Tree water status and growth of saplings and mature Norway spruce (Picea abies) at a dry distribution limit.
We evaluated the size effect on stem water status and growth in Norway spruce (Picea abies (L.) Karst.) occurring at the edge of its natural range in a dry inner Alpine environment (750 m asl, Tyrol, Austria). Intra-annual dynamics of stem water deficit (ΔW), maximum daily shrinkage (MDS), and radial growth (RG) were compared among saplings (stem diameter/height: 2.2 cm/93 cm; n = 7) and mature adult trees (25 cm/12.7 m; n = 6) during 2014. ΔW, MDS, and RG were extracted from stem diameter variations, which were continuously recorded by automatic dendrometers and the influence of environmental drivers was evaluated by applying moving correlation analysis (MCA). Additionally, we used Morlet wavelet analysis to assess the differences in cyclic radial stem variations between saplings and mature trees. Results indicate that saplings and mature trees were experiencing water limitation throughout the growing season. However, saplings exhibited a more strained stem water status and higher sensitivity to environmental conditions than mature trees. Hence, the significantly lower radial increments in saplings (0.16 ± 0.03 mm) compared to mature trees (0.54 ± 0.14 mm) is related to more constrained water status in the former, affecting the rate and duration of RG. The wavelet analysis consistently revealed more distinct diurnal stem variations in saplings compared to mature trees. Intra-annual RG was most closely related to climate variables that influence transpiration, i.e., vapor pressure deficit, relative air humidity, and air temperature. MCA, however, showed pronounced instability of climate-growth relationships, which masked missing temporal or significant correlations when the entire study period (April-October) was considered. We conclude that an increase in evaporative demand will impair regeneration and long-term stability of drought-prone inner Alpine Norway spruce forests.


Inhibitors of peptidases: how they influence the biological activities of substance P, neurokinins, kinins and angiotensins in isolated vessels.
Myotropic effects of various peptides were measured in three isolated vessels, the dog carotid artery, the rabbit pulmonary artery and the rat portal vein in the absence and in presence of several peptidase inhibitors, in order to evaluate the interference by metabolism with the peptides' biological activities. After adequate controls, captopril (4.6 x 10(-6) mol/l), thiorphan (1.0 x 10(-6) mol/l), phosphoramidon (4.6 x 10(-6) mol/l), chymostatin (1 mg/l), bestatin (8.1 x 10(-6) mol/l) or bacitracin (1.4 x 10(-5) mol/l) were left in contact with the tissues for 20-40 min to inhibit tissue peptidases before measuring again the biological effects of the various peptides. In some experiments, mergetpa (5.4 x 10(-6) mol/l) was used. All peptidase inhibitors were inactive on their own and only captopril potentiated the effects of substance P, neurokinins, bradykinin and inhibited angiotensin I in two preparations, the dog carotid artery, the rat portal vein, and, excluding bradykinin, also in the rabbit pulmonary artery. Captopril and thiorphan significantly potentiated the maximal response of the rat portal vein to substance P and mergetpa inhibited completely the effect of bradykinin on the rabbit pulmonary artery. The present findings suggest that the most active proteolytic enzyme interfering with the biological effects of vasoactive peptides on three isolated vessels is the angiotensin-converting enzyme (kininase II).


Effects of dietary sodium and genetic background on angiotensinogen and Renin in mouse.
Elements of a renin-angiotensin system expressed along the entire nephron, including angiotensinogen secreted by proximal tubule and renin expressed in connecting tubule, may participate in the regulation of sodium reabsorption at multiple sites of the nephron. The response of this tubular renin-angiotensin system to stepwise changes in dietary sodium was investigated in 2 mouse strains, the sodium-sensitive inbred C57BL/6 and the sodium-resistant CD1 outbred. Plasma angiotensinogen was not affected by sodium regimen, whereas plasma renin increased 2-fold under low sodium. In both strains, the variation in urinary parameters did not parallel the changes observed in plasma. Angiotensinogen and renin excretion were significantly higher under high sodium than under low sodium. Water deprivation, by contrast, induced significant activation in the tubular expression of angiotensinogen and renin. C57BL/6 exhibited significantly higher urinary excretion of angiotensinogen than did CD1 animals under both conditions of sodium intake. The extent to which these urinary parameters reflect systemic or tubular responses to challenges of sodium homeostasis may depend on the relative contribution of sodium restriction and volume depletion.


The length of training pilot: does anyone really know what time it takes?
With funding from the American Board of Family Medicine, the Review Committee for Family Medicine of the Accreditation Council for Graduate Medical Education has undertaken a project to examine the length of training for family medicine residents. This project comes at a time when concerns are being raised regarding how well family medicine residents are being prepared for independent practice, especially in view of the changing health care environment. The declining performance of recent graduates on the American Board of Family Medicine certification examination and reports of narrowing of the scope of practice of family physicians have only heightened these concerns. This special article is meant to provide a historical review of the issue as well as an overview of the project.


Insights in pediatric ventilation: timing of intubation, ventilatory strategies, and weaning.
Mechanical ventilation is a common intervention provided by pediatric intensivists. This fact notwithstanding, the management of mechanical ventilation in pediatrics is largely guided by a few pediatric trials along with careful interpretation and application of adult data. A low tidal volume, pressure limited approach to mechanical ventilation as established by the Acute Respiratory Distress Syndrome Network investigators, has become the prevailing practice in pediatric intensive care. Studies by these investigators suggest that high positive end expiratory pressure and recruitment maneuvers are not uniformly beneficial. High frequency oscillatory ventilation continues to be evaluated in an attempt to provide 'open lung' ventilation. Airway pressure release ventilation is a newer mode of ventilation that may combine the 'open lung' approach with spontaneous breathing. Prone positioning was demonstrated in a recent pediatric trial to have no effect on outcome, while calfactant was found to potentially improve outcomes in pediatric acute respiratory distress syndrome. Ventilator weaning protocols may not be as useful in pediatrics as in adults. Systemic corticosteroids decrease the incidence of post extubation stridor and may reduce reintubation rates. Mechanical ventilation with pressure limitation and low tidal volumes has become customary in pediatric intensive care units, and this lung protective approach will continue into the foreseeable future. Further investigation is warranted regarding use of high frequency oscillatory ventilation, airway pressure release ventilation, and surfactant to assist pediatric intensivists in application of these therapies.


Effectiveness of Facebook Groups and Pages on Participant Recruitment Into a Randomized Controlled Trial During the COVID-19 Pandemic: Descriptive Study.
In response to the unprecedented challenges posed by the COVID-19 pandemic, conventional recruitment approaches were halted, causing the suspension of numerous clinical trials. Previously, Facebook (Meta Platforms, Inc) has emerged as a promising tool for augmenting participant recruitment. While previous research has explored the use of Facebook for surveys and qualitative studies, its potential for recruiting participants into randomized controlled trials (RCTs) remains underexplored. This study aimed to comprehensively examine the effectiveness of using Facebook groups and pages to facilitate participant recruitment during the COVID-19 pandemic for an RCT on the effectiveness of a remote parenting program, 1-2-3 Magic, in families who have children with attention-deficit/hyperactivity disorder (ADHD) in the United Kingdom. We disseminated 5 Facebook posts with an attached digital flyer across 4 prominent ADHD UK support groups and pages run by the National Attention Deficit Disorder Information and Support Services, reaching an audience of around 16,000 individuals over 2 months (January 7 to March 4, 2022). Eligibility criteria mandated participants to be parents or caregivers of a child with diagnosed ADHD aged 12 years or younger, be residing in the United Kingdom, have access to stable internet, and have a device with the Zoom (Zoom Video Communications) app. Participants were required to have never attended 1-2-3 Magic training previously. Prospective participants expressed their interest through Microsoft Forms (Microsoft Corporation). The trial aimed to recruit 84 parents. It is important to note that the term "parent" or "caregiver" in the RCT and in this study within a trial refers to anybody who has legal responsibility for the child. Overall, 478 individuals registered their interest through Microsoft Forms within the stipulated 2-month window. After the eligibility check, 135 participants were contacted for a baseline meeting through Zoom. The first 84 participants who attended a baseline meeting and returned a completed consent form were enrolled. Subsequently, another 16 participants were added, resulting in a final sample of 100 participants. This recruitment strategy incurred negligible expenses and demanded minimal human resources. The approach yielded favorable outcomes by efficiently attracting eligible participants in a condensed time frame, transcending geographical barriers throughout the United Kingdom, which would have been tedious to achieve through traditional recruitment methods. Our experience demonstrated that digital flyers posted in the targeted Facebook groups were a cost-effective and quick method for recruiting for an RCT, which opened during the COVID-19 pandemic when lockdown restrictions were in place in the United Kingdom. Trialists should consider this low-cost recruitment intervention for trials going forward, and in the case of a global pandemic, this novel recruitment method enabled the trial to continue where many have failed. International Standard Randomized Controlled Trial Number (ISRCTN) 15281572; https://www.isrctn.com/ISRCTN15281572.


Effect of occupational polychlorinated biphenyls exposure on quality-adjusted life years over time at the HELPcB surveillance program.
HELPcB (Health Effects in High-Level Exposure to Polychlorinated Biphenyls [PCB]) is a surveillance program for former PCB-exposed workers of a capacitor recycling company and other concerned individuals. The aim of this study was to examine the influence of polychlorinated biphenyls (PCB) on the health-related quality of life (HRQL) and on quality-adjusted life years (QALY). The EQ-5D-3L questionnaire was used to determine the HRQL. After three cross-sectional examinations at intervals of 1 yr, the longitudinal development of QALY was compared by repeated-measurement analysis of covariance (ANCOVA). The cohort was split at the 95th percentile of the comparison group for each PCB congener; known confounders such as age were taken into account. A significant difference in height and development of QALY over time was shown for the higher chlorinated non-dioxin-like PCB (hcPCB) congeners. A significant between-groups effect was found on PCB 153, PCB 180, and the sum of hcPCB. It was found that QALY decreased in the high-burden group and QALY stabilized after yr 2 in the normal-burden group. Taking the dimensions of the EQ-5D into account, the between-groups effect seems to be based predominantly on the dimension anxiety. The development of the within-group effect, however, seems to be based on the dimension mobility. This study detected a significant influence of hcPCB on the development of HRQL and QALYs over time according to the level of internal PCB burden.


