Ultrasound evaluation of diaphragmatic mobility in different postures in healthy subjects.
To assess, using ultrasound, the effects that changes in body position have on diaphragmatic mobility in healthy subjects during spontaneous breathing. The study involved seven healthy female volunteers, all of whom were nonsmokers, well nourished, and free of any cardiopulmonary disease. They were submitted to pulmonary function testing and ultrasound evaluation of the mobility of the right diaphragm by the craniocaudal displacement of the left branch of the portal vein using an ultrasound device in mode B. The mobility of the right diaphragm was evaluated in right decubitus and in left decubitus. The order of evaluation was previously determined in a random drawing. The average mobility of the right diaphragm in right decubitus (51.30 +/- 9.69 mm) was significantly higher (p = 0.03) than that observed in left decubitus (45.93 +/- 10.37 mm). The results suggest that, during spontaneous ventilation, the dependent portion of the diaphragm presents greater mobility than does the nondependent portion, and that the technique used was sufficiently sensitive to detect variations in diaphragmatic mobility related to changes in posture.


Bony healing of large cranial and mandibular defects protected from soft-tissue interposition: A comparative study of spontaneous bone regeneration, osteoconduction, and cancellous autografting in dogs.
The purpose of this study was to compare spontaneous bone regeneration, osteoconduction, and bone autografting in critical size calvarial and mandibular defects (defects which do not heal spontaneously during the lifetime of the animal) that were protected from soft-tissue interposition. Eighteen adult mongrel dogs underwent osteotomies to create a unilateral 30-mm segmental defect in the midbody of the edentulated right mandible and bilateral 15-mm x 20-mm full-thickness window defects in the parietal bones. The defects were either left empty, implanted with coralline hydroxyapatite (HA) blocks, or autografted with iliac cancellous bone. All defects were protected with a macroporous titanium mesh and the segmental mandibular defects were additionally stabilized by internal plate fixation. Specimens were retrieved after 2 and 4 months and three undecalcified longitudinal central sections including the osteotomy interfaces were prepared from each specimen for histometry and histology. Sections were analyzed for volume fractions of bone, soft tissue, and implant using scanning electron microscopy, backscatter electron imaging and histometric computer software. In the mandibular model, the empty defects exhibited the greatest amount of bone formation after 4 months (47.3 percent), which was greater than the amount of bone in the autografted group (34.8 percent) and significantly greater than the amount of bone within the hydroxyapatite implants (19.0 percent, p < 0.05). In the cranial defects, the autografted specimens demonstrated the greatest volume fraction of bone after 4 months (27.3 percent), which was significantly greater than within both the empty defects (18.2 percent, p < 0.05) and the hydroxyapatite implants (18.2 percent, p < 0.05). New bone formation in the mandibular defects united the cut ends at 4 months regardless of treatment and originated predominantly from the periosteum which remained present only along the alveolar border after surgical closure. In the calvarial defects, periosteum was not preserved and bone regenerated centripetally, originating from the diploë without any evidence of dural osteogenesis. Bone bridging was incomplete in the empty cranial defects at 4 months. In both the mandibular and cranial specimens, new bone at 2 months was a mixture of woven and parallel fibered bone. At 4 months, the new bone had remodeled almost entirely into mature Haversian bone. This study demonstrated a remarkable ability of defect protection with a macroporous protective sheet to facilitate bone regeneration in critical size mandibular and cranial bone defects. When active osteogenic periosteum was present, as in our mandibular model, we concluded that defect protection alone was sufficient to allow for healing even of critical size defects. When periosteum was absent as in our cranial defects, the limited spontaneous bone formation benefited from the added contributions of cancellous grafting and osteoconductive implants, both of which promoted bone bridging across the defects. We suggest that in the future a resorbable macroporous protective sheet would be advantageous in comparison to a titanium mesh to facilitate bone regeneration by preventing soft-tissue prolapse and allowing the migration of mesenchymal cells and the proliferation of blood vessels from the adjacent soft tissues into the bone defect. Finally, this study identified the need to differentiate critical size defects into those with and without defect protection and periosteum.


Inpainting Saturation Artifact in Anterior Segment Optical Coherence Tomography.
The cornea is an important refractive structure in the human eye. The corneal segmentation technique provides valuable information for clinical diagnoses, such as corneal thickness. Non-contact anterior segment optical coherence tomography (AS-OCT) is a prevalent ophthalmic imaging technique that can visualize the anterior and posterior surfaces of the cornea. Nonetheless, during the imaging process, saturation artifacts are commonly generated due to the tangent of the corneal surface at that point, which is normal to the incident light source. This stripe-shaped saturation artifact covers the corneal surface, causing blurring of the corneal edge, reducing the accuracy of corneal segmentation. To settle this matter, an inpainting method that introduces structural similarity and frequency loss is proposed to remove the saturation artifact in AS-OCT images. Specifically, the structural similarity loss reconstructs the corneal structure and restores corneal textural details. The frequency loss combines the spatial domain with the frequency domain to ensure the overall consistency of the image in both domains. Furthermore, the performance of the proposed method in corneal segmentation tasks is evaluated, and the results indicate a significant benefit for subsequent clinical analysis.


An epidemiological survey of hemoplasma infection in Iriomote cats (Prionailurus bengalensis iriomotensis).
An epidemiological survey of Iriomote cats (Prionailurus bengalensis iriomotensis) was conducted to understand the prevalence and molecular characteristics of hemotropic mycoplasma (hemoplasma). A series of ecological surveys of Iriomote cats were performed between November 2003 and September 2010. During this period, 31 Iriomote cats were captured or found, and 39 blood samples were collected. Polymerase chain reaction screening for hemoplasmas and BLAST searches revealed that 4 of the 31 cats were positive for hemoplasma infection (n=3, Mycoplasma haemofelis [Mhf]; n=1, 'Candidatus M. turicensis' [CMt]). The 4 infected cats were captured or found in the northern area of the island of Iriomote. Phylogenetic analyses revealed close relationships between Mhf and CMt isolated from Iriomote cats compared with those from domestic cats and other wild felids. In our study, we identified two species of hemoplasma in Iriomote cats. The number and location of the hemoplasma-positive cats appeared to be limited; however, continuous surveillance of hemoplasma infection in Iriomote cats is necessary.


Efficacy and Safety of Everolimus and Mycophenolic Acid With Early Tacrolimus Withdrawal After Liver Transplantation: A Multicenter Randomized Trial.
SIMCER was a 6-mo, multicenter, open-label trial. Selected de novo liver transplant recipients were randomized (week 4) to everolimus with low-exposure tacrolimus discontinued by month 4 (n = 93) or to tacrolimus-based therapy (n = 95), both with basiliximab induction and enteric-coated mycophenolate sodium with or without steroids. The primary end point, change in estimated GFR (eGFR; MDRD formula) from randomization to week 24 after transplant, was superior with everolimus (mean eGFR change +1.1 vs. -13.3 mL/min per 1.73 m2 for everolimus vs. tacrolimus, respectively; difference 14.3 [95% confidence interval 7.3-21.3]; p < 0.001). Mean eGFR at week 24 was 95.8 versus 76.0 mL/min per 1.73 m2 for everolimus versus tacrolimus (p < 0.001). Treatment failure (treated biopsy-proven acute rejection [BPAR; rejection activity index score >3], graft loss, or death) from randomization to week 24 was similar (everolimus 10.0%, tacrolimus 4.3%; p = 0.134). BPAR was more frequent between randomization and month 6 with everolimus (10.0% vs. 2.2%; p = 0.026); the rate of treated BPAR was 8.9% versus 2.2% (p = 0.055). Sixteen everolimus-treated patients (17.8%) and three tacrolimus-treated patients (3.2%) discontinued the study drug because of adverse events. In conclusion, early introduction of everolimus at an adequate exposure level with gradual calcineurin inhibitor (CNI) withdrawal after liver transplantation, supported by induction therapy and mycophenolic acid, is associated with a significant renal benefit versus CNI-based immunosuppression but more frequent BPAR.


Early marriage and early childbearing in South Asia: trends, inequalities, and drivers from 2005 to 2018.
Early marriage (EM) and early childbearing (ECB) have far-reaching consequences. This study describes the prevalence, trends, inequalities, and drivers of EM and ECB in South Asia using eight rounds of Demographic and Health Survey data across 13 years. We report the percentage of ever-married women aged 20-24 years (n = 105,150) married before 18 years (EM) and with a live birth before 20 years (ECB). Relative trends were examined using average annual rate of reduction (AARR). Inequalities were examined by geography, marital household wealth, residence, and education. Sociodemographic drivers of changes for EM were assessed using regression decomposition analyses. We find that EM/ECB are still common in Bangladesh (69%/69%), Nepal (52%/51%), India (41%/39%), and Pakistan (37%/38%), with large subnational variation in most countries. EM has declined fastest in India (AARR of -3.8%/year), Pakistan (-2.8%/year), and Bangladesh (-1.5%/year), but EM elimination by 2030 will not occur at these rates. Equity analyses show that poor, uneducated women in rural areas are disproportionately burdened. Regression decomposition analysis shows that improvements in wealth and education explained 44% (India) to 96% (Nepal) of the actual EM reduction. Investments across multiple sectors are required to understand and address EM and ECB, which are pervasive social determinants of maternal and child wellbeing.


The Utility Of Pre-Procedural COVID-PCR Testing For Dental Aerosol Generating Procedures Is Questionable.
To compare the number of aerosol-generating procedures performed and the number of coronavirus disease-2019-positive workers in dental practice. The audit study was conducted in May 2021 at the Aga Khan University Hospital, Karachi, and comprised data from April 1, 2020, to March 31, 2021, which was retrieved from dental clinics at the main hospital and its Clifton branch as well as in three secondary care hospitals in Garden, Kharadar, Karimabad areas of Karachi, and one in Hyderabad, Pakistan. Data of individuals who followed mandatory pre 20 procedural polymerase chain reaction testing in addition to using personal protective equipment in the main hospital and Clifton branch was placed in group A, and of those using personal protective equipment only at the 4 satellite clinics with no testing was placed in group B. Dental charts of patients who underwent dental aerosol-generating procedures were analysed. Number of dental clinics affected by coronavirus disease 25 2019 and number of dental patients who were reported positive on pre-procedural polymerase chain reaction testing were evaluated. Data was analysed using SPSS 23. Of the 63 dental healthcare workers, 44(69.8%) were in group A and 19(30.2%) were in group B. In group A, 19(43.2%) were affected by coronavirus disease-2019 compared to 2(11%) in group B (p=0.01). Among 782(67.8%) patients who underwent polymerase chain reaction testing, 26(3.3%) turned out positive for coronavirus disease-2019. Due to the mandatory testing imposed on patients, 371/1153(32.2%) refused to get the desired dental treatment. The benefit of pre-procedural testing in dentistry remained uncertain.


Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome.
Glasdegib is a Hedgehog pathway inhibitor. This phase II, randomized, open-label, multicenter study (ClinicalTrials.gov, NCT01546038) evaluated the efficacy of glasdegib plus low-dose cytarabine (LDAC) in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome unsuitable for intensive chemotherapy. Glasdegib 100 mg (oral, QD) was administered continuously in 28-day cycles; LDAC 20 mg (subcutaneous, BID) was administered for 10 per 28 days. Patients (stratified by cytogenetic risk) were randomized (2:1) to receive glasdegib/LDAC or LDAC. The primary endpoint was overall survival. Eighty-eight and 44 patients were randomized to glasdegib/LDAC and LDAC, respectively. Median (80% confidence interval [CI]) overall survival was 8.8 (6.9-9.9) months with glasdegib/LDAC and 4.9 (3.5-6.0) months with LDAC (hazard ratio, 0.51; 80% CI, 0.39-0.67, P = 0.0004). Fifteen (17.0%) and 1 (2.3%) patients in the glasdegib/LDAC and LDAC arms, respectively, achieved complete remission (P < 0.05). Nonhematologic grade 3/4 all-causality adverse events included pneumonia (16.7%) and fatigue (14.3%) with glasdegib/LDAC and pneumonia (14.6%) with LDAC. Clinical efficacy was evident across patients with diverse mutational profiles. Glasdegib plus LDAC has a favorable benefit-risk profile and may be a promising option for AML patients unsuitable for intensive chemotherapy.


Kinetic basis for the donor nucleotide-sugar specificity of beta1, 4-N-acetylglucosaminyltransferase III.
The kinetic basis of the donor substrate specificity of beta1, 4-N-acetylglucosaminyltransferase III (GnT-III) was investigated using a purified recombinant enzyme. The enzyme also transfers GalNAc and Glc moieties from their respective UDP-sugars to an acceptor at rates of 0.1-0.2% of that for GlcNAc, but Gal is not transferred at a detectable rate. Kinetic analyses revealed that these inefficient transfers, which are associated with the specificity of the enzyme, are due to the much lower V(max) values, whereas the K(m) values for UDP-GalNAc and UDP-Glc differ only slightly from that for UDP-GlcNAc. It was also found that various other nucleotide-Glc derivatives bind to the enzyme with comparable affinities to those of UDP-GlcNAc and UDP-Glc, although the derivatives do not serve as glycosyl donors. Thus, GnT-III does not appear to distinguish UDP-GlcNAc from other structurally similar nucleotide-sugars by specific binding in the ground state. These findings suggest that the specificity of GnT-III toward the nucleotide-sugar is determined during the catalytic process. This type of specificity may be efficient in preventing a possible mistransfer when other nucleotide-sugars are present in excess over the true donor.


Demonstration of weak measurement based on atomic spontaneous emission.
We demonstrate a new type of weak measurement based on the dynamics of spontaneous emission. The pointer in our scheme is given by the Lorentzian distribution characterizing atomic exponential decay via emission of a single photon. We thus introduce weak measurement, so far demonstrated nearly exclusively with laser beams and Gaussian statistics, into the quantum regime of single emitters and single quanta, enabling the exploitation of a wide class of sources that are abundant in nature. We describe a complete analogy between our scheme and weak measurement with conventional Gaussian pointers. Instead of a shift in the mean of a Gaussian distribution, an imaginary weak value is exhibited in our scheme by a significantly slower-than-natural exponential distribution of emitted photons at the postselected polarization, leading to a large shift in their mean arrival time. The dynamics of spontaneous emission offer a broader view of the measurement process than is usually considered within the weak measurement formalism. Our scheme opens the path for the use of atoms and atomlike systems as sensitive probes in weak measurements, one example being optical magnetometry.


The role of "inert" surface chemistry in marine biofouling prevention.
The settlement and colonization of marine organisms on submerged man-made surfaces is a major economic problem for many marine industries. The most apparent detrimental effects of biofouling are increased fuel consumption of ships, clogging of membranes and heat exchangers, disabled underwater sensors, and growth of biofoulers in aquaculture systems. The presently common-but environmentally very problematic-way to deal with marine biofouling is to incorporate biocides, which use biocidal products in the surface coatings to kill the colonizing organisms, into the surface coatings. Since the implementation of the International Maritime Organization Treaty on biocides in 2008, the use of tributyltin (TBT) is restricted and thus environmentally benign but effective surface coatings are required. In this short review, we summarize the different strategies which are pursued in academia and industry to better understand the mechanisms of biofouling and to develop strategies which can be used for industrial products. Our focus will be on chemically "inert" model surface coatings, in particular oligo- and poly(ethylene glycol) (OEG and PEG) functionalized surface films. The reasons for choosing this class of chemistry as an example are three-fold: Firstly, experiments on spore settlement on OEG and PEG coatings help to understand the mechanism of non-fouling of highly hydrated interfaces; secondly, these studies defy the common assumption that surface hydrophilicity-as measured by water contact angles-is an unambiguous and predictive tool to determine the fouling behavior on the surface; and thirdly, choosing this system is a good example for "interfacial systems chemistry": it connects the behavior of unicellular marine organisms with the antifouling properties of a hydrated surface coating with structural and electronic properties as derived from ab initio quantum mechanical calculations using the electronic wave functions of oxygen, hydrogen, and carbon. This short review is written to outline for non-experts the hierarchical structure in length- and timescale of marine biofouling and the role of surface chemistry in fouling prevention. Experts in the field are referred to more specialized recent reviews.


Synchronization of developmental processes and defense signaling by growth regulating transcription factors.
Growth regulating factors (GRFs) are a conserved class of transcription factor in seed plants. GRFs are involved in various aspects of tissue differentiation and organ development. The implication of GRFs in biotic stress response has also been recently reported, suggesting a role of these transcription factors in coordinating the interaction between developmental processes and defense dynamics. However, the molecular mechanisms by which GRFs mediate the overlaps between defense signaling and developmental pathways are elusive. Here, we report large scale identification of putative target candidates of Arabidopsis GRF1 and GRF3 by comparing mRNA profiles of the grf1/grf2/grf3 triple mutant and those of the transgenic plants overexpressing miR396-resistant version of GRF1 or GRF3. We identified 1,098 and 600 genes as putative targets of GRF1 and GRF3, respectively. Functional classification of the potential target candidates revealed that GRF1 and GRF3 contribute to the regulation of various biological processes associated with defense response and disease resistance. GRF1 and GRF3 participate specifically in the regulation of defense-related transcription factors, cell-wall modifications, cytokinin biosynthesis and signaling, and secondary metabolites accumulation. GRF1 and GRF3 seem to fine-tune the crosstalk between miRNA signaling networks by regulating the expression of several miRNA target genes. In addition, our data suggest that GRF1 and GRF3 may function as negative regulators of gene expression through their association with other transcription factors. Collectively, our data provide new insights into how GRF1 and GRF3 might coordinate the interactions between defense signaling and plant growth and developmental pathways.


Selenium Modulates the Allergic Response to Whey Protein in a Mouse Model for Cow's Milk Allergy.
Cow's milk allergy is a common food allergy in infants, and is associated with an increased risk of developing other allergic diseases. Dietary selenium (Se), one of the essential micronutrients for humans and animals, is an important bioelement which can influence both innate and adaptive immune responses. However, the effects of Se on food allergy are still largely unknown. In the current study it was investigated whether dietary Se supplementation can inhibit whey-induced food allergy in an animal research model. Three-week-old female C3H/HeOuJ mice were intragastrically sensitized with whey protein and cholera toxin and randomly assigned to receive a control, low, medium or high Se diet. Acute allergic symptoms, allergen specific immunoglobulin (Ig) E levels and mast cell degranulation were determined upon whey challenge. Body temperature was significantly higher in mice that received the medium Se diet 60 min after the oral challenge with whey compared to the positive control group, which is indicative of impaired anaphylaxis. This was accompanied by reductions in antigen-specific immunoglobulins and reduced levels of mouse mast cell protease-1 (mMCP-1). This study demonstrates that oral Se supplementation may modulate allergic responses to whey by decreasing specific antibody responses and mMCP-1 release.


High-throughput immunophenotyping of 43 ferret lymphomas using tissue microarray technology.
To validate the use of the tissue microarray (TMA) method for immunophenotyping of ferret lymphomas, a TMA was constructed containing duplicate 1-mm cores sampled from 112 paraffin-embedded lymphoma tissue specimens obtained from 43 ferret lymphoma cases. Immunohistochemical (IHC) expression of CD3, CD79alpha, and Ki-67 (MIB-1) was determined by TMA and whole mount (WM) staining of each individual case for result comparison. There was a high correlation between CD79alpha and CD3 results comparing ferret TMA and WM sections (kappa statistic 0.71-0.73 for single-core TMA and 0.79-0.95 for duplicate-core TMA) and between continuous data from Ki-67 staining of ferret TMA sections and WM sections (concordance correlation coefficients 0.77 for single cores and 0.87 for duplicate cores). Subsequently, a panel of commercially available antibodies was applied to the TMA for the analysis of expression in ferret lymphomas. The results of this study confirmed previously published results suggesting specific cross-reactivity of the applied IHC markers (CD3, CD79alpha, Ki67) with ferret lymphoma tissue. Other IHC markers (CD45Ro, bcl2, bcl10, MUM1, CD30, vimentin) were also expressed in subsets of the included ferret lymphomas. Further studies are necessary to determine the usefulness of these markers for diagnostic and prognostic evaluation of ferret lymphomas. In conclusion, the TMA technology was useful for rapid and accurate analysis of protein expression in large archival cohorts of ferret lymphoma cases.


