Using multilayer perceptron and similarity-weighted machine learning algorithms to reconstruct the past: A case study of the agricultural expansion on grasslands in the Uruguayan savannas.
Changes in land use and land cover (LULC) have significant implications for biodiversity, ecosystem functioning, and deforestation. Modeling LULC changes is crucial to understanding anthropogenic impacts on environmental conservation and ecosystem services. Although previous studies have focused on predicting future changes, there is a growing need to determine past scenarios using new assessment tools. This study proposes a methodology for LULC past scenario generation based on transition analysis. Aiming to hindcast LULC scenario in 1970 based on the transition analysis of the past 35 years (from 1985 to 2020), two machine learning algorithms, multilayer perceptron (MLP) and similarity weighted (SimWeight), were employed to determine the driver variables most related to conversions in LULC and to simulate the past. The study focused on the Aristida spp. grasslands in the Uruguayan savannas, where native grasslands have been extensively converted to agricultural areas. Land use and land cover data from the MapBiomas project were integrated with spatial variables such as altimetry, slope, pedology, and linear distances from rivers, roads, urban areas, agriculture, forest, forestry, and native grasslands. The accuracy of the predicted maps was assessed through stratified random sampling of reference images from the Multispectral Scanner (MSS) sensor. The results demonstrate a reduction of approximately 659 934 ha of native grasslands in the study area between 1985 and 2020, directly proportional to the increase in cultivable areas. The MLP algorithm exhibited moderate performance, with notable errors in classifying agriculture and grassland areas. In contrast, the SimWeight algorithm displayed better accuracy, particularly in distinguishing grassland and agriculture classes. The modeled map using SimWeight accurately represented the transitions between grassland and agriculture with a high level of agreement. By modeling the 1970s scenario using the SimWeight model, it was estimated that the Aristida spp. grasslands experienced a substantial reduction in grassland coverage, ranging from 9982.31 to 10 022.32 km2 between 1970 and 2020. This represents a range of 60.8%-61.07% of the total grassland area in 1970. These findings provide valuable insights into the driving factors behind land use change in the Aristida spp. grasslands and offer useful information for land management, conservation, and sustainable development in the region. The study's main contribution lies in the hindcasting of past LULC scenarios, utilizing a tool used primarily for forecasting future scenarios. Integr Environ Assess Manag 2023;00:1-16. © 2023 SETAC.


ANTIMICROBIAL ACTIVITIES OF SOME SAUDI ARABIAN HERBAL PLANTS.
Several edible plants are used in Kingdom of Saudi Arabia since early time to control microbial infections. In the present study, twenty-four Saudi Arabian medicinal plants d according to traditionally used were select and investigated for the antimicrobial activities. This study was designed at evaluating the antimicrobial activities of the methanol extracts of twenty-four species of sixteen plant families used in the traditional medicine by Saudi Arabian people for the treatment of numerous ailments of the microbial and non-microbial origin against four Gram-positive, four Gram-negative bacteria and four fungi and yeast using the agar well diffusion method. Of most of the plants tested were found to be active against two to eight organisms. Five plants were active against eight organisms. The data appeared that extracts of Echium arabicum (SY-176), Rhantarium epapposum (SY-Rumex vesicarus (SY-181), Ziziphus nummularia (SY-188), Caylusea hexagyna (SY-197) and Artemisia monosperma (SY-198) have anti-microbial activity against the most of tested bacteria, fungi and yeast. Whereas (SY-, the extracts of Teucrium oliverianum (SY-175), Zilla spinosa (SY-187), and Rhazya stricta (SY-195) have poor action against the tested bacteria, fungi and yeast. The antimicrobial activity of plant extracts against bacteria was more effective than against fungi.


Prevalence of cervical myelomalacia in adult patients requiring a cervical magnetic resonance imaging.
A retrospective study. To determine the prevalence of cervical myelomalacia in patients requiring cervical magnetic resonance imaging. The presence of myelomalacia in the cervical spinal cord in has prognostic value after decompression surgery. Some surgeons consider operative treatment of all patients with myelomalacia based on the assumption that myelomalacia is a relatively uncommon finding. However, the prevalence of cervical myelomalacia in symptomatic patients has not been fully established. The sentences containing the key word "myelomalacia" were extracted from a large database of cervical magnetic resonance imaging reports and manually reviewed by an experienced neuroradiologist to determine whether the interpreting radiologists thought there was myelomalacia in the cervical spinal cord. The prevalence of myelomalacia was calculated for different age and sex groups, as well as for the medical specialties/subspecialties of the referring providers. A total of 964 of 23,139 patients who underwent magnetic resonance imaging findings consistent with cervical myelomalacia. The overall prevalence of myelomalacia in this population was 4.2%; 5.6% in males and 3.0% in females. The rates increased linearly with age until the eighth decade when it reached 7.6% overall, 9.2% for males and 6.2% for females, but dropped to 5.1% for patients older than 80. There were considerable variations in the prevalence of myelomalacia in patients referred by different specialties/subspecialties. Specialists in spinal cord injury had the highest rate (28.7%), followed by neurological (8.4%) and orthopedic (6.4%) spine surgeons, general neurosurgeons (5.5%), and neurologists (4.2%). Specialists who generally do not treat patients with spine problems had the lowest (1.2%) followed by nonspine orthopedists (1.6%) and primary care doctors (2.1%). The overall prevalence of cervical myelomalacia was relatively low in the studied population, and it was affected by age, sex, and the specialties/subspecialties of referring providers. These results may help direct treatment guidelines and allow for informed discussions with patients in terms of the risk versus the benefit of surgery. 1.


Leveraging the Preoperative Clinic to Engage Older Patients in Shared Decision Making About Complex Surgery: An Illustrative Case.
The decision to pursue surgery is often complicated in older adults. A multidisciplinary, shared approach to decision-making may improve communication between patients and their providers and facilitate complex risk assessment. We describe a case of an older adult presenting for complex surgery in which the preoperative anesthesia clinic visit was used to facilitate involvement of the geriatrics service. This multidisciplinary approach allowed for re-evaluation and reiteration of risks and benefits, in-depth discussion of the patient's values and goals, and recommendations for care teams downstream in the patient's surgical pathway to ensure treatment consistent with patient goals and clinical recommendations.


A study on total intravenous anesthesia in orthognathic surgical procedures.
To assess the use of propofol for induction and maintenance of anaesthesia among patients undergoing various combinations of orthognathic surgical procedures. Following Preoperative evaluation, patients were given Fentanyl (2 micrograms/kg) intravenously. Induction (2 mg/kg) and maintenance (10 mg/kg/hr) of anaesthesia was achieved by Propofol infusion. Blood Pressure and heart rate were maintained at >70 or 80 mm Hg and >50 respectively and were monitored continuously. Infusion was stopped approximately 30 to 40 minutes before the end of surgery. Immediate recovery recorded and was assessed. The average duration of anaesthesia and surgery were found to be 4 hrs 28 min (SD= 1 hr. 35 min) and 4 hrs 3 min (SD=1 hr 38 min). None of the patients experienced pain on injection of induction agent. No significant change was observed in the mean heart rate and mean BP at different time intervals from baseline value to 30 minutes after the recovery. The average time taken to obey simple commands after stopping Propofol infusion was 42.60 ± 9.09 min. Time taken for spontaneous eye opening, full orientation and to count backwards was 43.45 ± 9.11, 47.85 ± 8.18 and 50.9 ± 9.14 respectively. Face-Hand test performed at 15 min after extubation was positive in all the patients. The mean Aldrete score at 15 min after extubation was 11.65 ± 0.75. The mean value of unaided sitting time for at least 2 min was after 119.00 ± 20.56 min. The average score of picture card test, time taken in "picking up matches" test, Ball bearing test, time taken to walk and to void urine were 5.80 ± 1.47, 67.95 ± 5.72, 9.80 ± 2.57, 172.75 ± 39.25 and 163.75 ± 55.96 respectively. Ninety percent of the patients were amenable for a repeat of this anaesthetic using the same regime but 10% of them did not answer anything. Seven patients (35%) had chills post-operatively. Propofol is an excellent anaesthetic for day care procedures.


Measurement of transition dipole moments in lithium dimers using electromagnetically induced transparency.
We have observed electromagnetically induced transparency in a Doppler broadened molecular cascade system using fluorescence detection. We demonstrate that the power-dependent splitting of lines in the upper-level fluorescence excitation spectrum can be used as a new spectroscopic tool for the measurement of molecular transition dipole moment functions.


Effect of aspirin on coronavirus disease 2019: A nationwide case-control study in South Korea.
Several studies reported that aspirin can potentially help prevent infection and serious complications of coronavirus disease (COVID-19), but no study has elucidated a definitive association between aspirin and COVID-19. This study aims to investigate the association between aspirin and COVID-19.This case-control study used demographic, clinical, and health screening laboratory test data collected from the National Health Insurance Service database. Patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until June 4, 2020, were matched with control patients using propensity score matching according to their SARS-CoV-2 status, the composite of complications, and death. The composite of complications included intensive care unit admission, use of vasopressors, high-flow oxygen therapy, renal replacement therapy, extracorporeal membrane oxygenation, and death. Exposure to aspirin was defined as having a prescription for aspirin for more than 14 days, including the index date. After matching, multivariable-adjusted conditional logistic regression analysis was performed. To confirm the robustness of this study, we used 2 study groups, 3 propensity score matching methods, and 3 models for conditional logistic regression analyses.The crude odds ratio and 95% confidence interval for SARS-CoV-2 infection between the groups without and with exposure to aspirin were 1.21 (1.04-1.41), but the adjusted odds ratios (95% confidence interval) were not significant. There was no association between aspirin exposure and COVID-19 status. Multiple statistical analyses, including subgroup analysis, revealed consistent results. Furthermore, the results of analysis for complications and death were not significant. Aspirin exposure was not associated with COVID-19-related complications and mortality in COVID-19 patients.In this nationwide population-based case-control study, aspirin use was not associated with SARS-CoV-2 infection or related complications. With several ongoing randomized controlled trials of aspirin in COVID-19 patients, more studies would be able to confirm the effectiveness of aspirin in COVID-19.


Live cell imaging of cytoskeletal dynamics in neurons using fluorescence photoactivation.
Alzheimer's disease and other neurodegenerative disorders share some common features at the cellular level, which are often associated with a change in cytoskeletal dynamics. Live cell imaging has been applied to study various aspects of cell physiology including cytoskeletal dynamics. Recently, fluorescence photoactivation (FPA) has been developed as a novel approach to analyze protein dynamics in living cells with high sensitivity. Here, we describe the application of FPA to determine interactions and mobility of the microtubule-associated protein tau in neurons as an example for a disease-related cytoskeletal protein and discuss further applications of FPA to study cytoskeletal dynamics in neurodegenerative diseases.


