processed for light microscopy.


Functional crosstalk between DNA damage response proteins 53BP1 and BRCA1 regulates double strand break repair choice.
The aim of this study was to elucidate the impact of DNA damage response (DDR) proteins 53BP1 and BRCA1 on the double-strand break (DSB)-repair choice. This is important not only in order to understand the underlying mechanisms of DSB-repair pathway regulation but also to determine the therapeutic implications for BRCA1-associated tumors. Human tumor cell lines A549 and HeLa were used. Non-homologous end-joining (NHEJ) and homologous recombination (HR) were assessed using NHEJ and HR reporter constructs. Colocalization of HR-proteins RPA and RAD51 with 53BP1 was evaluated by confocal microscopy and 3D-analysis. We demonstrate a specific crosstalk between 53BP1 and BRCA1. While 53BP1 does not colocalize with RPA or RAD51 and prohibits the recruitment of BRCA1 to DSBs to stimulate NHEJ, BRCA1 promotes the 53BP1 displacement specifically in S/G2-phase to allow end-resection, initiating HR. HR-efficiency was restored in BRCA1-depleted cells upon additional 53BP1-knockdown. Further, we found that 53BP1-mediated end protection precedes BRCA1-dependent end-resection. These results demonstrate that the interplay between 53BP1/NHEJ and BRCA1/HR is of great relevance for tumor treatment, as the 53BP1 status would be highly important for the treatment response of BRCA1-associated tumors.


Role of Methoprene-tolerant in the regulation of oogenesis in Dipetalogaster maxima.
Juvenile hormone (JH) signalling, via its receptor Methoprene-tolerant (Met), controls metamorphosis and reproduction in insects. Met belongs to a superfamily of transcription factors containing the basic Helix Loop Helix (bHLH) and Per Arnt Sim (PAS) domains. Since its discovery in 1986, Met has been characterized in several insect species. However, in spite of the importance as vectors of Chagas disease, our knowledge on the role of Met in JH signalling in Triatominae is limited. In this study, we cloned and sequenced the Dipetalogaster maxima Met transcript (DmaxMet). Molecular modelling was used to build the structure of Met and identify the JH binding site. To further understand the role of the JH receptor during oogenesis, transcript levels were evaluated in two main target organs of JH, fat body and ovary. Functional studies using Met RNAi revealed significant decreases of transcripts for vitellogenin (Vg) and lipophorin (Lp), as well as their receptors. Lp and Vg protein amounts in fat body, as well as Vg in hemolymph were also decreased, and ovarian development was impaired. Overall, these studies provide additional molecular insights on the roles of JH signalling in oogenesis in Triatominae; and therefore are relevant for the epidemiology of Chagas´ disease.


Mechanisms in cyclophosphamide induction of cytogenetic damage in human lymphocyte cultures.
Low-dose cyclophosphamide treatment of human lymphocyte cultures in concentrations ranging from 0.001 to 0.00001 microgram/ml produced a statistically significant dose response in chromosome breakage and cell death. However, a dose as high as 0.2 micrograms/ml did not produce significant damage in comparably treated whole blood cultures. These results suggest that lymphocytes in culture have the ability to metabolize the nonmutagenic cyclophosphamide parent compound to its more mutagenic metabolite, but that such conversion may be prevented by binding of cyclophosphamide to red blood cells.


