"Phacoemulsification tip fracture and how to manage it."
To describe a rare complication of phacoemulsification (Phaco) cataract extraction. A phaco tip fracture occurred during the sculpting of the nucleus in a cataract extraction surgery of a 60-year-old woman. The surgeon introduced the second instrument through the side port to retrieve the broken portion of the tip while maintaining it inside the sleeve. Phaco tip fracture is a rare but serious complication that all cataract surgeons should be able to manage safely. Main risk factors for phaco tip fractures are: Aspiration Bypass System (ABS) phaco tip design and sterilization and reuse of instruments. A step by step plan of action was described in detail for a surgeon to manage a phaco tip fracture which mainly consists of removing the fractured phaco tip while it is still inside the sleeve to prevent any touch between the sharp broken edge of the tip and any intraocular component.


Alpha and beta forms of cytochrome c oxidase observed in rat heart myocytes by low temperature Fourier transform infrared spectroscopy.
Carbon monoxide bound to myoglobin and cytochrome c oxidase in separated adult rat heart myocytes has been observed with Fourier transform IR spectroscopy at low temperatures. CO complexes of these two proteins can be spectrally separated through temperature manipulation of the relaxation of the photolyzed systems. Photolyzed carboxymyoglobin relaxes very rapidly above 80 K, whereas the CO photolyzed from cytochrome a3 associates with CuB and relaxes very slowly below 140 K. Cytochrome c oxidase is found to be present in two major molecular forms which we designate alpha and beta. Each form contains an a3Fe and its associated CuB which we observe by their CO complexes. The predominant FeCO band, the alpha form of cytochrome oxidase, is similar to that previously seen in beef heart mitochondria, but with a slightly larger activation enthalpy, delta H = 46 kJ/mol. At least one of the beta forms is similar, but two have not been observed in beef heart mitochondria. Upon photolysis of alpha-FeCO, the alpha-CuCO species is formed. This band splits into two at low temperature. Up to half of the FeCO band area of the intact myocytes is distributed among three or more minor species (beta forms). The beta-FeCO bands all appear to be associated with only one beta-CuCO band which does not split at low temperature. After photo-dissociation of CO, the beta forms relax considerably faster than the alpha form, achieving 50% recombination in 10% of the time required for the alpha form. In a tissue slice from an opossum heart exposed to CO, we observed alpha and beta forms of cytochrome oxidase very similar to those in the rat heart myocytes. The cause of the differences between the alpha and beta forms of the enzyme is unknown, but their possible role in the control of respiration is discussed. Carboxymyoglobin contained within intact rat heart myocytes was very similar to sperm whale carboxymyoglobin, but with a much smaller amount of the lower frequency minor component.


Adjuvant radiotherapy in breast cancer. Are there factors that allow selection of patients who do not require adjuvant radiotherapy following breast-conserving surgery for breast cancer?
Postoperative adjuvant radiotherapy is used to reduce local recurrences following breast-conserving surgery for early breast cancer. This review examines factors that may be used to select patients at low risk of local failure following breast-conserving surgery alone.


Mutagenicity of carcinogenic nitrosamines when activated by hamster and human pancreatic duct epithelial cells.
We have measured the ability of pancreatic duct epithelial cells (DEC) from Syrian hamsters and humans and CK cells, immortalized hamster DEC, to metabolize chemical carcinogens to species that were mutagenic in S. typhimurium TA98 and in V79 cells. The chemicals were N-nitrosobis(2-oxopropyl)amine (BOP), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The ability of ethanol (EtOH) to modify the metabolizing efficiency was also measured. When an S9 preparation from EtOH-treated CK cells was used to metabolize NNK the number of revertants was 271 +/- 73 compared with 17 +/- 2 when the S9 from control CK cells was used. When hamster DEC were used there was no increase in the mutation frequency for BOP in V79 cells (64 +/- 20 mutants/10(6) survivors per mumol) when EtOH-DEC were used. However, the mutation frequencies of NNK and PhIP rose when the EtOH-treated DEC were used from 62 +/- 31 to 198 +/- 28 mutants/10(6) survivors per mumol for NNK and from 94 +/- 25 to 166 +/- 25 mutants/10(6) survivors per mumol for PhIP. A similar result was obtained when human DEC were used, i.e. no change in BOP mutagenicity and a slight increase in PhIP mutagenicity, from 34 +/- 14 to 65 +/- 12 mutants/10(6) survivors per mumol. There were large increases in the mutagenicity of NNK with each of the three samples of human DEC that were used, from 75 +/- 0 to 213 +/- 38, 75 +/- 13 to 175 +/- 25 and 38 +/- 13 to 285 +/- 25 mutants/10(6) survivors per mumol. The EtOH treatment regimen that was used more closely mimicked chronic exposure at low concentrations in vivo. These data show that hamster DEC are capable of metabolizing NNK, which is carcinogenic in these cells in vivo. Furthermore, human DEC metabolized NNK as efficiently as hamster DEC.


Diagnosis and Management of Anomalous Left Anterior Descending Coronary Artery from the Pulmonary Artery in an Asymptomatic Infant.
Anomalous origin of the left anterior descending coronary artery from the pulmonary artery is a rare variant of anomalous origin of the left main coronary artery from the pulmonary artery. We report on a seemingly asymptomatic patient with ALADCAPA and a small restrictive muscular ventricular septal defect diagnosed by echocardiogram in the neonatal period. Our patient underwent elective repair at 3.5 months of age after which feeding and growth improved dramatically. Multimodality imaging is helpful to confirm this rare anomaly; however, echocardiographic clues including lack of left coronary branching or an abnormal coronary course should raise suspicion for ALADCAPA. This case provides support for early repair in children with an incidental finding of this anomaly as subclinical ischemia may be under-recognized by available testing but may lead to symptoms later in life.


Clinical milestones as triggers for palliative care intervention in progressive Supranuclear palsy and multiple system atrophy.
not required for reviews.


Great debates in cardiac computed tomography: OPINION: "Artificial intelligence and the future of cardiovascular CT - Managing expectation and challenging hype".
This manuscript has been written as a follow-up to the "AI/ML great debate" featured at the 2021 Society of Cardiovascular Computed Tomography (SCCT) Annual Scientific Meeting. In debate style, we highlighti the need for expectation management of AI/ML, debunking the hype around current AI techniques, and countering the argument that in its current day format AI/ML is the "silver bullet" for the interpretation of daily clinical CCTA practice.


Regional distribution of ascorbate in human brain.
A comprehensive mapping of ascorbate distribution in human brain was carried out by liquid chromatography analysis. The data agree with earlier literature values where comparable and provide new information on several brain regions, including a detailed distribution in the thalamus. While ascorbate concentrations tend to be high in regions rich in catecholamines, there is no real correlation between the two.


Validation of the new STAR-CAP prognostic group staging system in prostate cancer patients treated with radiation therapy.
To externally validate the STAR-CAP prognostic system for prostate cancer (PCa) and compare it to the CAPRA score to predict for biochemical recurrence (BCR) after radiation therapy (RTx). We included patients treated with RTx between 2002 and 2021 for non-metastatic PCa at our institution. BCR was defined based on Phoenix criteria. The 5-year BCR-free survival was assessed by univariable Kaplan-Meier analyses and log-rank test. Multivariable Cox regression models tested the independent association of each model for BCR. Performance of both models to predict 5-year BCR-free survival was assessed using the area under the curve (AUC). The 2768 patients included were treated with high dose rate brachytherapy (13.3%) as a boost to external beam radiation therapy (EBRT), low dose rate seed brachytherapy (50.4%) or EBRT alone (35.9%). 14.4% of patients received concomitant androgen deprivation therapy (ADT). 222 patients experienced BCR (8%), with a median follow-up of 56 months. The 5-year BCR-free survival ranged from 88 (high risk) to 96% (low risk) in the STAR-CAP classification, and from 87 (high risk) to 97% (low risk) in the CAPRA system (p < 0.0001). Multivariate analyses, adjusted for ADT and type of treatment, confirmed the intrinsic ability of risk stratifications within each system to predict BCR (p < 0.001). Finally, AUC for the 5-year BCR prediction was 0.65 for STAR-CAP and 0.68 for CAPRA. Both CAPRA and STAR-CAP prognostic group staging systems provide sufficient stratification and their predictive ability for 5-year BCR-free survival is comparable, with a small advantage for CAPRA (3%).


Verrucous carcinoma of the bladder.
Verrucous carcinoma of the bladder unassociated with bilharzial cystitis is an exceedingly rare entity, with only 3 cases reported in the literature. We describe a patient and review the literature concerning verrucous carcinoma.


The specificity of parenting effects: Differential relations of parent praise and criticism to children's theories of intelligence and learning goals.
Individuals who believe that intelligence can be improved with effort (an incremental theory of intelligence) and who approach challenges with the goal of improving their understanding (a learning goal) tend to have higher academic achievement. Furthermore, parent praise is associated with children's incremental theories and learning goals. However, the influences of parental criticism, as well as different forms of praise and criticism (e.g., process vs. person), have received less attention. We examine these associations by analyzing two existing datasets (Study 1: N = 317 first to eighth graders; Study 2: N = 282 fifth and eighth graders). In both studies, older children held more incremental theories of intelligence, but lower learning goals, than younger children. Unexpectedly, the relation between theories of intelligence and learning goals was nonsignificant and did not vary with children's grade level. In both studies, overall perceived parent praise positively related to children's learning goals, whereas perceived parent criticism negatively related to incremental theories of intelligence. In Study 2, perceived parent process praise was the only significant (positive) predictor of children's learning goals, whereas perceived parent person criticism was the only significant (negative) predictor of incremental theories of intelligence. Finally, Study 2 provided some support for our hypothesis that age-related differences in perceived parent praise and criticism can explain age-related differences in children's learning goals. Results suggest that incremental theories of intelligence and learning goals might not be strongly related during childhood and that perceived parent praise and criticism have important, but distinct, relations with each motivational construct.


Genetics of pediatric movement disorders.
Movement disorders in children often have a genetic basis. An explosion of genetic information in the past decade has led to the discovery of genetic defects in many forms of ataxia, parkinsonism, dystonia, tremor, and spastic paraparesis. This review focuses on genetically defined, early-onset diseases characterized primarily or exclusively by movement disorders. Particular emphasis is placed on disorders for which clinical or research testing is available.