Recent advances in diagnosis and therapy of allergic rhinitis and asthma in childhood.
Some of the most recent advances in the diagnosis and treatment of childhood asthma and allergies are here reviewed. New perspectives have been opened by in vitro diagnostic tests for allergies based on a molecular approach and novel approaches to in vivo tests (SPT or FE(NO)). A better characterization of the patients is opening new classifications of allergic asthma and rhinitis phenotypes, which allow personalizing management disease programs and targeting pharmacotherapy. Educational programs and better communication are improving awareness and compliance with medical prescriptions and adherence to guidelines. Increasing information is being acquired on the mechanisms, efficacy and safety profiles of anti-asthma and anti-allergic drugs, including antihistamines, inhaled corticosteroids, long acting beta agonists, antibiotics, anti-IgE antibodies. Progress in biotechnologies is fostering new approaches to allergen-specific immunotherapy (subcutaneous, sublingual) concerning the quality, mechanisms, efficacy and safety of allergen products.


Mini-review: Microbial coaggregation: ubiquity and implications for biofilm development.
Coaggregation is the specific recognition and adherence of genetically distinct microorganisms. Because most biofilms are polymicrobial communities, there is potential for coaggregation to play an integral role in spatiotemporal biofilm development and the moderation of biofilm community composition. However, understanding of the mechanisms contributing to coaggregation and the relevance of coaggregation to biofilm ecology is at a very early stage. The purpose of this review is to highlight recent advances in the understanding of microbial coaggregation within different environments and to describe the possible ecological ramifications of such interactions. Bacteria that coaggregate with many partner species within different environments will be highlighted, including oral streptococci and oral bridging organisms such as fusobacteria, as well as the freshwater sphingomonads and acinetobacters. Irrespective of environment, it is proposed that coaggregation is essential for the orchestrated development of multi-species biofilms.


Anomalous transport in a one-dimensional Lorentz gas model.
Employing the generalized master equation proposed in [R. Friedrich et al., Phys. Rev. Lett. 96, 230601 (2006)], we derive a kinetic equation for a random kick model. For a particular choice of the time evolution kernel, a fractional master equation is obtained, which can be related to a Levy walk. In one dimension, we use this model to describe a stochastic Lorentz gas with an annealed disorder. Exact moment relations are obtained in Laplace space, and the long-time behavior of the moments is discussed. The results are compared to those of related models.


Ancient and modern duplication events and the evolution of stearoyl-CoA desaturases in teleost fishes.
Stearoyl-CoA desaturases (SCDs) are key enzymes of fatty acid biosynthesis whose regulation underpins responses to dietary, thermal, and hormonal treatment. Although two isoforms are known to exist in the common carp and human and four in mouse, there is no coherent view on how this gene family evolved to generate functionally diverse members. Here we identify numerous new SCD homologs in teleost fishes, using sequence data from expressed sequence tag (EST) and cDNA collections and genomic model species. Phylogenetic analyses of the deduced coding sequences produced only partially resolved molecular trees. The multiple SCD isoforms were, however, consistent with having arisen by an ancient gene duplication event in teleost fishes together with a more recent duplication in the tetraploid carp and possibly also salmonid lineages. Critical support for this interpretation comes from comparison across all vertebrate groups of the gene order in the genomic environments of the SCD isoforms. Using syntenically aligned chromosomal fragments from large-insert clones of common carp and grass carp together with those from genomically sequenced model species, we show that the ancient and modern SCD duplication events in the carp lineage were each associated with large chromosomal segment duplications, both possibly linked to whole genome duplications. By contrast, the four mouse isoforms likely arose by tandem duplications. Each duplication in the carp lineage gave rise to differentially expressed SCD isoforms, either induced by cold or diet as previously shown for the recent duplicated carp isoforms or tissue specific as demonstrated here for the ancient duplicate zebrafish isoforms.


Glycemia and Atherosclerotic Cardiovascular Disease: Exploring the Gap Between Risk Marker and Risk Factor.
There is consistent, unequivocal and reproducible epidemiological evidence derived from diverse populations that various indices of glycemia (fasting plasma glucose, post-prandial or post oral glucose challenge plasma glucose, HbA1c) are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), even in the prediabetic state. Furthermore, there is abundant experimental evidence demonstrating that hyperglycemia per se accelerates and aggravates the atherosclerotic process, providing biological plausibility to the concept that hyperglycemia is causally related or a true risk factor for ASCVD. Two studies in particular, DCCT and UKPDS, that enrolled a younger cohort of patients with type 1 diabetes or an older cohort with newly diagnosed type 2 diabetes, respectively, showed trends toward a reduction in ASCVD. The reductions in ASCVD reached statistical significance only after prolonged follow up, and when differences in HbA1c were no longer maintained (referred to by some as a "legacy effect"). More recent studies in those with established type 2 diabetes, in which glycemic control was improved by a variety of strategies, failed to demonstrate reductions in ASCVD. The gap in evidence supporting hyperglycemia as a true causative risk factor for ASCVD or simply a risk marker for some other confounding causative factor is discussed in this review. We conclude that hyperglycemia does appear to be at least partially causative of ASCVD (i.e., an ASCVD risk factor). We discuss how this evidence can be incorporated into an overall therapeutic strategy to prevent ASCVD in those with prediabetes and established diabetes.


Surgical management of esophageal perforation: role of primary closure.
Esophageal perforation is a life-threatening condition associated with high mortality and morbidity. Ambiguous clinical presentation is one of the most common causes of delayed and difficult diagnosis of esophageal perforation. In this retrospective single-center study, we reviewed the outcome of primary closure in patients with esophageal perforation between 2009 and 2017. The data of 65 patients attending our department of thoracic surgery (from 2009 to 2017) for esophageal perforation were reviewed. Primary repair was attempted in 63 patients irrespective of the site of perforation and time interval between injury and hospital admission. In intrathoracic lesions, continuous mediastinal and pleural irrigation was undertaken, whereas in cervical perforations, gauze packing and local irrigation were performed. Jejunotomy was carried out in patients with inadequate healing. Of the 65 patients, 63 underwent primary closure and 2 were left to heal spontaneously. The majority of patients ( n = 44) had an esophageal perforation at the thoracic level, and only one was admitted early (<24 h after injury). Among the 63 patients managed with primary closure, 55 had satisfactory healing with one surgery. Healing was delayed in the other 10 patients. No mortality was reported. Esophageal perforation can be well managed by primary closure, irrespective of the time interval between injury and hospital admission and the site of perforation. Conservative management might lead to an increased rate of complications such as empyema or necrotizing mediastinitis, and increased morbidity and mortality.


Effect of Photobiomodulation Therapy on Reducing Acute Pain and Inflammation Following Surgical Removal of Impacted Mandibular Third Molars: A Randomized, Split-Mouth Clinical Trial.
Objective: This study aimed to compare the effects of photobiomodulation therapy (PBMT) on analgesic and inflammatory reduction with that of ibuprofen following surgical removal of impacted mandibular third molars (IMTMs). Methods: A randomized, split-mouth clinical trial was performed on patients undergoing bilateral IMTM removal. PBMT [gallium aluminum arsenide (GaAlAs) laser] with specific parameters (wavelength of 810 nm, power of 0.5% ± 20% W, and energy density of 4 J/cm2) was applied randomly on one side of the mouth immediately after surgery and 1 and 2 days after surgery. The pain level was self-rated with a Likert scale at 2, 4, 6, 24, and 48 h postoperatively. Swelling and trismus were measured on the first and second day after surgery. Saliva was collected for measuring pre- and postoperative salivary immunoglobulin A (sIgA) concentrations with the sandwich ELISA test. Results: The study sample included 25 patients (average age of 22.88 years) with 50 bilateral symmetrical IMTMs. Pain level was highest at 2 h after surgery in both groups and gradually decreased over time (p < 0.01). Swelling and trismus at 48 h were higher than at 24 h (p < 0.01). Within the first 48 h postoperatively, pain level, swelling, and trismus were significantly lower in the PBMT group (p < 0.05). Postoperative sIgA was also significantly lower in the PBMT group (p < 0.05). Conclusions: In short-term and specific conditions of this study, it was found that PBMT helped promote postoperative pain relief and anti-inflammation after surgical removal of IMTMs. The results suggested that there may be a link between a decrease in salivary sIgA levels and decrease in inflammatory processes after PBMT. Trial Registration No. NCT04280809 at ClinicalTrials.gov.


Social values and decision making: a generation in the lifeboat.
The author introduced the "Lifeboat"exercise as a death-and-dying teaching technique in an article that appeared in the first volume of Death Studies (J. A.Thorson, 1978). It is a classroom exercise designed to illustrate the varying levels of social value placed on terminally ill patients. Using "Lifeboat" with different groups in succeeding years, the author has seen changes in the ways that individuals playing different roles are perceived by the audience. These reactions may indicate changes in social values.


Anticytotoxin-neutralizing antibodies in immune globulin preparations: potential use in hemolytic-uremic syndrome.
The pathogenesis of primary (classic) hemolytic-uremic syndrome (HUS) is thought to be related to cytotoxin-producing enteric pathogens such as Shigella dysenteriae serotype 1 and Escherichia coli serotypes O157:H7 and 026:H11. The relevant cytotoxins include Shiga toxin and the closely related Shiga-like toxins (SLTs) produced by some E. coli strains. Intravenously administered immune globulin (IVIG) therapy has been reported to be beneficial in a few children with HUS. We therefore examined commercially available immune globulin preparations for the presence of anticytotoxin-neutralizing antibodies. Cytotoxicity and neutralization of the HUS-associated cytotoxins were quantitatively determined by means of a (3H)thymidine-labeled HeLa cell assay. The immune globulin preparations tested almost completely neutralized Shiga toxin (produced by S. dysenteriae 1) and SLT-I (produced by E. coli serotype 026:H11). Twofold dilutions of the preparations showed significant (p less than 0.01) neutralizing titers of 1:64 to 1:128. No significant neutralization (greater than 20%) of SLT-II (produced by E. coli strain C600 (933W] was noted. The IVIG preparation lost its inhibitory activity when passed through a protein A-Sepharose column, which bound immune globulin, indicating that its neutralizing effect is related to the antibody content. We also examined sera from 30 children without diarrhea or HUS; only one child had neutralizing titers against Shiga toxin (1:64) and SLT-I (1:128). Immune globulin preparations contain anticytotoxin-neutralizing antibodies, a finding that warrants further investigation of the therapeutic role of these preparations in early treatment of children with HUS related to Shiga toxin and SLT-I.