ATP formation onset lag and post-illumination phosphorylation initiated with single-turnover flashes. II. Two modes of post-illumination phosphorylation driven by either delocalized or localized proton gradient coupling.
Two modes of chloroplast membrane post-illumination phosphorylation were detected, using the luciferin-luciferase ATP assay, one of which was not influenced by added permeable buffer (pyridine). That finding provides a powerful new tool for studying proton-membrane interactions during energy coupling. When ADP and Pi were added to the thylakoid suspension after a train of flashes [similar to the traditional post-illumination phosphorylation protocol (termed PIP- here)], the post-illumination ATP yield was influenced by pyridine as expected, in a manner consistent with the ATP formation, in part, being driven by protons present in the bulk inner aqueous phase, i.e., through a delocalized protonmotive force. However, when ADP and Pi were present during the flash train (referred to as PIP+), and ATP formation occurred during the flash train, the post-illumination ATP yield was unaffected by the presence of pyridine, consistent with the hypothesis that localized proton gradients were driving ATP formation. To test this hypothesis further, the pH and flash number dependence of the PIP- and PIP+ ATP yields were measured, the results being consistent with the above hypothesis of dual compartment origins of protons driving post-illumination ATP formation. Measuring proton accumulation during the attainment of the threshold energization level when no delta psi component was allowed to form (+ valinomycin, K+), and testing for pyridine effects on the proton uptake, reveals that the onset of ATP formation requires the accumulation of about 60 nmol H+ (mg Chl)-1. Between that level and about 110-150 nmol H+ (mg Chl)-1, the accumulation appears to be absorbed by localized-domain membrane buffering groups, the protons of which do not equilibrate readily with the inner aqueous (lumen) phase. Post-illumination phosphorylation driven by the dissipation of the domain protons was not affected by pyridine (present in the lumen), even though the effective pH in the domains must have been well into the buffering range of the pyridine. That finding provides additional insight into the localized domains, namely that protons can be absorbed by endogenous low pK buffering groups, and released at a low enough pH (less than or equal to 5.7 when the external pH was 8, less than or equal to 4.7 at pH 7 external) to drive significant ATP formation when no further proton production occurs due to the redox turnovers.(ABSTRACT TRUNCATED AT 400 WORDS)


Effective therapy of tocilizumab on systemic juvenile idiopathic arthritis-associated refractory macrophage activation syndrome.
To evaluate the safety and efficacy of tocilizumab (TCZ) on refractory macrophage activation syndrome (rMAS) associated with systemic juvenile idiopathic arthritis (sJIA-rMAS). We retrospectively reviewed the charts of 14 patients diagnosed with sJIA-rMAS, who were treated with TCZ after failing conventional therapies at three hospital centres from January 2016 to December 2020. Demographic, clinical, and laboratory characteristics were recorded at the onset of MAS, before TCZ (pre-TCZ), and 14 days after TCZ (post-TCZ). The clinical manifestation of sJIA-rMAS included fever (100%), skin rashes (35.7%), lymphadenomegaly (42.9%), hepatomegaly (57.1%), splenomegaly (7.1%), gastrointestinal symptoms (28.6%), arthritis (14.3%), myalgia (28.6%), and polyserositis (14.3%). After TCZ treatment, fever (100%, 14/14), gastrointestinal symptoms (100%, 4/4), and myalgia (100%, 4/4) were significantly improved after 1 week (P < 0.05). Skin rashes, lymphadenomegaly, and arthritis also improved in many patients, but these parameters did not reach statistical significance. In post-TCZ group, decreases in levels of C-reactive protein, erythrocyte sedimentation rate, and serum ferritin of sJIA-rMAS were observed compared with pre-TCZ (P < 0.05). No disease relapse or fatality was recorded during the follow-up (25 months, range 3-60 months). TCZ is safe and effective for the treatment of sJIA-rMAS after failure of conventional therapies.