Suppressing Anterior Cingulate Cortex Modulates Default Mode Network and Behavior in Awake Rats.
The default mode network (DMN) is a principal brain network in the mammalian brain. Although the DMN in humans has been extensively studied with respect to network structure, function, and clinical implications, our knowledge of DMN in animals remains limited. In particular, the functional role of DMN nodes, and how DMN organization relates to DMN-relevant behavior are still elusive. Here we investigated the causal relationship of inactivating a pivotal node of DMN (i.e., dorsal anterior cingulate cortex [dACC]) on DMN function, network organization, and behavior by combining chemogenetics, resting-state functional magnetic resonance imaging (rsfMRI) and behavioral tests in awake rodents. We found that suppressing dACC activity profoundly changed the activity and connectivity of DMN, and these changes were associated with altered DMN-related behavior in animals. The chemo-rsfMRI-behavior approach opens an avenue to mechanistically dissecting the relationships between a specific node, brain network function, and behavior. Our data suggest that, like in humans, DMN in rodents is a functional network with coordinated activity that mediates behavior.


Gender, ethnicity, health behaviour & self-rated health in Singapore.
Self-rated health and the factors that influence it have never been described in Singapore before. This paper presents a descriptive study of self-rated health in a nationally representative cross-sectional survey of 6236 persons. As part of the National Health Surveillance Survey 2001, 6236 subjects aged 18 years and above were interviewed in the homes of participants by trained interviewers. The subjects were asked "In general, how would you rate your health today?", and given 5 possible responses. These were then categorized as "Good" (very good and good) and "Poor" (moderate, bad and very bad) self-rated health. The association of socio-economic and health behaviour risk factors with good self-rated health was studied using univariate and multivariate logistic regression analysis. Univariate analyses suggest that gender, ethnicity, marital status, education, household income, age, self-reported doctor-diagnosed illnesses, alcohol intake, exercise and BMI are all associated with poor self-rated health. In multivariate regression analyses, gender, ethnicity, household income, age, self-reported illness and current smoking and BMI were associated with poor self-rated health. There are gender differences in the association of various factors such as household income, smoking and BMI to self-rated health. Socioeconomic factors and health behaviours are significantly associated with self-rated health, and gender differences are striking. We discuss why these factors may impact self-rated health and why gender differences may have been observed, propose directions for further research and comment on the public policy implications of our findings.


Resistance Training Volume Load with and without Exercise Displacement.
Monitoring the resistance training volume load (VL) (sets × reps × load) is essential to managing resistance training and the recovery⁻adaptation process. Eight trained weightlifters, seven of which were at national level, participated in the study. VL was measured both with (VLwD) and without (VL) the inclusion of barbell displacement, across twenty weeks of training, in order to allow for comparisons to be made of these VL calculating methods. This consisted of recording the load, repetition count, and barbell displacement for every set executed. Comparisons were made between VL and VLwD for individual blocks of training, select training weeks, and select training days. Strong, statistically significant correlations (r ≥ 0.78, p < 0.001) were observed between VL and VLwD between all training periods analyzed. t-tests revealed statistically significant (p ≤ 0.018) differences between VL and VLwD in four of the seven training periods analyzed. The very strong relationship between VL and VLwD suggest that a coach with time constraints and a large number of athletes can potentially spare the addition of displacement. However, differences in percent change indicate that coaches with ample time should include displacement in VL calculations, in an effort to acquire more precise workload totals.


An evaluation of a fluorescence polarization immunoassay of thyroxin and thyroxin-uptake.
We evaluated the fluorescence polarization immunoassay for total thyroxin (T4) and thyroxin-uptake (T-U) in the Abbott "TDx" Analyzer. Between-assay precision was good when we did once-fortnightly calibration and assayed samples in singleton. Measured T4 concentration was decreased in hemolyzed samples with obvious red coloration and undetectable in severely hemolyzed samples. The T-U assay was unaffected by hemolysis. Unlike the triiodothyronine-uptake methods, the T-U assay utilizes labeled T4 and measures a variable related to serum thyroxin-binding capacity rather than the concentration of unoccupied binding sites in serum. The T4 and T-U values of 422 samples correlated highly with a T4 (in-house) radioimmunoassay and a commercial assay for thyroxin-binding globulin, respectively. The free thyroxin ratio (ratio of T4 to T-U, FTI) correlated highly with free T4 concentration as measured by T4-analog-tracer radioimmunoassay (fT4 analog RIA). FTI and fT4 values were discordant in late pregnancy (normal FTI and low fT4) and euthyroid sick patients (above-normal or normal FTI and low fT4), suggesting that the FTI gives fewer misleading results in these patients.


[Prevalence of incidental prostatic adenocarcinoma after suprapubic adenomectomy with or without previous prostatic biopsy].
To establish the prevalence of incidental prostate cancer after transrectal ultrasound guided prostatic biopsy and subsequent suprapubic prostatic adenomectomy and to compare it with a similar group of patients who did not underwent biopsy before surgery. To evaluate treatment, outcomes, and disease progression in patients with incidental prostate cancer. Retrospective study of 549 suprapubic adenomectomy performed between 1996-2001 (6 yr.), comparing the group of patients with biopsies before surgery vs. the group of patients without biopsies. 291 (53%) patients did not undergo biopsy before adenomectomy. 258 (47%) underwent biopsies. 25 incidental prostate cancers were detected, 19 (76%) in the group of no biopsy and 6 (24%) in the biopsy group. 88% pT1a and 12%pT1b. Mean Gleason score 4.5 (3-7). 84% of the patients did not receive treatment (21) ("wait and see"); 8% (2) androgen blockade; 8% (2) finasteride (2). Three patients (12%) in the group of no biopsy had disease progression. Mean follow-up was 48.1 months (22-96). No case of cancer-specific mortality was detected. Global prevalence of incidental prostate cancer in our series of patients undergoing suprapubic prostatic adenomectomy was 4.55%. Prevalence was higher in the group of patients without previous biopsy (3.46%) than in the biopsy group (1.09%). Tumor progression was 12% and cancer specific survival 100% after a mean follow-up of 48.1 months (22-92). Previous prostatic biopsy in patients with suspicions digital rectal examination or elevated PSA diminishes the prevalence of incidental prostate cancer. Watchful waiting may be a valid option in some cases.


Body mass index and risk of adenocarcinomas of the esophagus and gastric cardia.
Incidence rates have risen rapidly for esophageal adenocarcinoma and moderately for gastric cardia adenocarcinoma, while rates have remained stable for esophageal squamous cell carcinoma and have declined steadily for noncardia gastric adenocarcinoma. We examined anthropometric risk factors in a population-based case-control study of esophageal and gastric cancers in Connecticut, New Jersey, and western Washington. Healthy control subjects (n = 695) and case patients with esophageal squamous cell carcinoma or noncardia gastric adenocarcinoma (n = 589) were frequency-matched to case patients with adenocarcinomas of esophagus or gastric cardia (n = 554) by 5-year age groups, sex, and race (New Jersey only). Classification of cases by tumor site of origin and histology was determined by review of pathology materials and hospital records. Data were collected using in-person structured interviews. Associations with obesity, measured by body mass index (BMI), were estimated by odds ratios (ORs). All ORs were adjusted for geographic location, age, sex, race, cigarette smoking, and proxy response status. The ORs for esophageal adenocarcinoma rose with increasing adult BMI. The magnitude of association with BMI was greater among the younger age groups and among nonsmokers. The ORs for gastric cardia adenocarcinoma rose moderately with increasing BMI. Adult BMI was not associated with risk of esophageal squamous cell carcinoma or noncardia gastric adenocarcinoma. Increasing prevalence of obesity in the United States population may have contributed to the upward trends in esophageal and gastric cardia adenocarcinomas.


Nitrosoureas: a review of experimental antitumor activity.
The chemical class of drugs known as the nitrosoureas are a recently developed group of very active alkylating-agent anticancer drugs which are best represented by BCNU, CCNU, and methyl-CCNU (meCCNU). The nitrosoureas are among the most active, if not the most active, anticancer drugs both quantitatively (log kill of sensitive tumor cells in vivo) and qualitatively (spectrum of mouse, rat, and hamster tumors responding to treatment). Therapeutic anticancer activity of the nitrosoureas has been consistently observed with oral as well as parenteral administration. The nitrosoureas are clearly the most active group of anticancer drugs observed against experimental meningeal leukemias and intracerebrally implanted transplantable primary tumors of central nervous system origin (eg, gliomas, ependymoblastomas, and astrocytomas in mice and hamsters). The nitrosoureas have been observed to be less than additive in lethal toxicity for vital normal cells in the mouse in combination with representatives of the other major classes of anticancer agents, eg, purine antagonists, pyrimidine antagonists, inhibitors of DNA polymerase(s) or ribonucleotide reductase(s), mitotic inhibitors, drugs that bind to or intercalate with DNA, and other alkylating agents. Therapeutic synergism against one or more transplantable or spontaneous tumors of mice, rats, or hamsters with one of several nitrosoureas in two-drug combinations with representatives of most of the major classes of anticancer agents listed above has been reported. With a number of advanced-stages mouse tumors, generally considered to be refractory to treatment with most anticancer agents, long-term cures have been obtained with combination-drug or combined-modality (surgery plus chemotherapy) treatment. The demonstrated lack of cross-resistance of several leukemias and solid tumors of mice selected for resistance to BCNU, meCCNU, or other alkylating agents suggests that the widely held opinion that all alkylating agents are very similar in biologic mechanism of action, and therefore resistance to one alkylating agent probably predicts cross-resistance to all alkylating agents, may no longer be tenable. If not, then alkylating-agent drug combinations, either used alone or combined with other treatment modalities (eg, surgery) which have been reported to result in therapeutic improvement in a number of experimental murine tumor systems, may be indicated for serious consideration as surgical adjuvant chemotherapy by surgeons or as primary therapy by medical oncologists.