The Association Between Neighborhood Public Transportation Usage and Youth Physical Activity.
Routine adolescent physical activity is a well-established predictor of positive health across the lifespan, although wide disparities in youth physical activity engagement persist across sex and race/ethnicity. Transportation barriers may be related to adolescents' ability to access physical activity opportunities. This study examines the association between neighborhood public transportation usage and adolescent physical activity using a national sample. Cross-sectional data were drawn from the Family Life, Activity, Sun, Health, and Eating study (2014), a national sample of adolescents aged 12-17 years. Linear regression examined the association between neighborhood public transportation usage on the basis of neighborhood-level public transportation use and individual-level youth moderate-to-vigorous physical activity minutes per week. Models were developed for weekday, weekend, and combined moderate-to-vigorous physical activity for all youth and across sex and race/ethnicity subgroups. Analyses were run in 2020. The final analytic data set included 1,247 adolescents aged 12-17 years (71% non-Hispanic White, 49% male, mean age=14.52 [SD=1.59] years). Adjusted models showed a stronger magnitude of association between high neighborhood public transportation usage and both weekday (β=8.79, 95% CI=1.00, 16.59) and combined (β=13.74, 95% CI=1.14, 26.35) moderate-to-vigorous physical activity than between low/moderate neighborhood public transportation usage and moderate-to-vigorous physical activity. The magnitude of the neighborhood public transportation usage-moderate-to-vigorous physical activity association was strongest among non-Hispanic Black and Hispanic adolescent girls. This study found an association between neighborhood public transportation usage and adolescent moderate-to-vigorous physical activity, particularly among non-Hispanic Black and Hispanic adolescent girls. Findings from this research have the potential to inform targeted interventions for promoting adolescent physical activity to ultimately reduce chronic health disparities across the lifespan.


Localization of the gene for Darier disease to a 5-cM interval on chromosome 12q.
Darier disease is an autosomal dominant abnormality of epidermal differentiation characterized clinically by the presence of hyperkeratotic papules on the skin and histologically by the loss of cell cohesion and by disorderly keratinization. Two groups recently found evidence that the gene whose mutations underlie this disease is located at chromosome 12q23-q24.1, a site on chromosome 12 that clearly is distal to the type II keratin gene cluster. We report here evidence for sublocalization to a 5-cM region of that site in an additional ten families of European and Middle Eastern ancestry with a combined lod score in excess of 20.


Preoperative radiotherapy improves overall survival of pT4 pancreatic ductal adenocarcinoma patients after surgical resection.
The aim of delivering radiotherapy for pancreatic ductal adenocarcinoma patients was to sterilize vessel margin, increase R0 resection rate and delay local progression. Whether preoperative radiotherapy could prolong overall survival of surgical candidates remained unknown. Pancreatic ductal adenocarcinoma patients receiving radical resection from surveillance, epidemiology and end result database were enrolled. Propensity score matching was conducted to balance difference in baseline characteristics, and survival analyses were performed to compare overall survival between preoperative radiotherapy and upfront resection groups. Cox proportional hazard regression model and subgroup analyses were utilized to identify prognostic factors. A total of 11 665 and 597 pancreatic ductal adenocarcinoma patients receiving upfront resection and preoperative radiotherapy followed by resection from 2004 to 2016 were identified, respectively, while baseline characteristics were distinct between groups. After propensity score matching, preoperative radiotherapy was not associated with better overall survival (upfront resection vs preoperative radiotherapy, 26 vs 27 months). Subgroup analyses showed that preoperative radiotherapy was a protective factor in pT4 (hazard ratio = 0.64, 95% confidence interval: 0.47-0.88) but a negative predictor in pT1 (hazard ratio = 1.79, 95% confidence interval: 1.08-2.97) patient populations. Survival analyses showed that preoperative radiotherapy improved overall survival of patients with pT4 stage (upfront resection vs preoperative radiotherapy, 19 vs 25 months) and involvement of celiac axis, superior mesenteric artery and aorta (upfront resection vs preoperative radiotherapy, 20 vs 27 months), while preoperative radiotherapy was associated with worse overall survival in patients with pT1 tumor (upfront resection vs preoperative radiotherapy, 39 vs 24 months). Preoperative radiotherapy could improve survival of resected pancreatic ductal adenocarcinoma patients with pT4 stage or with celiac axis, superior mesenteric artery and aorta invasion.


Heat shock protein 70 binding inhibits the nuclear import of apoptosis-inducing factor.
Heat shock protein 70 (HSP70) can inhibit apoptosis by neutralizing and interacting with apoptosis-inducing factor (AIF), a mitochondrial flavoprotein that translocates upon apoptosis induction to the nucleus, via the cytosol. Here, we show that only members of the HSP70 family interact with AIF. Systematic deletion mapping revealed the existence of three distinct functional regions in the AIF protein: (1) a region between amino acids 150 and 228 that binds HSP70, (2) a domain between residues 367 and 459 that includes a nuclear localization sequence (NLS) and (3) a C-terminal domain beyond residue 567 required for its chromatin-condensing activity. Deletion of the 150-268 domain completely abolished HSP70 binding and facilitated the nuclear import of AIF, resulting in a gain-of-function phenotype with enhanced AIF-mediated chromatin condensation as compared to wild-type AIF. This gain-of-function phenotype was observed in wild-type control cells (which express low but significant levels of HSP70), yet was lost when AIFDelta150-268 was introduced into HSP70 knockout cells, underscoring the functional importance of the AIF-HSP70 interaction. Altogether, our data demonstrate that AIF inhibition by HSP70 involves cytosolic retention of AIF. Moreover, it appears that endogenous HSP70 protein levels are sufficiently elevated to modulate the lethal action of AIF.


Albaconol from the mushroom Albatrellus confluens induces contraction and desensitization in guinea pig trachea.
The contraction and desensitization induced by albaconol and the influence of capsazepine, capsaicin and extracellular Ca2+ were investigated to see whether the actions were mediated via a specific VR receptor in guinea pig trachea spiral strips in vitro. Both albaconol and capsaicin were contractors of tracheal smooth muscle, but albaconol was not so potent as capsaicin, with -log (M) EC50 values of 4.23 +/- 0.18 (n = 10) and 7.33 +/- 0.21 (n = 10) respectively. 2.5 microM capsazepine competitively antagonized the contractile response to albaconol and capsaicin. Albaconol increased the contraction induced by a low dose of capsaicin (10(-10) to 10(-9) M), but non-competitively antagonized the contraction induced by a high dose of capsaicin (10(-8) to 10(-3) M). Either albaconol (1 or 100 mM) or capsaicin (3 or 10 microM) was able to desensitize the isolated guinea pig bronchi to subsequent addition of albaconol. Capsazepine (5.0 microM) significantly prevented the desensitization induced by either albaconol (1 or 100mM) or capsaicin (3 or 10 microM). Extracellular Ca2+ was essential for albaconol to induce excitation, but it did not affect albaconol- or capsaicin-induced desensitization. In summary, the results from the present study suggest that albaconol induces contraction and desensitization of guinea pig trachea in vitro as a partial agonist for VR.


[Psychiatrists and psychotherapists: a peaceful coexistence?].
Particular issues concerning the meeting between psychiatrists and psychotherapists in patients' treatments are developed. Standing conceptions of mental illness, its etiopathogeny, the place of each therapist, and split transferences induced by combined treatment are discussed.


[Average time of cell mitosis in the hematopoietic tissue of rats].
Rats (Wistar) were irradiated (60Co) with dose of 500 R at the dose-rate of 345 R/min. Using a curve of decrease of the mitotic index in hemopoietic tissue cells after irradiation, an attempt has been made to determine the average time of mitosis. The parameters (latent period, the minimum and average time of mitosis, resp., variance and density distribution type) were introduced in the mathematical equation which relates mitotic index postradiation decrease curve to mitosis time density distribution. It has been found that the actual average time of mitosis for hemopoietic tissues of rats is in the range of 25--27 min 32--33 min and 26--27 min. for thymocytes, promyelocytes--myelocytes and erythroblasts--normoblasts, respectively.


Are there racial/ethnic disparities in VA PTSD treatment retention?
Chronic posttraumatic stress disorder (PTSD) can result in significant social and physical impairments. Despite the Department of Veterans Affairs' (VA) expansion of mental health services into primary care clinics to reach larger numbers of Veterans with PTSD, many do not receive sufficient treatment to clinically benefit. This study explored whether the odds of premature mental health treatment termination varies by patient race/ethnicity and, if so, whether such variation is associated with differential access to services or beliefs about mental health treatments. Prospective national cohort study of VA patients who were recently diagnosed with PTSD (n = 6,788). Self-administered surveys and electronic VA databases were utilized to examine mental health treatment retention across racial/ethnic groups in the 6 months following the PTSD diagnosis controlling for treatment need, access factors, age, gender, treatment beliefs, and facility factors. African American and Latino Veterans were less likely to receive a minimal trial of pharmacotherapy and African American Veterans were less likely to receive a minimal trial of any treatment in the 6 months after being diagnosed with PTSD. Controlling for beliefs about mental health treatments diminished the lower odds of pharmacotherapy retention among Latino but not African American Veterans. Access factors did not contribute to treatment retention disparities. Even in safety-net healthcare systems like VA, racial and ethnic disparities in mental health treatment occur. To improve treatment equity, clinicians may need to more directly address patients' treatment beliefs. More understanding is needed to address the treatment disparity for African American Veterans.


Investigating the nature of noble gas-copper bonds by the quantum theory of atoms in molecules.
We investigated noble gas-copper bonds in linear complexes represented by the NgCuX general formula in which Ng and X stand for a noble gas (neon, argon, krypton, or xenon) and a halogen (fluorine, chlorine or bromine), respectively, by coupled cluster methods and modified cc-pVQZ basis sets. The quantum theory of atoms in molecules (QTAIM) shows a linear relation between the dissociation energy of noble gas-copper bonds and the amount of electronic charge transferred mainly from the noble gas to copper during complexation. Large changes in the QTAIM quadrupole moments of copper and noble gases resulting from this bonding and a comparison between NgCuX and NgNaCl systems indicate that these noble gas-copper bonds should be better interpreted as predominantly covalent. Finally, QTAIM atomic dipoles of noble gases in NgNaCl systems agree satisfactorily with atomic dipoles given by a simple model for these NgNa van der Waals bonds.


