Experimental pneumothorax detected by thermography.
After induction of pneumothorax in rabbits, thermograms showed decreased heat emission from the involved side. These observations suggest that noninvasive monitors of thoracic wall temperatures might be useful for early detection of air-leak phenomenon in high-risk neonates.


Obesity-insulin targeted genes in the 3p26-25 region in human studies and LG/J and SM/J mice.
Identifying metabolic syndrome (MetS) genes is important for novel drug development and health care. This study extends the findings on human chromosome 3p26-25 for an identified obesity-insulin factor QTL, with an LOD score above 3. A focused association analysis comprising up to 9578 African American and Caucasian subjects from the HyperGEN Network (908 African Americans and 1025 whites), the Family Heart Study (3035 whites in time 1 and 1943 in time 2), and the Framingham Heart Study (1317 in Offspring and 1320 in Generation 3) was performed. The homologous mouse region was explored in an F(16) generation of an advanced intercross between the LG/J and SM/J inbred strains, in an experiment where 1002 animals were fed low-fat (247 males; 254 females) or high-fat (253 males; 248 females) diets. Association results in humans indicate pleiotropic effects for SNPs within or surrounding CNTN4 on obesity, lipids and blood pressure traits and for SNPs near IL5RA, TRNT1, CRBN, and LRRN1 on central obesity and blood pressure. Linkage analyses of this region in LG/J×SM/J mice identify a highly significant pleiotropic QTL peak for insulin and glucose levels, as well as response to glucose challenge. The mouse results show that insulin and glucose levels interact with high and low fat diets and differential gene expression was identified for Crbn and Arl8b. In humans, ARL8B resides ~137kbps away from BHLHE40, expression of which shows up-regulation in response to insulin treatment. This focused human genetic analysis, incorporating mouse research evidenced that 3p26-25 has important genetic contributions to MetS components. Several of the candidate genes have functions in the brain. Their interaction with MetS and the brain warrants further investigation.


Annular erythema: a possible association with primary Sjögren's syndrome.
In four patients with primary Sjögren's syndrome a distinct annular erythema developed, which was characterized by a wide, elevated border (which can be likened to a doughnut ring) and central pallor. Histologically, there was a coat sleeve-like infiltration of lymphocytes around blood vessels and nuclear debris in the connective tissue. Vasculitis or epidermal changes suggestive of lupus erythematosus were not observed, and there was no immunoglobulin deposition along the basement membrane zone. This annular erythema may be a cutaneous manifestation of Sjögren's syndrome.


Modulation of lyso-platelet activating factor: acetyl-CoA acetyltransferase from rat splenic microsomes. The role of cyclic AMP-dependent protein kinase.
Incubation of rat splenic microsomes with the catalytic subunit of cyclic AMP-dependent protein kinase in the presence of Mg-ATP stimulated 2-3-fold lyso-platelet-activating factor: acetyltransferase activity. This activation was due to an increase in the Vmax of the acetylation reaction, whereas the Km for acetyl-CoA was not affected. The ATP derivative, AMPPNP, could not replace ATP and preincubation of the microsomes with the heat-stable inhibitor of protein kinase prevented the activation by Mg-ATP obtained in the presence of the protein kinase. Activation of the acetylation reaction by the protein kinase was reversible. Evidence is provided that the reversal of activation is due to dephosphorylation of the enzyme. These data provide evidence that in vitro lyso-platelet-activating factor: acetyltransferase from splenic microsomes is regulated by phosphorylation.