Assessment of Perception and Barriers toward Orthodontic Treatment Needs in the Saudi Arabian Adult Population.
Patients' decisions regarding orthodontic treatment are influenced by a variety of factors, such as their subjective opinions of how their oral cavity looks, age, gender, educational level, and income. The present study aimed to measure the orthodontic treatments needs for the Saudi Arabian population, and also to report potential barriers towards it. It is an observational study with cross sectional design. Data was collected from nationals and residents living in Saudi Arabia and who are at least 18 years old. A total of 1184 adult patients (880 females and 304 males) were included in this study. The population for the study was reached and chosen using a non-probability snowball sampling method. A validated and reliable questionnaire was distributed to the participants electronically through google form. Inferential statistics was applied using Pearson Chi Square test. p value < 0.05 was considered significant. The majority of the sample (73.2%) exhibited a favorable attitude toward orthodontic treatment. Most participants including male and female gender wanted orthodontic treatment primarily to have their protruding teeth fixed. The proportion of persons who cited chewing difficulty as the reason they needed orthodontic treatment was strongly influenced by the monthly income variable (p = 0.005). Cost and time of orthodontic therapy were the biggest obstacles to undergoing treatment, accounting for 34.5% and 19.5%, respectively. There was highly significant difference between the underlying medical conditions and the age and monthly income variables (p = 0.000). Based on the findings of the present study, it can be concluded that protruding teeth are the most important treatment needs perceived by the Saudi population, followed by spacing in between teeth, crowding of teeth, and unaesthetic smile. Cost of the orthodontic treatment was identified as the most significant barrier to the treatment needs, followed by long duration of orthodontic treatment, and pain.


Development of an outcomes management program at an academic medical center.
With the advent of managed care, academic medical centers have been challenged to lower costs and to document their claims of high quality outcomes. A successful method to achieve these objectives must not interfere with the academic missions of research and teaching. At M. D. Anderson Cancer Center, we initiated a program that would reduce practice variability and increase quality with a model that was familiar to the faculty. Professional staff members were divided into disease site groups that included physicians, nurses, and other allied health staff. Each group developed practice guidelines and Collaborative Care Paths, based on evidence in the publications and on expert opinion. Desired outcomes were prospectively defined during this process. Before implementation, paths and guidelines underwent peer review. The faculty actively participated in the development and implementation of the program that was viewed as a means of empowerment to deal with managed care. Nearly 1000 patients have been entered on the B8 paths that have been implemented to date. A physician-driven outcomes management program permits delivery of high quality care and supports outcomes research while decreasing cost in an academic setting.


The kidney in potassium depletion. II. K+ handling by the isolated perfused rat kidney.
In a companion paper we reported a large increment in Na+-K+-ATPase activity and [3H]ouabain binding in the inner stripe of outer medullary collecting tubules from K-depleted rats. To test the hypothesis that the increased number of Na+-K+ pumps in these animals may be involved in potassium reabsorption we examined the effect of ouabain on K excretion by isolated, perfused kidneys from rats fed a K-free diet for 3 wk. Kidneys from K-depleted rats retain potassium avidly, both the fractional (FEK) and absolute K excretion being approximately fivefold lower than in control kidneys. Ouabain (5 mM) increased FEK in kidneys from each K-depleted rat [mean from 8.5 to 34.4%, P less than 0.001, at average (4.5 mM) perfusate K]; similar results were obtained when kidneys were perfused with low (approximately 2 mM) and high (greater than or equal to 8 mM) potassium concentrations. In contrast, ouabain produced a variable effect in control kidneys, that depended on the perfusate potassium concentration. In K-depleted rats amiloride (10(-4) M) did not significantly alter K excretion and did not block the ouabain-induced kaliuresis, suggesting that the latter is not due to enhanced secretion secondary to increased distal fluid delivery. These results provide evidence for ouabain-sensitive potassium reabsorption in kidneys of chronically K-depleted rats, and suggest an explanation for the increased Na+-K+-ATPase observed in such animals.


Commissions and omissions are dissociable aspects of everyday action impairment in schizophrenia.
Prior research using performance-based assessment of functional impairment has informed a novel neuropsychological model of everyday action impairment in dementia in which omission errors (i.e., failure to complete task steps) dissociate from commission errors (i.e., inaccurate performance of task steps) and have unique neuropsychological correlates. However, this model has not been tested in other populations. The present study examined whether this model extends to schizophrenia. Fifty-four individuals with schizophrenia or schizoaffective disorder were administered a neuropsychological protocol and the Naturalistic Action Test (NAT), a performance-based measure of everyday action. A principal component analysis (PCA) was performed to examine the construct(s) comprising everyday action impairment, and correlations between the resultant component(s) and neuropsychological tests were examined. Results showed that omissions and a subset of commissions were distinct components of everyday action. However, results did not support unique associations between these components and specific neuropsychological measures. These findings extend the omission-commission model to schizophrenia and may have important implications for efficient assessment and effective rehabilitation of functional impairment, such as the potential efficacy of targeted interventions for the rehabilitation of omission and commission deficits in everyday functioning. Larger studies with prospective designs are needed to replicate the present preliminary findings.


The long pentraxin PTX3: A prototypical sensor of tissue injury and a regulator of homeostasis.
Tissue damage frequently occurs. The immune system senses it and enforces homeostatic responses that lead to regeneration and repair. The synthesis of acute phase molecules is emerging as a crucial event in this program. The prototypic long pentraxin PTX3 orchestrates the recruitment of leukocytes, stabilizes the provisional matrix in order to facilitate leukocyte and stem progenitor cells trafficking, promotes swift and safe clearance of dying cells and of autoantigens, limiting autoimmunity and protecting the vasculature. These non-redundant actions of PTX3 are necessary for the resolution of inflammation. Recent studies have highlighted the mechanisms by which PTX3 adapts the functions of innate immune cells, orchestrates tissue repair and contributes to select the appropriate acquired immune response in various tissues. Conversely, PTX3 continues to be produced in diseases where the inflammatory response does not resolve. It is therefore a valuable biomarker for more precise and personalized stratification of patients, often independently predicting clinical evolution and outcome. There is strong promise for novel therapies based on understanding the mechanisms with which PTX3 plays its homeostatic role, especially in regulating leukocyte migration and the resolution of inflammatory processes.


Attitudes of registered nurses about the end - of - life care in multi-profile hospitals: a cross sectional survey.
End-of-life care is provided in a variety of healthcare settings, not just palliative care hospitals. This is one reason why it is very important to assess all barriers to end-of-life care and to provide safe and quality services to patients. This study was aimed at describing nurses' attitudes in providing end-of-life care and exploring barriers and facilitating behaviors of nurses in multi-profile hospitals in Eastern Europe. A descriptive, correlational design was applied in this study, using a cross-sectional survey of 1320 registered nurses within 7 hospitals in Lithuania. Registered nurses working in the three different profiles emphasized safe and effective care and the importance of meeting the patient's spiritual needs at the end of life. The main barriers assigned by nurses caring for patients at the end of life were angry family members, inadequate understanding of nursing care by the patient's relatives; lack of time to talk to patients, lack of nursing knowledge to deal with the bereaved patient's family, lack of evaluation of nurses' opinions, and the evasion by physicians to talk about the diagnosis and their over-optimistic view of the situation. The main facilitating behaviors to improve nursing care were end-of-life training, volunteering, and family involvement. Spiritual needs were identified by nurses as the primary needs of patients at the end of life. Family-related barriers remain one of the main barriers to end-of-life care. Also, the behavior of physicians and their relationship with nurses remains one of the most sensitive issues in end-of-life care.


Impact of SOCS3 overexpression on human skeletal muscle development in vitro.
The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling cascade has been identified as a crucial factor for myogenesis. The STAT3 isoform is essential for satellite cell migration and myogenic differentiation as it mediates the expression of muscle specific myogenic factors. The SOCS (suppressors of cytokine signaling) family of proteins down-regulates STAT activation. Primary human skeletal muscle cells were isolated and cultured to investigate the effect of SOCS3 adenoviral overexpression on myotube maturation. It was demonstrated that STAT3 inhibition did not influence myotube development or survival. Moreover, SOCS3 overexpression enhances the mRNA expression of downstream targets of STAT3, c-FOS and VEGF. These increases were correlated with enhanced mRNA expression of genes associated with muscle maturation and hypertrophy. Thus SOCS3 influences myoblast differentiation and SOCS3 may be significant in regulating the activity of genes previously identified as transcriptionally regulated by STAT3.


Modulation of chromatin remodelling induced by the freshwater cyanotoxin cylindrospermopsin in human intestinal caco-2 cells.
Cylindrospermopsin (CYN) is a cyanotoxin that has been recognised as an emerging potential public health risk. Although CYN toxicity has been demonstrated, the mechanisms involved have not been fully characterised. To identify some key pathways related to this toxicity, we studied the transcriptomic profile of human intestinal Caco-2 cells exposed to a sub-toxic concentration of CYN (1.6 µM for 24hrs) using a non-targeted approach. CYN was shown to modulate different biological functions which were related to growth arrest (with down-regulation of cdkn1a and uhrf1 genes), and DNA recombination and repair (with up-regulation of aptx and pms2 genes). Our main results reported an increased expression of some histone-modifying enzymes (histone acetyl and methyltransferases MYST1, KAT5 and EHMT2) involved in chromatin remodelling, which is essential for initiating transcription. We also detected greater levels of acetylated histone H2A (Lys5) and dimethylated histone H3 (Lys4), two products of these enzymes. In conclusion, CYN overexpressed proteins involved in DNA damage repair and transcription, including modifications of nucleosomal histones. Our results highlighted some new cell processes induced by CYN.


Out-of-hospital cardiac arrests in patients with acute ST elevation myocardial infarctions in the East Bohemian region over the period 2002-2004.
Early reperfusion by direct percutaneous coronary intervention (PCI) in patients with ST segment elevation acute myocardial infarctions (STEMI) with an out-of-hospital cardiac arrest (OHCA) reduces hospital and longterm mortality. Evaluating the significance of direct PCI for the short-term (discharge from acute hospitalization) and 1-year survival in patients with acute STEMI after OHCA. In this prospective study, from April 1, 2002 up to August 31, 2004, a total of 26 hospitalized individuals (22 men, 4 women, aged 35-79 years, median 58.5) from the East Bohemian region with OHCA (primary group of 718 individuals) with acute STEMI were included. Urgent coronary angiography was performed in 20 individuals, and direct PCI was done in 19 of them. The remaining 6 patients did not undergo angiography. Fifteen patients (57.7%) survived acute hospitalization, of whom 11 were without neurological deficits. In the subgroup with urgent coronary angiography 14 patients (70%) survived hospitalization, and in the subgroup without coronarography only 1 patient survived hospitalization (16.7%). In the subgroup with PCIs, 13 out of the 19 patients survived (68.4%). None of the patients died during the 1-year follow-up after being discharged from acute hospitalization. According to the urgent coronarography the artery most commonly responsible for the infarction was the left anterior descending artery (50%). Initial TIMI flow grade 0-I was found in 17 patients and grade II-III in 3 individuals. After PCI, irrespective of stent implantation, an optimal angiographic success (TIMI flow grade II-III) was obtained in 17 cases. Short-term survival of patients after OHCA with STEMI treated with direct PCI was found to be 68.4%. Out of 6 patients not receiving reperfusion therapy 1 survived (16.7%). Over the course of the 1-year follow-up none of the patients died.