The role of pro-drug therapy in the treatment of cancer.
The administration of anti-cancer agents is currently associated with significant toxicity and lack of tumour specificity. Prodrugs are being designed to favourably alter the therapeutic index of these agents by improving their efficacy and reducing toxicity. Progress in the development of prodrugs including the cytotoxic agents most commonly used in cancer treatments namely 5-fluorouracil (5-FU), the anthracyclines, paclitaxel and platinum will be described. Many of these agents are at an early stage of development: however, this article will also describe those which have already made an impact in the clinic. It is likely that future improvements in care will come from refinement of the drugs already well established in clinical practice. In addition, this technology could be applied to novel agents with alternative cellular targets such as those involved in angiogenesis or in conferring metastatic potential. Thus, lessons learned with standard drugs may be applicable across a wider spectrum of therapeutics.


[The multifunctionality of CHIP protein in the protein quality-control system].
Selective protein degradation depends on their quality being controlled by the cellular system, which includes chaperones involved in protein folding and two degradation systems, the proteasomal and lysosomal. CHIP (carboxyl terminus of Hsp70-interacting protein), an E3 ubiquitin ligase and co-chaperone, serves as a chaperone-degradation system interface. This article reviews the molecular characteristics of CHIP protein, the mechanism of its action, and its role in cellular metabolism and discusses how CHIP dysfunction may lead to neurodegenerative diseases.


[Development of novel biomaterials for bone and cartilage tissue engineering].
Three-dimensional porous scaffolds play an important role in cartilage and bone tissue engineering as temporary templates for transplanted cells to control their adhesion and proliferation to guide the formation of the new tissues. The scaffolds should be biodegradable, biocompatible, mechanically strong, and capable of being formed into desired shapes. Biodegradable synthetic polymers and naturally derived collagen have their respective advantages and drawbacks. Hybridization of the two kinds of polymers has been carried out to combine their respective advantages. This review will summarize some of the recently developed porous scaffolds having hybrid, biphasic and leakproof structures, and their application to bone and cartilage tissue engineering.


Sodium profiling: the key to reducing symptoms of dialysis?
A systematic review was undertaken in order to critically appraise the current knowledge base of sodium profiling in hemodialysis. Between 15%-80% of patients on hemodialysis experience symptoms of dialysis intolerance every dialysis session. The purpose of this review was to identify whether sodium profiling is an effective intervention in removing or reducing these untoward effects. A literature search was undertaken using Medline and Embase. Inclusion criteria were primary research or controlled clinical trials published between January 1990 and June 2006 and studies in the chronic dialysis setting and studies that identified sodium profiling as the intervention in hemodialysis or hemodiafiltration. Articles excluded included: those that could not establish whether sodium profiling was the intervention responsible for the outcome; articles on hemofiltration; and review articles and research pertaining to the acute setting. Thirteen articles met the inclusion criteria and were included in the final review. A number of flaws were identified with methodological adequacy and consistency of findings. It was not possible to determine whether positive effects outweighed negative effects in this review. In the majority of studies, there was a lack offollow-up and the inability to determine long-term outcomes of patients who received sodium profiling. This evaluative review could not provide evidence to support the clinical use of sodium profiling in the population of patients on hemodialysis who are symptomatic. There remains a theoretical base for the use of sodium profiling, however further studies are needed providing consistency in methodology, looking not only at reduction in morbidity but effects on quality of life, long-term outcomes, and mortality.


Posterior cranial base natural growth and development: A systematic review.
To provide a synthesis of the published studies evaluating the natural growth and development of the human posterior cranial base (S-Ba). The search was performed on MEDLINE, Embase, PubMed, and all EBM Reviews electronic databases. In addition, reference lists of the included studies were hand-searched. Articles were included if they analyzed posterior cranial-base growth in humans specifically. Study selection, data extraction, and risk of bias assessment were completed in duplicate. A meta-analysis was not justified. Finally, 23 published studies were selected: 5 cross-sectional and 18 cohort studies. Articles were published between 1955 and 2015, and all were published in English. The sample sizes varied between 20 and 397 individuals and consisted of craniofacial measurements from either living or deceased human skulls. Validity of the measurements was not determined in any of the studies, while six papers reported some form of reliability assessment. All the articles included multiple time points within the same population or data from multiple age groups. Growth of S-Ba was generally agreed to be from spheno-occipital synchondrosis growth. Basion displaced downward and backward and sella turcica moved downward and backward during craniofacial growth. Timing of cessation of S-Ba growth was not conclusive due to limited identified evidence. Current evidence suggests that S-Ba is not totally stable, as its dimensions change throughout craniofacial growth and a minor dimensional change is observed even in late adulthood.


Invasive aspergillosis in liver transplant recipients.
Liver transplantation is increasing worldwide with underlying pathologies dominated by metabolic and alcoholic diseases in developed countries. We provide a narrative review of invasive aspergillosis (IA) in liver transplant (LT) recipients. We searched PubMed and Google Scholar for references without language and time restrictions. The incidence of IA in LT recipients is low (1.8%), while mortality is high (∼50%). It occurs mainly early (<3 months) after LT. Some risk factors have been identified before (corticosteroid, renal, and liver failure), during (massive transfusion and duration of surgical procedure), and after transplantation (intensive care unit stay, re-transplantation, re-operation). Diagnosis can be difficult and therefore requires full radiological and clinicobiological collaboration. Accurate identification of Aspergillus species is recommended due to the cryptic species, and susceptibility testing is crucial given the increasing resistance of Aspergillus fumigatus to azoles. It is recommended to reduce the dose of tacrolimus (50%) and to closely monitor the trough level when introducing voriconazole, isavuconazole, and posaconazole. Surgery should be discussed on a case-by-case basis. Antifungal prophylaxis is recommended in high-risk patients. Environmental preventative measures should be implemented to prevent outbreaks of nosocomial aspergillosis in LT recipient units. IA remains a very serious disease in LT patients and should be promptly sought and, if possible, prevented by clinicians when risk factors are identified.


Outcomes of Offenders With Co-Occurring Substance Use Disorders and Mental Disorders.
Whether a diagnosis of a mental disorder contributes to the risk of poorer correctional outcomes is controversial. This study aimed to clarify the extent to which mental and substance use disorders individually and in combination contribute to correctional outcomes in order to determine optimal treatment and promote public safety. Differences were examined between four groups of federal offenders in Canada (N=715): those with a mental disorder only, those with a substance use disorder only, those with co-occurring mental and substance use disorders, and those with no disorder. Groups were compared on profiles, criminal histories, charges while incarcerated (institutional charges), and reconvictions after release from incarceration by using chi-square tests and Cox regression analyses that controlled for risk factors. Of the four groups, those with co-occurring disorders had the most substantial criminal histories and the highest rates of institutional charges, transfers to segregation while incarcerated, and reconvictions. The group with only mental disorders had outcomes intermediate between the groups with only substance use disorders and the group with neither type of disorder. Having a substance use disorder appeared to be the key factor contributing to poorer correctional outcomes for offenders with mental disorders. Psychiatric services in correctional facilities must screen for substance use disorders and, if they are present, ensure provision of treatment to improve quality of life for this population and promote public safety.


[Diagnosis and therapy of infectious endocarditis. What measures are required?].
Infectious endocarditis remains a potentially life-threatening disease, the outcome of which can be substantially influenced by rapid diagnosis and initiation of suitable treatment. Leading clinical features are fever, a new sound suggestive of valvular insufficiency and, when the course is subacute, anemia. The main diagnostic procedures are transthoracic and transesophageal echocardiography that reliably identify vegetation, valvular insufficiency and abscess. Of decisive importance for treatment and prognosis is the rapid identification of the pathogen by means of blood culture and, if necessary, serologic and molecular-biologic measures. Antimicrobial treatment is applied in accordance with the recommendations of the American Heart Association. Surgical treatment is indicated in the event of refractory infection, severe valvular insufficiency with heart failure, valve avulsion, recurrent emboli or large floating vegetation with an elevated risk of embolism.


The multifunctional beta-oxidation enzyme is required for full symptom development by the biotrophic maize pathogen Ustilago maydis.
The transition from yeast-like to filamentous growth in the biotrophic fungal phytopathogen Ustilago maydis is a crucial event for pathogenesis. Previously, we showed that fatty acids induce filamentation in U. maydis and that the resulting hyphal cells resemble the infectious filaments observed in planta. To explore the potential metabolic role of lipids in the morphological transition and in pathogenic development in host tissue, we deleted the mfe2 gene encoding the multifunctional enzyme that catalyzes the second and third reactions in beta-oxidation of fatty acids in peroxisomes. The growth of the strains defective in mfe2 was attenuated on long-chain fatty acids and abolished on very-long-chain fatty acids. The mfe2 gene was not generally required for the production of filaments during mating in vitro, but loss of the gene blocked extensive proliferation of fungal filaments in planta. Consistent with this observation, mfe2 mutants exhibited significantly reduced virulence in that only 27% of infected seedlings produced tumors compared to 88% tumor production upon infection by wild-type strains. Similarly, a defect in virulence was observed in developing ears upon infection of mature maize plants. Specifically, the absence of the mfe2 gene delayed the development of teliospores within mature tumor tissue. Overall, these results indicate that the ability to utilize host lipids contributes to the pathogenic development of U. maydis.


The leukocyte response to fluid stress.
Leukocyte migration from a hemopoietic pool across marrow endothelium requires active pseudopod formation and adhesion. Leukocytes rarely show pseudopod formation while in circulation. At question then is the mechanism that serves to minimize leukocyte pseudopod formation in the circulation. We tested the hypothesis that fluid shear stress acts to prevent pseudopod formation. When individual human leukocytes (neutrophils, monocytes) spreading on glass surfaces in vitro were subjected to fluid shear stress ( approximately 1 dyn/cm2), an instantaneous retraction of pseudopods was observed. Removal of the fluid shear stress in turn led to the return of pseudopod projection and cell spreading. When steady shear stress was prolonged over several minutes, leukocyte swelling occurs together with an enhanced random motion of cytoplasmic granules and a reduction of cytoplasmic stiffness. The response to shear stress could be suppressed by K+ channel blockers and chelation of external Ca2+. In rat mesentery microvessels after occlusion, circulating leukocytes project pseudopods in free suspension or when attached to the endothelium, even though immediately after occlusion only few pseudopods were present. When flow was restored, pseudopods on adhering leukocytes were retracted and then the cells began to roll and detach from the endothelium. In conclusion, plasma shear stress in the circulation serves to reduce pseudopod projection and adhesion of circulating leukocytes and vice versa reduction of shear stress leads to pseudopod projection and spreading of leukocytes on the endothelium.