Efficacy and safety of nicoboxil/nonivamide ointment for the treatment of acute pain in the low back - A randomized, controlled trial.
Until now, nonivamide/nicoboxil ointment has not been tested in a randomized trial for the treatment of acute non-specific low back pain. This phase III randomized, double-blind, active- and placebo-controlled, multi-centre trial investigated efficacy, safety and tolerability of topical nicoboxil 2.5%/nonivamide 0.4% for treatment of acute non-specific low back pain [primary endpoint: pain intensity (PI) difference between pre-dose baseline and 8 h after the first application]. Patients (n = 805), 18-74 years of age were treated for up to 4 days with nicoboxil 2.5%/nonivamide 0.4%, nicoboxil 2.5%, nonivamide 0.4% or placebo ointment. Pre-dose baseline pain intensity (6.6 on a 0- to 10-point numerical rating scale) was reduced by 1.049 points with placebo, by 1.428 points with nicoboxil, by 2.252 points with nonivamide and by 2.410 points with nicoboxil/nonivamide after 8 h (p < 0.0001 for nicoboxil/nonivamide vs. placebo, nicoboxil; p = 0.4171 for nicoboxil/nonivamide vs. nonivamide). At the end of treatment, the combination provided more pronounced PI reduction (3.540 points) compared with nicoboxil (2.371, p < 0.0001), nonivamide (3.074, p = 0.0259) and placebo (1.884, p < 0.0001). Low back mobility scores on Day 1 were better for the combination compared with all other treatments (p < 0.044); on Day 2-4, scores were better than for placebo and nicoboxil (p < 0.003). Patients assessed efficacy of the combination as greater than of the comparators (p ≤ 0.0129). All treatments were tolerated well. No treatment-related serious adverse events were reported. Nicoboxil/nonivamide ointment is an effective, well-tolerated medication for the treatment of acute non-specific low back pain.


Delayed esophageal pseudodiverticulum after anterior cervical spine fixation: report of 2 cases.
Although perforation of the esophagus, in the anterior cervical spine fixation, is well established, cases with delayed onset, especially cases that present pseudodiverticulum, are not common. In addition, management of the perforation in this situation is debated. Delayed esophageal pseudodiverticulum was managed in two patients with a history of anterior spine fixation. Patients were operated on, the loose plate and screws were extracted, the wall of the diverticulum was excised, the perforation on the nasogastric tube was suboptimally repaired, and a closed suction drain was placed there. The NGT was removed on the 7th day and barium swallow demonstrated no leakage at the operation site; therefore, oral feeding was started without any problem. In cases with delayed perforation, fistula, or diverticulum removal of anterior fixation instruments, gentle repair of the esophageal wall without persistence on definitive and optimal perforation closure, wide local drainage, early enteral nutrition via NGT, and antibiotic prescription is suggested.


Polymorphism in fowl serum albumin. VI. Changes in in vitro protein synthesizing activity in developing embryonic fowl liver.
Cell-free protein synthesizing systems were prepared from the livers of chick embryos at selected ages and the characteristics of individual fractions were compared. While polysomes showed decreasing size with older embryos, isolated polysomes did not differ significantly in amino acid incorporating activity when assayed with standard cell sap. When assayed with standard polysomes, cell sap activity decreased with increasing developmental age whether incorporation was measured using (3H)lysine, (3H)leucine, or [3H]aminoacyl-tRNA. Free amino acid concentrations in the cell sap showed reproducidble independent variation during development which was taken into consideration in calculating net amino acid incorporation. A larger increase in ribonuclease activity was observed during development; however, nuclease inhibitor activity was absent before day 15 but increased thereafter. Aminoacyl-tRNA sythetase activity did not vary significantly. It is proposed that the observed changes in the rate of cell-free protein synthesis result not only from increasing ribonuclease activity with increasing developmental age but also from changes in the activity of other soluble factors.


Study of exhaled breath condensate sample preparation for metabolomics analysis by LC-MS/MS in high resolution mode.
Metabolomic analysis of exhaled breath condensate (EBC) requires an unavoidable sample preparation step because of the low concentration of its components, and potential cleanup for possible interferents. Sample preparation based on protein precipitation (PP), solid-phase extraction (SPE) by hydrophilic and lipophilic sorbents or lyophilization has demonstrated that the analytical sample from the last is largely the best because lyophilization allows reconstitution in a volume as small as required (preconcentration factors up to 80-times with respect to the original sample), thus doubling the number of detected compounds as compared with the other alternatives (47 versus 25). In addition, PP and/or SPE cleanup are unnecessary as no effect from the EBC components removed by these steps appears in the chromatograms. The total 49 EBC compounds tentatively identified and confirmed by MS/MS in this research include amino acids, fatty acids, fatty amides, fatty aldehydes, sphingoid bases, oxoanionic compounds, imidazoles, hydroxy acids and aliphatic acyclic acids.