Dielectric multilayer-based fiber optic sensor enabling simultaneous measurement of humidity and temperature.
A multilayer-based fiber optic sensor enabling simultaneous measurement of humidity and temperature is proposed and demonstrated. The sensitive elements were multilayer coatings consisting of nano-porous TiO(2) and SiO(2) films, which were deposited on fiber end-face to form a Fabry-Perot (F-P) filter structure. Relative-humidity (RH) sensing is correlated with the shift of interference fringe due to the change of effective refractive index of porous coatings when exposed to different RH environments. The sensor is sealed in a glass tube in case of temperature measurement. Experimental results show that the average sensitivity are 0.43nm/%RH and 0.63nm/°C respectively when environmental RH changes from 1.8%RH to 74.7%RH and temperature changes from 21.4°C to 38.8°C. The proposed sensors present high repeatability, and especially highly sensitive to lower moisture measure.


Genetic counseling, prenatal screening and diagnosis of Down syndrome in the second trimester in women of advanced maternal age: a prospective study.
The incidence of autosomal trisomy in livebirths is strongly dependent on maternal age. Special consideration is given to the provision of prenatal screening and cytogenetic testing to women of advanced maternal age (AMA). The aim of this study was to evaluate the effectiveness of second trimester prenatal screening and amniocentesis for Down syndrome (DS) and compare the trends of choice of screening and amniocentesis among AMA women. A total of 5404 AMA patients with natural singleton pregnancy were recruited for this prospective study from January 2008 to December 2010. The gestational weeks were from 15 weeks to 20(+6) weeks. The patients referred were grouped into a screening group (2107 cases) and an amniocentesis group (3297 cases) by their own decision. The prevalence of DS was compared between the two groups by chi-square test. Choice rates for each maternal age with trends were compared by regression analysis. There were 18 cases of fetal DS detected in the screening group with a prevalence of 8.54‰ (18/2107). Twenty-five cases of fetal DS were diagnosed in the amniocentesis group with a prevalence of 7.58‰ (25/3297). No statistical difference was observed in the prevalence of DS between the screening and amniocentesis group (P = 0.928). The invasive testing rate for DS in the amniocentesis group was 5.54 times higher than that of the screening group (1/131.88 vs. 1/23.78). With the increase of the maternal age, the choice of amniocentesis increased while the choice of the screening showed an opposite trend. The choice of the AMA women between the screening and amniocentesis was significantly age relevant (P = 0.012). The second trimester serum screening in combination with maternal age was more effective than maternal age alone to screen for DS. We suggest educating the patients by recommending AMA women be informed of both screening and amniocentesis options.


Suprarenal inferior vena cava filters: a 20-year single-center experience.
To assess the clinical safety and efficacy of suprarenal inferior vena cava (IVC) filters during long-term follow-up. In this retrospective study, the authors collected the following data about patients who underwent suprarenal IVC filter placement at their institution between 1988 and 2007: demographics, clinical presentation, indications for filter placement, reasons for placing the filter in the suprarenal IVC, type of filter, frequency of pulmonary embolism (PE) after filter placement, and filter-related problems during follow-up. Seventy patients (32 male and 38 female patients; mean age, 60 years) had suprarenal IVC filters. Sixty-two patients presented with symptoms of venous thromboembolism (VTE) and eight had incidental asymptomatic VTE at imaging. Indications for filter placement were as follows: contraindication to anticoagulation (n = 48), complications and/or failure of anticoagulation (n = 12), added protection (n = 8), and prophylaxis (n = 2). Suprarenal placement was chosen due to IVC thrombus (n = 41), intrinsic and/or extrinsic narrowing of the infrarenal IVC (n = 9), renal and/or gonadal vein thrombus (n = 3), congenital IVC anomalies (n = 6), pelvic mass (n = 5), pregnancy (n = 3), and other reasons (n = 3). The following filters were used: Greenfield (n = 29), Simon Nitinol (n = 5), Vena-Tech (n = 3), TrapEase (n = 22), OptEase (n = 3), Tulip (n = 6), Bird's Nest (n = 1), and Recovery (n = 1). During follow-up (mean, 573 days +/- 953), postfilter PE was suspected in 10 patients; eight patients underwent computed tomography (CT), one of whom had PE at CT. None developed new symptoms of caval thrombosis. Abdominal CT (performed in 30 patients at a mean of 543 days +/- 768) showed thrombus in the filter in three patients, fracture in one patient, and penetration of the IVC wall in two patients. Suprarenal filters are safe and effective in preventing PE. The placement of IVC filters above the renal veins does not carry an added risk of complications.


Internal/structures containing transcriptase-related proteins in top component particles of mammalian orthoreovirus.
The structure of mammalian orthoreovirus top component particles, which are profoundly deficient in the content of double-stranded RNA genome, was determined at 30 A resolution by transmission cryoelectron microscopy and three-dimensional image reconstruction. Previously undetected, ordered densities, appearing primarily as pentameric flowers in the reconstruction, were seen to extend 65 A inwardly from the inner capsid at the icosahedral fivefold axes. Identically positioned but lower density elements were observed in two types of partially uncoated top component particles obtained by limited proteolysis. The levels of three inner-capsid proteins-lamda 1, lamda 3, and mu 2-were reduced in concert with the internal densities during proteolytic uncoating. Since lamda 3 contains the catalytic regions of the viral RNA polymerase and since both lamda 1 and mu 2 appear to play roles in transcription or mRNA capping, the internal structures are concluded to be complexes of the viral transcriptase-related enzymes. The findings have implications for the mechanisms of transcription and mRNA capping by orthoreovirus particles.


Reproducible parallel inference and simulation of stochastic state space models using odin, dust, and mcstate.
State space models, including compartmental models, are used to model physical, biological and social phenomena in a broad range of scientific fields. A common way of representing the underlying processes in these models is as a system of stochastic processes which can be simulated forwards in time. Inference of model parameters based on observed time-series data can then be performed using sequential Monte Carlo techniques. However, using these methods for routine inference problems can be made difficult due to various engineering considerations: allowing model design to change in response to new data and ideas, writing model code which is highly performant, and incorporating all of this with up-to-date statistical techniques. Here, we describe a suite of packages in the R programming language designed to streamline the design and deployment of state space models, targeted at infectious disease modellers but suitable for other domains. Users describe their model in a familiar domain-specific language, which is converted into parallelised C++ code. A fast, parallel, reproducible random number generator is then used to run large numbers of model simulations in an efficient manner. We also provide standard inference and prediction routines, though the model simulator can be used directly if these do not meet the user's needs. These packages provide guarantees on reproducibility and performance, allowing the user to focus on the model itself, rather than the underlying computation. The ability to automatically generate high-performance code that would be tedious and time-consuming to write and verify manually, particularly when adding further structure to compartments, is crucial for infectious disease modellers. Our packages have been critical to the development cycle of our ongoing real-time modelling efforts in the COVID-19 pandemic, and have the potential to do the same for models used in a number of different domains.


Evolution of nephrotic-associated focal segmental glomerulosclerosis and relation to the glomerular tip lesion.
Several entities or variants within focal segmental glomerulosclerosis (FSGS) have been described, but their changes with time and interrelationships are undetermined. Changes with time were studied in two series of segmental sclerosing lesions in the nephrotic syndrome, one of 22 specimens from ten patients in a trial, the other of 176 specimens from 121 consecutive patients. The earliest lesions were probably all at the tubular origin, equivalent to the tip variant of FSGS. In some patients, lesions remained at this site, but progression to renal failure was accompanied by morphologic progression, with development of lesions at various sites, equivalent to FSGS, not otherwise specified (NOS). Progression was more likely if there were large lesions, abnormal mesangium, and extensive acute tubular damage. Patients with lesions at the tubular origin at presentation had a shorter duration of symptoms and less chronic renal damage than those with multiple lesions, were more likely to have a complete response of the nephrotic syndrome, and were less likely to progress to renal failure. Recurrent nephrotic syndrome occurred in 12 of 14 allografts at risk, and was usually accompanied by lesions at the tubular origin, then multiple lesions. At least some patients with FSGS (NOS) have evolved from the tip variant. The tip variant has been considered a distinct entity. Another interpretation is that it includes two conditions, one an early form of classic FSGS, and the other closely related to minimal change nephropathy (MCN), equivalent to the glomerular tip lesion as originally defined.


Effect of combination treatment with analogs of luteinizing hormone-releasing hormone (LH-RH) or somatostatin and 5-fluorouracil on pancreatic cancer in hamsters.
Ductal pancreatic cancers were induced with N-nitrosobis(2-oxopropyl)amine (BOP) in female Syrian golden hamsters. The animals were then treated for 2 months with 5-fluorouracil (5-FU) and with sustained delivery systems of the LH-RH agonist D-Trp-6-LH-RH antagonist (Ac-D-Nal(2)'-D-Phe(4Cl)2-D-Pal(3)3-D-Cit6,D-Ala10)LH- RH(SB-75) and somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160), and with some combinations thereof. In the first experiment, the treatment with D-Trp-6-LH-RH plus 5-FU resulted in 52% inhibition of tumorous pancreas weight, a smaller number of tumor nodules on histology, a marked increase of programmed cell death (apoptosis) and a reduced number of AgNOR (argyrophilic nucleolar organizer region) in tumor cells, as compared with controls. The inhibitory effects of this combination were greater than those obtained with 5-FU and D-Trp-6-LH-RH treatment alone. In the 2nd experiment, a 76% inhibition of tumorous pancreas weight, a significant decrease in the number of tumor nodules, an increased amount of stroma, enhanced apoptosis and decreased AgNORs were observed after therapy with somatostatin analog RC-160 plus 5-FU. Most of these tumor inhibition parameters were superior to those in the group treated with 5-FU alone, and in some cases slightly better than those treated with RC-160 alone. Both LH-RH antagonist SB-75 and somatostatin analog RC-160 caused a significant inhibition of tumors, and their combination had the strongest tumor inhibitory effect, with the best survival of animals, the lowest tumorous pancreas weight and the highest apoptosis index among groups. Our results suggest that the combinations of LH-RH analogs with somatostatin analogs or of either type of analog with 5-FU may be superior to single agents in the therapy of pancreatic cancer.