Plasma Fibrinogen Correlates with Metastasis and is Associated with Prognosis in Human Nasopharyngeal Carcinoma.
Background: The purpose of this observational study was to evaluate the prognostic significance of the pre-treatment plasma fibrinogen level for survival outcomes in nasopharyngeal carcinoma (NPC). Methods: A total of 998 patients with NPC treated at a single centre in China were retrospectively enrolled, of whom 182 (18.2%) developed distant metastasis during follow-up. Survival analyses were performed by the Kaplan-Meier method and Cox regression modelling to measure 3-year overall survival (OS) and distant metastasis-free survival (DMFS). Results: Median OS for the entire cohort was 37.8 months. Using the cut-off value of 3.345 g/L identified in receiver operating curve analysis for fibrinogen, a high pre-treatment plasma fibrinogen level were associated with older age (P = 0.034), advanced TNM stage (P = 0.004) and development of distant metastasis (P < 0.001; Chi-square test). Multivariate Cox proportional hazard analysis demonstrated the pre-treatment plasma fibrinogen level was an independent significant prognostic factor for OS and DMFS in both the entire cohort and also among patients who developed distant metastasis during follow-up. Conclusions: This study suggests the pre-treatment plasma fibrinogen level may serve as an independent prognostic marker to predict the survival outcomes of patients with NPC, including patients with metastatic disease.


Effects of caspase-9 and survivin gene polymorphisms in pancreatic cancer risk and tumor characteristics.
This case-control study was performed to evaluate the association between a specific caspase-9 polymorphism as well as the genetic polymorphism -31G/C located in the cycle-dependent elements/cell cycle homology regions repressor element of the human survivin promoter and the risk of pancreatic cancer. Eighty patients with pancreatic cancer and 160 healthy controls were investigated for genotype and allelic frequencies of caspase-9 1263A/G and survivin -31G/C polymorphisms by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism. The G carrier group of patients and the G allele of caspase-9 1263A/G were overrepresented among the pancreatic cancer cases. With regard to tumor characteristics, a statistically significant association was detected between the survivin C carrier group of patients and the advanced T stage as well as the presence of lymph node metastasis. The caspase-9 G allele confers increased susceptibility to pancreatic cancer development, and the survivin C carriage status may be related to aggressive features of this malignancy.


Human Umbilical Cord Blood Serum-derived α-Secretase: Functional Testing in Alzheimer's Disease Mouse Models.
Alzheimer's disease (AD) is an age-related disorder that affects cognition. Our previous studies showed that the neuroprotective fragment of amyloid procurer protein (APP) metabolite, soluble APPα (sAPPα), interferes with β-site APP-cleaving enzyme 1 (BACE1, β-secretase) cleavage and reduces amyloid-β (Aβ) generation. In an attempt to identify approaches to restore sAPPα levels, we found that human cord blood serum (CBS) significantly promotes sAPPα production compared with adult blood serum (ABS) and aged blood serum (AgBS) in Chinese hamster ovary cells stably expressing wild-type human APP. Interestingly, CBS selectively mediated the α-secretase cleavage of human neuron-specific recombinant APP695 in a cell-free system independent of tumor necrosis factor-α converting enzyme (TACE; a disintegrin and metalloproteinase domain-containing protein 17 [ADAM17]) and ADAM. Subsequently, using 3-step chromatographic separation techniques (i.e., diethylaminoethanol, size-exclusion, and ion-exchange chromatography), we purified and ultimately identified a CBS-specific fraction with enhanced α-secretase catalytic activity (termed αCBSF) and found that αCBSF has more than 3,000-fold increased α-secretase catalytic activity compared with the original pooled CBS. Furthermore, intracerebroventricular injection of αCBSF markedly increased cerebral sAPPα levels together with significant decreases in cerebral Aβ production and abnormal tau (Thr231) phosphorylation compared with the AgBS fraction with enhanced α-secretase activity (AgBSF) treatment in triple transgenic Alzheimer's disease (3xTg-AD) mice. Moreover, AgBSF administered intraperitoneally to transgenic mice with five familial Alzheimer's disease mutations (5XFAD) via an osmotic mini pump for 6 weeks (wk) ameliorated β-amyloid plaques and reversed cognitive impairment measures. Together, our results propose the necessity for further study aimed at identification and characterization of α-secretase in CBS for novel and effective AD therapy.


Ceftazidime combined with mecillinam: serum bactericidal titres compared with in-vitro synergy against gram-negative bacilli.
In a study of the possible interaction between mecillinam and ceftazidime against Gram-negative bacilli, ten volunteers received on separate days: ceftazidime 20 mg/kg iv in 15 min, mecillinam 10 mg/kg iv in 15 min, or the combination. Blood samples were obtained before and 1 and 6 h after the end of the infusion. Ten strains each of Klebsiella pneumoniae, Serratia marcescens, Citrobacter freundii, Salmonella spp. and Yersinia spp. and nine strains each of Acinetobacter spp., and Pseudomonas aeruginosa were selected. Most of the strains were resistant to ampicillin and cefazolin. Serum levels of ceftazidime and mecillinam were measured by bioassay. Serum bacteriostatic (SBS) and bactericidal (SBA) titration was done in microtitre plates in cation supplemented Mueller-Hinton broth and 50% human serum. Chequerboard titration was also studied to assess in-vitro synergy between ceftazidime and mecillinam in Mueller-Hinton broth with or without 50% serum. The mean serum concentrations (SD) were for mecillinam: 6.1 (1.7) at 1 h, and less than 0.3 at 6 h and for ceftazidime: 36.3 (5.5) at 1 h and less than 5 at 6 h. Identical concentrations were measured for the combination. By chequerboard titration, no synergy occurred for Acinetobacter spp. and Ps. aeruginosa, whereas it was observed in 37/60 (FIC) and 33/60 (FBC) of the strains of other species in Mueller-Hinton; from the strains showing synergy, 28/37 (FIC) and 30/33 (FBC) showed also synergy in Mueller-Hinton with 50% human serum. In SBS and SBA, on the other hand, the combination of mecillinam with ceftazidime showed an additive effect against most Enterobacteriaceae tested, synergy being shown for only 10-35% of tests.(ABSTRACT TRUNCATED AT 250 WORDS)


Interaction of the mu-opioid receptor with synaptophysin influences receptor trafficking and signaling.
There is increasing evidence that the signal transduction of opioid receptors is modulated by receptor-associated proteins. In the search for proteins regulating mu-opioid receptor (MOPr) endocytosis, synaptophysin was found to bind to the rat micro-opioid receptor in yeast two-hybrid assay. Coimmunoprecipitation experiments and bioluminescence resonance energy transfer assays confirmed that the micro-opioid receptor constitutively interacts with synaptophysin in human embryonic kidney 293 cells overexpressing MOPr and synaptophysin. In this study, we show that overexpression of synaptophysin enhances the micro-opioid receptor endocytosis. One explanation for the observed effects is that synaptophysin recruits dynamin to the plasma membrane, facilitating fission of clathrin-coated vesicles. This suggestion is supported by our finding that overexpression of a synaptophysin truncation mutant, which breaks the interaction between synaptophysin and dynamin, prevents agonist-mediated micro-opioid receptor endocytosis. In addition, the synaptophysin-augmented micro-opioid receptor trafficking leads to attenuated agonist-induced receptor desensitization and faster receptor resensitization. Taken together, our findings strongly suggest that synaptophysin plays an important role in the regulation of micro-opioid receptor trafficking and signaling.


HydG, the "dangler" iron, and catalytic production of free CO and CN-: implications for [FeFe]-hydrogenase maturation.
The organometallic H-cluster of the [FeFe]-hydrogenase consists of a [4Fe-4S] cubane bridged via a cysteinyl thiolate to a 2Fe subcluster ([2Fe]H) containing CO, CN-, and dithiomethylamine (DTMA) ligands. The H-cluster is synthesized by three dedicated maturation proteins: the radical SAM enzymes HydE and HydG synthesize the non-protein ligands, while the GTPase HydF serves as a scaffold for assembly of [2Fe]H prior to its delivery to the [FeFe]-hydrogenase containing the [4Fe-4S] cubane. HydG uses l-tyrosine as a substrate, cleaving it to produce p-cresol as well as the CO and CN- ligands to the H-cluster, although there is some question as to whether these are formed as free diatomics or as part of a [Fe(CO)2(CN)] synthon. Here we show that Clostridium acetobutylicum (C.a.) HydG catalyzes formation of multiple equivalents of free CO at rates comparable to those for CN- formation. Free CN- is also formed in excess molar equivalents over protein. A g = 8.9 EPR signal is observed for C.a. HydG reconstituted to load the 5th "dangler" iron of the auxiliary [4Fe-4S][FeCys] cluster and is assigned to this "dangler-loaded" cluster state. Free CO and CN- formation and the degree of activation of [FeFe]-hydrogenase all occur regardless of dangler loading, but are increased 10-35% in the dangler-loaded HydG; this indicates the dangler iron is not essential to this process but may affect relevant catalysis. During HydG turnover in the presence of myoglobin, the g = 8.9 signal remains unchanged, indicating that a [Fe(CO)2(CN)(Cys)] synthon is not formed at the dangler iron. Mutation of the only protein ligand to the dangler iron, H272, to alanine nearly completely abolishes both free CO formation and hydrogenase activation, however results show this is not due solely to the loss of the dangler iron. In experiments with wild type and H272A HydG, and with different degrees of dangler loading, we observe a consistent correlation between free CO/CN- formation and hydrogenase activation. Taken in full, our results point to free CO/CN-, but not an [Fe(CO)2(CN)(Cys)] synthon, as essential species in hydrogenase maturation.


The Crucial Role of Biofilms in Cryptococcus neoformans Survival within Macrophages and Colonization of the Central Nervous System.
Cryptococcus neoformans is an encapsulated yeast-like fungus capable of causing life threatening meningoencephalitis in patients with impaired immunity. This microbe primarily infects the host via inhalation but has the ability to disseminate to the central nervous system (CNS) either as a single cell or inside of macrophages. Upon traversing the blood brain barrier, C. neoformans has the capacity to form biofilm-like structures known as cryptococcomas. Hence, we will discuss the C. neoformans elements contributing to biofilm formation including the fungus' ability to survive in the acidic environment of a macrophage phagosome and inside of the CNS. The purpose of this mini-review is to instill fresh interest in understanding the importance of biofilms on fungal pathogenesis.