Use of two-dimensional projection for estimating hand surface area of Chinese adults.
Accurate estimates of the surface area of burns are important for initial fluid resuscitation and prognosis of burn victims. The area of the surface of the open hand is often used to estimate the area of a burn. Although it is accepted that hand surface area is generally equal to 1% of total body surface area among Caucasians, this ratio has not been verified for Chinese people. We used two-dimensional projection to estimate the hand surface areas of Chinese adults. The area of the palm was 0.44% of total body surface area among men and 0.42% among women. The area of the hand, including that of the thumb and fingers, was 0.76% of total body surface area among men and 0.73% among women. We conclude that the ratio between hand and total body surface area among Chinese adults differs from the ratio among Caucasians, and suggest an adjustment of the ratio for use with Chinese people.


Calcium antagonists: effects on cerebral blood flow and blood-brain barrier permeability in the rat.
1 Because they affect isolated cerebral arteries, some calcium antagonists have been studied on the intact cerebral circulation of the rat.2 Global cerebral blood flow ((133)Xe clearance technique) was measured in anaesthetized rats. Neither perhexiline (0.1 mug/kg to 1.0 mg/kg, i.v.) nor diltiazem (0.06-0.6 mg/kg, i.v.) had any significant effect on resting cerebral blood flow when measured 5 min after each dose. A high dose of nifedipine (1.0 mg/kg, i.v.) was administered during induced hypocapnia. Nifedipine failed to modify the hypocapnic vasoconstriction of the cerebral vasculature when compared to vehicle-treated rats.3 The possibility of discrete changes in regional cerebral blood flow was investigated. Local cerebral blood flow was measured in a number of brain regions by the [(14)C]-ethanol technique 15 min after the administration of nifedipine (20 or 100 mug/kg, i.v.). Nifedipine had no apparent effect on regional blood flow in the rat brain.4 Acute arterial hypertension increases protein leakage into the brain, a phenomenon susceptible to drugs that act on endothelial pinocytosis which is known to be calcium-dependent. The increase in protein extravasation, induced by the intravenous administration of either angiotensin II or adrenaline, was unchanged in rats previously treated with either nimodipine (20 mug/kg, i.v.) or nifedipine (50 mug/kg, i.v.) when dissolved in ethanol alone. However, nifedipine (20 mug/kg, i.v.) when dissolved in a solution of polyethylene glycol and ethanol further enhanced the hypertension-induced increase in brain albumin permeability.5 In conclusion, we have been unable to demonstrate any apparent effects of various calcium antagonists on the intact cerebral circulation of the rat, despite the number of different experimental models used.


Acute Hemodynamic Effect of a Novel Dual-Vein, Multisite Biventricular Pacing Configuration.
Biventricular pacing (BVP) from multiple left ventricular (LV) sites could enhance the efficacy of cardiac resynchronization therapy (CRT) by engaging a greater myocardial mass. The goal of this study was to evaluate the acute hemodynamic effect of various multisite pacing (MSP) configurations against conventional BVP. Twenty patients with nonischemic dilated cardiomyopathy and left bundle branch block (mean age: 59 ± 14 years; LV ejection fraction: 27% ± 6%; native QRS: 171 ± 16 milliseconds) were investigated during a routine CRT implant procedure. In addition to conventional right atrial and right ventricular leads, 2 quadripolar leads were placed in the distant coronary venous branches. LV hemodynamics was evaluated by using a micromanometer-tipped catheter during atrioventricular BVP with 4 LV lead configurations: single-lead conventional BVP; single-lead multipoint pacing; triventricular pacing from distal dipoles of 2 LV leads; and maximum MSP (MSP-Max) from 4 dipoles of 2 LV leads. Compared with right atrial pacing, any BVP configuration produced a significant increase in the maximal LV diastolic pressure rise (LVdP/dTMax) (a median relative increase of 28% [IQR: 8%-45%], 25% [IQR: 18%-46%], 36% [IQR: 18%-54%], and 38% [IQR: 28%-58%], respectively; all, P < 0.001). MSP-Max but no other multisite BVP generated a significant increase of the maximal LVdP/dTMax than conventional BVP (P = 0.041). Increased LVdP/dTMax during MSP-Max was associated with greater LV diameter and lower LV ejection fraction, independently of the QRS width. The study shows the hemodynamic advantage of a novel dual-vein MSP-Max configuration that could be useful for CRT in patients with advanced LV remodeling.