[Studies on multiwavelength absorbance ratio difference spectrophotometry and its application].
This paper provides a new method to determine mixed component system by multiwavelength absorbance ratio difference spectrophotometry and summarized the basic principle and experimental technique of this method. This method was applied to assay the contents of two kinds of mixed component system of diphenhydramine hydrochloride and ephedrine hydrochloride, amidopyrine and caffeine without separation. The mean recoveries with coefficient of variation (%) was 101.0% (1.0%) for ephedrine hydrochloride; 94.86% (0.56%) for diphenhydramine hydrochloride; 100.3% (0.70%) for amidopyrine and 100.1% (0.75%) for caffeine. The results obtained are satisfactory both in recovery and in precision. It is a simple and rapid method to determine mixed component system.


Total skin-sparing mastectomy: a systematic review of oncologic outcomes and postoperative complications.
Despite the potential aesthetic and psychological benefits of total skin-sparing mastectomy (TSSM) with preservation of the nipple-areolar complex (NAC) skin, there is still reluctance to use the technique due to concern for increased recurrence rates or higher postoperative complication rates. The rapidly expanding literature describing outcomes after TSSM enables a comprehensive review of recurrence rates and surgical complications. Studies describing nipple-sparing or TSSM were identified from the MEDLINE and Cochrane databases. Studies that reported oncologic outcomes and/or data on postoperative complications were included. Twenty-seven studies were identified that met inclusion criteria, representing a total of 3331 mastectomies. Review of oncologic outcomes in the 10 studies (representing 1148 mastectomies) with documented mean/median follow-up of 2 years demonstrated an overall local-regional recurrence rate of 2.8%. Ischemic complications involving the NAC were reported in 24 studies (representing 3091 mastectomies), with 9.1% of cases reported to have some degree of NAC necrosis and 2.0% of cases complicated by complete necrosis leading to NAC loss. Sixteen studies (representing 2213 mastectomies) reported rates of skin flap necrosis, which occurred in 9.5% of cases. Eighty-one percent of the total cases reviewed involved expander-implant reconstruction; in the 16 studies (representing 2343 reconstructions) that reported outcomes after expander-implant reconstruction, overall expander-implant loss was 3.4%. There is now a significant body of literature demonstrating low rates of early local-regional recurrence and postoperative complications after TSSM. These data support the use of TSSM techniques, which improve psychological and aesthetic outcomes without compromising therapeutic efficacy.


Elucidating stygofaunal trophic web interactions via isotopic ecology.
Subterranean ecosystems host highly adapted aquatic invertebrate biota which play a key role in sustaining groundwater ecological functioning and hydrological dynamics. However, functional biodiversity studies in groundwater environments, the main source of unfrozen freshwater on Earth, are scarce, probably due to the cryptic nature of the systems. To address this, we investigate groundwater trophic ecology via stable isotope analysis, employing δ13C and δ15N in bulk tissues, and amino acids. Specimens were collected from a shallow calcrete aquifer in the arid Yilgarn region of Western Australia: a well-known hot-spot for stygofaunal biodiversity. Sampling campaigns were carried out during dry (low rainfall: LR) and the wet (high rainfall: HR) periods. δ13C values indicate that most of the stygofauna shifted towards more 13C-depleted carbon sources under HR, suggesting a preference for fresher organic matter. Conversion of δ15N values in glutamic acid and phenylalanine to a trophic index showed broadly stable trophic levels with organisms clustering as low-level secondary consumers. However, mixing models indicate that HR conditions trigger changes in dietary preferences, with increasing predation of amphipods by beetle larvae. Overall, stygofauna showed a tendency towards opportunistic and omnivorous habits-typical of an ecologically tolerant community-shaped by bottom-up controls linked with changes in carbon flows. This study provides baseline biochemical and ecological data for stygofaunal trophic interactions in calcretes. Further studies on the carbon inputs and taxa-specific physiology will help refine the interpretation of the energy flows shaping biodiversity in groundwaters. This will aid understanding of groundwater ecosystem functioning and allow modelling of the impact of future climate change factors such as aridification.


Regional variation in patient selection and treatment for carotid artery disease in the Vascular Quality Initiative.
Previous studies involving large administrative data sets have revealed regional variation in the demographics of patients selected for carotid endarterectomy (CEA) and carotid artery stenting (CAS) but lacked clinical granularity. This study aimed to evaluate regional variation in patient selection and operative technique for carotid artery revascularization using a detailed clinical registry. All patients who underwent CEA or CAS from 2009 to 2015 were identified in the Vascular Quality Initiative (VQI). Deidentified regional groups were used to evaluate variation in patient selection, operative technique, and perioperative management. χ2 analysis was used to identify significant variation across regions. A total of 57,555 carotid artery revascularization procedures were identified. Of these, 49,179 patients underwent CEA (asymptomatic: median, 56%; range, 46%-69%; P < .01) and 8376 patients underwent CAS (asymptomatic: median, 36%; range, 29%-51%; P < .01). There was significant regional variation in the proportion of asymptomatic patients being treated for carotid stenosis <70% in CEA (3%-9%; P < .01) vs CAS (3%-22%; P < .01). There was also significant variation in the rates of intervention for asymptomatic patients older than 80 years (CEA, 12%-27% [P < .01]; CAS, 8%-26% [P < .01]). Preoperative computed tomography angiography or magnetic resonance angiography in the CAS cohort also varied widely (31%-83%; P < .01), as did preoperative medical management with combined aspirin and statin (CEA, 53%-77% [P < .01]; CAS, 62%-80% [P < .01]). In the CEA group, the use of shunt (36%-83%; P < .01), protamine (32%-89%; P < .01), and patch (87%-99%; P < .01) varied widely. Similarly, there was regional variation in frequency of CAS done without a protection device (1%-8%; P < .01). Despite clinical benchmarks aimed at guiding management of carotid disease, wide variation in clinical practice exists, including the proportion of asymptomatic patients being treated by CAS and preoperative medical management. Additional intraoperative variables, including the use of a patch and protamine during CEA and use of a protection device during CAS, displayed similar variation in spite of clear guidelines. Quality improvement projects could be directed toward improved adherence to benchmarks in these areas.


Protective effect of lupeol and lupeol linoleate in hypercholesterolemia associated renal damage.
The association between hypercholesterolemia and kidney damage has been well known for last few decades. The oxidative stress and inflammatory responses are involved in renal injury, which is upregulated in hypercholesterolemic condition. The present study is aimed to evaluate the possible effect of lupeol and its ester derivative, lupeol linoleate in renal damage associated with hypercholesterolemic rats. Hypercholesterolemia was induced in male Wistar rats by feeding them with a high cholesterol diet (HCD) comprising normal rat chow supplemented with 4% cholesterol and 1% cholic acid for 30 days. Lupeol and lupeol linoleate were supplemented (50 mg/kg body wt/day) to HCD fed rats during the last 15 days. Increased levels of renal total cholesterol, triglycerides and phospholipids, along with altered serum biochemical parameters of tissue injury indices and elevated activities of renal marker enzymes (lactate dehydrogenase and alkaline phosphatase) were noted in HCD fed rats. Elevated lipid peroxidation levels coupled with decreased antioxidant status (enzymatic and non enzymatic antioxidants) were observed in hypercholesterolemic rats, which indicate the onset of oxidative changes in the renal tissue. Renal lysosomal acid hydrolase activities (ACP, beta-Glu, beta-Gal, NAG and Cat-D) and acute phase proteins like C-Reactive protein and fibrinogen were significantly increased in HCD fed rats, which further indicates the heightening of inflammation. In addition, histopathological findings also confirmed the renal damage in hypercholesterolemic condition. Lupeol and lupeol linoleate effectively reverted the above abnormalities and was comparable with that of the control. These observations highlight the protective effect of lupeol and its ester derivative in ameliorating the renal injury associated with hypercholesterolemia.


Zr-Metal-Organic Frameworks Featuring TEMPO Radicals: Synergistic Effect between TEMPO and Hydrophilic Zr-Node Defects Boosting Aerobic Oxidation of Alcohols.
Metal-organic frameworks (MOFs) featuring multiple catalytic units are excellent platforms for heterogeneous catalysis. However, the synergism between multiple catalytic units for catalysis is far from being well understood. Herein, we reported the synthesis of a robust 2,2,6,6-tetramethylpiperidinyloxy (TEMPO) radical-functionalized Zr-MOF (UiO-68-TEMPO) in the form of single-crystalline and microsized crystals with varied missing linker defects. Detailed catalytic studies and theoretical calculations reveal that the synergistic effect between the TEMPO radicals and hydrophilic and defective Zr-nodes endows UiO-68-TEMPO with superior catalytic activity toward aerobic oxidation of alcohols. Our work not only offers a new route to design and synthesize highly effective MOF catalysts but also provides insights into the synergism between multiple catalytic sites.


Emergency abdominal surgery after solid organ transplantation: a systematic review.
Due to the increasing number of solid organs transplantations, emergency abdominal surgery in transplanted patients is becoming a relevant challenge for the general surgeon. The aim of this systematic review of the literature is to analyze morbidity and mortality of emergency abdominal surgery performed in transplanted patients for graft-unrelated surgical problems. The literature search was performed on online databases with the time limit 1990-2015. Studies describing all types of emergency abdominal surgery in solid organ transplanted patients were retrieved for evaluation. Thirty-nine case series published between 1996 and 2015 met the inclusion criteria and were selected for the systematic review. Overall, they included 71671 transplanted patients, of which 1761 (2.5 %) underwent emergency abdominal surgery. The transplanted organs were the heart in 65.8 % of patients, the lung in 22.1 %, the kidney in 9.5 %, and the liver in 2.6 %. The mean patients' age at the time of the emergency abdominal surgery was 49.4 ± 7.4 years, and the median time from transplantation to emergency surgery was 2.4 years (range 0.1-20). Indications for emergency abdominal surgery were: gallbladder diseases (80.3 %), gastrointestinal perforations (9.2 %), complicated diverticulitis (6.2 %), small bowel obstructions (2 %), and appendicitis (2 %). The overall mortality was 5.5 % (range 0-17.5 %). The morbidity rate varied from 13.6 % for gallbladder diseases to 32.7 % for complicated diverticulitis. Most of the time, the immunosuppressive therapy was maintained unmodified postoperatively. Emergency abdominal surgery in transplanted patients is not a rare event. Although associated with relevant mortality and morbidity, a prompt and appropriate surgery can lead to satisfactory results if performed taking into account the patient's immunosuppression therapy and hemodynamic stability.