Multisite Implementation and Evaluation of 12-Month Standard Dialectical Behavior Therapy in a Public Community Setting.
Dialectical behavior therapy (DBT) is an effective intervention for treating adults with emotional and behavioral dysregulation. The National DBT Project, Ireland was established in 2013 to coordinate the implementation of DBT across public community mental health settings at a national level. This study describes the implementation and evaluation of DBT across multiple independent sites in adult mental health services (AMHS). The Consolidated Framework for Implementation Research was used to guide this national implementation where barriers and facilitators to DBT implementation were considered. Nine AMHS teams completed DBT training and delivered the standard 12-month program. One hundred and ninety-six adults with borderline personality disorder participated in the program, and outcome measures were recorded at four time points. Significant reductions on outcome measures, including frequency of self-harm and suicidal ideation, were observed. This study highlights that DBT can be successfully implemented in community mental health settings as part of a coordinated implementation.


MicroRNA-146b: A Novel Biomarker and Therapeutic Target for Human Papillary Thyroid Cancer.
Papillary thyroid cancer (PTC) is the most common tumor subtype of thyroid cancer. However, not all PTCs are responsive to current surgical and radioiodine treatment. The well-established clinical prognostic factors include tumor size, lymph node/distal metastasis, and extrathyroidal invasion. The RET/PTC-RAS-BRAF linear molecular signaling cascade is known to mediate PTC pathogenesis. However, whether presence of BRAF mutation, the most common genetic alteration in PTC, can affect PTC behavior and prognosis is controversial. MicroRNAs (miRNAs) have been labeled as promising molecular prognostic markers in several tumor types. Our recent studies demonstrated that microRNA-146b (miR-146b) deregulation is associated with PTC aggressiveness and prognosis. Here we summarize the current knowledge related to the functional roles, regulated target genes, and clinical applications of miR-146b in PTC and discuss how these studies provide insights into the key role of miR-146b as an oncogenic regulator promoting cellular transformation as well as a prognosis marker for tumor recurrence in PTC. In conjunction with the current perspectives on miRNAs in a wide variety of human cancers, this review will hopefully translate these updated findings on miR-146b into more comprehensive diagnostic or prognostic information regarding treatment in PTC patients before surgical intervention and follow up strategies.


Near-band-edge exciton polarization change in ZnO nanowires.
Using the atomistic pseudopotential method complemented by configuration interaction calculations, we have studied the electronic and optical properties of ZnO nanowires (NWs) in the presence of quantum confinement effects. Our results indicate that the near-band-edge exciton experiences a crossover from an in-plane polarized A-exciton (for D≥ 3 nm) to an out-of-plane polarized C-exciton (for D < 3 nm) due to quantum confinement. This transition leads to a non-monotonic variation of Stokes shift, exhibiting a maximum value around the critical diameter of 3 nm. The observed behavior is analyzed by a stepwise inclusion of correlation effects, leading to a comprehensive description of the excitonic fine structure.


Transcatheter aortic valve replacement-state of the art and a glimpse to the future: 'the Tailored Approach'.
Transcatheter aortic valve replacement determined a paradigm shift in the treatment of high-risk patients with severe symptomatic aortic valve stenosis. Notwithstanding the impressive results of the first-generation prostheses, a fast-paced technological evolution is taking place to overcome their limitations, in particular the vascular access damage and the paravalvular leak. Nowadays, with the availability of several different devices, the expert operator can select the right prosthesis for the specific anatomical and clinical situation. As 'One does not fit all', the 'Tailored TAVR Approach' we describe will conceivably become the future of this therapy.


Protein kinase R, IkappaB kinase-beta and NF-kappaB are required for human rhinovirus induced pro-inflammatory cytokine production in bronchial epithelial cells.
Rhinovirus infections cause the majority of acute exacerbations of airway diseases such as asthma and chronic obstructive pulmonary disease, with increased pro-inflammatory cytokine production by infected bronchial epithelial cells contributing to disease pathogenesis. Theses diseases are a huge cause of morbidity worldwide, and contribute a major economic burden to healthcare costs. Current steroid based treatments are only partially efficient at controlling virus induced inflammation, which remains an unmet therapeutic goal. Although NF-kappaB has been implicated, the precise mechanisms of rhinovirus induction of pro-inflammatory gene expression in bronchial epithelial cells are unclear. We hypothesised that rhinovirus replication and generation of dsRNA was an important process of pro-inflammatory cytokine induction. Using pharmalogical (2-aminopurine and a new small molecule inhibitor) and genetic inhibition of the dsRNA binding kinase protein kinase R, striking inhibition of dsRNA (polyrIC) and rhinovirus induced CCL5, CXCL8 and IL-6 protein was observed. Using confocal microscopy, rhinovirus induced protein kinase R phosphorylation co-located with NF-kappaB p65 nuclear translocation. Focusing on CXCL8, both rhinovirus infection and dsRNA treatment required IkappaB kinase-beta for induction of CXCL8. Analysis of cis-acting sites in the CXCL8 promoter revealed that both rhinovirus infection and dsRNA treatment upregulated CXCL8 promoter activation via NF-kappaB and NF-IL6 binding sites. Together, the results demonstrate the importance of dsRNA in induction of pro-inflammatory cytokines by rhinoviruses, and suggest that protein kinase R is involved in NF-kappaB mediated gene transcription of pro-inflammatory cytokines via IkappaB kinase-beta. These molecules regulating rhinovirus induction of inflammation represent therapeutic targets.


Dramatic Reduction in Corneal Transplants for Keratoconus 15 Years After the Introduction of Corneal Collagen Crosslinking.
The aim of this study was to investigate the effect of the implementation of corneal collagen crosslinking (CXL) on the frequency of corneal transplants among patients with keratoconus (KC) in the same region. Before the introduction of CXL in 2007, 55 primary corneal transplants had been conducted in patients with KC (2005 and 2006) at the Department of Ophthalmology, Oslo University Hospital, Norway. We collected data from our corneal transplant registry for 2021 and 2022. The primary outcome was the number of corneal transplants performed in patients with KC. Age, sex, visual acuity (logarithm of the minimal angle of resolution), KC stage according to the Amsler-Krumeich classification system, and steepest keratometry reading (maximum keratometry, Pentacam, HR) were recorded. Furthermore, we registered the annual number of CXL treatments conducted from 2007 to 2022. A total of 352 corneal transplants were performed in 2021 and 2022. Among them, 11 (3.1%) were transplants for patients with KC. All included patients were male; further, 90.1% and 9.1% of the patients were graded stages 4 and 3, respectively. The mean maximum keratometry was 79.0 diopter (range 61.0-109). The mean best-corrected visual acuity (logarithm of the minimal angle of resolution) was 1.3 (range 0.2-3.0). In 2021 to 2022, 431 CXL treatments were performed. There was a significant decrease in the number of corneal transplants performed in patients with KC 15 years after the introduction of CXL. This indicates that the availability of CXL treatment over many years may considerably reduce the need for keratoplasties in this group of patients.


Granulocyte transfusions in the management of invasive fungal infections.
Granulocyte transfusions have a long history of being used in patients with neutropenia or neutrophil dysfunction to prevent and treat invasive fungal infections. However, there are limited and conflicting data concerning its clinical effectiveness, considerable variations in current granulocyte transfusion practices, and uncertainties about its benefit as an adjunct to modern antifungal therapy. In this review, we provide an overview on granulocyte transfusions and summarize the evidence on their role in the prevention and treatment of invasive fungal infections.


Observations on the host specificity of Pomphorhynchus patagonicus (Acanthocephala) from the Alicura Reservoir (Patagonia, Argentina).
The acanthocephalan Pomphorhynchus patagonicus was found in 3 species of fish in the Alicura Reservoir (Patagonia, Argentina). These included Oncorhynchus mykiss, Patagonina hatcheri, and Percichthys trucha. Prevalence, intensity, size of the parasites, and percentage of gravid females were analyzed. The relatively low prevalence and intensity were probably due to the low consumption of the intermediate host, Hyalella patagonica. The highest values of intensity, length, and percentage of gravid females were found in Percichthys trucha. This species is considered to be the preferred host of P. patagonicus in the reservoir. No mature eggs were found in O. mykiss; this, together with the parasite's low growth rate, underlines the hypothesis that this species is not a suitable host for P. patagonicus.


Combination therapy of rosiglitazone, a peroxisome proliferator-activated receptor-gamma ligand, and NMDA receptor antagonist (MK-801) on experimental embolic stroke in rats.
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists have been found to have potent anti-inflammatory actions and suggested as potential therapies for brain ischaemia. Glutamate is the most common excitatory neurotransmitter in the central nervous system and is released excessively during ischaemia. Stroke therapy will require combinations of drug classes, because no single drug class has yet been proven efficacious in human beings. The present study was conducted to assess whether N-methyl-d-aspartate (NMDA) receptor antagonist (MK-801) treatment can improve recovery from ischaemic brain injury and whether rosiglitazone, a PPAR-gamma ligand, can increase its neuroprotective effect in an embolic model of stroke. Stroke was induced in rats by embolizing a preformed clot into the middle cerebral artery. Rosiglitazone (0.1 mg/kg, intraperitoneally) and MK-801 (0.1 mg/kg, intravenously) were injected immediately after embolization. Forty-eight hours later, the brains were removed, sectioned and stained with triphenyltetrazolum chloride and analysed by a commercial image processing software programme. Rosiglitazone and MK-801 alone or in combination decreased infarct volume by 49.16%, 50.26% and 81.32%, respectively (P < 0.001). Moreover, the combination therapy significantly decreased the infarct volume when compared to any drug used alone (P < 0.05). MK-801 reduced the brain oedema by 68% compared to the control group (P < 0.05), but rosiglitazone or combination did not show any significant effect. The drugs alone or in combination also demonstrated improved neurological function, but combination therapy was more effective on neurological deficits improving. Our data show that the combination of MK-801 and rosiglitazone is more neuroprotective in thromboembolic stroke than given alone; this effect perhaps represents a possible additive effect in the brain infarction.