Comparison of outcome of Ponseti method with traditional clubfoot treatment in children up to five years of age at tertiary care hospital.
To compare the outcomes of Ponseti treatment with the traditional treatment method for clubfoot. A cross-sectional comparative study was conducted at the orthopedic department of Nishtar Medical Hospital & University Multan for one year. The study included 40 children (29 clubfeet) treated with conventional treatment (pre-Ponseti group) who were compared with 55 Ponseti-treated children (72 clubfeet) (Ponseti group). All children were aged under five years. The traditional treatment involved casting and surgery (if required). All the participants were evaluated by a single orthopedic surgeon. The questionnaire was administered to the parents to collect relevant data. X-ray studies were conducted of all feet and patients' records were checked for surgical history. Children in the pre-Ponseti group had a significantly higher number of surgeries (54) than those in Ponseti group eight. According to the reports of the parents, children in Ponseti group had significantly better motion in the ankle, lesser pain, and higher satisfaction (p<0.05.whereas, the pre-Ponseti group had a higher incidence of moderate or severe talar flattening rate (p=0.01). Ponseti treatment is better than earlier treatment in terms of lesser need of surgeries, higher flexibility of ankle or foot, and lower presence of X-ray guided talar flattening.


Photoendocrine transduction in cultured chick pineal cells: effects of light, dark, and potassium on the melatonin rhythm.
Several laboratories have demonstrated the persistence of photosensitive rhythms related to melatonin secretion in cultured chick pineals. We describe here a system using dispersed chick pineal cells in static culture, which displays a rhythm of melatonin release for at least two weeks under cyclic lighting conditions, and for at least 4 cycles under constant red light. Using a rapid and specific extraction assay for the [14C]melatonin formed (from [14C]tryptophan) and secreted by these cells, we have examined the effects of perturbations (light, dark, and potassium) on the amplitude, period, and phase of the melatonin rhythm. The period in constant red light was close to 20 h, but in constant white light (or 12:12 cycles) it was closer to 24 h. Four-hour pulses of white light (in otherwise constant red light) caused an acute fall in melatonin output, and phase-dependent phase shifts of the rhythm relative to controls. Pulses of darkness (in otherwise constant red light) tended to increase melatonin output, and caused phase-dependent phase shifts. Elevated potassium concentrations increased melatonin output and the amplitude of the rhythm, but did not change the period. Four-hour pulses of low (5.4 mM) potassium (in otherwise constant high potassium) mimicked the acute effect of light, reducing melatonin output, but did not induce appreciable phase shifts. Changes in membrane potential appear more likely to be involved in the regulation of melatonin output (and thus be regulated by the pacemaker) than to be involved in regulation of the pacemaker which generates the melatonin rhythm.


Associations of Prestroke Physical Activity With Stroke Severity and Mortality After Intracerebral Hemorrhage Compared With Ischemic Stroke.
Prestroke physical activity may protect the brain from severe consequences of stroke. However, previous studies on this subject included mainly ischemic stroke cases, and the association between prestroke physical activity and outcomes after intracerebral hemorrhage is uncertain. Therefore, we sought to examine the associations between prestroke physical activity, stroke severity, and all-cause mortality after intracerebral hemorrhage in comparison with ischemic stroke. This was a longitudinal, register-based cohort study. All adult patients with intracerebral hemorrhage or ischemic stroke admitted to 3 stroke units in Gothenburg, Sweden, between November 1, 2014, and June 30, 2019, were screened for inclusion. Physical activity was defined as light physical activity ≥4 h/wk or moderate physical activity ≥2 h/wk the year before stroke. Stroke severity was assessed on admission using the NIH Stroke Scale. All-cause mortality rates were followed up to 7 years, from the time of incident stroke until death or censoring. Ordinal logit models and Cox proportional hazards models were used to estimate adjusted associations of prestroke physical activity. We included 763 patients with intracerebral hemorrhage and 4,425 with ischemic stroke. Prestroke physical activity was associated with less severe strokes by an adjusted odds ratio of 3.57 (99% CI 2.35-5.47) for intracerebral hemorrhages and 1.92 (99% CI 1.59-2.33) for ischemic strokes. During a median follow-up of 4.7 (interquartile range 3.5-5.9) years, 48.5% of patients with intracerebral hemorrhage died, compared with 37.5% with ischemic stroke. Prestroke physical activity was associated with decreased short-term mortality (0-30 days) by an adjusted hazard ratio of 0.30 (99% CI 0.17-0.54) after intracerebral hemorrhage and 0.22 (99% CI 0.13-0.37) after ischemic stroke. Prestroke physical activity was further associated with decreased long-term mortality (30 days-2 years) by an adjusted hazard ratio of 0.40 (99% CI 0.21-0.77) after intracerebral hemorrhage and 0.49 (99% CI 0.38-0.62) after ischemic stroke. Prestroke physical activity was associated with decreased stroke severity and all-cause mortality after intracerebral hemorrhage and ischemic stroke, independent of other risk factors. Based on current knowledge, health care professionals should promote physical activity as part of primary stroke prevention.