Association of loop diuretics use and dose with outcomes in outpatients with heart failure: a systematic review and meta-analysis of observational studies involving 96,959 patients.
There is ongoing controversy regarding the association between loop diuretics (LD), especially in high doses, and adverse clinical outcomes in outpatients with heart failure (HF). We performed a systematic review of the evidence for LD in outpatients with HF. We searched MEDLINE, EMBASE, and Cochrane Clinical Trial Collection to identify controlled studies, evaluating the association between LD and morbidity and mortality in patients with HF. The primary endpoint was all-cause mortality and secondary endpoint HF hospitalizations. Quantitative analysis was performed by generating forest plots and pooling adjusted risk estimates across studies using random effects models. Between-study heterogeneity was assessed through Q and I2 statistics. Twenty-four studies with a total of 96,959 patients were included. No randomized studies were identified. Use of LD was associated with increased all-cause mortality compared with non-use (pooled adjusted risk estimates, 1.18; P = 0.001) and increased HF hospitalization rates (pooled adjusted risk estimates, 1.81; P < 0.001). These associations remained significant after excluding studies that included HF patients at discharge from hospital (pooled adjusted risk estimates, 1.31 and 1.89, respectively; P < 0.001 for both). High-dose LD (median dose 80 mg) were also associated with increased all-cause mortality (pooled adjusted risk estimates, 1.99; P < 0.001) compared with low-dose LD. Again, this association remained significant after excluding studies that included HF patients at discharge from hospital (pooled adjusted risk estimates, 1.33; P < 0.001). Existing evidence indicates that LD, especially in high doses, are associated with increased all-cause mortality and HF hospitalization rates. For this reason, prospective, randomized studies are warranted to clarify whether these associations indicate causality or are merely an epiphenomenon due to disease severity. Systematic review registration: PROSPERO database registration number CRD42020153239. Date of registration: 28 April 2020.


Completing phaco following anterior capsular tear.
A primary tear-out of the capsulorrhexis or a later anterior capsule tear occurs in less than 1% of phacoemulsification procedures (Marques et al., 2006). It is a relatively uncommon complication but a hazardous and important one, although comparatively little has been published on its management. With the nucleus still in the bag at this stage, the surgeon is faced with the sizeable challenge of completing surgery without propagating a wrap-around tear to the posterior capsule. These are perilous conditions to face, but by using the right techniques the surgeon can still prevail. There is a clear set of principles that are based on self-knowledge of the surgeon's own skills and experience, combined with their understanding of how to control the forces acting on the tear and the tolerances of the capsular bag to surgical manipulation. Applying these principles in practice has enabled the development of a range of techniques now available to safely remove the nucleus under these challenging conditions. However, by far the most important principle of all is that if in doubt, not to proceed.


Has the Expansion of Health Insurance Coverage via the Implementation of the Affordable Care Act Influenced Inequities in Coronary Revascularization in New York City?
In 2014, New York City implemented the Affordable Care Act (ACA) leading to insurance coverage gains intended to reduce inequities in healthcare services use. The paper documents inequalities in coronary revascularization procedures (percutaneous coronary intervention and coronary artery bypass grafting) usage by race/ethnicity, gender, insurance type, and income before and after the implementation of the ACA. We used data from the Healthcare Cost and Utilization Project to identify NYC patients hospitalized with the diagnosis of coronary artery disease (CAD) and/or congestive heart failure (CHF) in 2011-2013 (pre-ACA) and 2014-2017 (post-ACA). Next, we calculated age-adjusted rates of CAD and/or CHF hospitalization and coronary revascularization. Logistic regression models were used to identify the variables associated with receiving a coronary revascularization in each period. Age-adjusted rates of CAD and/or CHF hospitalization and coronary revascularization in patients 45-64 years of age and 65 years of age and older declined in the post-ACA period. Disparities by gender, race/ethnicity, insurance type, and income in the use of coronary revascularization persist in the post-ACA period. Although this health care reform law led to the narrowing of inequities in the use of coronary revascularization, disparities persist in NYC in the post-ACA period.