A Micropatterning Assay for Measuring Cell Chirality.
Chirality is an intrinsic cellular property, which depicts the asymmetry in terms of polarization along the left-right axis of the cell. As this unique property attracts increasing attention due to its important roles in both development and disease, a standardized quantification method for characterizing cell chirality would advance research and potential applications. In this protocol, we describe a multicellular chirality characterization assay that utilizes micropatterned arrays of cells. Cellular micropatterns are fabricated on titanium/gold-coated glass slides via microcontact printing. After seeding on the geometrically defined (e.g., ring-shaped), protein-coated islands, cells directionally migrate and form a biased alignment toward either the clockwise or the counterclockwise direction, which can be automatically analyzed and quantified by a custom-written MATLAB program. Here we describe in detail the fabrication of micropatterned substrates, cell seeding, image collection, and data analysis and show representative results obtained using the NIH/3T3 cells. This protocol has previously been validated in multiple published studies and is an efficient and reliable tool for studying cell chirality in vitro.


Secure Screw Placement in Management of Acetabular Fractures Using the Suprapectineal Quadrilateral Buttress Plate.
Acetabular fractures involving predominantly the anterior column associated with a disruption of the quadrilateral surface can be treated with instrumentation implementing the stabilization of the quadrilateral surface. The recently introduced suprapectineal quadrilateral buttress plate is specifically designed to prevent secondary medial subluxation of the femoral head, especially in elderly patients with reduced ability for partial weight bearing. Whereas there are guidelines available for safe screw fixation for the anterior and posterior columns, there might be a concern for intra-articular placement of screws placed through the infrapectineal part of the quadrilateral buttress plate. Within this report we analyzed retrospectively screw placement in 30 plates in postoperative CT scans using algorithms for metal artifact reduction. None of the screws of the buttress plate penetrated the hip joint. We describe the placement, length, and spatial orientation of the screws used for fracture fixation and suggest that the use of intraoperative image intensifiers with a combined inlet-obturator view of 30-45° best projects the screws and the hip joint. Preoperative knowledge of approximate screw placement and information for accurate intraoperative imaging may contribute to safe acetabular fracture fixation and may reduce operating time and limit radiation exposure to the patient and the personnel. This trial is registered with KEK-BE: 266/2014.


Cesarean section on a rise-Does advanced maternal age explain the increase? A population register-based study.
In Denmark, the cesarean section rate has increased by 49% between 1998 and 2015 and accounts for 21% of all births. Cesarean sections may cause short- as well as long-term consequences for both the mother and the child and impose further risks in future pregnancies. Delaying pregnancy until advanced maternal age at childbirth has been suggested as contributing to the increase. The proportion of women giving birth at 35 years or above increased from 15% (1998) to 21% (2015). Advanced maternal age at childbirth has been found to be related to increased pre-pregnancy morbidity and associated risk factors that may contribute to an increased risk of cesarean section. The aim of this study was to examine the association between advanced maternal age and cesarean section in a Danish population and the influence of demographic, anthropometric, health, and obstetric factors on this association. This study draws on a national population-based cohort study of all Danish births between 1998 and 2015 (N = 1,122,964). Maternal age less than 30 years serves as reference with the following age categories: (30-34 years); (35-39 years), and (40 years and above). The primary outcome was a cesarean section. Multivariate regression models with adjustment for demographic, health, pregnancy, fetal, and obstetric characteristics were performed with the results further stratified by parity. In general, a positive association between advanced maternal age and cesarean section was found. Only minor changes in the risk estimate occurred after adjustment for relevant confounders. In comparison with the reference category, nulliparous women aged 35-39- years had twice the risk for cesarean section (adjusted odds ratio (AOR) 2.18, 95% confidence interval (CI) [2.11-2.26]) whereas for women of 40 years or above, the risk was more than tripled (AOR 3.64, 95% CI [3.41-3.90]). For multiparous women aged 35-39-years the risk was more moderate, but still with an AOR of 1.56, 95% CI [1.53-1.60], and for those 40 years and above, the AOR was 2.02, 95% CI [1.92-2.09]. Overall, cesarean section increased with increasing maternal age. Adjustment for maternal and obstetric risk factors had only a minor influence on the association. The association was stronger in nulliparous women compared to multiparous women. Given the lack of impact of demographic and health risks on the relationship between maternal age and cesarean section, the authors suggest obstetric culture could be added to the list of risk factors for a cesarean. Future research on obstetric culture is recommended as are studies on a possible age-related decrease in the ability to maintain the progression of labor. The study uses depersonalized register data and has been approved by the Danish Data Protection Agency (2015-41-4168).


Asymmetric distribution of type IV pili triggered by directional light in unicellular cyanobacteria.
The type IV pili (T4P) system is a supermolecular machine observed in prokaryotes. Cells repeat the cycle of T4P extension, surface attachment, and retraction to drive twitching motility. Although the properties of T4P as a motor have been scrutinized with biophysics techniques, the mechanism of regulation remains unclear. Here we provided the framework of the T4P dynamics at the single-cell level in Synechocystis sp. PCC6803, which can recognize light direction. We demonstrated that the dynamics was detected by fluorescent beads under an optical microscope and controlled by blue light that induces negative phototaxis; extension and retraction of T4P was activated at the forward side of lateral illumination to move away from the light source. Additionally, we directly visualized each pilus by fluorescent labeling, allowing us to quantify their asymmetric distribution. Finally, quantitative analyses of cell tracking indicated that T4P was generated uniformly within 0.2 min after blue-light exposure, and within the next 1 min the activation became asymmetric along the light axis to achieve directional cell motility; this process was mediated by the photo-sensing protein, PixD. This sequential process provides clues toward a general regulation mechanism of T4P system, which might be essentially common between archaella and other secretion apparatuses.


UCK2 upregulation might serve as an indicator of unfavorable prognosis of hepatocellular carcinoma.
Uridine-cytidine kinases (encoded by UCK1, UCKL1, and UCK2) catalyze the phosphorylation of uridine and cytidine to uridine monophosphate (UMP) and cytidine monophosphate (CMP). In this study, using data from the Cancer Genome Atlas (TCGA), we analyzed the expression profile of uridine-cytidine kinase genes in hepatocellular carcinoma (HCC), their prognostic value, and the epigenetic alterations associated with their dysregulation. Results showed that UCKL1 and UCK2, but not UCK1 were significantly upregulated in HCC tissues than in adjacent normal tissues. Only UCK2 was significantly upregulated in the deceased group and the recurrence group, compared to the control groups. Multivariate analysis confirmed that increased UCK2 expression was an independent prognostic indicator of shorter overall survival (OS) (HR: 1.760, 95% CI: 1.398-2.216, P < 0.001) and recurrence-free survival (RFS) (HR: 1.543, 95% CI: 1.232-1.933, P < 0.001). Two CpG sites (cg09277749 and cg21143899) were significantly hypomethylated in HCC tissues than in adjacent normal tissues and were negatively correlated with UCK2 expression. However, survival analysis showed that only high methylation of cg0927774 was associated with better OS and RFS of HCC patients. Based on the findings above, we infer that UCK2 upregulation might be a valuable prognostic marker in HCC. The methylation of status cg0927774 might play a critical role in its expression. © 2018 IUBMB Life, 71(1):105-112, 2019.


Studies on Escherichia coli as a cause of acute diarrhoea in Calcutta.
The prevalence of different types of diarrhoea-producing Escherichia coli among 240 patients with acute diarrhoea in hospital was investigated. The 25 patients (10.4% of the total) from whose faeces we isolated enteropathogenic E. coli (EPEC) were all less than 5 years old but the 29 (12.1%) from whom we isolated enterotoxigenic E. coli (ETEC) were of various ages, most of them greater than 12 years old. No enteroinvasive E. coli (EIEC) strains were isolated. ETEC strains that produced heat-labile toxin (LT) were encountered more often than those that produced either heat-stable toxin (ST) alone or both LT and ST. The ETEC isolates were distributed among eight different serotypes, the commonest being O148:H28 (38%). Correlations between enterotoxin production, serotype pattern and possession of colonisation factor antigens I and II were observed.


Impact of the intensive use of urban construction land on carbon emission efficiency: evidence from the urban agglomeration in the middle reaches of the Yangtze River.
Urban construction land, as the main carrier of socioeconomic activities, is also a land type that is associated with large carbon emissions. This study uses statistical data of the urban agglomeration in the middle reaches of the Yangtze River (UAMRYR) from 2006 to 2020 to examine the mechanism of the intensive use of urban construction land (IUUCL) on carbon emission efficiency (CEE) from the perspective of urban land resource utilization. The study shows that the capital-intensive and technology-intensive use of urban construction land can significantly increase CEE, while increased labor and energy intensification inhibits CEE. In addition, there is regional heterogeneity in the effect of the IUUCL on CEE. The external control factor industrial structure has the most obvious inhibiting effect on the CEE of the Wuhan urban circle, the intensive use of energy has become the crucial constraint on the carbon emission reduction of the city cluster around Poyang Lake, and the intensive use of science and technology is the key factor in realizing the green and low-carbon development of the Chang-Zhu-Tan city cluster. This study innovatively constructs a theoretical framework of IUUCL versus CEE and conducts a heterogeneous study on the CEE of intensive use of construction land from the perspective of urban agglomerations. By providing a better understanding of the intrinsic influence mechanism of both these processes, this study provides a new perspective for reducing carbon emissions.


Immobilization of antimony waste slag by applying geopolymerization and stabilization/solidification technologies.
During the processing of antimony ore by pyrometallurgical methods, a considerable amount of slag is formed. This antimony waste slag is listed by the European Union as absolutely hazardous waste with a European Waste Catalogue code of 10 08 08. Since the levels of antimony and arsenic in the leachate of the antimony waste slag are generally higher than the landfilling limits, it is necessary to treat the slag before landfilling. In this study, stabilization/solidification and geopolymerization technologies were both applied in order to limit the leaching potential of antimony and arsenic. Different combinations ofpastes by using Portland cement, fly ash, clay, gypsum, and blast furnace slag were prepared as stabilization/solidification or geopoljymer matrixes. Sodium silicate-sodium hydroxide solution and sodium hydroxide solution at 8 M were used as activators for geopolymer samples. Efficiencies of the combinations were evaluated in terms of leaching and unconfined compressive strength. None of the geopolymer samples prepared with the activators yielded arsenic and antimony leaching below the regulatory limit at the same time, although they yielded high unconfined compressive strength levels. On the other hand, the stabilization/solidification samples prepared by using water showed low leaching results meeting the landfilling criteria. Use of gypsum as an additive was found to be successful in immobilizing the arsenic and antimony.