How to depolarise the ethical debate over human embryonic stem cell research (and other ethical debates too!).
The contention of this paper is that the current ethical debate over embryonic stem cell research is polarised to an extent that is not warranted by the underlying ethical conflict. It is argued that the ethical debate can be rendered more nuanced, and less polarised, by introducing non-binary notions of moral rightness and wrongness. According to the view proposed, embryonic stem cell research--and possibly other controversial activities too--can be considered 'a little bit right and a little bit wrong'. If this idea were to become widely accepted, the ethical debate would, for conceptual reasons, become less polarised.


Clinical experience with distal transradial access for endovascular treatment of various noncoronary interventions in a multicenter study.
Transradial access is a well-known alternative to conventional transfemoral access for interventional procedures. Recently, transradial access through the "snuffbox", which lies in the radial dorsal aspect of the hand, has been introduced as a new technique with positional versatility. In this study, we aimed to evaluate the clinical feasibility and safety of distal transradial access for interventional procedures in a retrospective, multicenter study. Distal transradial access was attempted in 46 patients (36 men and 10 women; mean age, 64 years) who underwent 47 consecutive procedures from January 2018 to December 2019. Procedures included chemoembolization (19/47, 40.4%), bronchial artery embolization (7/47, 14.9%), renal intervention (3/47, 6.4%), arteriovenous fistula angioplasty (7/47, 14.9%), subclavian artery stenting (5/47, 10.6%), other embolization (5/47, 10.6%), and uterine artery embolization (1/47, 2.1%). We recorded the success rate of the procedures, complications, and postprocedural hemostasis time during the follow-up period. The technical success of distal transradial access without major complications was 97.9% (46/47). Of the 46 patients, one patient (2.2%) had a minor complication, which was a thrombotic segmental occlusion of the distal radial artery. Of the enrolled patients, only one patient did not complete the transradial access procedure via the snuffbox because the left proximal subclavian artery was occluded and a crossover to conventional transfemoral access was performed. The mean postprocedural hemostasis time was 131.7 minutes (range, 120-360 minutes). Distal transradial access can be a valid option for the endovascular treatment of various noncoronary interventions with technical feasibility and safety.