Burkholderia cepacia Complex Bacteria: a Feared Contamination Risk in Water-Based Pharmaceutical Products.
Burkholderia cepacia (formerly Pseudomonas cepacia) was once thought to be a single bacterial species but has expanded to the Burkholderia cepacia complex (Bcc), comprising 24 closely related opportunistic pathogenic species. These bacteria have a widespread environmental distribution, an extraordinary metabolic versatility, a complex genome with three chromosomes, and a high capacity for rapid mutation and adaptation. Additionally, they present an inherent resistance to antibiotics and antiseptics, as well as the abilities to survive under nutrient-limited conditions and to metabolize the organic matter present in oligotrophic aquatic environments, even using certain antimicrobials as carbon sources. These traits constitute the reason that Bcc bacteria are considered feared contaminants of aqueous pharmaceutical and personal care products and the frequent reason behind nonsterile product recalls. Contamination with Bcc has caused numerous nosocomial outbreaks in health care facilities, presenting a health threat, particularly for patients with cystic fibrosis and chronic granulomatous disease and for immunocompromised individuals. This review addresses the role of Bcc bacteria as a potential public health problem, the mechanisms behind their success as contaminants of pharmaceutical products, particularly in the presence of biocides, the difficulties encountered in their detection, and the preventive measures applied during manufacturing processes to control contamination with these objectionable microorganisms. A summary of Bcc-related outbreaks in different clinical settings, due to contamination of diverse types of pharmaceutical products, is provided.


Geographic variability and operator trends of transcatheter edge-to-edge repair in the United States.
Transcatheter edge-to-edge repair (TEER) devices are used for primary mitral regurgitation (MR) and secondary MR. Despite the growing use of TEER devices, there have not been many studies on operator experience or procedure volumes by state. We aimed to investigate nationwide operator volume trends and geographic variation in access to TEER. The United States Center for Medicare and Medicaid Services (CMS) National Medicare Provider Utilization and Payment Database (MPUPD) was analyzed between 2015 and 2020 for initial TEER procedures. Procedure volume and total operators increased yearly from 2015 to 2019 but declined in 2020. Mean annual procedure volume per operator varied significantly by state, between 0 in multiple states and 35 in North Dakota. In 2019, 994 unique operators were identified, with 295 operators documented performing 10 or more procedures (29.68%). Operators performing 10 or more TEER procedures provided 68.46% of all operations in 2019, averaging 20.94 procedures per operator. TEER procedures are becoming increasingly common as more operators are being trained. However, significant variability exists in the procedural volume per operator.


Clinical and pathologic findings in hemochromatosis type 3 due to a novel mutation in transferrin receptor 2 gene.
Although most patients with hereditary hemochromatosis are homozygous for a single mutation of the HFE gene on chromosome 6p, accumulating evidence indicates that the disease is genetically heterogeneous. Type 3 hemochromatosis, recently described in 4 families, is linked to mutations of the gene encoding transferrin receptor 2 on chromosome 7q22. Here we report data from a family carrying a new mutation of the transferrin receptor 2 gene. Detailed clinical and histopathologic documentation was available for most family members. The entire coding sequence and exon/intron boundaries of the transferrin receptor 2 gene were analyzed by direct sequencing. A 12-nucleotide deletion in exon 16, causing the loss of 4 amino acids (AVAQ 594-597 del), was detected at the homozygous state in the 3 patients with histologically proven iron overload. The deletion segregated with the disease within the family and was not found in 100 healthy controls. Some clinical and pathologic characteristics, such as low penetrance in the premenopausal woman, and early iron deposition in periportal hepatocytes resembled those of classic, HFE-related hemochromatosis. Our data support the role of the transferrin receptor 2 gene in hemochromatosis type 3 as well as its critical involvement in the maintenance of iron homeostasis in humans.


Cigarette smoking and diabetic retinopathy.
A sample of 181 diabetics with diabetic retinopathy was statistically investigated with regard to association of smoking with proliferative retinopathy. The numbers of patients with proliferative retinopathy rose with increasing tobacco consumption. In non-smokers no association existed between diabetes duration and proliferative retinopathy, but in smokers the number with proliferative retinopathy rose with increasing diabetes duration.


KCNQ Potassium Channels Modulate Sensitivity of Skin Down-hair (D-hair) Mechanoreceptors.
M-current-mediating KCNQ (Kv7) channels play an important role in regulating the excitability of neuronal cells, as highlighted by mutations in Kcnq2 and Kcnq3 that underlie certain forms of epilepsy. In addition to their expression in brain, KCNQ2 and -3 are also found in the somatosensory system. We have now detected both KCNQ2 and KCNQ3 in a subset of dorsal root ganglia neurons that correspond to D-hair Aδ-fibers and demonstrate KCNQ3 expression in peripheral nerve endings of cutaneous D-hair follicles. Electrophysiological recordings from single D-hair afferents from Kcnq3(-/-) mice showed increased firing frequencies in response to mechanical ramp-and-hold stimuli. This effect was particularly pronounced at slow indentation velocities. Additional reduction of KCNQ2 expression further increased D-hair sensitivity. Together with previous work on the specific role of KCNQ4 in rapidly adapting skin mechanoreceptors, our results show that different KCNQ isoforms are specifically expressed in particular subsets of mechanosensory neurons and modulate their sensitivity directly in sensory nerve endings.


Toxicological analysis of amobarbital and glutethimide from bone tissue.
Author examined cadaver organs and bone samples (sternum, rib) of drug poisoning cases. Following suitable procedures, active drug components (amobarbital, glutethimide, and so forth) were identified by gas chromatography/mass spectrometry (GC/MS). Based on results of quantitative GC analysis, relationships were sought between the active agent concentrations measured in the organs and the bone samples.


Improved functional recovery of ischemic rat hearts due to singlet oxygen scavengers histidine and carnosine.
There is increasing evidence that reactive oxygen species (ROS) contribute to post-ischemic reperfusion injury, but determination of the specific ROS involved has proven elusive. In the present study electron paramagnetic resonance (EPR) spectroscopy was used in vitro to measure the relative quenching of singlet oxygen (1O2) by histidine and carnosine (beta-alanyl-L-histidine) utilizing the hindered secondary amine 2,2,6,6-tetramethyl-4-piperidone HCl (4-oxo-TEMP). The relative effect of histidine and carnosine on functional recovery of isolated perfused rat hearts was also studied. Functional recovery was measured by left ventricular developed pressure (LVDP), first derivative of left ventricular pressure (dP/dt), heart rate (HR) and coronary flow (CF). EPR measurements and Stern-Volmer plots showed that 400 microM carnosine quenched 1O2 twice as effectively as equimolar histidine in vitro. Moreover, 10 mM histidine improved functional recovery of isolated rat hearts significantly more than 1 mM histidine. Furthermore, 1 mM carnosine improved functional recovery significantly more than equimolar histidine and as effectively as 10 mM histidine. Experiments with 1 mM mannitol, a known hydroxyl radical scavenger, did not show an improvement in functional recovery relative to control hearts, thereby decreasing the likelihood that hydroxyl radicals are the major damaging species. On the other hand, the correlation between improved functional recovery of isolated rat hearts with histidine and carnosine and their relative 1O2 quenching effectiveness in vitro provides indirect evidence for 1O2 as ROS participating in reperfusion injury.


Early-life iron deficiency anemia alters the development and long-term expression of parvalbumin and perineuronal nets in the rat hippocampus.
Early-life iron deficiency anemia (IDA) alters the expression of critical genes involved in neuronal dendritic structural plasticity of the hippocampus, thus contributing to delayed maturation of electrophysiology, and learning and memory behavior in rats. Structural maturity in multiple cortical regions is characterized by the appearance of parvalbumin-positive (PV(+)) GABAergic interneurons and perineuronal nets (PNNs). Appearance of PV(+) interneurons and PNNs can serve as cellular markers for the beginning and end of a critical developmental period, respectively. During this period, the system progresses from an immature yet highly plastic condition, to a more mature and efficient state that is however less flexible and may exhibit poorer potential for recovery from injury. To test if fetal-neonatal IDA alters parvalbumin (PV) mRNA expression, protein levels, and the number of PV(+) interneurons and PNNs in the male rat hippocampus, pregnant dams were given an iron-deficient (ID) diet (3 mg iron/kg chow) from gestational day 2 to postnatal day (P) 7 and then placed on an iron-sufficient (IS) diet (198 mg/kg) for the remainder of the experiment. On this regimen, formerly ID animals become fully iron-replete by P56. Minimal levels of PV (mRNA and protein), PV(+) interneurons, and PNNs were found in IS and ID P7 rats. By P15, and continuing through P30 and P65, ID rats had reduced PV mRNA expression and protein levels compared to IS controls. While there were no differences in the number of PV(+) neurons at either P30 or P65, the percentage of PV(+) cells surrounded by PNNs was slightly greater in ID rats as compared to IS controls. The lower levels of these acknowledged critical period biomarkers in the ID group are consistent with studies that demonstrate later maturation of the acutely ID hippocampus and lower plasticity in the adult formerly ID hippocampus. The findings provide additional potential cellular bases for previously described electrophysiologic and behavioral abnormalities found during and following early-life IDA.


Brown trout Salmo trutta f. Fario liver ultrastructure as a biomarker for assessment of small stream pollution.
T he effects of environmental pollutants from two small streams in south-west Germany on the liver of brown trout (S almo trutta f. Fario) were studied as biomarkers by means of quantitative and semi-quantitative electron microscopy, and quantitatively by morphometrical measurements. Cellular damage was assessed semi-quantitatively based on a classification of ultrastructural responses. Both methods revealed more severe cellular effects in the liver of trout which had been exposed to the highly polluted stream than in those exposed to the lightly polluted river. Morphometrical studies showed a significant reduction of glycogen storage and a significant increase in number of mitochondria, peroxisomes and cisternae of the endoplasmic reticulum. The biomarker responses of this study were correlated with the results obtained by limnological and analytical investigations, and reflect the levels of pollution in each stream.