Importin β1 targeting by hepatitis C virus NS3/4A protein restricts IRF3 and NF-κB signaling of IFNB1 antiviral response.
In this study, newly identified host interactors of hepatitis C virus (HCV) proteins were assessed for a role in modulating the innate immune response. The analysis revealed enrichment for components of the nuclear transport machinery and the crucial interaction with NS3/4A protein in suppression of interferon-β (IFNB1) induction. Using a comprehensive microscopy-based high-content screening approach combined to the gene silencing of nuclear transport factors, we showed that NS3/4A-interacting proteins control the nucleocytoplasmic trafficking of IFN regulatory factor 3 (IRF3) and NF-κB p65 upon Sendai virus (SeV) infection. Notably, importin β1 (IMPβ1) knockdown-a hub protein highly targeted by several viruses-decreases the nuclear translocation of both transcription factors and prevents IFNB1 and IFIT1 induction, correlating with a rapid increased of viral proteins and virus-mediated apoptosis. Here we show that NS3/4A triggers the cleavage of IMPβ1 and inhibits nuclear transport to disrupt IFNB1 production. Importantly, mutated IMPβ1 resistant to cleavage completely restores signaling, similar to the treatment with BILN 2061 protease inhibitor, correlating with the disappearance of cleavage products. Overall, the data indicate that HCV NS3/4A targeting of IMPβ1 and related modulators of IRF3 and NF-κB nuclear transport constitute an important innate immune subversion strategy and inspire new avenues for broad-spectrum antiviral therapies.


Sleep Apnea and Chronic Kidney Disease: A State-of-the-Art Review.
Patients with chronic kidney disease have increased morbidity and mortality, mainly due to cardiovascular disease. Compared with the general population, patients with chronic kidney disease have an increased prevalence of both OSA and central sleep apnea, and the presence of sleep apnea in this population has been associated with an increased risk of cardiovascular events and mortality. Although OSA can lead to an increase in the rate of kidney function decline, there is also evidence that the presence of end-stage renal disease can lead to worsening of sleep apnea, indicating a bidirectional relation between sleep apnea and chronic kidney disease. The objective of this review was to describe the epidemiology of sleep apnea in chronic kidney disease, understand the pathophysiological mechanisms by which OSA can lead to progression of chronic kidney disease, and consider the role of treatment with CPAP in this regard. The review also explores the pathophysiological mechanism by which end-stage renal disease can lead to sleep apnea and considers how intensification of renal replacement therapy or extra fluid removal by ultrafiltration may attenuate the degree of sleep apnea severity in this population.


Macrophage Activation Syndrome in a Child with Juvenile Idiopathic Arthritis Secondary to SARS-CoV-2.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a pandemic affecting many countries and millions of people. Physicians have encountered some rare and challenging cases related to SARS-CoV-2, a novel virus with still many unknowns. In order to share our experience of a such clinical picture, we present here a child with SARS-CoV-2-induced macrophage activation syndrome in the setting of juvenile idiopathic arthritis.


Randomized control study of the use of faropenem for treating patients with pulmonary tuberculosis.
Faropenem has antituberculosis activity in vitro but its utility in treating patients with tuberculosis (TB) is unclear. We conducted an open-label, randomized trial in China, involving newly diagnosed, drug-susceptible pulmonary TB. The control group was treated with the standard 6-month regimen. The experimental group replaced ethambutol with faropenem for 2 months. The primary outcome was the treatment success rate after 6 months of treatment. Noninferiority was confirmed if the lower limit of a 95% one-sided confidence interval (CI) of the difference was greater than -10%. A total of 227 patients eligible for the study were enrolled in the trial group and the control group in a ratio of 1:1. Baseline characteristics of participants were similar in both groups. In the modified intention-to-treat population, 88.18% of patients in the faropenem group achieved treatment success, and 85.98% of those in the control group were successfully treated, with a difference of 2.2% (95% CI, -6.73-11.13). In the per-protocol population, treatment success was 96.04% in the faropenem group and 95.83% in the control group, with a difference of 2.1% (95% CI, -5.31-5.72). The faropenem group showed noninferiority to the control group in the 6-month treatment success rates. The faropenem group had significantly fewer adverse events (P <0.01). Our study proved that oral faropenem regimen can be used for the treatment of TB, with fewer adverse events. (Chinese Clinical Trial Registry, ChiCTR1800015959).


Post-COVID-19 fatigue and anhedonia: A cross-sectional study and their correlation to post-recovery period.
Individuals infected by the novel coronavirus (SARS-CoV-2) have experienced different psychiatric manifestations during the period of infectivity and post-COVID-19 infection. Fatigue and anhedonia are among the frequently reported manifestations after recovery from this novel viral pandemic, leading to early evaluation of those patients and proper management of their complaints which have a drastic burden on different domains of life. Also, the period after recovery might have an effect on the severity of these two psychiatric presentations. This cross-sectional observational study aimed to investigate the occurrence of post-COVID-19 fatigue and anhedonia and whether the duration after 2 consecutive PCR-negative tests has an implication on the severity of the above-mentioned psychiatric manifestations. Socio-demographic characteristics of 200 post-COVID-19 patients were collected, and also, the self-assessment anhedonia scale was used to evaluate the degree of anhedonia. Fatigue assessment scale used to investigate this domain. The study targeted to find a possible correlation between the period after recovery and the other variables including anhedonia and fatigue. The study revealed high scores of different subtypes of self-assessment anhedonia scale (including total intensity, total frequency, and total changes scores) in the studied group, also high score of fatigue assessment scale in those patients. Positive statistically significant correlation between anhedonia and fatigue in post-COVID-19 group, also negative statistically significant correlation between duration after recovery and the other 2 variables(anhedonia and fatigue) in the examined patients. Post-COVID-19 fatigue and anhedonia were prevalent and commonly reported in the post-COVID-19 period, also the duration after 2 consecutive negative PCR tests has an implication on the severity rating scale of both anhedonia and fatigue. These findings directed our attention to those reported manifestations which affected the socio-occupational functioning of the individuals during this whole world pandemic.


Increases in plasma cyclic AMP dependent on endogenous catecholamines.
Administration of tyramine (with or without phentolamine) as well as induction of ether anesthesia or insulin hypoglycemia caused a sharp increase in plasma cyclic AMP in rats. Based on the findings that the treatment of rats with reserpine, 6-hydroxydopamine, cocaine or propranolol totally abolished tyramine-induced increases in plasma cyclic AMP, it was concluded that catecholamines released from sympathetic neuronal terminals by tyramine could activate adenylate cyclase via the stimulation of postsynaptic beta-adrenoceptors. In contrast, catecholamines secreted from adrenal medulla were largely responsible for the increase in plasma cyclic AMP induced by ether anesthesia; whereas glucagon, in addition to adrenal catecholamines, played a significant role in hypoglycemia-induced increases in plasma cyclic AMP. Assay of plasma cyclic AMP following these stimuli is very promising as a test for adrenergic activities in experimental and clinical studies.


Association between sternal wound complications and 10-year mortality following coronary artery bypass grafting.
To evaluate the association between sternal wound complications (SWC) and long-term mortality in the Arterial Revascularization Trial. Participants in the Arterial Revascularization Trial were stratified according to the occurrence of postoperative SWC. The primary outcome was all-cause mortality at long-term follow-up. The secondary outcome was major adverse cardiovascular events. Three thousand one hundred two patients were included in the analysis; the median follow-up was 10 years. 115 patients (3.7%) had postoperative SWC: 85 (73.9%) deep sternal wound infections and 30 (26.1%) sterile SWC that required sternal reconstruction. Independent predictors of SWC included diabetes (odds ratio [OR], 2.77; 95% CI, 1.79-4.30; P < .001), female sex (OR, 2.73; 95% CI, 1.71-4.38; P < .001), prior stroke (OR, 2.59; 95% CI, 1.12-5.98; P = .03), chronic obstructive pulmonary disease (OR, 2.44; 95% CI, 1.60-3.71; P < .001), and use of bilateral internal thoracic artery (OR, 1.70; 95% CI, 1.12-2.59; P = .01). Postoperative SWC was significantly associated with long-term mortality. The Kaplan-Meier survival estimate was 91.3% at 5 years and 79.4% at 10 years in patients without SWC, and 86.1% and 64.3% in patients with SWC (log rank P < .001). The rate of major adverse cardiovascular events was also higher among patients who had SWC (n = 51 [44.3%] vs 758 [25.4%]; P < .001). Using multivariable analysis, the occurrence of SWC was independently associated with long-term mortality (hazard ratio, 1.81; 95% CI, 1.30-2.54; P < .001). In the Arterial Revascularization Trial, postoperative SWC although uncommon were significantly associated with long-term mortality.


Labor induction with prostaglandin F2alpha. Influence on psychomotor evolution of the child in the first 30 months.
The long-term effects of elective induction of labor at term by amniotomy and the intravenous infusion of prostaglandin F2alpha were studied in 40 children. No untoward effect of this procedure on the psychomotor development of the children during the first 30 months could be demonstrated.


An electron microscope study of the relative positions of the 4S and ribosomal RNA genes in HeLa cells mitochondrial DNA.
The 4S RNA genes in HeLa mitochondrial DNA (mtDNA) have been mapped by electron microscopy using the electron-opaque label ferritin. This method is based on the high affinity interaction between the protein, avidin,and biotin. 4S RNA, covalently coupled to biotin, was hybridized to single-stranded mtDNA. The hybrids were then labeled with ferritin-avidin conjugates. The positions of ferritin-labeled 4S RNA genes were determined relative to the rRNA genes on both heavy (H) and light (L) strands of mtDNA. This region was recognized as a duplex segment after hybridization either with rRNA in the case of H strands or with DNA complementary to rRNA in the case of L strands. Our studies suggest that at least nineteen 4S RNA genes are present in the HeLa mitochondrial genome. On the H strand, we have confirmed the nine map positions found in a previous electron microscope mapping study (Wu et al., 1972) and obtained evidence for three additional 4S RNA genes. On the L strand, seven 4S RNA genes have been mapped. The nineteen genes are distributed more or less uniformly around the genome. There is a pair of closely spaced genes, approximately 150 nucleotides apart, on the H strand, and another closely spaced pair on the L strand.


[The search for photosensitive agents specifically binding to human serum albumin].
Binding of tetrasulfophenylporphyn with human serum albumin was studied by spectral methods. The presence on the protein of one centre of porphyrin binding with high affinity was shown.