Plaque pH in caries-free and caries-active young individuals before and after frequent rinses with sucrose and urea solution.
To examine pH in the approximal dental biofilm after acid and alkali formation from sucrose and urea, after an adaptation period to these substances, in caries-free (CF) and caries-active (CA) individuals. Saliva flow and buffer capacity, and aciduric bacteria in saliva and plaque were also examined. Twenty adolescents and young adults (15-21 years) with no caries (n = 10, D(m + i)MFS = 0) or ≥1 new manifest lesions/year (n = 10, DmMFS = 3.4 ± 1.8) participated. After plaque sampling, interproximal plaque pH was measured using the strip method before (baseline) and up to 30 min (final pH) after random distribution of a 1-min rinse with 10 ml of 10% sucrose or 0.25% urea. This procedure was repeated after a 1-week adaptation period of rinsing 5 times/day with 10 ml of the selected solution. After a 2-week washout period the second solution was similarly tested. Mutans streptococci, lactobacilli and pH 5.2-tolerant bacteria were analyzed by culturing. In the CF group, acid adaptation resulted in lowering of baseline and final plaque pH values after a sugar challenge, and in increased numbers of bacteria growing at pH 5.2, which was increased also after alkali adaptation. In the CA group, the final pH was decreased after acid adaptation. No clear effects of alkali adaptation were seen in this group. One-week daily rinses with sucrose and urea had the most pronounced effect on the CF group, resulting in increased plaque acidogenicity from the sugar rinses and increased number of acid-tolerant plaque bacteria from both rinses.


Quantitative spectroscopic and theoretical study of the optical absorption spectra of H2O, HOD, and D2O in the 125-145 nm region.
The room temperature absorption spectra of water and its isotopomers D2O and HOD have been determined in absolute cross section units in the 125 to 145 nm wavelength region using synchrotron radiation. The experimental results for these B band spectra are compared with results from quantum mechanical calculations using accurate diabatic ab initio potentials. A Monte Carlo sampling over the initial rotational states of the molecules is applied in order to calculate the cross sections at a temperature of 300 K. The overall rotation of the water molecule is treated exactly. Both for the experimental and for the theoretical spectrum an analysis is made in terms of a component attributed to rapid direct dissociation processes and a component attributed to longer-lived resonances. The agreement between the results from experiment and theory is excellent for H2O and D2O. In the case of HOD in the results of theory two more resonances are found at low energy. It is demonstrated that the width of the resonances of 0.04 eV is the result of overlapping and somewhat narrower resonances in the spectra of molecules differing in rotational ground state.


Is thirty-two three tens and two ones? The embedded structure of cardinal numbers.
The acquisition and representation of natural numbers have been a central topic in cognitive science. However, a key question in this topic about how humans acquire the capacity to understand that numbers make 'infinite use of finite means' (or that numbers are generative) has been left unanswered. While previous theories rely on the idea of the successor principle, we propose an alternative hypothesis that children's understanding of the syntactic rules for building complex numerals-or numerical syntax-is a crucial foundation for the acquisition of number concepts. In two independent studies, we assessed children's understanding of numerical syntax by probing their knowledge about the embedded structure of cardinal numbers using a novel task called Give-a-number Base-10 (Give-N10). In Give-N10, children were asked to give a large number of items (e.g., 32 items) from a pool that is organized in sets of ten items. Children's knowledge about the embedded structure of numbers (e.g., knowing that thirty-two items are composed of three tens and two ones) was assessed from their ability to use those sets. Study 1 tested English-speaking 4- to 10-year-olds and revealed that children's understanding of the embedded structure of numbers emerges relatively late in development (several months into kindergarten), beyond when they are capable of making a semantic induction over a local sequence of numbers. Moreover, performance in Give-N10 was predicted by other task measures that assessed children's knowledge about the syntactic rules that govern numerals (such as counting fluency), demonstrating the validity of the measure. In Study 2, this association was tested again in monolingual Korean kindergarteners (5-6 years), as we aimed to test the same effect in a language with a highly regular numeral system. It replicated the association between Give-N10 performance and counting fluency, and it also demonstrated that Korean-speaking children understand the embedded structure of cardinal numbers earlier in the acquisition path than English-speaking peers, suggesting that regularity in numerical syntax facilitates the acquisition of generative properties of numbers. Based on these observations and our theoretical analysis of the literature, we propose that the syntax for building complex numerals, not the successor principle, represents a structural platform for numerical thinking in young children.


[Antithrombin therapy of no value in sepsis according to a large clinical trial].
Antithrombin has been used for over two decades as adjuvant therapy in severe sepsis, especially when associated with coagulopathy. A positive effect has been demonstrated in several experimental sepsis models and a number of small clinical trials have suggested a beneficial effect. A large confirmatory randomized clinical trial with 2,314 evaluable patients with severe sepsis was recently completed [1]. No treatment effect of antithrombin was demonstrated (28 day overall mortality was 38.9% and 38.7% in the treatment and placebo groups, respectively). Among various secondary effect and subgroup analyses, it is noteworthy that no trend indicating a beneficial effect of antithrombin substitution was found even in the subgroup of patients with plasma levels of antithrombin < 60% on randomization (n = 1,117). In summary, there is presently no support for the general use of antithrombin as adjuvant therapy in severe sepsis/septic shock.


Social and behavioral science priorities for genomic translation.
This commentary highlights the essential role of the social and behavioral sciences for genomic translation, and discusses some priority research areas in this regard. The first area encompasses genetics of behavioral, social, and neurocognitive factors, and how integration of these relationships might impact the development of treatments and interventions. The second area includes the contributions that social and behavioral sciences make toward the informed translation of genomic developments. Further, there is a need for behavioral and social sciences to inform biomedical research for effective implementation. The third area speaks to the need for increased outreach and education efforts to improve the public's genomic literacy such that individuals and communities can make informed health-related and societal (e.g., in legal or consumer settings) decisions. Finally, there is a need to prioritize representation of diverse communities in genomics research and equity of access to genomic technologies. Examples from National Institutes of Health-based intramural and extramural research programs and initiatives are used to discuss these points.


A Culturally Adapted, Telehealth, Community Health Worker Intervention on Blood Pressure Control among South Asian Immigrants with Type II Diabetes: Results from the DREAM Atlanta Intervention.
South Asians face a high prevalence of type II diabetes (DMII) and comorbid hypertension (HTN). Community health worker (CHW) interventions have the potential to improve chronic disease outcomes, yet few have been tailored to South Asian populations in the United States. To test the effectiveness of an evidence-based CHW-led and culturally-tailored HTN and DMII management program for South Asian adults with diabetes and comorbid uncontrolled HTN (systolic blood pressure (SBP) > 130 mmHg or diastolic blood pressure (DBP) > 80 mmHg). Randomized-controlled Trial. South Asian adults with DMII and comorbid HTN. The Diabetes Research, Education, and Action for Minorities (DREAM) Atlanta intervention was a CHW telehealth intervention designed to improve blood pressure (BP). The treatment group received five virtual group-based health education sessions, an action plan, and follow-up calls to assess goal setting activities. The control group received only the first session. Main Measures included: feasibility, improvement in BP control, and decreases in SBP, DBP, weight, and hemoglobin A1c (HbA1c). A total of 190 South Asian adults were randomized (97 to the treatment group and 93 to the control group); 94% of treatment group participants completed all 5 telehealth sessions. At endpoint, BP control increased 33.7% (95% CI: 22.5, 44.9, p < 0.001) in the treatment group and 16.5% (95%: 6.2, 26.8, p = 0.003) in the control group; the adjusted intervention effect was 1.8 (95% CI: 1.0, 3.2, p = 0.055). Mean weight decreased by 4.8 pounds (95% CI: -8.2, -1.4, p = 0.006) in the treatment group, and the adjusted intervention effect was -5.2 (95% CI: -9.0, -1.4, p = 0.007. The intervention had an overall retention of 95%. A culturally-tailored, CHW-led telehealth intervention is feasible and can improve BP control among South Asian Americans with DMII. NCT04263311.


[Current antiplatelet agents, new inhibitors and therapeutic targets].
Cardiovascular diseases are the leading cause of deaths in the world. Platelets play a major role in the occurrence of these diseases and the development of antiplatelet drugs is a priority in the fight against cardiovascular diseases-associated mortality. Aspirin and thienopyridine-based P2Y12 inhibitors are the main drugs currently used. These molecules target the initiation of platelets activation and are responsible for a moderate inhibitory action. Other antiplatelet agents, as glycoprotein (GP) IIb/IIIa antagonists, inhibit platelet aggregation independently of initial activation-associated pathways, but are responsible for increased hemorrhagic events. Regarding each antiplatelet agent's specific characteristics, the prescription of these drugs must take into account the type of cardiovascular event, the age of the patient, the past medical history, and the potential hemorrhagic adverse events. Thus, there is a need for the development of new molecules with a more targeted effect, maintaining optimal efficiency but with a reduction of the hemorrhagic risk, which is the principal limitation of these treatments.


A generalized method for the analysis of planar biaxial mechanical data using tethered testing configurations.
Simulation of the mechanical behavior of soft tissues is critical for many physiological and medical device applications. Accurate mechanical test data is crucial for both obtaining the form and robust parameter determination of the constitutive model. For incompressible soft tissues that are either membranes or thin sections, planar biaxial mechanical testing configurations can provide much information about the anisotropic stress-strain behavior. However, the analysis of soft biological tissue planar biaxial mechanical test data can be complicated by in-plane shear, tissue heterogeneities, and inelastic changes in specimen geometry that commonly occur during testing. These inelastic effects, without appropriate corrections, alter the stress-traction mapping and violates equilibrium so that the stress tensor is incorrectly determined. To overcome these problems, we presented an analytical method to determine the Cauchy stress tensor from the experimentally derived tractions for tethered testing configurations. We accounted for the measured testing geometry and compensate for run-time inelastic effects by enforcing equilibrium using small rigid body rotations. To evaluate the effectiveness of our method, we simulated complete planar biaxial test configurations that incorporated actual device mechanisms, specimen geometry, and heterogeneous tissue fibrous structure using a finite element (FE) model. We determined that our method corrected the errors in the equilibrium of momentum and correctly estimated the Cauchy stress tensor. We also noted that since stress is applied primarily over a subregion bounded by the tethers, an adjustment to the effective specimen dimensions is required to correct the magnitude of the stresses. Simulations of various tether placements demonstrated that typical tether placements used in the current experimental setups will produce accurate stress tensor estimates. Overall, our method provides an improved and relatively straightforward method of calculating the resulting stresses for planar biaxial experiments for tethered configurations, which is especially useful for specimens that undergo large shear and exhibit substantial inelastic effects.