Effects of prenatal exposure to PM2.5 and its composition on cognitive and motor functions in children at 12 months of age: The Shanghai Birth Cohort Study.
Prenatal fine particulate matter (PM2.5) exposure has been linked to infant cognitive and motor functions, but the effects of PM2.5 chemical composition remain unclear. We aimed to explore the associations of prenatal PM2.5 and its composition exposure with infant cognitive and motor functions. We studied 2,435 mother-infant pairs in the Shanghai Birth Cohort Study. PM2.5 and its seven compositions [primary particles (black carbon, mineral dust and sea salts) and secondary particles (NH4+, NO3-, SO42- and organic matter)] during thethreetrimesters ofpregnancy were retrieved from the V4.CH.03 product developed by using a combined geoscience-statistical method. At the 12-month-old follow-up, infant cognitive and motor functions in five domains were assessed using the Ages and Stages Questionnaire (ASQ). We used multivariable linear regressions to estimate the effects of PM2.5 and its composition on the ASQ scores, for all infants and stratifying by sex and breastfeeding duration. PM2.5 exposure was negatively associated with gross motor, problem-solving and personal-social scores for all infants. PM2.5 compositions were inversely associated with ASQ scores in all five domains, and the effects of different compositions varied across domains. Specifically, all compositions except organic matter were correlated with lower problem-solving scores [e.g., ( [Formula: see text] = - 10.79, 95 % CI: -17.40, -4.18) ∼ ( [Formula: see text] = - 4.68, 95 % CI: -7.84, -1.53); for each 10 μg/m3 increase in PM2.5 compositions during the third trimester]. Primary and some secondary particles (organic matter, NO3-) were related to lower gross motor scores. Secondary particles were also inversely associated with communication (organic matter and NO3-), fine motor (NH4+, NO3-, SO42-) and personal-social (NH4+) scores. Additionally, boys and infants breastfed for < 6 months appeared to be more susceptible. We found negative associations of PM2.5 and its compositions with infant cognitive and motor functions over a range of domains, especially the problem-solving domain.


Roasted garlic protects against leaky gut syndrome in dextran sodium sulfate-induced colitis mice.
Garlic (Allium sativum) is a potentially beneficial functional food that is extensively grown around the globe. We have investigated the effect of roasted garlic on a dextran sodium sulfate (DSS)-induced intestinal permeability model in mice. Mice were divided into four diet groups: CON, DSS, RG (roasted garlic), and RG + Purple bamboo salt (RGP) in the AIN 93G diet for 3 weeks. All groups except the CON group received 2% DSS in drinking water at the last week of the experiment. DSS groups showed significantly elevated gut permeability levels and decreased tight junction protein expression compared to CON. However, RG and RGP displayed remarkably lower trends of gut permeability, increased tight junction protein expression, increased number of goblet cells than the DSS group in hematoxylin and eosin and alcian blue-nuclear fast red stained colon sections. These results indicate that roasted garlic could prevent gut leakage induced by DSS. The online version contains supplementary material available at 10.1007/s10068-022-01116-w.


N fertilizers promote abscisic acid-catabolizing bacteria to enhance heavy metal phytoremediation from metalliferous soils.
Bacterial-assisted phytoextraction is an attractive strategy to enhance the phytoremediation efficiency of heavy metal (HM)-contaminated soils. In the present study, we investigated the synergistic effects of N fertilizers and abscisic acid (ABA)-catabolizing bacteria on the HM (Cd, Zn, and Pb) phytoremediation efficiency of Brassica juncea L. (B. juncea). Compared with Rhodococcus qingshengii (R. qingshengii) alone, urea, ammonium‑nitrogen (NH4+-N), and nitrate‑nitrogen (NO3--N) fertilizers combined with R. qingshengii increased HM concentrations in B. juncea by 13.8 %-48.2 %, 44.2 %-54.4 %, and 59.4 %-113.6 %, respectively, and enhanced the biomass of B. juncea by 7.7 %-38.8 %, 10.9 %-29.5 %, and 19.9 %-46.8 %, respectively. Consequently, the bioconcentration factor increased by 3.4 %-30.9 % and the phytoextraction rate increased by 18.5 %-98.7 %. Treatment with NO3--N showed the most significant effect. In structural equation modeling, R. qingshengii inoculation showed greater path coefficients with soil pH and ABA and indoleacetic acid concentrations of B. juncea than N fertilization, indicating that R. qingshengii contributed more to HM extraction efficiency than N fertilizers. Additionally, differences in the extraction rates of Cd, Zn, and Pb from B. juncea were reduced following N fertilization. In summary, synergistic R. qingshengii inoculation and N fertilization have substantial potential to enhance phytoremediation efficiency. Combined application of R. qingshengii and NO3--N fertilizers is recommended.