Novel JAK3-Activating Mutations in Extranodal NK/T-Cell Lymphoma, Nasal Type.
Inhibition of the Janus kinase (JAK)-STAT pathway has been implicated as a treatment option for extranodal natural killer/T-cell lymphoma, nasal type (NTCL). However, JAK-STAT pathway alterations in NTCL are variable, and the efficacy of JAK-STAT pathway inhibition has been poorly evaluated. JAK3 mutation and STAT3 genetic alterations were investigated by direct sequencing and immunohistochemistry in 84 patients with newly diagnosed NTCL. Five of 71 patients with NTCL (7.0%) had JAK3 mutations in the pseudokinase domain: two JAK3A573V, two JAK3H583Y, and one JAK3G589D mutation. Proliferation of Ba/F3 cells transduced with novel JAK3 mutations (JAK3H583Y and JAK3G589D) was independent of IL-3 and was inhibited by the JAK3 inhibitor tofacitinib (means ± SD drug concentration causing a 50% inhibition of the desired activity, 85 ± 10 nmol/L and 54 ± 9 nmol/L). Ribbon diagrams revealed that these JAK3 pseudokinase domain mutations were located at the pseudokinase-kinase domain interface. Although phosphorylated STAT3 was overexpressed in 35 of 68 patients with NTCL (51.4%), a STAT3 mutation (p.Tyr640Phe; STAT3Y640F) at the SRC homology 2 domain was detected in 1 of the 63 patients (1.5%). A STAT3 inhibitor was active against STAT3-mutant SNK-6 and YT cells. Novel JAK3 mutations are oncogenic and druggable in NTCL. The JAK3 or STAT3 signal was altered in NTCL, and pathway inhibition might be a therapeutic option for patients with JAK3- or STAT3-mutant NTCL.


Vaccine hesitancy due to vaccine country of origin, vaccine technology, and certification.
Vaccine hesitancy is a global health threat which may hinder the widespread acceptance of several COVID-19 vaccines. Following the collection of 2470 responses from an anonymous questionnaire distributed between October and November 2020 across Israel, we analyzed the responses of physicians, life science graduates (biology, virology, chemistry, etc.), and the general public to whether they would obtain a COVID-19 vaccine with particular vaccine characteristics such as vaccine country of origin, technology, side effect profile, efficacy, and other attributes. Physicians and life science graduates were least likely to accept a vaccine based on mRNA technology (30%) while the general population seemed to adopt any vaccine technology if the declared efficacy is above 90% and the country of manufacturing is the USA/UK rather than China or Russia. However, current inoculation rates in Israel far outpace our predicted rate. Our results highlight the importance of tailored vaccine educational campaigns based on population demographic details and specific vaccine concerns.


Endobain E, a brain endogenous factor, is present and modulates NMDA receptor in ischemic conditions.
We have isolated from rat cerebral cortex an endogenous Na(+), K(+)-ATPase inhibitor, termed endobain E, which modulates glutamatergic N-methyl-d-aspartate (NMDA) receptor. This endogenous factor allosterically decreases [(3)H]dizocilpine binding to NMDA receptor, most likely acting as a weak channel blocker. In the present study we investigated whether endobain E is present in the cerebral cortex of rats subjected to ischemia and modulates NMDA receptor exposed to the same conditions. Ischemia-reperfusion was carried out by bilateral occlusion of common carotid arteries followed by a 15-min reperfusion period. Elution profile of brain soluble fraction showed that endobain E is present in cerebral cortex of ischemia-reperfusion rats. On assaying its effect on synaptosomal membrane Na(+), K(+)-ATPase activity and [(3)H]dizocilpine binding to cerebral cortex membranes prepared from animals without treatment, it was found that the endogenous modulator isolated from ischemia-reperfusion rats was able to inhibit both enzyme activity and ligand binding. On the other hand, endobain E prepared from rats without treatment also decreased binding to cerebral cortex or hippocampal membranes obtained from animals exposed to ischemia-reperfusion. Since ischemia decreases tissue pH and NMDA receptor activity varies according to proton concentration, pH influence on endobain E effect was tested. Endobain E ( approximately 80 mg original tissue) decreased [(3)H]dizocilpine binding 25% at pH 7.4 or 8.0 but 90% at pH 6.5. These results demonstrate that endobain E is present and also able to modulate NMDA receptor in the short-term period that follows cerebral ischemia and that its effect depends on proton concentration, suggesting greater NMDA receptor modulation by endobain E at low pH, typical of ischemic tissues.


Reinnervation of denervated iris by transplanted sympathetic ganglia: effect of neuronal age.
Neuronal outgrowth in vivo is aggressive postnatally, but is diminished with increasing age. This may be attributable to intrinsic features of the neuron or its interaction with other components of the developing organism. The purpose of this study was to determine if there is an age-dependent reduction in the intrinsic ability of sympathetic neurons to initiate fiber outgrowth. Superior cervical ganglia from donor rats aged 3-4, 11-12, 27-28 and 45-46 days were removed and transplanted to the anterior chamber of the sympathectomized eye of host rats 85-89 days of age. Ganglia with host irides were removed at 3, 6 and 10 days post-transplant and whole mounts were analysed using catecholamine histofluorescence for maximum sympathetic fiber density, length and initial rate of outgrowth. Fluorescent fibers were present in host irides of donors of all ages and at all post-transplant times. However, maximum fiber density was less for the 3-4-day-old donor ganglia (e.g. 43-71% of 11-46-day-old donor ganglia at 600 microns, 10 days post-transplant). Maximum fiber length was also less in the youngest group (e.g. 35-49% of 11-46-day-old donor ganglia, 10 days post-transplant). Further, the initial rate of outgrowth was decreased for the 3-4-day-old donor ganglia (128 +/- 46 microns/day for the 3-4-day-old ganglia vs 253 +/- 48 microns/day for the 11-12-day-old ganglia, 307 +/- 35 microns/day for the 27-28-day-old ganglia and 260 +/- 22 microns/day for the 45-46-day-old ganglia).(ABSTRACT TRUNCATED AT 250 WORDS)


Investigation of mechanisms involved in seed germination enhancement, enzymatic activity and seedling growth of rice (Oryza Sativa L.) using LPDBD (Ar+Air) plasma.
The study investigates the effect of LPDBD (Low Pressure Dielectric Barrier Discharge) (Ar + Air) plasma on seed germination, seedling growth and antioxidant enzyme activity of rice. Rice seeds were treated with LPDBD (Ar + Air) plasma for 2min, 4min, 6min, 8min and 10min. Seed germination rate, seedling growth, total chlorophyll content, enzymatic activity, total soluble sugar and protein concentration were increased in plants grown from the LPDBD (Ar + Air) plasma treated seeds. It was observed that the sprouting of seeds and the growth of seedlings of rice depends on the feed gases used to generate plasma and plasma processing time. In the case of plantlets germinated from the plasma-treated seeds of rice, the H2O2 level was increased significantly both in leaves and roots for 6min, 8min and 10min treatment respectively. No significant change was observed in Nitric Oxide (NO) concentration in seed, leaf, or root of plants grown from LPDBD (Ar + Air) plasma-treated seeds. The amount of total soluble sugar and protein increased significantly in the case of 2min, 4min, 6min, 8min and 10min seed treatment. Although plants exhibited no significant increase in APX activities, but a significant increase of CAT and SOD activity in the leaf and root was found. This study reveals that LPDBD (Ar + Air) plasma is involved in the elevation of ROS species in leaf and root of rice plants which is tightly regulated by the upregulation of CAT activity that ultimately enhances the seed germination and growth of rice plantlets.


Intraventricular hemorrhage in adults: clinical-computed tomographic correlations.
The clinical and computed tomographic (CT) findings in 100 consecutive adult nontraumatic intraventricular hemorrhage (IVH) cases are analyzed. There were 74 parenchymal brain hemorrhages with secondary ventricular extension. The ventricles were filled with blood and asymmetrically enlarged. If the hemorrhage involved putamen, cerebellum, pons, or subcortical cerebral hemispheric white matter, IVH was associated with large parenchymal hematomas; these patients had poor clinical outcome. With thalamic or caudate hematomas, IVH frequently occurred with large hematomas but may occur with small hematomas. The small hematomas were located directly contiguous to the ventricular walls and caused extensive ventricular blood. Patients with small thalamic and caudate hemorrhage with intraventricular blood had good clinical outcome; whereas patients with large hematomas had poor outcome. Primary IVH occurred in 24 cases. In these cases, blood was seen in all ventricular chambers. Aneurysms involving the anterior cerebral-anterior communicating artery region were the most common etiology for primary IVH.


Bioconversion of alperujo into an alternative feed for ruminants by pretreatment with live yeasts and/or exogenous fibrolytic enzymes.
Extraction of olive oil through a two-stage centrifugation process produces a large amount of phytotoxic waste known as alperujo. This research was performed to bioconvert alperujo into enriched ruminant feed by pretreatment with exogenous fibrolytic enzymes (EFE) or/and live yeasts (LY). These additives were used in a completely randomized design with 3 EFE doses (0, 4, and 8 µl/g dry matter) and 3 LY doses (0, 4, and 8 mg/g dry matter) in a 3 × 3 factorial arrangement. Fermented alperujo with both EFE doses converted some of their hemicellulose and cellulose to simple sugars and increased bacterial abundance in the rumen. As a result, it shortens the lag time of rumen fermentation, increases the rate and amount of rumen fermentation, and improves digestibility. This improvement provides additional energy that can be used by ruminants to produce milk and by rumen microbiota to produce short-chain fatty acids. Fermented alperujo with a high dose of LY decreased their antinutritional compounds and reduced their high content of lipid. In the rumen, this waste became rapidly fermentable, and rumen bacteria became more abundance. Fermented alperujo with a high dose of LY + EFE accelerated rumen fermentation and improved rumen digestibility, energy available for milk production, and short-chain fatty acids compared to the use of LY or EFE alone. This synergistic interaction between these two additives increased protozoa abundance in rumen and the ability of rumen microbiota to bioconvert ammonia-nitrogen to microbial protein. Ultimately, fermentation alperujo with EFE + LY is a good strategy with minimum investment for a social sustainable economy and environment.


Copayment policy reforms and effective care utilization by patients with persistent asthma in Taiwan.
Reforms to the Taiwan National Health Insurance copayment scheme in 2005 imposed a notable increase in the cost of outpatient visits. This provided an ideal situation to determine whether such reforms lead to a reduction in the utilization of effective care by patients with persistent asthma. This study applied the pretest-posttest non-randomized control group design in our analysis of nationwide claims data (2002 to 2010). Based on propensity score matching, the patients were divided into two groups, subject and not subject to copayment reform. Medication Management for People with Asthma measure was used to identify patients with persistent asthma and instances of effective care. Matching yielded a final panel of 7,890 individuals with persistent asthma (3,945 individuals in each cohort) eligible for the study. GEE analysis revealed that policy reforms had significant effects over the short-term (OR = 0.745, p < 0.05), medium-term (OR = 0.752, p < 0.01), and long-term (OR = 0.721, p < 0.01). Reforms to copayment policy were significantly correlated with a reduction in the utilization of effective care by patients with persistent asthma over the short-, medium- and long-term. Government should develop implementation strategies aimed at protecting the economically disadvantaged patients.