[Differential protein expression in developmental stages of Trypanosoma cruzi I isolated from a patient with chronic chagasic cardiomyopathy].
Trypanosoma cruzi is the causative agent of Chagas disease. During infection in mammalian hosts, two main forms of the parasite are observed: trypomastigotes and amastigotes. During differentiation, each stage of the parasite expresses a pattern of proteins specific to each phase-proteins which are responsible for the cell's morphological, biochemical and biological properties. These properties ultimately govern the infectivity, virulence and survival of the parasite. A differential expression analysis was conducted to compare trypomastigote and amastigote stages of T. cruzi I isolate, and to identify proteins differentially expressed by means of mass spectrometry. A T. cruzi clone of the strain MHOM/07/338 was used to analyze the differential expression between trypomastigote stages of a T. cruzi isolate, using two-dimensional electrophoresis and identification of differentially expressed proteins by mass spectrometry. The protein profiles of the stages of the parasite were obtained by two-dimensional gel electrophoresis and visualized in gels dyed with Coomassie blue. The images were analyzed with PDQuest software and the differential expression of the proteins was identified by MALDI TOF or LC MS/MS. The two-dimensional gels revealed an average of 325 protein spots in each stage. The comparative analyses detected 21 spots that were over expressed in the trypomastigote stage and 30 in the amastigote stage. Sixteen of the over expressed proteins were selected for identification by mass spectrometry and classified in several functional categories. Mass spectrophotometry determined that the proteins were associated mainly with glucolytic metabolism and assembly of the cytoskeleton constituents. The differential expression between trypomastigote and amastigote stages consisted of proteins specific to T. cruzi and are potential targets for the design of treatment drugs.


Defect in the Joint Spectrum of Hydrogen due to Monodromy.
In addition to the well-known case of spherical coordinates, the Schrödinger equation of the hydrogen atom separates in three further coordinate systems. Separating in a particular coordinate system defines a system of three commuting operators. We show that the joint spectrum of the Hamilton operator, the z component of the angular momentum, and an operator involving the z component of the quantum Laplace-Runge-Lenz vector obtained from separation in prolate spheroidal coordinates has quantum monodromy for energies sufficiently close to the ionization threshold. The precise value of the energy above which monodromy is observed depends on the distance of the focus points of the spheroidal coordinates. The presence of monodromy means that one cannot globally assign quantum numbers to the joint spectrum. Whereas the principal quantum number n and the magnetic quantum number m correspond to the Bohr-Sommerfeld quantization of globally defined classical actions a third quantum number cannot be globally defined because the third action is globally multivalued.


Rovibronic bands of the A (2)B2 <-- X (2)B1 transition of C6H5O and C6D5O detected with cavity ringdown absorption near 1.2 microm.
We recorded several rovibronic bands of C(6)H(5)O and C(6)D(5)O in their A (2)B(2)<--X (2)B(1) transitions in the range 1.14-1.31 microm with the cavity ringdown technique. While the electronic transition is forbidden, several vibronic bands are observed. By comparison of rovibronic contours of observed and simulated bands to determine their types of transition, and by consideration of vibrational wavenumbers of the upper state based on quantum-chemical calculations, we were able to provide vibronic assignments of observed bands and derive several experimental vibrational wavenumbers (given as nu in unit of cm(-1) in this paper) for the A (2)B(2) state, namely, nu(12)=947, nu(13)=793, nu(14)=417, nu(15)=964, nu(16)=866, nu(17)=723, nu(18)=680, and nu(19)=499 for C(6)H(5)O, and nu(12)=772, nu(13)=626, nu(14)=365, nu(15)=812, nu(17)=599, nu(18)=532, and nu(19)=436 for C(6)D(5)O. Transitions involving vibrationally excited levels of nu(20) were also observed; nu(20) of the A state is greater by 50 cm(-1) than the X state of C(6)H(5)O. A weak origin at 7681 cm(-1) for the A<--X transition of C(6)H(5)O (7661 cm(-1) for C(6)D(5)O) with a c-type contour was observed. Observed isotopic ratios of vibrational wavenumbers for the A state of C(6)H(5)O to those of C(6)D(5)O are in good agreement with the predictions from quantum-chemical calculations at the B3LYP/aug-cc-pVTZ level.


Preventing wound infection after appendicectomy: a review.
An exponential increase in the number of published prospective studies reflects both a continuing interest in, and a lack of consensus on, the optimal prophylaxis of wound sepsis after appendicectomy. Review of the literature over the last 25 years leads us to emphasize both the importance of adequate study size and of stratification of the severity of the sepsis found at operation. For critical comparison of prophylactic regimens the high percentage of wound infections disclosed after discharge from hospital must be taken into account. Antibiotics reduce the frequency of wound sepsis and although low wound sepsis rates have been reported with systemic antibiotics active against only anaerobes, the cumulative evidence favours a spectrum of antibacterial activity against both aerobic and anaerobic organisms. Topical antiseptics have no significant effect but topical antibiotics are beneficial. Wide variations in outcome for similar antibiotic regimens reflect the importance of technical factors in determining the frequency of wound sepsis.


Mental health distress in homebound older adults: Importance of the aging network.
Homebound older adults may be at risk of suicide due to elevated loneliness, social isolation, and depression. The Interpersonal Theory of Suicide posits that thwarted belongingness, perceived burdensomeness, and reduced fear of death are key components of suicide risk. To better understand suicide risk among culturally diverse, homebound older adults, we collected baseline data on the prevalence of psychological distress, thwarted belongingness, perceived burdensomeness, and past/present suicidality. Standardized measures were completed by 493 adults (ages 60-103) during in-home interviews, and results were compared to existing cutoffs to assess current risk. In total, 15.62% scored above the suicide risk cutoff, 23.73% of homebound older adults reported a history of suicidal ideation or behavior, 65 adults in this sample (13.18%) indicated the possibility of attempting suicide in the future, and 2.43% described a future attempt as "likely" or "very likely." There were no differences in suicide risk, thwarted belongingness, or perceived burdensomeness based on sex and race. However, there was a significant difference in psychological distress (F(3,428) = 2.624, p = .05), with White females (M = 7.90, SD = 5.63; N = 78) scoring higher than Black males (M = 5.43, SD = 5.04; N = 81). Using Aging Network services such as nutrition services (e.g.home-delivered meal programs) to intervene with at-risk older adults represents a strategy to prevent suicide. Implications for suicide intervention, including the potential to deliver services by linking them to nutrition services programs, are discussed.


Infections following bispecific antibodies in myeloma: a systematic review and meta-analysis.
Bispecific antibodies, a novel immunotherapy with promising efficacy against multiple myeloma, form immune synapses between T-cell surface marker CD3 and malignant cell markers, including B-cell maturation antigen (BCMA), FcRH5, and G protein-coupled receptor GPRC5D. These bispecific antibodies so effectively deplete plasma cells (and to some extent T-cells) that patients are at increased risk of developing infections. A systematic review and meta-analysis of infections in published studies of patients with myeloma treated with bispecific antibodies was conducted to better characterize the infection risks. A literature search used MEDLINE, EMBASE, and Cochrane to identify relevant studies between inception and February 10, 2023, including major conference presentations. Phase 1b-3 clinical trials and observational studies were included. Sixteen clinical trials comprising 1666 patients were included. Median follow-up was 7.6 months and 38% of the cohort had penta-drug refractory disease. Pooled prevalence of all-grade infections was 56%, whereas the prevalence of grade ≥3 infections was 24%. Patients who were treated with BCMA-targeted bispecifics had significantly higher rates of grade ≥3 infections than non-BCMA bispecifics (25% vs 20%). Similarly, patients treated with bispecifics in combination with other agents had significantly higher rate of all-grade infection than those receiving monotherapy (71% vs 52%). In observational studies (n = 293), excluded from the primary analysis to ensure no overlap with patients in clinical trials, several infections classically associated with T-cell depletion were identified. This systematic review identifies BCMA-targeted bispecifics and bispecific combination therapy as having higher infection risk, requiring vigilant infection screening and prophylaxis strategies.


Open boundaries in a cellular automata model for synchronized flow: effects of nonmonotonicity.
In this paper, we have discussed the traffic situations arising from the open boundary conditions (OBC) of a cellular automata model that can reproduce the synchronized flow. The model is different from the slow-to-start (STS) model in that the upper branch of the fundamental diagram in the periodic boundary conditions (PBC) is not monotonous but has an extremum. The phase diagram and the fundamental diagram of the model in the OBC are investigated. The results are compared with those of the STS model and those in the PBC. The current in the OBC as well as the density profiles in the different phases is also investigated.


Menopause transition promotes distinct modulation of mRNAs and miRNAs expression in calvaria and bone marrow osteoblastic cells.
Investigation on functional genome research may contribute to the knowledge of functional roles of different mRNAs and miRNAs in bone cells of osteoporotic animals. Currently, few studies indicate the changes in gene modulation that osteoporosis causes in osteoblastic cells from different sites. Thus, the purpose of this investigation was to evaluate cell viability, alkaline phosphatase activity and modulation of mRNAs/miRNAs in osteoblastic cells from calvaria and bone marrow by means of microarray technology. Wistar female rats were divided in sham operated and ovariectomized groups. After 150 days of ovariectomy, cells were isolated from both sites to perform cell culture. Results showed that calvaria cells from ovariectomized rats had a decrease in viability when compared to control groups and to bone marrow cells from osteoporotic rats after 3 days. Alkaline phosphatase activity decreased in calvaria cells from ovariectomized rats whereas it was increased in bone marrow osteoblastic cells in the same group. Microarray data analysis showed 5447 differentially expressed mRNAs and 82 differentially expressed miRNAs in calvaria cells. The same way, 4399 mRNAs and 54 miRNAs were expressed in bone marrow cells. mRNAs associated with bone metabolism such as Anxa5, Sp7, Spp1, Notch1 were distinctively modulated in both sites, as well as miRNAs such as miR-350, miR-542-3p, miR-204-5p, and miR-30e-3p. The RNA species identified in this study could be further used as targets for treatment or prevention of osteoporosis.