[The diagnostic value of high-resolution ultrasonography for detecting anterior disc displacement without reduction of temporomandibular joint].
To assess the diagnostic value of high-resolution ultrasonography for detecting of anterior disc displacement without reduction (ADDWR) of temporomandibular joint (TMJ). Thirty-five participants with 40 TMJs which were initially diagnosed as ADDWR were included. All the participants got both high-resolution ultrasonography and MRI examination. The results of MRI in diagnosis of ADDWR were considered as gold standard. Sensitivity, specificity, accuracy, positive predict value, negative predict value, positive likelihood ratio and negative likelihood ratio were calculated. In 40 TMJs, MRI revealed that there were 23 TMJs with ADDWR, and 17 disease-free. The sensitivity, specificity, accuracy, positive predict value, negative predict value, positive likelihood ratio and negative likelihood ratio of high-resolution ultrasonography were 82.6%, 94.1%, 92.5%, 0.95, 0.80, 14.04, 0.19, respectively. The high-resolution ultrasonography has a relatively high diagnostic value in detecting ADDWR of TMJ.


Moderate haemophilia B in a female carrier caused by preferential inactivation of the paternal X chromosome.
The case of a female with moderate haemophilia B is reported. She is the only affected member of her family, and factor IX RFLP analysis shows her to have inherited no maternal markers for polymorphisms located in the first intron and 8 Kb 3' of the polyadenylation signal (DdeI and HhaI, respectively). This clearly indicates a deletion involving at least the last 7 exons of the factor IX gene. Her other factor IX gene inherited from her healthy father is normal as her son is also healthy. This suggests the patient's haemophilia to be due to gross bias in the proportion of factor IX-producing cells with an inactive paternal X chromosome. Methylation studies on the 5' region of the PGK gene show that virtually all the patient's lymphocytes carry a hypermethylated and presumably an inactive paternal X chromosome. The reason for this bias in the activity of her two X chromosomes is not clear, as no chromosomal alterations were found.


Working Alliance, Interpersonal Problems, and Depressive Symptoms in Tele-Interpersonal Psychotherapy for HIV-infected Rural Persons: Evidence for Indirect Effects.
Interpersonal psychotherapy (IPT) has demonstrated efficacy for the treatment of depression, yet little is known about its therapeutic mechanisms. As a specific treatment, IPT has been shown to directly reduce depressive symptoms, although it is unclear whether these reductions occur via interpersonal changes. Within IPT, the potential role of the working alliance, a common factor, as a predictor of depression and interpersonal changes is also unclear. Participants were 147 depressed persons living with HIV in rural communities of 28 U.S. states enrolled in a randomized clinical trial. Seventy-five patients received up to 9 sessions of telephone-administered IPT (tele-IPT) plus standard care and 72 patients received standard care only. Two models were tested; one included treatment condition (tele-IPT vs. control) and another included the working alliance as independent variables. The first model found an indirect effect whereby tele-IPT reduced depression via decreased social avoidance. There was a direct effect between tele-IPT and reduced depression. In the second model, the working alliance influenced depressive symptom relief via reductions in social avoidance. Both goal and task working alliance subscales were indirectly associated with reductions in depressive symptoms, also through reductions in social avoidance. There were no direct effects involving the working alliance. Tele-IPT's influence on depressive symptom reduction was primarily through a direct effect, whereas the influence of working alliance depression was almost entirely via an indirect effect through interpersonal problems. Study findings have implications for IPT when intervening with depressed rural people living with HIV/AIDS over the telephone.


Thyroid paraganglioma: a case series of a rare head and neck tumor.
Thyroid paragangliomas are rare neuroendocrine tumors. We present two cases analyzing their clinical presentation and pathology findings. A 44-year-old woman presented with a 33 mm left thyroid lobe mass. A 27-year-old male presented with a 27-mm right thyroid lobe mass and a FNA biopsy suggesting a follicular thyroid tumor. Both patients underwent total thyroidectomy. Vigorous bleeding was noted on the first case. Histologic sections revealed encapsulated tumors, whereas immunochemical stains were positive for chromogranin A, synaptophysin and NSE and negative for thyroglobulin, calcitonin, CEA and S-100. After an 18- and 12-month follow-up, respectively, both patients have no signs of local recurrence or distant metastasis. Preoperative diagnosis of thyroid paragangliomas was never attained in this series. Immunohistochemistry is mandatory for proper differential diagnosis. For the surgeon, the operation is technically demanding mainly due to the increased vascularity and friability of the tumor.


Structural determinants of vascular endothelial growth factor-D receptor binding and specificity.
Vascular endothelial growth factors (VEGFs) and their tyrosine kinase receptors (VEGFR-1-3) are central mediators of angiogenesis and lymphangiogenesis. VEGFR-3 ligands VEGF-C and VEGF-D are produced as precursor proteins with long N- and C-terminal propeptides and show enhanced VEGFR-2 and VEGFR-3 binding on proteolytic removal of the propeptides. Two different proteolytic cleavage sites have been reported in the VEGF-D N-terminus. We report here the crystal structure of the human VEGF-D Cys117Ala mutant at 2.9 Å resolution. Comparison of the VEGF-D and VEGF-C structures shows similar extended N-terminal helices, conserved overall folds, and VEGFR-2 interacting residues. Consistent with this, the affinity and the thermodynamic parameters for VEGFR-2 binding are very similar. In comparison with VEGF-C structures, however, the VEGF-D N-terminal helix was extended by 2 more turns because of a better resolution. Both receptor binding and functional assays of N-terminally truncated VEGF-D polypeptides indicated that the residues between the reported proteolytic cleavage sites are important for VEGF-D binding and activation of VEGFR-3, but not of VEGFR-2. Thus, we define here a VEGFR-2-specific form of VEGF-D that is angiogenic but not lymphangiogenic. These results provide important new insights into VEGF-D structure and function.


Associations Between Feeding Problems and Maternal Sensitivity Across Infancy: Differences in Very Preterm and Full-Term Infants.
To determine the influence of maternal sensitivity on infant feeding problems in very preterm/very low birth weight (VP/VLBW) and full-term (FT) infants. Longitudinal study of 178 infants (73 VP/VLBW and 105 FT). Feeding problems and maternal sensitivity were assessed at term, 3 and 18 months. A cross-lagged path model was tested to assess the longitudinal associations. The direction of the association between maternal sensitivity and feeding problems differed among VP/VLBW and FT infants. In VP/VLBW infants, higher feeding problems at term and 3 months were associated with less maternal sensitivity at 3 months (β = -.27, p < .05) and at 18 months (β = -.36, p < .05), respectively. In FT infants, a reciprocal relationship of feeding problems and maternal sensitivity over time was found. Feeding problems at 3 months were associated with decreased maternal sensitivity at 18 months (β = -.32, p < .05), whereas decreased maternal sensitivity at 3 months was related to increased feeding problems at 18 months (β = -.25, p < .05). Feeding problems are frequent in VP/VLBW infants and subsequently are associated with poorer maternal sensitivity. In FT infants, poorer levels of maternal sensitivity were both predicted by feeding problems but also were associated with more feeding problems over time.


Ab Initio Calculations for Spin-Gaps of Non-Heme Iron Complexes.
We employed our recently proposed multireference approach CASPT2/CC to calculate the quintet-triplet gaps ΔETQ of a series of non-heme FeIV═O species and subsequently used these results to benchmark density functional theory (DFT) as well as two variants of local coupled-cluster approaches (DLPNO-CCSD(T) and LUCCSD(T0)). We showed that current implementations of the local coupled-cluster method are not sufficiently accurate. DLPNO-CCSD(T) systematically overstabilizes the quintet state, whereas LUCCSD(T0) overestimates the triplet one. This sort of systematic bias may be helpful in improving local correlation methods and can also be used as the basis for a simple correction scheme.


A Review of the Association of Blue Food Coloring With Attention Deficit Hyperactivity Disorder Symptoms in Children.
Attention Deficit Hyperactivity Disorder, also known as ADHD, is a neurodevelopmental disorder diagnosed in children. The exact cause of ADHD is not known, but, along with genetic factors, it is possible that environmental factors including toxins and diet may affect symptom severity. Of these dietary components, artificial food coloring (AFC), while approved by the Food and Drug Administration (FDA), has been suspected to be associated with ADHD symptoms. Of the nine FDA-certified food colors, two are used for artificial blue coloring: Blue No. 1 and Blue No. 2. There is limited literature describing the possible role of blue AFC in causing symptoms of ADHD in children. This paper provides a review of the literature surrounding artificial food coloring and its ability to affect the neurodevelopment of children in a way that could increase the behavioral indicators of ADHD. To do this, search criteria were established using a combination of MeSH terms about blue AFCs and ADHD and were entered into PubMed, along with limits on article types and publication dates from January 2000 to June 2022. There was a total of 20 articles that met this search criterion. These articles were reviewed by authors, and the ones not relevant to the topic were excluded. In total, four studies were chosen to be included in this article. After reviewing the literature, it was found that restriction diets, specifically those excluding AFCs, may affect symptom severity. The source of these changes is not known, but possible mechanisms include AFCs causing nutritional deficiencies and allergic reactions or altering neurotransmitter levels. More research is necessary to describe the neurotoxicity of artificial blue dyes in humans.


Nitric oxide in vascular biology.
Nitric oxide is a highly versatile heterodiatomic molecule that effects a variety of actions in the vasculture. Originally identified as a principal determination of vascular tone, nitric oxide has since been recognized to exert anti thrombotic, antiproliferative, and anti-inflammatory effects in the vasculture. At higher concentrations and in the setting of other oxidants, nitric oxide can promote vascular pathology. In this review, we summarize the molecular mechanisms of nitric oxides actions in vascular biology and pathology.


Correlated vibration-solvent effects on the non-Condon exciton spectroscopy.
Excitation energy transfer is crucially involved in a variety of systems. During the process, the non-Condon vibronic coupling and the surrounding solvent interaction may synergetically play important roles. In this work, we study the correlated vibration-solvent influences on the non-Condon exciton spectroscopy. Statistical analysis is elaborated for the overall vibration-plus-solvent environmental effects. Analytic solutions are derived for the linear absorption of monomer systems. General simulations are accurately carried out via the dissipaton-equation-of-motion approach. The resulted spectra in either the linear absorption or strong field regime clearly demonstrate the coherence enhancement due to the synergetic vibration-solvent correlation.


Botulinum toxin for cerebral palsy; where are we now?
In this article, the evidence base for botulinum-A treatment acquired in recent years is outlined, and the practicalities involved in providing this service are described. Botulinum-A is relatively new, and possible improvements for the future are considered.