Three-dimensional evaluation of bracket placement accuracy and excess bonding adhesive depending on indirect bonding technique and bracket geometry: an in-vitro study.
This study aimed at comparing bracket placement and excess bonding adhesive depending on different indirect bonding (IDB) techniques and bracket geometries. Four hundred eighty brackets without hook (WOH) and 360 with hook (WH) were placed on 60 plaster models. Three IDB techniques were tested: polyvinyl-siloxane vacuum-form (PVS-VF), polyvinyl-siloxane putty (PVS-putty), and translucence double-polyvinyl-siloxane (double-PVS). PVS-VF and PVS-putty were combined with chemically, and double-PVS was combined with light cured bonding adhesive. Virtual images of models before and after bracket transfer were generated, and computerized images were compared. Linear, angular deviations, and excess bonding adhesive were measured. Linear differences between the three groups were obtained for PVS-VF (WH: 1.08, SD 0.50 mm; WOH: 0.86, SD 0.25 mm), PVS-putty (WH: 0.73, SD 0.51 mm; WOH: 0.58, SD 0.28 mm), and double-PVS (WH: 0.65, SD 0.45 mm; WOH: 0.59, SD 0.33 mm) (P < 0.001). Hooks affected bracket placement accuracy in PVS-VF (P < 0.001) and PVS-putty (P = 0.029). Angular differences were observed for brackets WOH between the PVS-VF (0.64, SD 0.48°) and double-PVS group (0.92, SD 0.76°) (P < 0.001) and within double-PVS group (WH: 0.66, SD 0.51° vs. WOH: 0.92, SD 0.76°, P < 0.001). Highest amount of excess adhesive was obtained for PVS-putty group (WH: 6.54, SD 5.31 mm 2). The double-PVS group revealed promising results with respect to transfer accuracy, whereas the PVS-VF group provided least excess bonding adhesive. Basically, hooks lead to lower precision and higher excess bonding adhesive. PVS trays for IDB generate high bracket placement accuracy. PVS-putty is the easiest to handle with and also the cheapest, but leads to large excess bonding adhesive, especially in combination with hooked brackets or tubes.


Long-Term Implant Survivability of an Implant Having Direct Contact with Cementum-Like Tissue in a Preexisting Mandibular Intraosseous Lesion with a 16-Year Longitudinal Follow-up.
This case report demonstrates long-term implant stability associated with focal cemento-osseous dysplasia (FCOD). The nature of the cementum-like tissue (CLT) of FCOD around the titanium surface of the implant is described clinically, radiologically, and histologically. A dental implant placed directly into the FCOD lesion was successfully integrated, and the stability was maintained for 15 years. However, at the 16-year follow-up, the implant and a sclerotic mass were removed due to peri-implantitis, and the entire specimen was evaluated with conventional histology and microcomputed tomography. The analysis revealed that the sclerotic mass attached to the implant was CLT that was free of any intervening soft tissue. The implant placed into the FCOD lesion achieved integration similar to that of conventional osseointegration. Rather than bone, the CLT was in direct contact with the titanium surface. The integrity of the union was maintained for up to 16 years.


Taller-than-wide sign for predicting thyroid microcarcinoma: comparison and combination of two ultrasonographic planes.
The aims of this study were to investigate the accuracy of using the taller-than-wide (TTW) sign in two ultrasonographic planes to predict thyroid microcarcinoma, and to confirm the hypothesis that the presence of a TTW sign in both the transverse and longitudinal ultrasonographic planes strongly suggests thyroid microcarcinoma. Nine hundred forty-two thyroid nodules ≤1 cm were submitted to surgical-histopathologic and ultrasonographic examination. TTW signs were divided into three types based on their detection only in the transverse plane (TTTW type, n = 100), only in the longitudinal plane (LTTW type, n = 61) or in both planes (BTTW type, n = 131). The areas under the receiver operating characteristic curves (A(z)) for the three different TTW signs, as well as for the combination of all TTW signs (ATTW, n = 292), were compared. The results indicated that the A(z) values of the TTTW, LTTW, BTTW and ATTW signs in predicting thyroid microcarcinoma were 0.544, 0.531, 0.627 and 0.702, respectively. The ATTW sign was the most accurate (p < 0.05), and the BTTW sign was 100% accurate for predicting thyroid microcarcinoma. However, there was no significant difference between the A(z) values for the TTTW and LTTW signs (p > 0.05). Therefore, both the LTTW and TTTW signs are reliable markers of thyroid microcarcinoma. The BTTW sign strongly suggests thyroid microcarcinoma.


Isolation of phosphate-solubilizing fungi from phosphate mines and their effect on wheat seedling growth.
Three phosphate-solubilizing fungi, identified as Penicillium expansum, Mucor ramosissimus, and Candida krissii, were isolated from phosphate mines (Hubei, People's Republic of China) and characterized. All the isolates demonstrated diverse levels of phosphate-solubilizing capability in National Botanical Research Institute's phosphate growth medium containing rock phosphate as sole phosphate source. Acidification of culture medium seemed to be the main mechanism for rock phosphate solubilization. Indeed, citric acid, oxalic acid, and gluconic acid were shown to be present in the culture medium inoculated with these isolates. Moreover, the isolates produced acid and alkaline phosphatases in culture medium, which may also be helpful for RP solubilization. A strong negative correlation between content of soluble phosphorus and pH (r = - 0.89; p < 0.01) in culture medium was observed in this study. All the isolates promoted growth, soil available phosphorus, phosphorus, and nitrogen uptake of wheat seedling in field soil containing rock phosphate under pot culture conditions, thus demonstrating the capability of these isolates to convert insoluble form of phosphorus into plant available form from rock phosphate, and therefore hold great potential for development as biofertilizers to enhance soil fertility and promote plant growth.


Treatment options for sleep dysfunction in Parkinson's disease.
Sleep disturbance is an important feature of Parkinson's disease (PD) that deserves clinical attention. Various disorders need to be considered and treatment should be customized to the patient's specific symptoms and lifestyle. Evaluation of a PD patient complaining of difficulty sleeping begins with a detailed history from the patient and bed partner about the specific problem the patient is experiencing. It is important to inquire about difficulties with sleep onset, frequent awakenings, increased movements during sleep, acting out dreams, uncomfortable motor symptoms, disordered breathing, and nocturia. Current medications should be reviewed to determine whether the recent addition of a drug or a change in dose may be contributing to sleep difficulties, and one should ask about daytime sleepiness, frequent daytime naps, and sleep hygiene in the evening that can contribute to problems sleeping at night. The goal of therapy is to restore quality nighttime sleep without excessive daytime sedation and to improve the patient's daily mental and physical function and overall quality of life.


Resolving mass fractions and congener group patterns of C8-C17 chlorinated paraffins in commercial products: Associations with source characterization.
Commercial chlorinated paraffins (CPs) are a source of CPs in the environment, and clarification of the different CP groups present in commercial products is important for source characterization. Resolving CP congener groups is hindered by the complex CP compositions of commercial products. We used comprehensive two-dimensional gas chromatography coupled with electron capture negative ionization high-resolution time-of-flight mass spectrometry to profile 57 C8 - C17 CP congener groups in 18 CP-42, CP-52, and CP-70 commercial products. Very short-chain CPs (vSCCPs), including C8Cl5-8 and C9Cl5-9 CPs, and other chlorinated aromatic compounds were identified in the commercial products. The mass fractions of total vSCCPs, short-chain CPs (SCCPs) and medium-chain CPs (MCCPs) in the commercial products ranged from 0.02% to 3.61%, 0.75% to 51.4%, and 0.39% to 69.1%, respectively. Two-dimensional hierarchical cluster analysis with a heat map plot highlighted variations in the C8 - C17 CP congener group patterns among different commercial CP formulations. The principal component analysis results indicated that commercial CPs products might be important contributors to vSCCPs, SCCPs, and MCCPs in various environmental matrices. This study provides comprehensive and well-resolved compositional data for CPs in commercial products, which will be helpful for CP source characterization.


[Charcot's neuroarthropathy].
Diabetes is the most common cause of neuropathic arthropathy. The most frequent localization is the tarsus. In clinical practice, the insidious painful onset and discrete inflammatory signs of this disease often lead to a mistaken interpretation by the physicians who usually manage these patients (endocrinologists, rheumatologists, podiatrists, etc.), delaying diagnosis with devastating consequences. We report four cases of neuropathic arthropathy in diabetic patients diagnosed in our service. The clinical features that may suggest a diagnosis in the early stages of this entity are stressed.


Challenging definitions and diagnostic approaches for ancient rare diseases: The case of poliomyelitis.
This paper aims to contribute to the definition of ancient rare diseases in skeletons displaying pathologies associated with paralysis. It uses a new suite of methods, which can be applied to challenging cases of possible paralysis in archaeologically-derived human skeletal material, specifically applied to the identification of poliomyelitis. An adult male skeleton from Roman Halbturn, Austria. Morphological and entheseal change analyses, CT scans, X-rays, cross-section morphology, and histology, alongside modern clinical, as well as historic, literature were used to discuss paralyses. The results suggest a diagnosis of poliomyelitis; now considered a rare disease, but perhaps ubiquitous in antiquity, thus complicating the definition of 'rare disease'. The integrated methodological procedures employed for this case constitutes a replicable and thorough approach to diagnosis, and explores the nature of ancient rare diseases. Due to the socio-environmental aspects of poliomyelitis transmission, it is likely that polio was likely not rare in the past. Therefore, the definition of 'rare diseases in the past' must include rarely occurring rarely diagnosed diseases due to biases and challenges within the archaeological and environmental record. The developed suite of methods has not been applied to establish a diagnosis of polio in the past. The individual considered in this study is fairly well-preserved; thus, this set of analyses may not be applicable to all remains where preservation is poor or highly fragmentary, and the discussion of rare diseases requires relatively secure diagnoses and context. Large collections and series of skeletal human remains are recommended to develop definitive conclusions.


Identifying the effect of fluorination on cation and anion redox activity in Mn based cation-disordered cathode.
Li-rich disordered rock-salt cathode (DRX) materials with advantage of low cost, long cycle life, nature abundant resource and high power and energy density attracted a great deal of scholarly attention. However, the poor cycle stability and the unclear realization of cation and anion redox activity in low-cost element system have severely hindered the construction of high-performance DRX. Herein, a promising class of Ti-Mn based cathode materials Li1.25Mn0.25Nb0.25Ti0.25O2 and Li1.25Mn0.25Ti0.5O1.75F0.25 were designed and successfully synthesized to construct high energy density DRX and investigate the effect of fluorination on cation and anion redox activity. The results show that both fluoridized and unfluoridized DRX possess a similar structure (Fm-3 m), but distinctly different charge/discharge profiles. The fluoridized cathode shows high initial charge/discharge capacity of 317.3/283.9 mAh g-1, specific energy density of 1370.4/735.5 Wh kg-1 and stable capacity retention with a discharge capacity of 202.6 mAh g-1 after 20 cycles at 20 mA g-1. Combining relevant spectroscopic results and HRTEM images, we revealed that the excellent cyclability of Li1.25Mn0.25Ti0.5O1.75F0.25 is rooted in the weakened adverse effects of moderated oxygen redox and the reduced Jahn-Teller distortion effect resulting from Mn3+, endowing the fluoridized DRX with better structural stability and larger Mn2+/Mn4+ reservoir. The strategy of constructing low cost oxyfluoride and the understanding of the mechanism of fluorination induced cation and anion redox activity would provide reference for the development of high-performance DRX materials.