Radiologic Evolution after Scapholunate Dorsal Capsulodesis for Chronic Tears.
Background Many debates are still ongoing for the management of chronic scapholunate (SL) injuries. We have proposed an arthroscopic technique of dorsal capsulodesis with good clinical results. We now propose a radiological follow-up. Purpose To determine if arthroscopic dorsal capsulodesis can improve the radiographic SL angle and maintain this correction over time. Methods From January 2020 to January 2021, we included every patient with an SL instability and sorted them according to the European Wrist Arthroscopy Society (EWAS) classification. All patients had bilateral X-rays with a measurement of the radiolunate (RL) and SL angles for both the pathologic and healthy side. We also included patients with lunotriquetral or triangular fibrocartilage complex lesions. The exclusion criteria were the presence of arthritis and persistent intraoperative SL instability after capsulodesis. An arthroscopic dorsal capsulodesis was performed in all patients as originally described by Mathoulin. The RL and SL angles were then again measured on the immediate postoperative X-ray, and then again at 3, 6, and 12 months postoperatively. The statistical analysis was done using a paired Student's t -test with 145 degrees of freedom and α = 0.05. Results We included a total of 146 patients with a 1-year follow-up. Both the RL angle and the SL angles approach the healthy side at 12 months postoperatively. The RL angle has increased from -7.23 degrees to 4.37 degrees; the difference is still statistically significative, but it is almost equal to the healthy side (5.16 degrees). The SL angle has lowered from 74.55 to 54.95; the difference is still statistically and radiologically significative (6.788 degrees) but has been lowered by 74.3%. Conclusion This study shows that this technique can normalize the dorsal intercalated segment instability (DISI) over time without the need for any pinning or invasive ligament reconstructive surgery. Level of Evidence Level IV, cohort study. Clinical Relevance Dorsal capsulodesis should be considered in all reducible SL injuries, even when DISI is present.


[The venture financing of scientifically-innovative projects: teaching experience in medical high school].
The authors presented an original material, devoted to first experience of teaching of theoretical bases of venture financing of scientifically-innovative projects in medical high school. The results and conclusions were based on data of the questionnaire performed by the authors. More than 90% of young scientist physicians recognized actuality of this problem for realization of their research work results into practice. Thus, experience of teaching of theoretical bases of venture financing of scientifically-innovative projects in medical high school proves reasonability of further development and inclusion the module "The venture financing of scientifically-innovative projects in biomedicine" in the training plan.


[Evaluation of changes made in the peri-operative care in patients submitted to elective abdominal surgery].
To evaluate the results of the introduction of new measures to accelerate the postoperative recovery of patients undergoing elective abdominal surgery. We observed 162 patients and interviewed them on two distinct periods: the first between October to December 2009 (n = 81) comprised patients who underwent conventional perioperative monitoring (pre-intervention) and the second between March and May 2010 (n = 81), formed by a new group of patients, submitted to the new protocol of perioperative monitoring. Data collection in the two periods occurred without the knowledge of the professionals in the service. The variables were: indication for preoperative nutritional support, duration of fasting, post-operative volume of hydration, use of catheters and drains, length of stay and postoperative morbidity. when comparing the two periods we observed a decrease of 2.5 hours in the time of preoperative fasting (p = 0.0002) in the post-intervention group. As for the reintroduction of oral diet, there was no difference between the two periods (p = 0.0007). When considering the patients without postoperative complications, there was a significantly decreased length of stay (p = 0.001325). There was a reduction of approximately 50% in antibiotic use in the post-intervention group (p = 0.00001). The adoption of multidisciplinary perioperative measures is feasible within our reality, and although there was no statistically significant changes in the present study, it may improve morbidity and reduce length of stay in general surgery.


Update on human alpha1-adrenoceptor subtype signaling and genomic organization.
Alpha1-adrenoceptors are G-protein-coupled receptors that bind catecholamines. Sixteen distinct human alpha1A-adrenoceptor isoforms have been identified from human tissues, including five full-length and 11 truncated versions. An updated scheme for the identification of alpha1A-adrenoceptor splice variants is proposed. Given the established roles of alpha1-adrenoceptors in benign prostatic hyperplasia, myocardial hypertrophy and other cardiovascular disorders, elucidation of the biological significance of the signaling diversity and potential pharmacological roles of alpha1A-adrenoceptor splice variants are important areas of future research.


Presence of Coxiella burnetii DNA in inflamed bovine cardiac valves.
Bacterial endocarditis is a recognised disease in humans and animals. In humans, infection with Coxiella burnetii can cause endocarditis, but this has not been investigated thoroughly in animals. Endocarditis in cattle is a common post-mortem finding in abattoirs and studies have identified Trueperella pyogenes as a major cause. Despite exposure of cattle to C. burnetii, the significance of this particular bacterium for development and progression of endocarditis has not been studied in detail. Cardiac valves of cattle affected with endocarditis (n = 100) were examined by histology, fluorescence in situ hybridization (FISH) and real time quantitative polymerase chain reaction (PCR). Serum was examined for anti-C. burnetii antibodies by enzyme-linked immunosorbent assay (ELISA). Serology revealed that 70% of the cattle were positive for antibodies to C. burnetii, while PCR analysis identified 25% of endocarditis valve samples as being positive. C. burnetii was not detected by FISH, probably due to the low infection levels. Most cattle had chronic valvular vegetative endocarditis with lesions being characterised by a core of fibrous tissue covered by significant amounts of fibrin, sometimes with areas of liquefaction, and with a coagulum covering the surface. In a few cases, including the case with the highest infection level, lesions were characterized by extensive fibrosis and calcification. Histologically, bacteria other than C. burnetii were observed in most cases. The presence of C. burnetii DNA is relatively common in cattle affected with valvular endocarditis. The role of C. burnetii remains however unknown as lesions did not differ between C. burnetii infected and non-infected cattle and because T. pyogenes-like bacteria were present in the inflamed valves; a bacterium able to induce the observed lesions. Heart valves of normal cattle should be investigated to assess if C. burnetii may be present without preexisting lesions.


The influence of pk/pd on the structure of optimal controls in cancer chemotherapy models.
Mathematical models for cancer chemotherapy as optimal control problems are considered. Results on scheduling optimal therapies when the controls represent the effectiveness of chemotherapeutic agents, or, equivalently, when the simplifying assumption is made that drugs act instantaneously, are compared with more realistic models that include pharmacokinetic (PK) equations modelling the drug's plasma concentration and various pharmaco-dynamic (PD) models for the effect the concentrations have on cells.


L-citrulline: A preclinical safety biomarker for the small intestine in rats and dogs in repeat dose toxicity studies.
Gastrointestinal (GI) toxicity is still an issue within drug development, especially for novel oncology drugs. The identification of GI mucosal damage at an early stage with high sensitivity and specificity across preclinical species and humans remains difficult. To date, in preclinical studies, no qualified mechanistic, diagnostic or prognostic biomarkers exist for GI mucosal toxicity. L-citrulline is one of the most promising biomarker candidates used in clinical settings to quantify enterocyte integrity in various small intestinal diseases. L-citrulline is an intermediate metabolic amino acid produced mainly by functional enterocytes of the small intestine, whereby enterocyte loss will cause a drop in circulating L-citrulline. In several repeat-dose toxicity studies, plasma L-citrulline has been evaluated as a potential safety biomarker for intestinal toxicity in beagle dogs and Wistar (Han) rats treated with different oncological drug candidates in drug development. Clinical observations and body weight determinations were performed during the pretreatment, treatment and treatment-free recovery period as well as toxicokinetic, gross and histopathology examinations. The quantitative determination of plasma L-citrulline levels during the pretreatment (only dogs), treatment and treatment-free recovery period were performed using an HPLC MS/MS assay. In cynomolgus monkeys, the first investigations on baseline L-citrulline levels were performed. In dogs, a dose- and exposure-dependent decrease of up to 50% in plasma L-citrulline was seen without histopathological alterations. However, a decrease of more than 50% in comparison to the individual animal pretreatment value of L-citrulline correlated very well with histopathological findings (intestinal crypt necrosis, villus atrophy, enterocyte loss) and clinical signs (bloody faeces and diarrhoea). During a treatment-free recovery period, a trend of increasing levels was observed in dogs. In rats, absolute L-citrulline plasma levels of treated animals decreased compared to the values of the concurrent control group. This decrease also correlated with the histopathological findings in the small intestine (single cell necrosis and mucosa atrophy). Because of a large physiological variation in L-citrulline plasma levels in dogs and rats, a clear cut-off value for absolute L-citrulline levels predictive of intestinal mucosal toxicity was difficult to establish. However, a > 50% decrease in L-citrulline plasma levels during the treatment period strongly correlated with histopathological findings. Based on the performed analysis, a longitudinal investigation of L-citrulline plasma levels for individual animals in the control and treatment groups is essential and pretreatment values of L-citrulline levels in rodents would be highly informative. Overall, further cross-species comparison (Cynomolgus monkey, mouse) and implementation in clinical trials as exploratory biomarker is essential to foster the hypothesis and to understand completely the clinical relevance of L-citrulline as a small intestine biomarker.


Bloodless medicine: current strategies and emerging treatment paradigms.
Advances in our understanding of the risks associated with allogeneic blood transfusions (ABTs) and the growing number of patients who wish to avoid ABTs have led to the emergence of new treatment paradigms for "bloodless" medicine and surgery. Here, we review prior studies and summarize current strategies for bloodless care used at our institution. We advocate three basic principles: 1) diagnosing and aggressively treating anemia, 2) minimizing blood loss from laboratory testing and invasive procedures, and 3) identifying and managing bleeding diatheses. Anemia is treated with erythropoiesis-stimulating agents as well as iron, folate, and B12 when indicated. Low-volume phlebotomy tubes are used for laboratory testing. Autologous blood salvage is used for childbirth and surgical patients who have the potential for substantial bleeding. Although there have been few retrospective studies and no prospective studies to guide management, prior studies suggest that outcomes for surgical patients managed without ABTs are comparable to those of historic controls. Given the emerging evidence that patients who avoid ABTs do as well if not better than patients who accept ABTs, further efforts are needed to determine whether all patients could benefit from bloodless strategies. Bloodless approaches in selected patients could reduce risks, improve outcomes, and decrease costs for all patients.