Efficacy of 3T Multiparametric MR Imaging followed by 3T in-Bore MR-Guided Biopsy for Detection of Clinically Significant Prostate Cancer Based on PIRADSv2.1 Score.
To evaluate the diagnostic yield of 3T in-Bore magnetic resonance-guided biopsy (3T IB-MRGB) for detection of clinically significant prostate cancer (csPCa), based on assessment using the Prostate Imaging Reporting and Data System version 2.1 (PIRADSv2.1). This single-center study examined individuals who underwent 3T multiparametric prostate magnetic resonance (MR) imaging and subsequent 3T IB-MRGB. The final study cohort included 379 men (with 475 targets) divided into 3 subcohorts: biopsy-naïve men (n = 123), individuals with a history of negative trans-rectal-ultrasonography (TRUS) biopsy results (n = 106), and men with low-grade PCa under active surveillance (n = 150). csPCa was defined as having a Gleason score (GS) ≥3+4. 3T IB-MRGB detected PCa and csPCa in 69.1% (262 of 379) and 50.3% (193 of 379) of patients, respectively. The PCa and csPCa detection rates per target were 64.2% (305 of 475) and 43.8% (208 of 475), respectively. The rate of urosepsis, treated with intravenous antibiotics, was 1% (4 patients). In TRUS biopsy negative results and biopsy-naïve subcohorts, csPCa was found in 36.8% (39 of 106) and 52.8% (65 of 123), respectively. In 50.7% (76 of 150) of the active surveillance subcohort, 3T IB-MRGB upgraded the GS assigned in prior TRUS biopsies. Positive predictive values of PIRADSv2.1 categories 3, 4, and 5 for csPCa detection were 24.8%, 44.4%, and 67.1%, respectively. Higher PIRADSv2.1 categories were significantly associated with PCa (odds ratio [OR], 3.97; 95% confidence interval [CI], 2.98-5.28) and csPCa (OR, 1.41; 95% CI, 1.03-1.94) detection. Of 137 PIRADSv2 category 3 lesions, 28 were downgraded to PIRADSv2.1 category 2, in which there were no occurrences of csPCa in histology. Use of 3T IB-MRGB resulted in detection of csPCa in 50.9% of individuals. 3T IB-MRGB has a high diagnostic yield in individuals with negative TRUS biopsy results and those under active surveillance. The PIRADSv2.1 category is a strong predictor of PCa and csPCa detection.


Measuring and assessing the effects of extremely low-frequency electromagnetic fields (ELF-EMF) on blood parameters and liver enzymes of personnel working in high voltage power stations in a petrochemical industry.
Exposure to electric and magnetic fields (EMF) is a phenomenon that has always been present. In the last two decades, there have been numerous worries about the possible effects of extremely low-frequency (ELF) fields on human health. Consequently, this study aims to measure and evaluate the effect of ELF fields on blood parameters and liver enzymes of personnel working in high-voltage power stations in the petrochemical industry. This cross-sectional, descriptive-analytical study was done in a petrochemical industry in southern Iran in 2021. Two groups of 50 people were selected to attain the research goals and classify jobs with the risk of exposure to extremely low-frequency electromagnetic fields (ELF-EMF) and the time spent on work. One group was exposed to ELF-EMF, and the other was regarded as the control group. Electromagnetic fields were measured using the HI-3604 device and the standard method of IEEE 1994-644. The workers' demographic data, blood parameters, and liver enzymes were also obtained from the workers' medical records. The course of changes in each of the blood parameters and liver enzymes and demographic variables in the control and case groups were then examined. In the last stage, the effect of the electric field and magnetic field on the blood parameters and liver enzymes of the two control and subject groups was conducted using the multiple regression model. The measured points in all stations are 200, and the minimum and maximum values of the magnetic field was 0.8 and 2019 mG, respectively. The minimum and maximum values of the electric field intensity was 0.003 and 215 V/m, respectively. The average results of the demographic variables and blood and liver indices in the control and case groups from 2018 to 2020 revealed that the average variables were not significantly different in the case and control groups (p-value>0.05). Moreover, workers' exposure to ELF-EMF was below the permissible limit. Based on the results of the present study, ELF-EMF does not have any significant effects on demographic factors, blood parameters, and liver enzymes.


Expression of an adhesion molecule and homing in B-cell chronic lymphocytic leukaemia: I. Application of the HEV-binding assay to a clinical series.
High endothelial venule (HEV)-binding of peripheral blood mononuclear cells (PBMCs) from 43 patients with B-cell chronic lymphocytic leukaemia (B-CLL) was investigated with a HEV-binding in vitro assay. Immunophenotyping of HEV-adherent PBMCs proved that most of them belonged to the B-cell proliferation. B-CLL cells stringently expressed CD44 molecules (Hermes-1, -3 and H90). The patients were subgrouped according to Binet's classification, as well as according to the organ manifestations, i.e. patients with B-cell monoclonal lymphocytosis of undetermined significance (B-MLUS) and patients with lymphocytosis (LY), lymph node enlargement (LN) and splenomegaly (SM). The HEV-binding activity of the cells was the highest in Binet stage A patients and in patients with B-MLUS (p < 0.05 in B-MLUS versus B-CLL LY, LN, SM). Based on these findings it is suggested that B-CLL patients show not only a clinical and immunophenotypical heterogeneity, but a diverse function of adhesion molecules.