Effect of fat and microflora on hepatic, small intestinal and colonic HMG CoA reductase, cytochrome P450 and cytochrome B5.
High levels of dietary fat caused a significant reduction in HMG CoA reductase activity in the liver of germ-free rats whereas significantly elevated small intestinal enzyme activity was observed. Dietary fat had no significant effect on HMG CoA reductase activity in any tissue studied in the conventional rat. No significant change in colonic HMG CoA reductase activity was observed between any of the experimental groups. Rats fed a high-fat diet tended to exhibit higher cytochrome P450 levels in all tissues studied, regardless of the presence of intestinal microflora.


miR‑203 inhibits the expression of collagen‑related genes and the proliferation of hepatic stellate cells through a SMAD3‑dependent mechanism.
Activation of hepatic stellate cells (HSCs) is a pivotal event during hepatic fibrogenesis. Activated HSCs are the main source of collagen and other extracellular matrix (ECM) components, and emerging antifibrotic therapies are aimed at preventing ECM synthesis and deposition. MicroRNAs (miRNAs) have been demonstrated to exert regulatory effects on HSC activation and ECM synthesis. In the present study, the HSC‑T6 rat hepatic stellate cell line was transiently transfected with a miRNA (miR)‑203 mimic, which is an artificial miRNA that enhances the function of miR‑203, with a miR‑203 inhibitor or with a scramble miRNA negative control. mRNA and protein expression levels of collagen (COL) 1A1, COL3A1, α‑smooth muscle actin (α‑SMA) and mothers against decapentaplegic homolog 3 (SMAD3) were assessed using reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. The interaction between miR‑203 and the 3'‑untranslated region (UTR) of SMAD3 mRNA was examined using a dual‑luciferase reporter assay. The proliferative capabilities of activated HSCs were measured using an MTT assay. The present results demonstrated that the mRNA and protein expression levels of COL1A1, COL3A1, α‑SMA and SMAD3 were significantly upregulated following transfection of HSC‑T6 cells with the miR‑203 inhibitor. Conversely, COL1A1, COL3A1, α‑SMA, and SMAD3 mRNA and protein expression appeared to be downregulated in rat HSCs transfected with miR‑203 mimics. Notably, the inhibition of miR‑203 expression was revealed to promote HSC proliferation, whereas increased miR‑203 expression suppressed the proliferative capabilities of HSC‑T6 cells. Furthermore, SMAD3 was revealed to be a direct target of miR‑203. The present study suggested that miR‑203 may function to prevent the synthesis and deposition of ECM components, including COL1A1, COL3A1 and α‑SMA, and to inhibit the proliferation of HSCs through a SMAD3‑dependent mechanism. Therefore, it may be hypothesized that miR‑203 has potential as a novel target for the development of alternative therapeutic strategies for the treatment of patients with hepatic fibrosis in clinical practice.


Angiotensin receptor blocker use is associated with upregulation of the memory-protective angiotensin type 4 receptor (AT4R) in the postmortem brains of individuals without cognitive impairment.
The reported primary dementia-protective benefits of angiotensin II type 1 receptor (AT1R) blockers (ARB) are believed, at least in part, to arise from systemic effects on blood pressure. However, there is a specific and independently regulated brain renin-angiotensin system (RAS). Brain RAS acts mainly through three receptor subtypes; AT1R, AT2R, and AT4R. The AT1R promotes inflammation and mitochondrial reactive oxygen species generation. AT2R increases nitric oxide. AT4R is essential for dopamine and acetylcholine release. It is unknown whether ARB use is associated with changes in the brain RAS. Here, we compared the impact of treatment with ARB on not cognitively impaired individuals and individuals with Alzheimer's dementia using postmortem frontal-cortex samples of age- and sex-matched participants (70-90 years old, n = 30 in each group). We show that ARB use is associated with higher brain AT4R, lower oxidative stress, and amyloid-β burden in NCI participants. In AD, ARB use was associated with lower brain AT1R but had no impact on inflammation, oxidative stress, or amyloid-β burden. Our results may suggest a potential role for AT4R in the salutary effects for ARB on the brains of not cognitively impaired older adults.


Rod fractures and nonunions after long fusion to the sacrum for primary presentation adult spinal deformity: a comparison with and without interbody fusion in the distal lumbar spine.
Retrospective cohort study. To investigate the prevalence and incidence rate of rod fractures (RF) in patients undergoing surgery for correction of adult spinal deformity (ASD) with or without the use of interbody fusions in the caudal levels of the fusion construct. Data: Pseudarthrosis and rod fracture after long spinal fusion to the sacrum for correction of ASD remain a concern. We reviewed clinical records of patients who underwent surgery for correction of ASD between 2004 and 2014. All cases were primary (no prior spine fusion) surgeries with long fusion to the sacrum and bilateral spinopelvic fixation. Patients were dichotomized into one of two groups based on whether an interbody fusion was performed at the caudal levels of the fusion construct. The primary outcome of interest was the prevalence and incidence rate of RFs. A total of 230 patients underwent a long segment fusion for correction of ASD with mean follow-up of 55 months. 117 patients had an interbody fusion (IF) while 113 patients did not (NIF). At last follow-up, there was no significant difference in the prevalence of RFs between the cohort of patients IF vs NIF (IF cohort: n = 20, 17.9% vs NIF cohort: n = 15, 14.2%, p = 0.49). However, the incidence rate for bilateral rod fractures was 1.6%/year for IF group vs 1.0%/year for NIF group (p = 0.02). Location of RF was different between the two groups; RF (unilateral and bilateral) above L4 was the most common location in the IF group (n = 17/20; 85%) compared to L4-S1 in the NIF group (n = 11/15; 73%) (p = 0.02). Interbody fusion does not fully protect against rod failure in the lumbar spine in ASD patients with long posterior spinal fusion and may encourage failure at L2-L4, the levels above the interbody fusion. III.


An easy way of intruding an upper central incisor.
Discrepancies of the incisal edges of the anterior teeth, particularly in the upper jaw, could adversely affect dental aesthetics. This paper presents an easy and straight forward treatment of such a case, which was accomplished taking the patient's demands and profession into consideration. In dentistry, the social status of the patient could affect the treatment plan.


The Association Between Distinct Frontal Brain Volumes and Behavioral Symptoms in Mild Cognitive Impairment, Alzheimer's Disease, and Frontotemporal Dementia.
Our aim was to investigate the association between behavioral symptoms of agitation, disinhibition, irritability, elation, and aberrant motor behavior to frontal brain volumes in a cohort with various neurodegenerative diseases. A total of 121 patients with mild cognitive impairment (MCI, n = 58), Alzheimer's disease (AD, n = 45) and behavioral variant frontotemporal dementia (bvFTD, n = 18) were evaluated with a Neuropsychiatric Inventory (NPI). A T1-weighted MRI scan was acquired for each participant and quantified with a multi-atlas segmentation method. The volumetric MRI measures of the frontal lobes were associated with neuropsychiatric symptom scores with a linear model. In the regression model, we included CDR score and TMT B time as covariates to account for cognitive and executive functions. The brain volumes were corrected for age, gender and head size. The total behavioral symptom score of the five symptoms of interest was negatively associated with the volume of the subcallosal area (β = -0.32, p = 0.002). High disinhibition scores were associated with reduced volume in the gyrus rectus (β = -0.30, p = 0.002), medial frontal cortex (β = -0.30, p = 0.002), superior frontal gyrus (β = -0.28, p = 0.003), inferior frontal gyrus (β = -0.28, p = 0.005) and subcallosal area (β = -0.28, p = 0.005). Elation scores were associated with reduced volumes of the medial orbital gyrus (β = -0.30, p = 0.002) and inferior frontal gyrus (β = -0.28, p = 0.004). Aberrant motor behavior was associated with atrophy of frontal pole (β = -0.29, p = 0.005) and the subcallosal area (β = -0.39, p < 0.001). No significant associations with frontal brain volumes were found for agitation and irritability. We conclude that the subcallosal area may be common neuroanatomical area for behavioral symptoms in neurodegenerative diseases, and it appears to be independent of disease etiology.


Frontier and hot topics in electrochemiluminescence sensing technology based on CiteSpace bibliometric analysis.
Electrochemiluminescence (ECL) is a process in which luminescence is produced by oxidizing or reducing luminophores to transfer radiant charges between electrochemically generated free radicals. Although about 7000 electrochemiluminescence articles have been published in the past 20 years (2000-2021), only a few review articles have summarized the development and application of ECL. In order to better understand the development status, research hotspots and future development trends of ECL technology, it is very necessary to conduct a comprehensive retrospective analysis. This review is based on the bibliometric analysis method of CiteSpace software to quantitatively analyze, visually review and comment on the articles published in the field of ECL in the past 20 years. Quantitatively analyze the authors, the institutional and other basic information to understand the basic development status of ECL, and then visually analyze the high-frequency keywords, burst keywords, keyword clusters, etc., to understand each the evolution of the main research hotspots and development directions of the period, and finally a detailed review and analysis of the selected highly cited articles. We particularly emphasized the development needs of electrochemiluminescence technology in improving the performance of ECL sensors, developing materials with excellent ECL performance, innovating and cooperating with other devices, and developing high-speed and high-throughput ECL sensors. We hope to provide new ideas for promoting the industrial development and clinical application of electrochemiluminescence technology.


Translocation of transition metal oxide nanoparticles to breast milk and offspring: The necessity of bridging mother-offspring-integration toxicological assessments.
Although infant nanomaterial exposure is a worldwide concern, breastfeeding transfer of transition metal-oxide nanoparticles to as well as their toxicity to offspring are still unclear. Breastfeeding transmits nutrition and immunity from mothers to their offspring; it also provides a portal for maternal toxins to enter offspring. Thus, a toxicology assessment of both mothers and their offspring should be established to monitor nanomaterial exposure during lactation. Here, we determined the effects of the exposure route on the biodistribution, biopersistence, and toxicology of nanoparticles (titanium dioxide, zinc oxide, and zirconium dioxide) in both mouse dams and their offspring. Oral and airway exposure routes were tested using gavage and intranasal administration, respectively. Biodistribution in the main organs (breast, liver, spleen, lung, kidney, intestine, and brain) and biopersistence in the blood and milk were determined using inductively coupled plasma mass spectrometry. Hematology and histomorphology analyses were performed to determine the toxicology of the nanoparticles. A reduced offspring body weight was found with the reduced nanoparticle size. Furthermore, both oral and airway exposure increased the nanoparticle concentrations in the main tissues and milk. More nanoparticles were transferred into maternal tissues and milk via airway exposure than via oral exposure. During the transfer of the metal from the exposed nanoparticles to milk, the immune cell pathway played a more important role in the airway route than in the oral exposure route. Finally, maternal exposure via both the oral and airway routes reduced the body weight and survival rate of their breastfeeding offspring, which could possibly be attributed to the toxicity of nanoparticles to blood cells and organs. In conclusion, maternal exposure to nanoparticles led to a reduced body weight and survival rate in breastfed offspring, and nanoparticle exposure via the airway route led to a higher immune response and tissue injury than that via the oral exposure route. This study suggests that the use of products containing metal nanoparticles in breastfeeding mothers and their offspring should be reconsidered to maintain a safe breastfeeding system.