Smoking cessation as a therapeutic and preventive intervention: a meeting report.
In November 2000, a meeting took place on "Smoking cessation as a therapeutic and preventive intervention". The venue of the meeting was Venice, in the old Monastery of the Isola San Giorgio, and it was jointly organised by the Italian Association of Hospital Pulmonologists (AIPO) and the European Section of the Society for Research on Nicotine and Tobacco (SRNT--Europe). The meeting was also sponsored by the European Respiratory Society (ERS). The importance of the topic cannot be underestimated. According to the World Health Organisation (WHO) tobacco smoking is the most important cause of preventable death in the industrialised world. When tobacco smoking constitutes a repetitive and compulsive behaviour, for instance when a person continues smoking when suffering from a smoking related disease, it is due to tobacco dependence, which both WHO and the American Psychiatric Association classify as a disease. Tobacco smoking is not only a disease in itself but can also cause other diseases, such as chronic obstructive lung disease, lung cancer and cardiovascular disease, and can worsen pre-existent disease, e.g. asthma. In the WHO European region, according to WHO estimates, tobacco smoking causes at least 1,200,000 deaths each year (14% of all deaths). So far, a preventive strategy based on protection of children and adolescents from initiation has not worked in decreasing the prevalence among young generations. Even with the best educational programs success is partial and ephemeral. Smoking cessation with behavioural and pharmacological aid is a well established therapeutic intervention, supported by strong scientific evidence. But smoking cessation can also be a preventive intervention, because it can reduce the prevalence of smokers in a community. Obviously, smoking cessation is to be used together with all other interventions recognized as effective in tobacco control (cigarette and tobacco product pricing, regulatory approaches, smoking bans, health education).


[Comparative study on the mutagenic activity of rat liver and bladder S9 by fluctuation test].
Mutagenicity of seven aromatic amines, two heterocyclic amines, two azo compounds and one polycyclic aromatic hydrocarbon was examined with a fluctuation test modified by Gatehouse. The test was performed by using Salmonella typhimurium TA98 in the presence of liver and bladder S9 from PCB pretreated rats. Seven out of 12 compounds showed mutagenic activities with liver S9 and seven with bladder S9. Benzidine, 3-methylcholanthrene and 2-acetylaminofluorene showed a negative response with bladder S9 but a positive response with liver S9. The mutagenicity of the seven compounds observed with bladder S9 had a lower sensitivity than with liver S9. 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole and 3-amino-1-methyl-5H-pyrido[4,3-b]indole showed mutagenic activity at lower concentrations than the other compounds which showed mutagenic activity either with bladder S9 or liver S9. Mutagenicity of 3-methylcholanthrene was observed at high concentration only in the presence of liver S9. The findings from the present study suggested that aromatic amines, heterocyclic amines and polycyclic aromatic hydrocarbons were more likely to be activated to strong mutagens with liver S9 than with bladder S9.


Connexin-Dependent Neuroglial Networking as a New Therapeutic Target.
Astrocytes and neurons dynamically interact during physiological processes, and it is now widely accepted that they are both organized in plastic and tightly regulated networks. Astrocytes are connected through connexin-based gap junction channels, with brain region specificities, and those networks modulate neuronal activities, such as those involved in sleep-wake cycle, cognitive, or sensory functions. Additionally, astrocyte domains have been involved in neurogenesis and neuronal differentiation during development; they participate in the "tripartite synapse" with both pre-synaptic and post-synaptic neurons by tuning down or up neuronal activities through the control of neuronal synaptic strength. Connexin-based hemichannels are also involved in those regulations of neuronal activities, however, this feature will not be considered in the present review. Furthermore, neuronal processes, transmitting electrical signals to chemical synapses, stringently control astroglial connexin expression, and channel functions. Long-range energy trafficking toward neurons through connexin-coupled astrocytes and plasticity of those networks are hence largely dependent on neuronal activity. Such reciprocal interactions between neurons and astrocyte networks involve neurotransmitters, cytokines, endogenous lipids, and peptides released by neurons but also other brain cell types, including microglial and endothelial cells. Over the past 10 years, knowledge about neuroglial interactions has widened and now includes effects of CNS-targeting drugs such as antidepressants, antipsychotics, psychostimulants, or sedatives drugs as potential modulators of connexin function and thus astrocyte networking activity. In physiological situations, neuroglial networking is consequently resulting from a two-way interaction between astrocyte gap junction-mediated networks and those made by neurons. As both cell types are modulated by CNS drugs we postulate that neuroglial networking may emerge as new therapeutic targets in neurological and psychiatric disorders.


Transcatheter arterial embolization combined with radiofrequency ablation activates CD8(+) T-cell infiltration surrounding residual tumors in the rabbit VX2 liver tumors.
To evaluate the effect of transcatheter arterial embolization (TAE) combined with radiofrequency ablation (RFA) treatment (TAE + RFA) on the expression of heat shock protein 70 (HSP70) in residual tumors and explore the relationship between the HSP70 and CD8(+) T-cell infiltrate surrounding residual tumors in the rabbit VX2 liver tumor model. Animals with VX2 liver tumors were randomized into four groups (control, TAE, RFA, and TAE + RFA) with 15 rabbits in each group. Five rabbits in each group were sacrificed on days 1, 3, and 7 after treatment. HSP70 expression and infiltration of CD8(+) T-cells in the liver and residual tumors surrounding the necrosis zone were detected by immunohistochemistry staining. The maximal diameters of tumor necrosis, numbers of metastases, and tumor growth rate were compared on day 7 after treatment. TAE + RFA achieved larger maximal diameter of tumor necrosis, lower tumor growth rate, and fewer metastatic lesions, compared with other treatments on day 7. The number of CD8(+) T-cells in the TAE + RFA group was significantly higher than in other groups on days 1, 3, and 7. There was a positive correlation between HSP70 expression level and infiltration of CD8(+) T-cells surrounding the residual tumor on day 1 (r=0.9782, P=0.012), day 3 (r=0.93, P=0.021), and day 7 (r=0.8934, P=0.034). In the rabbit VX2 liver tumor model, TAE + RFA activated the highest number of CD8(+) T-cells surrounding residual tumors. TAE + RFA appears to be a beneficial therapeutic modality for tumor control and antitumor immune response in this model.


Graph-Theory-Based Degree Centrality Combined with Machine Learning Algorithms Can Predict Response to Treatment with Antipsychotic Medications in Patients with First-Episode Schizophrenia.
Schizophrenia (SCZ) is associated with disrupted functional brain connectivity, and antipsychotic medications are the primary and most commonly used treatment for schizophrenia. However, not all patients respond to antipsychotic medications. The study is aimed at investigating whether the graph-theory-based degree centrality (DC), derived from resting-state functional MRI (rs-fMRI), can predict the treatment outcomes. rs-fMRI data from 38 SCZ patients were collected and compared with findings from 38 age- and gender-matched healthy controls (HCs). The patients were treated with antipsychotic medications for 16 weeks before undergoing a second rs-fMRI scan. DC data were processed using DPABI and SPM12 software. SCZ patients at baseline showed increased DC in the frontal and temporal gyrus, anterior cingulate cortex, and precuneus and reduced DC in bilateral subcortical gray matter structures. However, those abnormalities showed a clear renormalization after antipsychotic medication treatments. Support vector machine analysis using leave-one-out cross-validation achieved a correct classification rate of 84.2% (sensitivity 78.9%, specificity 89.5%, and area under the receiver operating characteristic curve (AUC) 0.925) for differentiating effective subjects from ineffective subjects. Brain areas that contributed most to the classification model were mainly located within the bilateral putamen, left inferior frontal gyrus, left middle occipital cortex, bilateral middle frontal gyrus, left cerebellum, left medial frontal gyrus, left inferior temporal gyrus, and left angular. Furthermore, the DC change within the bilateral putamen is negatively correlated with the symptom improvements after treatment. Our study confirmed that graph-theory-based measures, combined with machine-learning algorithms, can provide crucial insights into pathophysiological mechanisms and the effectiveness of antipsychotic medications.


Metal-organic frameworks with exceptionally high methane uptake: where and how is methane stored?
Metal-organic frameworks (MOFs) are a novel family of physisorptive materials that have exhibited great promise for methane storage. So far, a detailed understanding of their methane adsorption mechanism is still scarce. Herein, we report a comprehensive mechanistic study of methane storage in three milestone MOF compounds (HKUST-1, PCN-11, and PCN-14) the CH(4) storage capacities of which are among the highest reported so far among all porous materials. The three MOFs consist of the same dicopper paddlewheel secondary building units, but contain different organic linkers, leading to cagelike pores with various sizes and geometries. From neutron powder diffraction experiments and accurate data analysis, assisted by grand canonical Monte Carlo (GCMC) simulations and DFT calculations, we unambiguously revealed the exact locations of the stored methane molecules in these MOF materials. We found that methane uptake takes place primarily at two types of strong adsorption site: 1) the open Cu coordination sites, which exhibit enhanced Coulomb attraction toward methane, and 2) the van der Waals potential pocket sites, in which the total dispersive interactions are enhanced due to the molecule being in contact with multiple "surfaces". Interestingly, the enhanced van der Waals sites are present exclusively in small cages and at the windows to these cages, whereas large cages with relatively flat pore surfaces bind very little methane. Our results suggest that further, rational development of new MOF compounds for methane storage applications should focus on enriching open metal sites, increasing the volume percentage of accessible small cages and channels, and minimizing the fraction of large pores.


Epidemiology of osteoporosis and osteoporotic fractures in South Korea.
Several epidemiologic studies suggested that osteoporosis and osteoporotic fractures are not uncommon in South Korea. However, these previous cohort studies had limitations that may have influenced their results and the generalizability of the study conclusions, including small sample sizes, inclusion of only women, enrollment of participants from specific areas, and nonrandom selection of participants. Recently, epidemiologic studies using a nationwide claim register have been performed to overcome these limitations through collaboration between the Korean Society of Bone and Mineral Research and Health Insurance Review Assessments. Our review of the Korean Nationwide-database Osteoporosis Study could be helpful to obtain accurate incidence and prevalence estimations of osteoporosis and osteoporosis-related fractures in Korea.