The effect of diets enriched in cabbage and collards on murine pulmonary metastasis.
Feeding mice with diets enriched in dried cruciferous vegetables (cabbage and collards) resulted in a significant decrease in the number of pulmonary metastases after the animals were injected intravenously with mammary tumor cells. No differences in weight gain or calorie consumption were seen between the mice fed the different diets. These results support other evidence that diets high in cruciferous vegetables may be beneficial in cancer prevention.


Changes to porcine blastocyst vitrification methods and improved litter size after transfer.
The objective was to improve the protocol that was used to obtain the first reported piglets from transferred vitrified and warmed zona-intact blastocysts. Blastocysts were collected from superovulated sows and gilts, centrifuged to polarize lipid, vitrified, warmed and cultured for 24h or transferred immediately. Removing the zona pellucida after warming increased the number of cells in the surviving blastocysts (zona-free 60.8+/-4.3, zona-intact 39.1+/-2.8; P<0.05). Thinning the zona pellucida produced similar results to zona removal. Changing the basal medium of the vitrification and warming solutions from modified PBS to phosphate buffered NCSU-23 increased the number of cells (44.7+/-2.2 versus 56.0+/-3.9, respectively; P<0.05). Reducing the plunge temperature of the liquid nitrogen from -196 degrees C to less than -204 degrees C improved the embryo survival rate (61.9% versus 82.9%, respectively; P<0.05). These modifications were incorporated into the vitrification protocol that was used to vitrify and warm 105 blastocysts (that were subsequently transferred into four recipients). Three recipients became pregnant, farrowing three litters (average litter size, 5.3; 18.8% embryo survival in farrowing sows). Changing the warming protocol to using sucrose rather than ethylene glycol resulted in a trend towards improved embryo survival (73.5% versus 91.2%) but this was not statistically significant. Incorporating this modification, 203 blastocysts were vitrified, warmed and transferred into seven recipients. Five became pregnant and 36 fetuses were recovered (average litter size 7.2; 24.8% embryo survival in pregnant sows) at Day 40 of pregnancy. In conclusion, changes made to the vitrification protocol improved pregnancy rate and in vivo embryo survival compared to an earlier study using the original protocol.


One to Two Days of Rest Is Recommended Before Returning to Sport After Intra-Articular Corticosteroid Injection in the High-Level Athlete.
Return to sport following a corticosteroid injection is a complex decision. Multiple considerations should be taken into account, including steroid dose and formulation, involvement of the affected joint in the activity, and intensity of the activity. Research investigating the adverse effects of corticosteroid injections with early initiation of high-intensity activity is limited and has produced mixed results. Rest following injections has typically been recommended to minimize both chondrotoxic effects and systemic absorption. Based on the current research and extensive experience treating professional athletes, we recommend 1 to 2 days of rest of the affected joint or region with a progressive increase of activity following a corticosteroid injection with possible benefits including maximizing the beneficial effects of the injection and a reduced systemic effect. Level V, expert opinion.


Age-dependent changes in thermoperception in human anterior teeth.
Subjects (110) divided into three different age groups participated in a follow-up study investigating thermoperception in human anterior teeth. Deciduous teeth (51) were tested in 17 children (3.7 +/- 0.5 yr) and a total of 531 permanent teeth in two other groups of subjects: older children with an average age of 12.4 +/- 1.9 yr and adults with an age of 44.7 +/- 11.7 yr. In all three populations, the subjects' ability in cold perception in teeth was determinable. No data were obtained, however, to prove the existence of a corresponding warm perception. The differences in percentages of correctly-identified cold stimuli and in recorded mean latencies proved to be age-dependent. Variations in degree of dental decay and prior dental therapy did not show a significant effect on cold perception. No differences were found in the data obtained from female and male volunteers.


Immunologic benefits of breast milk in relation to human milk banking.
A review of the immunologic benefits of human milk is presented, with emphasis on the antiviral properties of human milk. These properties are so important to infant health that the World Health Organization has restated its recommendation. "In all populations, irrespective of HIV infection rates, breast-feeding should continue to be protected, promoted, and supported." Infection control procedures are described for human milk banking, which should be supported as an immunologically beneficial feeding alternative for infants.