Autodisplay of human PIP5K1α lipid kinase on Escherichia coli and inhibitor testing.
The human phosphatidylinositol 4-phosphate 5-kinase type I α (hPIP5K1α) plays a major role in the PI3K/AKT/mTOR signaling pathway. As it has been shown before that hPIP5K1α is involved in the development of different types of cancer in particular prostate cancer, inhibitors of the enzyme might be a new option for the treatment of this disease. Here we report on the expression of hPIP5K1α on the surface of E. coli using Autodisplay. Autodisplay is defined as the surface display of a recombinant protein on a gramnegative bacterium by the autotransporter secretion pathway. After verification of surface expression, enzyme activity of whole cells displaying hPIP5K1α was determined by a capillary electrophoresis based assay. When using cells at an OD578 of 2.5, the artificial substrate phosphatidylinositol4-phosphate (PI(4)P) fluorescein was converted by a rate of 10.7 ± 0.2 fmol/min. Using this substrate inhibition of three pyranobenzoquinone type compounds was tested. The most active compound was 4-(2-amino-3-cyano-6-hydroxy-5,8-dioxo-7-undecyl-5,8-dihydro-4H-chromen-4-yl) benzoic acid with an IC50 value of 8.6 μM. Because until now, all attempts to purify hPIP5K1α failed, we suggest the use of whole cells of E. coli displaying the enzyme as a convenient tool for inhibitor identification.


Histological and diffusion-weighted magnetic resonance imaging data from normal and degenerated optic nerve and chiasm of the rat.
Diffusion-weighted magnetic resonance imaging (dMRI) is widely used to infer microstructural characteristics of tissue, particularly in cerebral white matter. Histological validation of the metrics derived from dMRI methods are needed to fully characterize their ability to capture biologically-relevant histological features non-invasively. The data described here were used to correlate metrics derived from dMRI and quantitative histology in an animal model of axonal degeneration ("Histological validation of per-bundle water diffusion metrics within a region of fiber crossing following axonal degeneration" [1]). Unilateral retinal ischemia/reperfusion was induced in 10 rats, by the elevation of pressure of the anterior chamber of the eye for 90 min. Five rats were used as controls. After five weeks, injured animals were intracardially perfused to analyze the optic nerves and chiasm with dMRI and histology. This resulted in 15 brain scans, each with 80 diffusion-sensitizing gradient directions with b = 2000 and 2500 s/mm2 and 20 non-diffusion-weighted images (b = 0 s/mm2), with isometric voxel resolution of 125 μm3. Histological sections were obtained after dMRI. Optical microscopy photomicrographs of the optic nerves (stained with toluidine blue) are available, as well as their corresponding automatic segmentations of axons and myelin.


Primary structure of the soluble lactose binding lectin L-29 from rat and dog and interaction of its non-collagenous proline-, glycine-, tyrosine-rich sequence with bacterial and tissue collagenase.
A lactose-binding lectin from rat lung (RL-29) and a related lectin from Madin-Darby canine kidney (MDCK) cells have been analyzed with the primary goal of identifying post-translational modifications. The sequences show that RL-29 and the dog lectin are homologues of a lectin designated here as L-29 and elsewhere as CBP-35, epsilon BP, Mac-2, or L-34. RL-29 has a 140-amino-acid COOH-terminal carbohydrate-binding domain, a 20-amino-acid NH2-terminal domain, and an intervening domain consisting of 11 repeating elements rich in Pro, Gly, and Tyr (R-domain). The dog homologue has 14 repeating elements in its R-domain explaining its larger size. The sensitivity of the R-domain to bacterial collagenase allowed us to isolate the NH2-terminal domain and show that the NH2 terminus was blocked by acetylation and, in the accompanying paper (Huflejt, M. E., Turck, C. W., Lindstedt, R., Barondes, S. H., and Leffler, H. (1993) J. Biol. Chem. 268, 26712-26718), that the NH2-terminal domain is phosphorylated. In addition, we unexpectedly found an endogenous component, resembling 92-kDa type IV collagenase, that co-purified with L-29 and slowly digested the R-domain. Hence, L-29 is a substrate for bacterial and tissue collagenases even though the R-domain is non-collagenous. Moreover, the co-purification suggests a non-enzymatic interaction between 92-kDa collagenase and L-29.


Effects of alpha 2-adrenoceptor antagonists and imidazoline2-receptor ligands on neuronal damage in global ischaemia in the rat.
1. In the present study the neuroprotective effects of 3 mg/kg idazoxan, an alpha 2-adrenoceptor antagonist and imidazoline2-receptor (I2-receptor) ligand, 3 mg/kg methoxyidazoxan, a specific alpha 2-adrenoceptor antagonist, and 0.6 and 3 mg/kg BU224, a selective I2-receptor ligand, were evaluated following 10 min of global ischaemia in rats. 2. Neuronal cell counts in the CA1 region of the hippocampus 8 days postischaemia indicated 46-96% cell loss compared with control (P < 0.001) and a 320% increase in [3H]-PK11195 binding (P < 0.001) used as a marker of gliosis. No significant neuroprotective effect could be detected on these markers of neuronal damage in the active treatment groups. In a subset of idazoxan-treated rats, neuronal loss and gliosis was minimal. 3. Mean body temperature over 3 h postischaemia was lower in idazoxan-treated rats than in the other treatment groups (P < 0.001) and there was a correlation between mean body temperature and cell counts (P < 0.01) and mean body temperature and gliosis in this group (P = 0.057). 4. These results indicate that at the doses used neither BU224 nor methoxyidazoxan are neuroprotective in this ischaemia model and they raise the possibility that any neuroprotective effect of idazoxan may be related to hypothermic effects of the drug.


Practical therapy for primary autoimmune hemolytic anemia in adults.
Autoimmune hemolytic anemias (AIHA) constitute a rare and heterogeneous group of diseases whose therapy differs according to the type of antibody involved in the genesis of the disease and the existence or not of an identified cause. With the aim of providing a practical guide for the therapy of AIHA, we summarize the emergency therapy and general measures habitually used in all forms of AIHA, as well as the specific treatment of the most frequent primary forms of AIHA: primary warm AIHA and AIHA from cold agglutinin disease (AIHA from CAD). We discuss the dependence of the treatment of the secondary forms on their underlying causes and the changes in the treatment of the primary forms in recent years. We examined the options available for the treatment of primary warm AIHA and AIHA from CAD. We found many differences and only one similarity in their treatment. The differences, particularly due to the non-responsiveness of AIHA from CAD to many treatments useful for primary warm AIHA, such as steroids, splenectomy and immunosuppressive agents, must be considered in the face of each, single case of AIHA. Preliminary identification of the type of antibody involved in the genesis of the disease and careful exclusion of a secondary form are particularly important. Rituximab plays a central role in the treatment of primary warm AIHA and AIHA from CAD.


Efficient production of nanobodies against urease activity ofHelicobacter pylori in Pichia pastoris.
Helicobacter pylori is a major health problem. One of the therapeutic approaches is administration of antibody against H. pylori. The methylotrophic Pichia pastoris is a suitable host for expression of recombinant antibody fragments. The aims of this study were the expression and the evaluation of camelid nanobody in the yeast Pichia pastoris. The camelid-derived heavy-chain antibody (nanobody) against the UreC subunit of urease from H. pylori was subcloned in the pPink-HC shuttle vector and transferred into Escherichia coli TOP10. After digestion and purification, the shuttle vector was transformed in the PichiaPink expression system. The expression was evaluated in an in vitro system. The yield of the nanobody expressed in P. pastoris was estimated to be 5 mg/L as compared to 2 mg/L expressed by E. coli. The nanobody was purified and binding affinity to the UreC antigen was evaluated using ELISA. Neutralization abilities of the two nanobodies expressed in yeast and E. coli were compared. The yeast-expressed nanobody specifically detected recombinant UreC and inhibited urease activity with high efficiency. The results suggest attribution of the enhanced quality and quantity of the nanobody produced in P. pastoris to better posttranslational modification and folding in the yeast cell.


In vitro activities of ceftriaxone and fusidic acid against 13 isolates of Coxiella burnetii, determined using the shell vial assay.
The susceptibilities of 13 isolates of Coxiella burnetii to fusidic acid and ceftriaxone were determined by use of the recently described shell vial assay (D. Raoult, H. Torres, and M. Drancourt, Antimicrob. Agents Chemother, 35:2070-2077, 1991). At a concentration of 4 micrograms/ml, ceftriaxone was bacteriostatic for four isolates and slowed the multiplication of the other nine. Fusidic acid at a concentration of 2 micrograms/ml was bacteriostatic for six isolates and slowed the multiplication of three others. These results show that these compounds could be effective in the phagolysosome of C. burnetii-infected cells.


Type I and type II reactions in TRAIL-induced apoptosis -- results from dose-response studies.
Death receptor-induced apoptosis is paradigmatically mediated via the recruitment of FADD adapter molecule to the ligand/receptor complex and subsequent activation of caspase-8. However, several observations provided evidence that components of the mitochondrial apoptosis pathway are involved in death receptor-mediated apoptosis. In this regard, caspase-8-mediated activation of Bid induces the release of cytochrome c from the mitochondria, which, in turn, triggers the formation of the apoptosome protein complex, resulting in the activation of caspase-9. Whereas Bax or Bak were shown to be required for the proapoptotic effect of Bid, Bcl-2 was described to interfere with its action. Up to now, contradictory results regarding the role of Bcl-2 in TRAIL-induced apoptosis have been published. In order to study the influence of Bcl-2 on TRAIL-induced cell death more detailed, we utilized a tetracycline-regulated Bcl-2 expression system in Jurkat T cells. After having analysed the dose response for TRAIL-induced activation of caspase-8, -9, -3, breakdown of the mitochondrial membrane potential, and changes in the apoptotic morphology in cells expressing different Bcl-2 levels, we conclude that overexpression of Bcl-2 mediates a partial resistance towards lower doses of TRAIL that can be overcome when higher doses of TRAIL are applied. Thus, the requirement of the mitochondrial pathway for death receptor-induced apoptosis in type II cells should be reconsidered, since the protective effect of Bcl-2 is limited to lower TRAIL doses or early observation time points.