Clinical and hemodynamic effects of dobutamine in acute myocardial infarction with left heart failure.
We studied the clinical and hemodynamic effects of dobutamine infused for 24 hr into 10 patients with acute myocardial infarction (less than 4 days) complicated by left heart failure (pulmonary wedge pressure greater than 15 mm Hg, cardiac index less than 3.0 liters/min/m2). We measured pulmonary arterial pressures, pulmonary wedge pressure, right atrial pressure, and intravascular systemic blood pressures. The thermodilution method was used for determinations of cardiac output, and the electrocardiogram was followed with a computerized arrhythmia monitoring system. After 1 and 3 hr of infusion with the optimal dose (averaging 8 micron/kg/min), there was a very significant increase of cardiac index (29%) and a decrease of pulmonary wedge pressure (37%) with a moderate increase of heart rate (20%) an without significant changes in blood pressure. After 24 hr of dobutamine infusion, much of the improvement in left ventricular function was lost. This may be attributed either to a decrease of drug action or to an unfavorable evolution of the clinical status. We conclude that infusion of dobutamine is an effective, potent, and well-tolerated short-term procedure in the management of left heart failure during the acute stage of myocardial infarction.


Preliminary validation of the Perceived Locus of Causality scale for academic motivation in the context of university studies (PLOC-U).
Research has shown that self-determination theory can be useful in the study of motivation in sport and other forms of physical activity. The Perceived Locus of Causality (PLOC) scale was originally designed to study both. The current research presents and validates the new PLOC-U scale to measure academic motivation in the university context. We tested levels of self-determination before and after academic examinations. Also, we analysed degree of internalization of extrinsic motivation in students' practical activities. Two hundred and eighty-seven Spanish university students participated in the study. Data were collected at two time points to check the reliability and stability of PLOC-U by a test-retest procedure. Confirmatory factor analysis was performed on the PLOC-U. Also convergent validity was tested against the Academic Motivation Scale (EME-E). Confirmatory factor analysis showed optimum fit and good reliability of PLOC-U. It also presented excellent convergent validity with the EME-E and good stability over time. Our findings did not show any significant correlation between self-determination and expected results before academic examinations, but it did so afterwards, revealing greater regulation by and integration of extrinsic motivation. The high score obtained for extrinsic motivation points to a greater regulation associated with an external contingency (rewards in the practical coursework). PLOC-U is a good instrument for the measurement of academic motivation and provides a new tool to analyse self-determination among university students.


Accurate calculation of the dissociation energy of the highly anharmonic system ClHCl(-).
Accurate bond dissociation energies (D0) are reported for different isotopologues of the highly anharmonic system ClHCl(-). The mass-independent equilibrium dissociation energy De was obtained by a composite method with frozen-core (fc) CCSD(T) as the basic contribution. Basis sets as large as aug-cc-pV8(+d)Z were employed, and extrapolation to the complete basis set (CBS) limit was carried out. Explicitly correlated calculations with the CCSD(T)-F12b method were also performed to support the conventionally calculated values. Core-core and core-valence correlation, scalar relativity, and higher-order correlation were considered as well. Two mass-dependent contributions, namely, the diagonal Born-Oppenheimer correction and the difference in zero-point energies between the complex and the HCl fragment, were then added in order to arrive at precise D0 values. Results for (35)ClH(35)Cl(-) and (35)ClD(35)Cl(-) are 23.81 and 23.63 kcal/mol, respectively, with estimated uncertainties of 0.05 kcal/mol. In contrast to FHF(-) ( Stein , C. ; Oswald , R. ; Sebald , P. ; Botschwina , P. ; Stoll , H. , Peterson , K. A. Mol. Phys. 2013 , 111 , 2647 - 2652 ), the D0 values of the bichloride species are larger than their De counterparts, which is an unusual situation in hydrogen-bonded systems.


Dysregulation of Alzheimer's disease-related genes and proteins following cardiac arrest.
Cardiac arrest, usually occurring in the aged population, is the most important cause of high morbidity and death in developed countries. Commonly, attention, depression, cognitive impairment, spatial memory, short- and long-term memory, executive functions, decreased quality of life and social participation are disturbed following circulation arrest. Deficits in cognitive function, similar to prodromal Alzheimer's disease dementia, following cardiac arrest remain an area of concern. Recent research has focused on the post-resuscitation period to identify mechanisms of long-term brain damage and cognitive impairment. As more patients survive longer periods after cardiac arrest, attention is focused on interventions that may enhance cognitive and psychosocial perceptions. Here, we review the new data influencing the cognitive and functional outcome in the post-resuscitation period..


Triatomines involved in domestic and wild Trypanosoma cruzi transmission in Concepción, Corrientes, Argentina.
An entomological and serological survey was performed in three localities of the Department of Concepción, Province of Corrientes, Argentina in 1998 and 1999, to identify triatomines species involved in domestic and wild transmission of Chagas disease. Triatomines were collected by man/hour capture in 32 houses randomly selected and 44 nearby outdoor ecotopes. Trypanosoma cruzi infection in triatomines was assessed by direct microscopic observation (400x) of feces and polymerase chain reaction. Serological techniques used for people were Indirect Hemagglutination Test and Indirect Fluorescent Test. Triatomines were collected in 28.1% of the houses and 31.8% of the wild biotopes. Triatoma infestans (Klug 1834) was exclusively found indoors and T. cruzi infected 60% of them. Triatoma sordida (Stål 1859) was mainly found in extradomestic ecotopes where trypanosome infection rate reached 12.7%. Serological study of 98 local people showed that 29.6% were seroreactive; most of their houses were closed to wild biotopes colonized by T. sordida. Results indicate that there is an active T. infestans mediated transmission of Chagas disease in this zone that yields important human prevalence and that the populations of T. sordida in wild biotopes not only sustain the wild T. cruzi cycle but also represent an actual risk for people living in the area.


Is caching the key to exclusion in corvids? The case of carrion crows (Corvus corone corone).
Recently, two corvid species, food-caching ravens and non-caching jackdaws, have been tested in an exclusion performance (EP) task. While the ravens chose by exclusion, the jackdaws did not. Thus, foraging behaviour may affect EP abilities. To investigate this possibility, another food-caching corvid species, the carrion crow (Corvus corone corone), was tested in the same exclusion task. We hid food under one of two cups and subsequently lifted either both cups, or the baited or the un-baited cup. The crows were significantly above chance when both cups were lifted or when only the baited cup was lifted. When the empty cup was lifted, we found considerable inter-individual variation, with some birds having a significant preference for the un-baited but manipulated cup. In a follow-up task, we always provided the birds with the full information about the food location, but manipulated in which order they saw the hiding or the removal of food. Interestingly, they strongly preferred the cup which was manipulated last, even if it did not contain any food. Therefore, we repeated the first experiment but controlled for the movement of the cups. In this case, more crows found the food reliably in the un-baited condition. We conclude that carrion crows are able to choose by exclusion, but local enhancement has a strong influence on their performance and may overshadow potential inferential abilities. However, these findings support the hypothesis that caching might be a key to exclusion in corvids.


The role of supplementary environmental surveillance to complement acute flaccid paralysis surveillance for wild poliovirus in Pakistan - 2011-2013.
More than 99% of poliovirus infections are non-paralytic and therefore, not detected by acute flaccid paralysis (AFP) surveillance. Environmental surveillance (ES) can detect circulating polioviruses from sewage without relying on clinical presentation. With extensive ES and continued circulation of polioviruses, Pakistan presents a unique opportunity to quantify the impact of ES as a supplement to AFP surveillance on overall completeness and timeliness of poliovirus detection. Genetic, geographic and temporal data were obtained for all wild poliovirus (WPV) isolates detected in Pakistan from January 2011 through December 2013. We used viral genetics to assess gaps in AFP surveillance and ES as measured by detection of 'orphan viruses' (≥1.5% different in VP1 capsid nucleotide sequence). We compared preceding detection of closely related circulating isolates (≥99% identity) detected by AFP surveillance or ES to determine which surveillance system first detected circulation before the presentation of each polio case. A total of 1,127 WPV isolates were detected by AFP surveillance and ES in Pakistan from 2011-2013. AFP surveillance and ES combined exhibited fewer gaps (i.e., % orphan viruses) in detection than AFP surveillance alone (3.3% vs. 7.7%, respectively). ES detected circulation before AFP surveillance in nearly 60% of polio cases (200 of 346). For polio cases reported from provinces conducting ES, ES detected circulation nearly four months sooner on average (117.6 days) than did AFP surveillance. Our findings suggest ES in Pakistan is providing earlier, more sensitive detection of wild polioviruses than AFP surveillance alone. Overall, targeted ES through strategic selection of sites has important implications in the eradication endgame strategy.


Uncovering the Fundamentals of Polarity within the EEG: A Closer Look.
A thorough understanding of the governing concepts of polarity behavior within electroencephalograph (EEG) promotes analytical and thus technical proficiency of the technologist by providing a skill set to logically resolve the myriad of waveform presentations that are expected across all montage derivations. In addition to avoiding a reliance on cursory conceptualization techniques, a solid grasp of the underlying theory of EEG polarity permits a fundamental realization of the cause-effect relationships between the various directions of eye movement and the resulting multitude of wave deflection presentations observed across all montages. Such wisdom can logically account for the futility of using a particular bipolar montage to localize discharges of interest that are located at end-of-chain. Further, it provides a logical template from which to make sense of physiological and nonphysiological contamination within referential electrodes. Regardless of montage formatting, an EEG epoch can be deconstructed into discrete components; all of the left-sided electrodes within each pair of leads, or channel, are classified as input 1, whereas the right-sided ones are termed input 2. The Polarity Rule states that if input 1 is more negative with respect to input 2, there will be an upward deflection of the associated wave. All wave deflections within any montage arrangement can be explained from this core rule. For those expected to take examinations that include EEG polarity questions, this deeper appreciation may assist by shifting away from the need to memorize a plethora of scenario-dependent wave behaviors.


Vertical field enhancement of a spot-size converter using a nanopixel waveguide and window structure.
Spot-size converter (SSC) is an essential building block for integrated photonic circuits applied as a mode transformer between optical components. One typical issue for SSC is the difficulty of broadening the vertical field profile. Herein, we propose a nanopixel SSC (1 × 2 μm2) with changing hole size and density. Unlike a typical SSC, this configuration controls both the lateral and vertical field profiles relatively easily by enhancing the nanopixel density. A vertical field expansion of 1.21 μm was obtained by enhancing the nanopixel density. In addition, we designed the optical field in the lateral direction using deep neural network (DNN)-based learning to realize a perfect circular spot for high coupling efficiency that reached -3 dB at λ0 = 1.572 μm when the optical field aspect ratio was adjusted to 1 after training for 200 epochs. Furthermore, the vertical expansion was increased from 1.21 to 4.9 μm and the coupling efficiency from -3 to -0.41 dB by combining it a silicon dioxide window structure (5 × 15 × 10 μm3). The 1-dB operating bandwidth of the designed SSC structure is 100 nm (1.5-1.6 μm), while fabrication tolerance of the nanopixels and window structure length for the designed SSC structure are ±15 nm and ±250 nm when the coupling efficiency drops by 1 dB.