Acceptance of external infusion pumps in patients with advanced breast cancer receiving continuous infusion fluorouracil.
We investigated the physical and psychological adaptation to a protracted continuous infusion system in a series of patients receiving protracted continuous infusion of 5-fluorouracil for advanced breast cancer. The protracted continuous infusion of 5-fluorouracil was administered by means of a portable elastomeric pump (Baxter Seven-Day Infusor, 0.5 mL/hr) via an indwelling Groshong catheter. Patients were asked to complete a questionnaire exploring the impact of the continuous infusion system upon various aspects of daily life, the overall level of disturbance, the general judgement on its quality, and their willingness to resume the same kind of treatment in the future. All items were graded on a 4-point scale from 0 = not at all, to 4 = very much. Seventy-one patients were evaluated. All patients received 5-fluorouracil at the dose of 250 mg/m2/day as a protracted continuous infusion alone (n = 14) or in combination with vinorelbine (n = 45) or Taxol (n = 12). The median duration of the protracted continuous infusion before evaluation was 9 months (3-31). The mean level of disturbance to daily activities was 0.86 points. The activities most frequently disturbed by treatment included daily personal care (mean, 1.76 points) and sexual activity (mean, 1.20 points). Twenty-one patients required medical intervention because of problems related to the protracted continuous infusion system. The overall level of disturbance was rated at a mean level of 0.72 points, whereas the overall merits of the protracted continuous infusion system and the willingness of the patient to resume protracted continuous infusion in the future were rated at a mean level of 2.90 and 2.55 points, respectively. The system for the protracted continuous infusion of 5-fluorouracil was well tolerated by the patients, who were able in most cases to perform their daily activities with little or no disturbance, needing only occasional help, and were willing to resume the same treatment modality if necessary.


Thigmomorphogenetic responses of an aquatic macrophyte to hydrodynamic stress.
The response of aquatic plants to abiotic factors is a crucial study topic, because the diversity of aquatic vegetation is strongly related to specific adaptations to a variety of environments. This biodiversity ensures resilience of aquatic communities to new and changing ecological conditions. In running water, hydrodynamic disturbance is one of the key factors in this context. While plant adaptations to resource stress (nutrients, light…) are well documented, adaptations to mechanical stress, particularly flow, are largely unknown. The submerged species Egeria densa was used in an experiment to detect whether the presence or absence of hydrodynamic stress causes plant thigmomorphogenetic responses (i) in terms of plant biogenic silica (BSi), cellulose and lignin concentrations, and (ii) in terms of plant strength. Plant silica concentrations, as well as lignin concentrations were significantly higher in presence of hydrodynamic stress. These physiological changes are accompanied by some significant changes in stem biomechanical traits: stem resistance to tensile forces (breaking force and breaking strength) and stiffness were higher for plants exposed to hydrodynamic stress. We conclude that the response of this aquatic plant species to mechanical stress is likely the explaining factor for a higher capacity to tolerate stress through the production of mechanically hardened shoots.


HIV treatment optimism and unsafe anal intercourse among HIV-positive men who have sex with men: findings from the positive connections study.
This study was designed to examine the impact of HIV treatment optimism on sexual risk among a racially diverse sample of HIV-positive MSM. Survey data were collected from 346 racially diverse HIV-positive MSM. 18 years of age, male, at least one incident of unprotected anal intercourse (UAI) in the last year, currently on treatment. Other variables included demographics, sexual risk, depression, internalized homonegativity, HIV treatment history, alcohol/drug use and beliefs about HIV treatments (Susceptibility to transmit HIV, Severity of HIV infection and Condom Motivation). Those with lower income were more likely to report that HIV was less transmissible. A self-reported decrease in condom motivation was associated with being White, well-educated and increased alcohol/drug use. A decrease in Severity of HIV was associated with better mental health, being non-White and undetectable viral load. Sexual risk appears related to beliefs about how treatment affects the transmissibility of HIV. Race, socioeconomic status, alcohol/drug use, mental health and viral load were also associated with treatment beliefs.


Intersection between genetic polymorphisms and immune deviation in type 1 diabetes.
Above 60 non-HLA genes have been associated with T1D, many of which are immune-related genes. One challenge following identification of these genes is finding causative connections between risk alleles and disease. Phenotypes linked to T1D-associated genetic variants are beginning to help us better understand the cellular and molecular mechanisms underlying T1D. The list of immune-related genes with T1D-associated polymorphisms will be reviewed and cellular phenotypes correlating with these variants will be described highlighting recent finding from variants in the PTPN22 gene and genes encoding proteins in theIL-2/IL2R signaling pathway. Building from extensive genome-wide association studies, we are discovering cellular and molecular phenotypes that may help unravel the underlying causes of T1D.


GDF-15 for prognostication of cardiovascular and cancer morbidity and mortality in men.
The objective was to evaluate the hypothesis that growth-differentiation factor 15 (GDF-15) is an independent marker of the long-term risk for both cardiovascular disease and cancer morbidity beyond clinical and biochemical risk factors. Plasma obtained at age 71 was available from 940 subjects in the Uppsala Longitudinal Study of Adult Men (ULSAM) cohort. Complete mortality and morbidity data were obtained from public registries. At baseline there were independent associations between GDF-15 and current smoking, diabetes mellitus, biomarkers of cardiac (high-sensitivity troponin-T, NT-proBNP) and renal dysfunction (cystatin-C) and inflammatory activity (C-reactive protein), and previous cardiovascular disease (CVD). During 10 years follow-up there occurred 265 and 131 deaths, 115 and 46 cardiovascular deaths, and 185 and 86 events with coronary heart disease mortality or morbidity in the respective total cohort (n=940) and non-CVD (n=561) cohort. After adjustment for conventional cardiovascular risk factors, one SD increase in log GDF-15 were, in the respective total and non-CVD populations, associated with 48% (95%CI 26 to 73%, p<0.001) and 67% (95%CI 28 to 217%, p<0.001) incremental risk of cardiovascular mortality, 48% (95%CI 33 to 67%, p<0.001) and 61% (95%CI 38 to 89%, p<0.001) of total mortality and 36% (95%CI 19 to 56%, p<0.001) and 44% (95%CI 17 to 76%, p<0.001) of coronary heart disease morbidity and mortality. The corresponding incremental increase for cancer mortality in the respective total and non-cancer disease (n=882) population was 46% (95%CI 21 to 77%, p<0.001) and 38% (95%CI 12 to 70%, p<0.001) and for cancer morbidity and mortality in patients without previous cancer disease 30% (95%CI 12 to 51%, p<0.001). In conclusion, in elderly men, GDF-15 improves prognostication of both cardiovascular, cancer mortality and morbidity beyond established risk factors and biomarkers of cardiac, renal dysfunction and inflammation.


Transfer of Care in Perioperative Settings: A Descriptive Qualitative Study.
Transfer of care is defined as the exchange of information and professional accountability for patient care between individuals. This article describes a qualitative content analysis (N = 19) using a closed-claims database generated by the American Association of Nurse Anesthetists (AANA) Foundation. The purpose of this study was to explore perioperative transfer-of-care events that contributed to professional malpractice claims to identify general themes, antecedents, and consequences to improve clinical practices and guide future research. A brief summary of the 6 themes that emerged in this study is as follows. (1) Patients should be transferred to an appropriate level of care based on their needs. (2) Production pressure leads to normalization of deviance. (3) Clinicians need to conduct their own patient assessments and health record reviews without relying solely on another clinician's report. (4) Interdisciplinary team communication failure is a leading cause of adverse outcomes. (5) Inadequate patient monitoring and physical assessment after the transfer of care is completed is a leading cause of adverse outcomes. (6) Transfer of care should not occur during high-risk patient care events or during periods of patient hemodynamic or respiratory instability.


Atmospheric H2S exposure does not affect stomatal aperture in maize.
Stomatal aperture in maize is not affected by exposure to a subtoxic concentration of atmospheric H2S. At least in maize, H2S, thus, is not a gaseous signal molecule that controls stomatal aperture. Sulfur is an indispensable element for the physiological functioning of plants with hydrogen sulfide (H2S) potentially acting as gasotransmitter in the regulation of stomatal aperture. It is often assumed that H2S is metabolized into cysteine to stimulate stomatal closure. To study the significance of H2S for the regulation of stomatal closure, maize was exposed to a subtoxic atmospheric H2S level in the presence or absence of a sulfate supply to the root. Similar to other plants, maize could use H2S as a sulfur source for growth. Whereas sulfate-deprived plants had a lower biomass than sulfate-sufficient plants, exposure to H2S alleviated this growth reduction. Shoot sulfate, glutathione, and cysteine levels were significantly higher in H2S-fumigated plants compared to non-fumigated plants. Nevertheless, this was not associated with changes in the leaf area, stomatal density, stomatal resistance, and transpiration rate of plants, meaning that H2S exposure did not affect the transpiration rate per stoma. Hence, it did not affect stomatal aperture, indicating that, at least in maize, H2S is not a gaseous signal molecule controlling this aperture.


Treatment of high- and intermediate-high-risk pulmonary embolism by the Pulmonary Embolism Response Team: Focus on catheter-directed therapies.
Multidisciplinary Pulmonary Embolism Response Teams (PERTs) were established to individualize the treatment of high-risk (HR) and intermediate-high-risk (IHR) pulmonary embolism (PE) patients, which pose a challenge in clinical practice. We retrospectively collected the data of all HR and IHR acute PE patients consulted by PERT CELZAT between September 2017 and October 2022. The patient population was divided into four different treatment methods: anticoagulation alone (AC), systemic thrombolysis (ST), surgical embolectomy (SE), and catheter-directed therapies (CDTx). Baseline clinical characteristics, risk stratification, PE severity parameters, and treatment outcomes were compared between the four groups. Of the 110 patients with HR and IHR PE, 67 (61%) patients were treated with AC only, 11 (10%) with ST, 15 (14%) underwent SE, and 17 (15%) were treated with CTDx. The most common treatment option in the HR group was reperfusion therapy, used in 20/24 (83%) cases, including ST in 7 (29%) patients, SE in 5 (21%) patients, and CTDx in 8 (33%) patients. In contrast, IHR patients were treated with AC alone in 63/86 (73%) cases. The in-hospital mortality rate was 9/24 (37.5%) in the HR group and 4/86 (4.7%) in the IHR group. The number of advanced procedures aimed at reperfusion was substantially higher in the HR group than in the IHR PE group. Despite the common use of advanced reperfusion techniques in the HR group, patient mortality remained high. There is a need further to optimize the treatment of patients with HR PE to improve outcomes.