Transcranial Doppler in reversible migrainous vasospasm causing cerebellar infarction: report of a case.
A young woman with a history of classic migraine suffered a large cerebellar infarction. Comprehensive evaluation did not disclose any potential causes for the stroke and she had no other risk factors. Transcranial Doppler (TCD) was useful in identifying vasospasm of the vertebral arteries. Following treatment with propranolol, angiography and repeat TCD revealed resolution of the vasospastic disorder. TCD is a useful noninvasive tool in detecting vasospasm associated with ischemic lesions in certain patients with migraine.


Correlated x-ray diffraction and freeze-fracture studies on membrane model systems. Perturbations induced by freeze-fracture preparative procedures.
Lipid-water and protein-lipid-water phases have been examined by X-ray methods before and after freezing. Frozen samples have been subsequently fractured and replicated, thus permitting an evaluation of the nature of structural perturbations in samples examined by freeze-fracture electron microscopy. Important results are summarized: (1) Freezing low water content (approx. less than 25%) phases causes perturbations in the packing of hydrocarbon chains. The results suggest that freezing liquied paraffin chains produces a condensed "glass-like" packing. (2) Additional perturbations occur in high water content samples. After freezing, much smaller lamellar repeat distances, intense ice reflections, and extensive perturbation of fracture faces are consistant with the expulsion of water from between lamellae. Presence of glycerol generally relieves these perturbations but in some cases introduces additional lattice disorder. (3) Surprisingly, cooling by a stream of cold N2 gas (-140 degrees C) produces qualitatively the same results as rapid cooling in liquid Freon-22 (-160 degrees C). (4) Complex perturbations occur in phases containing integral membrane proteins. Interesting results have been obtained with cytochrome b5-lecithin lamellar associations which display both smooth and rough fracture faces without clearly defined particles.


A reversible valve-assisted chip coupling with integrated sample treatment and CRISPR/Cas12a for visual detection of Vibrio parahaemolyticus.
Vibrio parahaemolyticus (V. parahaemolyticus) is regarded as a major cause of seafood-associated illnesses, which has aroused widespread public concern. Here, a rapid and convenient detection method for V. parahaemolyticus detection was established by a reversible valve-assisted chip coupling with CRISPR/Cas12a. With optimized lysis buffer, loop mediated isothermal amplification (LAMP) reagents and CRISPR reagents, the whole detection process from sampling to results could be finished within 50 min. The structure of chip was simple and the cost was low. By relying on three reversible rotary valves and the rotation direction-dependent Coriolis pseudo force, the flow order of liquid and the direction of liquid flow could be precisely controlled. The LAMP amplicons were specifically and sensitively identified by CRISPR/Cas12a. Positive amplification would produce green fluorescent signal while negative amplification generated no fluorescent signal, which could be clearly distinguished by the naked eye. With 600 μL of samples processed, the limit of detection (LOD) for both pure cultured V. parahaemolyticus or spiked shrimp samples could achieve 30 copies/reaction. These illustrated the established method displayed great feasibility for real samples detection. In the future, the chip could also combine with other amplification reactions, like PCR or recombinase polymerase amplification reaction (RPA), to conduct detection by changing the corresponding lyophilized amplification reagents. Overall, the proposed detection platform displays great potential for food safety analysis and clinical diagnostics, especially in resource-limited areas.


Intussusception of the appendix: comprehensive review of the literature.
Intussusception of the appendix is a rare disease that constitutes a diagnostic challenge to the surgeon. The literature on this condition is limited to case reports. The demographics, presentation, and treatment remain debatable in the absence of a comprehensive review of the literature. This article reports a case of a 40-year-old woman who presented with intussusception of the appendix caused by endometriosis. A comprehensive review of the English literature in PubMed was performed. The trends in incidence, sex predilection, presentation, and treatment of appendiceal intussusception were derived based on the reports of 191 patients. The incidence was more common in adults (76%) than in children (24%). Female patients (72%) were 2 times more affected in adults than in children, whereas male patients (58%) seem to be more affected in the pediatric population. Intussusception of the appendix has most commonly a chronic presentation (63%). Endometriosis (33%) and inflammation (76%) were the most common pathologic findings in adults and children, respectively. Only 49% of patients were treated by simple appendectomy; 49% patients underwent partial colectomy; and 2% of patients had their appendixes endoscopically removed.


The effects of chemotherapy and radiotherapy on fertility in premenopausal women.
With the improved survival rate of childhood and young adult cancer patients, the long-term sequelae of the treatments used are increasingly important. In this review, current knowledge of the gonadotoxicity of commonly employed chemotherapeutic agents and radiotherapy regimens is examined. Differences between the effect of "high-risk" and "low-risk" agents are discussed. Tailoring treatment to suit the individual and counseling patients regarding reduced fertility have resulted in the best practice. Obstetricians & Gynecologists, Family Physicians. After completing this CME activity, physicians should be better able to evaluate and use appropriate methods to estimate ovarian reserve, assess the risk of infertility caused by commonly used cytotoxic chemotherapy regimens and radiation, and counsel patients regarding the gonadotoxic effects of cancer treatment.


Effectiveness of a school-community linked program on physical activity levels and health-related quality of life for adolescent girls.
This study evaluated the effectiveness of a school-community program on Health-Related Quality of Life (HRQoL; the primary outcome), physical activity (PA), and potential mediators of PA among adolescent girls living in low-socioeconomic rural/regional settings. The study was a cluster-randomized controlled trial. Twelve communities with the requisite sports clubs and facilities were paired according to relevant criteria; one of each pair was randomly assigned to the intervention or control condition. Eight schools per condition were randomly selected from these communities and the intervention was conducted over one school year (2011). Female students in grades 7-9 in intervention schools participated in two 6-session PA units - a sport unit (football or tennis) and a recreational unit (leisure centre-based). These were incorporated into physical education (PE) curriculum and linked to PA opportunities for participation outside school. Students were surveyed at baseline and endpoint, self-reporting impact on primary and secondary outcome measures (HRQoL, PA) and PA mediators (e.g. self-efficacy). Linear mixed models for two-group (intervention, control) and three-group (completers, non-completers, control) analyses were conducted with baseline value, age and BMI as covariates, group as a fixed effect and school as random cluster effect. Participants completing baseline and endpoint measures included: 358 intervention (baseline response rate 33.7%, retention rate 61.3%) and 256 control (14.1% and 84.0%). Adjustment for age and BMI made no substantive difference to outcomes, and there were no cluster effects. For HRQoL, after adjustment for baseline scores, the intervention group showed significantly higher scores on all three PedsQL scores (physical functioning: M ± SE = 83.9 ± 0.7, p = .005; psychosocial: 79.9 ± 0.8, p = .001; total score: 81.3 ± 0.7, p = .001) than the control group (80.9 ± 0.8; 76.1 ± 0.9 and 77.8 ± 0.8). The three-group analysis found intervention non-completers had significantly higher PedsQL scores (84.0 ± 0.8, p = .021; 80.4 ± 0.9, p = .003; 81.7 ± 0.8, p = .002;) than controls (80.9 ± 0.8, 76.1 ± 0.9 and 77.8 ± 0.8). There were no significant differences for any PA measure. Intervention completers had significantly higher scores than non-completers and controls for some mediator variables (e.g. self-efficacy, behavioural control). Positive outcomes were achieved from a modest school-community linked intervention. The school component contributed to maintaining HRQoL; students who completed the community component derived a range of intra-personal and inter-personal benefits. ACTRN12614000446662. April 30th 2014.


[Contribution of laparoscopy-biopsy to the diagnosis of primary liver neoplasms].
After a review of the literature, personal observations of primary benign and malignant tumours of the liver, studied using laparoscopic biopsy are presented and the importance of this examination in the early diagnosis of primary hepatic tumours is stressed. This examination, particularly when associated with biopsy, is very useful since it reduces diagnosis time with little or no risk to the patient with a high percentage of positive results.


Upregulation of miR-519 enhances radiosensitivity of esophageal squamous cell carcinoma trough targeting PI3K/AKT/mTOR signaling pathway.
MicroRNA-519 (miR-519) has been previously reported to function as a tumor suppressor in several types of malignancies. This study aimed to probe the biological role of miR-519 in esophageal squamous cell carcinoma (ESCC). qRT-PCR was utilized to test the miR-519 expression level in ESCC tissues and cells. Clinical value of miR-519 was investigated by Kaplan-Meier method. Function assays were conducted to determine the role of miR-519 in radioresistance of ESCC cells. The miR-519-regulated pathways were determined by Kyoto Encyclopedia of Genes and Genomes pathway analysis. Low expression level of miR-519 was closely correlated with the poor prognosis for overall survival of ESCC patients or patients who received radiotherapy. Functional assays indicated that upregulation of miR-519 made ESCC cells more sensitive to γ-ray radiation and facilitated ESCC cell apoptosis triggered by irradiation treatment via regulating DNA response. Ectopic expression of miR-519 decreased the level of p-AKT and p-mTOR, thus inactivating PI3K/AKT/mTOR signaling pathway after irradiation. These observations elucidated that upregulated miR-519 is closely correlated with the radiosensitivity of ESCC cells, which may contribute to finding a new promising target for improving the efficiency of radiotherapy in patients with ESCC.


Preoperative CT parameters to predict tibiofibular syndesmosis injury associated with ankle fracture: a propensity score-matched analysis.
Untreated ankle fractures with concomitant tibiofibular syndesmosis injury often lead to postoperative pain and early traumatic arthritis. CT has advantages in the preoperative diagnosis of combined ankle injuries. However, a few studies have investigated the best preoperative CT parameters to predict tibiofibular syndesmosis injuries associated with ankle fractures. This study aimed to identify and evaluate the optimal preoperative CT parameters for predicting tibiofibular syndesmosis injuries associated with ankle fractures. We retrospectively analyzed 129 patients who underwent preoperative CT of an ankle fracture treated between January 2016 and April 2022 at a tertiary A hospital. All patients underwent open reduction and internal fixation and intraoperative stability testing. Based on the Cotton test, the patients were divided into the stable group (n = 83, 64.3%) and unstable group (n = 46, 35.7%). After 1:1 propensity score matching, the general conditions, anterior tibiofibular distance (TFD), posterior TFD, maximum TFD, tibiofibular syndesmosis area, sagittal fracture angle, Angle-A, and Angle-B were compared between the stable and unstable groups. The propensity score-matched cohort comprised 82 patients. There were no significant differences between the stable and unstable groups in sex, age, affected side, operation interval, injury mechanism, Lauge-Hansen classification, sagittal fracture angle, and Angle-A (all P > 0.05). Compared with the stable group, the unstable group had a significantly greater aTFD, pTFD, maxTFD, and area (all P < 0.05). PTFD, maxTFD, and area were positively correlated with joint instability. Angle-B was smaller in the unstable group (57.13°) than the stable group (65.56°). ROC analysis showed that Area (AUC 0.711) and maxTFD (AUC 0.707) had the highest diagnostic efficacy. MaxTFD and Area were the best predictive parameters; a larger Area was associated with a higher likelihood of instability of the tibiofibular syndesmosis after ankle fracture fixation.