Spatial attention triggered by eye gaze enhances and speeds up visual processing in upper and lower visual fields beyond early striate visual processing.
The detection of a lateralized visual target is faster when preceded by a face gazing to the location of this stimulus. Here we aimed to clarify the time-course of the visual processing modulated by these reflexive shifts of attention. ERPs were measured on 16 subjects performing a speeded location task on a circular checkerboard. The checkerboard target appeared either on the left or right of the upper or lower visual field, and was preceded by a central face orienting its gaze obliquely to one of the four possible corner locations for the target to appear. Congruently cued targets were located faster than incongruently cued targets and were associated with larger and earlier occipital P1 (approximately 110 ms) and occipito-parieto-temporal N1 (approximately 150 ms) components. However, no such attentional modulations were found on the earlier C1 visual component, best observed with a negative polarity for upper visual field stimulations, and thought to originate largely from primary visual cortex. These results show that reflexive shifts of attention following oblique eye gaze to upper and lower visual fields increase and speed up the processing of visual information beyond the feedforward flow of information in primary visual cortex.


The proangiogenic effect of iroquois homeobox transcription factor Irx3 in human microvascular endothelial cells.
Angiogenesis is a dynamic process required for embryonic development. However, postnatal vascular growth is characteristic of multiple disease states. Despite insights into the multistep process in which adhesion molecules, extracellular matrix proteins, growth factors, and their receptors work in concert to form new vessels from the preexisting vasculature, there remains a lack of insight of the nuclear transcriptional mechanisms that occur within endothelial cells (ECs) in response to VEGF. Iroquois homeobox gene 3 (Irx3) is a transcription factor of the Iroquois family of homeobox genes. Irx homeodomain transcription factors are involved in the patterning and development of several tissues. Irx3 is known for its role during embryogenesis in multiple organisms. However, the expression and function of Irx3 in human postnatal vasculature remains to be investigated. Here we show that Irx3 is expressed in human microvascular endothelial cells, and expression is elevated by VEGF stimulation. Genetic Irx3 gain and loss of function studies in human microvascular endothelial cells resulted in the modulation of EC migration during wound healing, chemotaxis and invasion, and tubulogenesis. Additionally, we observed increased delta-like ligand 4 (Dll4) expression, which suggests an increase in EC tip cell population. Finally, siRNA screening studies revealed that transient knockdown of Hey1, a downstream Notch signaling mediator, resulted in increased Irx3 expression in response to VEGF treatment. Strategies to pharmacologically regulate Irx3 function in adult endothelial cells may provide new therapies for angiogenesis.


Improvements in Genomic Technologies: Application to Crop Genomics.
Second-generation sequencing (SGS) has advanced the study of crop genomes and has provided insights into diversity and evolution. However, repetitive DNA sequences in crops often lead to incomplete or erroneous assemblies because SGS reads are too short to fully resolve these repeats. To overcome some of these challenges, long-read sequencing and optical mapping have been developed to produce high-quality assemblies for complex genomes. Previously, high error rates, low throughput, and high costs have limited the adoption of long-read sequencing and optical mapping. However, with recent improvements and the development of novel algorithms, the application of these technologies is increasing. We review the development of long-read sequencing and optical mapping, and assess their application in crop genomics for breeding improved crops.


[The situation of American nurses].
The following article aims at giving some informations on the evolution of the role of the nurses int the managed care context. Their responsibilities have changed a lot. The article also bring certain characteristics on the change in the jobs of nurses. There are also different sorts of nurses. Their responsabilities have been revamped. There were also numerous measures of economies among those were cost reductions and organisational innovations.


Secular growth changes in the stature and weight of Amerindian schoolchildren and adults in the Chilean Andes, 1972-1987.
A positive secular trend for stature and weight is evident in rural Aymara-speaking Indians of the Parinacota Province (>3,000 m) in the northern Chilean Andes. The study is based on two cross-sectional growth surveys carried out in 1972 and 1987. In the survey of 1972, which was undertaken by other authors, a sample of 190 individuals was considered. The 1987 survey, performed by the present author, comprises a sample of 170 Indians. Both children and adults of each sex, ages 6-29 years, are included. Secular comparisons of age-grouped means indicate a secular increase in stature and weight in Aymara children, adolescents, and adults in the Parinacota Province between 1972 and 1987. The Aymara tend to be taller and heavier in 1987. The estimated secular increase for stature is 2.1 cm/decade for males and 1.8 cm/decade for females. For weight, the increase is 2.3 kg/decade for males and 1.5 kg/decade for females. In all cases, growth gains tend to be greater in males than in females. The body mass index also increases slightly. The secular changes in stature and weight are statistically significant in both sexes. From additional nutritional data on the Aymara samples compared, it is concluded that the observed secular increases might primarily reflect improved food supply over the past two decades. Am. J. Hum. Biol. 10:607-617, 1998. © 1998 Wiley-Liss, Inc.


A New Repair Technique in Pronator Quadratus in Management of Distal Radius Fracture: Comparison with Primary Repair and Unrepaired Techniques.
Objective We aimed to compare the functional and clinical results between our new repair technique in the groups with and without pronator quadratus (PQ) repair in distal radius fractures treated with plate fixation using the volar approach. Methods The medical records of patients who underwent open reduction and volar plate fixation due to distal radius fracture between 2018 and 2020 were studied. In group A, PQ cannot be sutured or tension may occur, the intact radial fascia of the deep anterior fascia (DAF) was placed under the flexors toward the PQ and it was sutured with a 3-0 slow-absorbable monofilament suture to DAF. In group B, no repair was performed. In group C, PQ was sutured with traditional method. Range of motion (ROM) of wrist and handgrip strengths were measured at final examination. Pain was assessed with Visual Analogue Score (VAS), and functional status was evaluated with Quick - Disabilities of the Arm, Shoulder, and Hand (DASH). Complications which included tendinopathy, neuritis, tendon rupture due to plate irritation, implant failure, and malunion were also compared. Results Seventy-seven patients (group A, 21, group B, 24, group C, 32 patients) were included in the final follow-up examination who met our inclusion criteria. Among the clinical, functional, and radiological results such as ROM, VAS, DASH, grip strength, and complications in the all group at a mean postoperative of 16.6 months no significant difference was observed. Conclusion Although there was no significant difference between the groups in this study, we think that covering the plate may prevent long-term complications.


Discovery and Validation of Nitroxoline as a Novel STAT3 Inhibitor in Drug-resistant Urothelial Bladder Cancer.
Repeated cycles of first-line chemotherapy drugs such as doxorubicin (DOX) and cisplatin (CIS) trigger frequent chemoresistance in recurrent urothelial bladder cancer (UBC). Nitroxoline (NTX), an antibiotic to treat urinary tract infections, has been recently repurposed for cancer treatment. Here we aimed to investigate whether NTX suppresses drug-resistant UBC and its molecular mechanism. The drug-resistant cell lines T24/DOX and T24/CIS were established by continual exposure of parental cell line T24 to DOX and CIS, respectively. T24/DOX and T24/CIS cells were resistant to DOX and CIS, respectively, but they were sensitive to NTX time- and dose-dependently. Overexpressions of STAT3 and P-glycoprotein (P-gp) were identified in T24/DOX and T24/CIS, which could be reversed by NTX. Western blot revealed that NTX downregulated p-STAT3, c-Myc, Cyclin D1, CDK4, CDK6, Bcl-xL, Mcl-1, and Survivin, which were further confirmed by Stattic, a selective STAT3 inhibitor. In vivo, NTX exhibited the significant anti-tumor effect in T24/DOX and T24/CIS tumor-bearing mice. These results suggested that NTX-induced P-gp reversal, G0/G1 arrest, and apoptosis in drug-resistant UBC were mediated by inhibition of STAT3 signaling. Our findings repurpose NTX as a novel STAT3 inhibitor to induce P-gp reversal, G0/G1 arrest, and apoptosis in drug-resistant UBC.


Drug-resistant tuberculosis in human immunodeficiency virus infected persons in Italy. The Italian Drug-Resistant Tuberculosis Study Group.
To describe the prevalence and epidemiological-clinical characteristics of tuberculosis (TB) resistance to first-line drugs in Italian human immunodeficiency virus (HIV)-infected subjects. Prospective, observational multicenter (25 Centers of Infectious Diseases) study. Mycobacterium tuberculosis strains from 167 HIV co-infected subjects with TB (149 new cases, 18 relapses) were tested at a central laboratory for susceptibility to rifampin (R), isoniazid (H), pyrazinamide (Z), ethambutol (E) and streptomycin (S) and for DNA fingerprint type. Drug susceptibility results were related to patients' epidemiological, clinical and laboratory features. Drug resistance patterns among new TB cases were as follows: R = 1%, Z = 6%, S = 8%, H + S = 3%, S + Z = 4%. TB resistant to at least R + H (MDR-TB) was detected in 36% of new cases due to an MDR-TB outbreak which was the largest thus far in Europe, involving 7/25 participating institutions, and was demonstrated by conventional and molecular epidemiology evidence. With multivariate analysis, MDR-TB was associated with hospital exposure to MDR-TB (OR = 39.3, P < 0.001) and previous use of anti-TB drugs (OR = 9.8, P = 0.008). As drug-resistant tuberculosis in Italy is thus far relatively scarce, detection of a large MDR-TB epidemic among HIV-infected subjects was alarming. Aggressive control measures are urgently needed to prevent the spread of MDR-TB throughout the country and among the general population.


Altered circadian rhythms of natural killer (NK) cell activity in patients with autoimmune rheumatic diseases.
Natural Killer (NK) cells are a lymphocyte subset actively involved in cytotoxicity against tumor-transformed and virus-infected cells; they are a reliable model for the study of neuroendocrine-immune interactions. In previous works we demonstrated that in healthy subjects NK activity of peripheral blood mononuclear cells (PBMC) and susceptibility to endogenous modifiers display statistically validated circadian rhythms. In rheumatoid arthritis (RA) and in other autoimmune rheumatic diseases abnormalities of the circadian rhythm of serum cortisol and altered levels of NK cell activity have been reported. We evaluated the circadian pattern of NK cell activity in 7 hospitalized patients with autoimmune rheumatic diseases (4 RA, 1 scleroderma, 2 mixed connective tissue disease). Temporal variations of in vitro responses to either positive recombinant (immune interferon, r IFN-gamma IFN-gamma: 650 IU/ml; recombinant interleukin-2, r IL-2 IL-2: 100 IU/ml) or negative (cortisol: 10(-6) M) modifiers were also studied. Blood was drawn at 4h intervals for 24 h, starting at 0800. PBMC preparations were immediately separated and incubated for 20h in the presence or absence of modifiers. NK activity was assessed with a direct non-radiometric 4h cytolytic assay, using K 562 cells as targets. Significant circadian variations of spontaneous NK activity were documented only in women with RA, with a peak in the evening hours and a minimum in the night or in the early morning (p < 0.05, PR 51.5%, phi 1829). Population-mean cosinor analysis did not yield detection of significant circadian variations of in vitro responsiveness to modifiers.(ABSTRACT TRUNCATED AT 250 WORDS)


Subacute Oxidative Stress and Glial Reactivity in the Amygdala are Associated with Increased Anxiety Following Blast Neurotrauma.
Behavioral symptoms, such as anxiety, are widely reported after blast overpressure (BOP) exposure. Amygdalar vulnerability to increasing magnitudes of BOP has not been investigated, and single exposures to blast have been limited to acute (<72 h) assessment. Rats were exposed to a single low, moderate, or high BOP (10, 14, or 24 psi) with an advanced blast simulator to test the susceptibility of the amygdala. Anxiety-like behavior was observed in the low- and moderate-pressure groups when subjected to the light/dark box assessment 7 days after the blast but not in high-pressure group. Immunohistochemistry was performed to measure apoptosis (cleaved caspase-3), neuronal loss (NeuN), reactive astrocytes (glial fibrillary acidic protein), microglia (Iba-1), and oxidative stress (CuZn superoxide dismutase). Slower progression of injury cascades was associated with a significant increase in anxiety, apoptosis, and astrogliosis in the low pressure group compared with others. A significant increase of CuZn superoxide dismutase in the low pressure group could be associated with neuroprotection from cell death caused by oxidative stress because neuronal loss was significant in the moderate- and high- but not the low-pressure group. Overall, this study demonstrated that overpressure as low as 10 psi can induce subacute anxiety, in addition to neuropathologic changes in the amygdala.


Evaluation of Antibiotic Resistance and Biofilm Production among Clinical Strain Isolated from Medical Devices.
Microbial biofilms pose a serious threat to patients requiring medical devices (MDs). Prolonged periods of implantation carry a high risk of device-related infections (DRIs). Patients with DRIs often have negative outcomes following the failure of antibiotic treatment. Resistant DRIs are mainly due to the MDs contamination by bacteria producing biofilm. The present study aimed to detect biofilm formation among MD bacterial isolates and to explore their antibiotic resistance profile. The study was conducted on 76 MDs, collected at University Hospital of Campania "Luigi Vanvitelli," between October 2019 and September 2020. Identification of isolates and antibiotic susceptibility testing were performed using Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) and Phoenix Becton Dickinson, respectively. Biofilm-forming abilities were assessed using the tissue culture plate (TCP) method. Among the 94 MDs isolated strains, 42.7% were Gram-positive, 40.3% Gram-negative, and 17% Candida species. Among 78 bacterial strains, 43.6% were non-biofilm producers while 56.4% produced biofilms. All biofilm producing isolates were sensitive to a limited spectrum of antibiotic classes. All moderate and strong biofilm producers and 81% of weak biofilm producers were Multidrug Resistance (MDR) strains. In contrast, among non-biofilm producers, only 11.8% were classified as MDR strains. Our results highlighted that Sulfamides and Glycopeptides for the major Gram-positive strains and Fluoroquinolones, Carbapenems, and Aminoglycosides for the most represented Gram-negative isolates could be the most suitable therapeutic choice for most biofilm-DRIs.


Repetitive elements regulate circular RNA biogenesis.
It was long assumed that eukaryotic precursor mRNAs (pre-mRNAs) are almost always spliced to generate a linear mRNA that is subsequently translated to produce a protein. However, it is now clear that thousands of protein-coding genes can be non-canonically spliced to produce circular noncoding RNAs, some of which are expressed at much higher levels than their associated linear mRNAs. How then does the splicing machinery decide whether to generate a linear mRNA or a circular RNA? Recent work has revealed that intronic repetitive elements, including sequences derived from transposons, are critical regulators of this decision. In most cases, circular RNA biogenesis appears to be initiated when complementary sequences from 2 different introns base pair to one another. This brings the splice sites from the intervening exon(s) into close proximity and facilitates the backsplicing event that generates the circular RNA. As many pre-mRNAs contain multiple intronic repeats, distinct circular transcripts can be produced depending on which repeats base pair to one another. Intronic repeats are thus critical regulatory sequences that control the functional output of their host genes, and potentially cause the functions of protein-coding genes to be highly divergent across species.


Homo- and Heteroligand Poly-NHC Metal Assemblies: Synthesis by Narcissistic and Social Self-Sorting.
Homoleptic and heteroleptic cylinder-shaped poly-NHC metallosupramolecular assemblies [Ag3 (L)2 ](BF4 )3 have been prepared by control of the shape, size, and electronic properties of disk-shaped trisimidazolium salts of type H3 -L(BF4 )3 . Both imidazolium salts with an electron-deficient triazine backbone H3 -A(BF4 )3 or an electron-rich benzene backbone H3 -D(BF4 )3 have been employed. Reaction of H3 -A(BF4 )3 or H3 -D(BF4 )3 with Ag2 O yield trinuclear homoligand complexes [Ag3 (L)2 ](BF4 )3 (L=A, D). However, equimolar mixtures of H3 -A(BF4 )3 and H3 -D(BF4 )3 react with Ag2 O under social self-sorting to give the heteroligand assembly [Ag3 (A)(D)](BF4 )3 . The same heteroligand assembly was obtained by transmetallation from mixtures of complexes [Ag3 (A)2 ](BF4 )3 and [Ag3 (D)2 ](BF4 )3 . The transmetallation from [Ag3 (A)(D)](BF4 )3 to [Au3 (A)(D)](BF4 )3 is also demonstrated. The study expands to concepts of narcissistic and social self-sorting from classical Werner-type ligands to organometallic NHC chemistry thereby opening new routes for the construction of poly-NHC metal assemblies with increasing complexity.


Laparoscopic treatment of ovarian remnant syndrome in dogs and cats: 7 cases (2010-2013).
To describe the technique and evaluate the outcome of laparoscopic treatment of ovarian remnant syndrome (ORS) in dogs and cats. Retrospective case series. 7 client-owned dogs and cats. Medical records of dogs and cats with ORS that were treated laparoscopically at 3 large veterinary teaching hospitals were reviewed. Laparoscopic ovarian remnant resection was performed by means of either a 3-port or single-port technique with the patient in dorsal recumbency. The area caudal to both kidneys was thoroughly inspected for evidence of ovarian tissue by tilting the patient laterally. Any ovarian remnant tissue in these areas was resected with a bipolar vessel sealer. 5 female dogs and 2 female cats that had previously undergone ovariectomy or ovariohysterectomy were included in the study. Six procedures were performed with a standard 3-port technique, and 1 was performed with a single-port technique. Median surgery time was 90 minutes (range, 50 to 150 minutes). No patient required conversion to laparotomy. Six of the 7 patients had complete resolution of clinical signs after surgery. One patient underwent laparotomy 7 weeks after surgery for management of stump pyometra, but no further ovarian tissue was detected. Laparoscopic management of ORS in this cohort of dogs and cats was associated with minimal morbidity. Laparoscopic treatment of ORS in dogs and cats may be recommended for appropriately selected patients.


Mastoparan reduces the supraspinal analgesia mediated by mu/delta-opioid receptors in mice.
Intracerebroventricular (i.c.v.) administration of the venom peptide, mastoparan, to mice decreased to a limited extent opioid-induced supraspinal analgesia in a non-competitive fashion. The mu-opioid receptor agonists, [D-Ala2,N-MePhe4,Gly-ol5]-enkephalin (DAMGO) and morphine, the mu/delta-opioid receptor ligands, human beta-endorphin-(1-31) and [D-Ala2,D-Leu5]-enkephalin (DADLE), and the selective ligands of delta-opioid receptors, [D-Pen2,5]enkephalin (DPDPE) and [D-Ala2]deltorphin II, showed an impaired analgesic effect in mice given mastoparan. Mastoparan diminished the analgesic activity of DPDPE and [D-Ala2]deltorphin II to the same extent as observed after giving the delta-opioid receptor-selective antagonist, ICI 174864. The mu-opioid receptor-mediated analgesia that remained after mastoparan was abolished in the presence of the opioid antagonist, naloxone. Mastoparan after binding to Gi alpha/Go alpha subunits could block opioid antinociception. The existence of a class of G protein functionally coupled to mu-opioid receptors, but resistant to the effect of mastoparan is suggested.


A VECTOR MOMENTA FORMULATION OF DIFFEOMORPHISMS FOR IMPROVED GEODESIC REGRESSION AND ATLAS CONSTRUCTION.
This paper presents a novel approach for diffeomorphic image regression and atlas estimation that results in improved convergence and numerical stability. We use a vector momenta representation of a diffeomorphism's initial conditions instead of the standard scalar momentum that is typically used. The corresponding variational problem results in a closed-form update for template estimation in both the geodesic regression and atlas estimation problems. While we show that the theoretical optimal solution is equivalent to the scalar momenta case, the simplification of the optimization problem leads to more stable and efficient estimation in practice. We demonstrate the effectiveness of our method for atlas estimation and geodesic regression using synthetically generated shapes and 3D MRI brain scans.


Developing weight loss interventions for African-American women: elements of successful models.
This review examines published reports of weight-loss interventions targeted to overweight African-American women and identifies specific factors that may account for the variability in observed outcomes. The review will identify program elements that have been associated with weight loss in obese African-American women, describe behavior modification elements of weight loss programs, and provide a list of "lessons learned" that may be useful in planning future weight-loss intervention programs for this target population.