Safety and efficacy of a novel three-step anti-acne regimen formulated specifically for women.
Due to ambient environmental- and lifestyle-associated stressors, the prevalence of acne in adult women has been increasing. Classical anti-acne treatments using benzoyl peroxide technology are associated with dehydration of the skin, which may accelerate aging and further reduce treatment compliance. The addition of bio-functional actives intended to replenish hydration and improve barrier function may hasten the onset of anti-acne benefits while restoring a healthy appearance and counteracting skin aging effects. The objective of this study was to test the safety and efficacy of a new three-step topical anti-acne regimen designed specifically to improve the overall condition and appearance of the skin in women with acne. Safety and efficacy were tested in an 8-week study of women ages 22 to 44 years with mild to moderate acne. Skin endpoints were monitored at baseline and weeks 1, 4, and 8 by clinical grading, measurement of sebum secretion using a sebumeter, standardized pictures, and self-validation questionnaires. A total of 31 women completed the study. Acne severity and lesion counts, including comedones and papules, improved gradually starting from week 1 and continued to improve throughout the study period, reaching statistical and clinical relevance at weeks 4 and 8. Moreover, significant improvements in skin roughness, radiance, overall healthy appearance, and oiliness (further confirmed with decreased sebum production) were observed. Compared with baseline responses, participants reported noticeable improvements in acne lesions and overall healthier-looking skin. Participants also noticed overall younger-looking skin at the end of the study period. This three-step regimen provided efficacious anti-acne benefits to the skin that were also gentle, safe, and well tolerated.


Analysis of environmental sustainability of e-waste in developing countries - a case study from Pakistan.
The electronic waste generation rate is increasing drastically at a rate of 3 to 5% per year in developing countries. The aim of this study is to analyze the environmental sustainability and economic benefits of such e-waste management in the developing economies like Pakistan. The life cycle assessment (LCA) method has been employed for streamlined impact analysis of the end-of-life processing of e-waste focusing mainly on laptop computers and liquid crystal display (LCD) desktop computers in Pakistan. The method of cumulative exergy extraction from the natural environment (CEENE) has also been deployed for the relative assessment of resources' consumption of e-waste recycling versus landfilling scenario. The determined impact scores are 1.79E + 03 kg CO2 eq., 7.19E-07 kg CFC-11 eq., 1.02E + 03 kg 1,4-DCB, 7.13E + 01 kg 1,4-DCB, and 3.41E-03 kg Cu eq. in climate change potential, stratospheric ozone depletion, ecotoxicity potential, human noncarcinogenic potential, and mineral resource depletion impact categories, respectively. The results of CEENE analysis reveal that approximately 80% of the impact on natural resources is reduced by the efficient recycling of e-waste. The comparative assessment of respective scores for current and target material weight recovery (MWR) indicators represented that by increasing the MWR indicator by 33.8% for laptop computers and by 27.2% for LCD computers, the country will achieve an annual economic benefit of US $191.56 million. This is greatly significant for a transitional shift towards e-waste revalorization while realizing the objectives of sustainable resource consumption. Innovative improvement measures ensuring economically feasible, energy-efficient, and environment friendly waste collection, treatment, and recycling practices present an invaluable opportunity for developing countries.


Diagnostic hospitalizations before patient inclusion on the waiting list for kidney transplantation.
For kidney transplantation is indicated any patient with chronic kidney disease in the terminal stage, unless it has a contraindication for this operation. The aim of this work is to evaluate the benefit of diagnostic hospitalizations of the patients before inclusion on the waiting list for kidney transplantation and to identify the most common differential diagnostic problems for the indication / contraindication for kidney transplantation. This is a retrospective analysis, which included all potential recipients who underwent the examination process before inclusion on the waiting list and living donors in the form of diagnostic hospitalization at the Transplant Center at Martin University Hospital in 2016-2019. A total of 49 patients were included in the cohort, the average length of hospitalization was 5.6 days. Kidney trans plantation subsequently underwent 22 of these patients, 3 patients were clearly contraindicated.


C-reactive protein distribution and correlation with traditional cardiovascular risk factors in the Italian population.
C-reactive protein (CRP) increases during an inflammatory response; its plasma levels are believed to be an independent predictor of future atherosclerotic disease. We report the distribution of plasma levels of CRP and its possible relationship with other cardiovascular risk factors in an Italian cohort. CRP was assessed in frozen plasma samples of 1949 participants in the CHECK study (2001-2005), which collected clinical and biochemical data from randomly selected subjects (40-79 years) in the setting of Italian general practice. Median CRP (interquartile range) was higher in women (1.42 [0.58-2.86] vs 1.28 [0.58-2.50]; p=.163), in people aged ≥ 65 years (1.74 [0.89-3.34] vs 1.11 [0.52-2.45]; p<.001), in patients with obesity (2.37 [1.27-4.15] vs 1.16 [0.52-2.41]; p<.001), metabolic syndrome (2.12 [1.16-3.72] vs 1.10 [0.50-2.38]; p<.001), or higher cardiovascular risk (2.03 [1.01-3.42] vs 1.19 [0.53-2.50]; p<.001). Stepwise regression analysis showed significant associations (R(2)=.264) of circulating log(e)CRP with body mass index, fibrinogen, apoB, age, gender, smoking habits, physical inactivity, creatinine levels, and systolic blood pressure. This study provides epidemiological data of CRP in the Italian population and reinforces the existing evidences about the close correlation between CRP and markers of inflammation and adiposity.


Effect of pilocarpine on substance P and calcitonin gene-related peptide releases correlate with salivary secretion in human saliva and plasma.
Pilocarpine, a muscarinic receptor agonist, has been used for the treatment of dry mouth. Salivary glands are supplied with nerve fibres that contain neuropeptides, such as substance P, calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP), which are important modulators of salivation. It is known that measurement of salivary and plasma levels of neuropeptides is useful for assessing the dose-pharmacological effect relationship of drugs. The relationship between the action of pilocarpine and neuropeptides in humans has not been studied. Moreover, studies evaluate the usefulness of drug salivary levels in the pharmacological evaluation of drugs are scarce. The aim of this study was to examine the effects of pilocarpine on the levels of substance P-, CGRP- and VIP-like immunoreactive substances (IS) in saliva and plasma taken in healthy humans. Five healthy male subjects participated in this study. Pilocarpine tablet (10 mg) or placebo tablet was orally administered with 100 mL of water. Each subject was administered placebo and drug with an interval of 4 weeks in between. Saliva was sampled before and at 20, 40, 60, 90, 120, 180 and 240 min after administration of the test substances. Venous blood samples (10 mL) were also taken from a forearm vein at each time interval. The samples were then enzyme immunoassayed using a highly sensitive system for substance P-, CGRP- and VIP-IS. The amount of saliva was measured by the Saxon test. A single oral administration of pilocarpine increased the release of salivary substance P-IS (the area under the concentration-time curve: AUC(0→240 min)) compared with the placebo. Pilocarpine also significantly increased the release of salivary CGRP-IS (AUC(0→240 min)). Pilocarpine significantly increased the release of plasma CGRP-IS. The salivary volume correlated with the salivary level of substance P and CGRP-IS (r = 0·84, P < 0·05 and r = 0·59, P < 0·05, respectively). AUC(0→240 min) for substance P-IS in saliva correlated with that for plasma (r = 0·78, P < 0·05). Pilocarpine increases the release of salivary substance P and CGRP-IS. This suggests that one mechanism by which pilocarpine improves dry mouth is by local stimulation of neuropeptidergic nerves. Moreover, saliva levels of substance P showed good correlation with the plasma levels. The substance P levels in saliva and plasma may be good indicators of the effects of drugs used in dry mouth/xerostomic patients.


Controlled human exposure to diesel exhaust: a method for understanding health effects of traffic-related air pollution.
Diesel exhaust (DE) is a major component of air pollution in urban centers. Controlled human exposure (CHE) experiments are commonly used to investigate the acute effects of DE inhalation specifically and also as a paradigm for investigating responses to traffic-related air pollution (TRAP) more generally. Given the critical role this model plays in our understanding of TRAP's health effects mechanistically and in support of associated policy and regulation, we review the methodology of CHE to DE (CHE-DE) in detail to distill critical elements so that the results of these studies can be understood in context. From 104 eligible publications, we identified 79 CHE-DE studies and extracted information on DE generation, exposure session characteristics, pollutant and particulate composition of exposures, and participant demographics. Virtually all studies had a crossover design, and most studies involved a single DE exposure per participant. Exposure sessions were typically 1 or 2 h in duration, with participants alternating between exercise and rest. Most CHE-DE targeted a PM concentration of 300 μg/m3. There was a wide range in commonly measured co-pollutants including nitrogen oxides, carbon monoxide, and total organic compounds. Reporting of detailed parameters of aerosol composition, including particle diameter, was inconsistent between studies, and older studies from a given lab were often cited in lieu of repeating measurements for new experiments. There was a male predominance in participants, and over half of studies involved healthy participants only. Other populations studied include those with asthma, atopy, or metabolic syndrome. Standardization in reporting exposure conditions, potentially using current versions of engines with modern emissions control technology, will allow for more valid comparisons between studies of CHE-DE, while recognizing that diesel engines in much of the world remain old and heterogeneous. Inclusion of female participants as well as populations more susceptible to TRAP will broaden the applicability of results from CHE-DE studies.


Frontal sinus hamartomas.
To review the entity of respiratory epithelial adenomatoid hamartoma of the paranasal sinuses using an illustrative case example of frontal sinus hamartoma. Case report with review of the literature. Respiratory epithelial adenomatoid hamartoma represents a benign process that is generally cured with conservative surgical resection of the involved area. Nevertheless, as shown in our case example, this can be a locally aggressive process that can lead to significant morbidity if left untreated. Hamartomas of the paranasal sinuses represent a rare entity, which should be considered in the differential diagnosis of expansile sinonasal lesions. Treatment of choice is surgical resection. Frontal sinus involvement may extend into the surrounding orbit and intracranial cavities, which may need to be addressed with standard skull base surgery techniques.