Recent progress of aptamer‒drug conjugates in cancer therapy.
Aptamers are single-stranded DNA or RNA sequences that can specifically bind with the target protein or molecule via specific secondary structures. Compared to antibody-drug conjugates (ADC), aptamer‒drug conjugate (ApDC) is also an efficient, targeted drug for cancer therapy with a smaller size, higher chemical stability, lower immunogenicity, faster tissue penetration, and facile engineering. Despite all these advantages, several key factors have delayed the clinical translation of ApDC, such as in vivo off-target effects and potential safety issues. In this review, we highlight the most recent progress in the development of ApDC and discuss solutions to the problems noted above.


Scanning electron microscope observations on tegument maturation in Schistosoma mansoni grown in permissive and non-permissive hosts.
Observations were made on details of tegument development of schistosomes grown in mouse, hamster, and rat hosts. In permissive hosts (mouse and hamster) the surface of the worm alters rapidly during early maturity and is characterized by fusing of a highly undulate surface network into smooth folds and spine-covered tubercles. In non-permissive hosts maturation of the tegument is both delayed and incomplete, and the tubercles are aspinous. Scanning views of the oral cavity and the gynegophoral canal, both sites of transitional tegumental organization, are also shown. The gynecophoral canal tegument seems to be a site of active lipid secretion.


Ultrafast laser ablation simulator using deep neural networks.
Laser-based material removal, or ablation, using ultrafast pulses enables precision micro-scale processing of almost any material for a wide range of applications and is likely to play a pivotal role in providing mass customization capabilities in future manufacturing. However, optimization of the processing parameters can currently take several weeks because of the absence of an appropriate simulator. The difficulties in realizing such a simulator lie in the multi-scale nature of the relevant processes and the high nonlinearity and irreversibility of these processes, which can differ substantially depending on the target material. Here we show that an ultrafast laser ablation simulator can be realized using deep neural networks. The simulator can calculate the three-dimensional structure after irradiation by multiple laser pulses at arbitrary positions and with arbitrary pulse energies, and we applied the simulator to a variety of materials, including dielectrics, semiconductors, and an organic polymer. The simulator successfully predicted their depth profiles after irradiation by a number of pulses, even though the neural networks were trained using single-shot datasets. Our results indicate that deep neural networks trained with single-shot experiments are able to address physics with irreversibility and chaoticity that cannot be accessed using conventional repetitive experiments.


Successful treatment of auditory perceptual disorder in individuals with Friedreich ataxia.
Friedreich ataxia (FRDA) is a neurodegenerative disease affecting motor and sensory systems. This study aimed to investigate the presence and perceptual consequences of auditory neuropathy (AN) in affected individuals and examine the use of personal-FM systems to ameliorate the resulting communication difficulties. Ten individuals with FRDA underwent a battery of auditory function tests and their results were compared with a cohort of matched controls. Friedreich ataxia subjects were then fit with personal FM-listening devices and evaluated over a 6 week period. Basic auditory processing was affected with each FRDA individual showing poorer temporal processing and figure/ground discrimination than their matched control. Speech perception in the presence of background noise was also impaired, with FRDA listeners typically able to access only around 50% of the information available to their normal peers. The use of personal FM-listening devices did however, dramatically improve their ability to hear and communicate in everyday listening situations.


Mutations in C12orf62, a factor that couples COX I synthesis with cytochrome c oxidase assembly, cause fatal neonatal lactic acidosis.
We investigated a family in which the index subject presented with severe congenital lactic acidosis and dysmorphic features associated with a cytochrome c oxidase (COX)-assembly defect and a specific decrease in the synthesis of COX I, the subunit that nucleates COX assembly. Using a combination of microcell-mediated chromosome transfer, homozygosity mapping, and transcript profiling, we mapped the gene defect to chromosome 12 and identified a homozygous missense mutation (c.88G>A) in C12orf62. C12orf62 was not detectable by immunoblot analysis in subject fibroblasts, and retroviral expression of the wild-type C12orf62 cDNA rescued the biochemical phenotype. Furthermore, siRNA-mediated knockdown of C12orf 62 recapitulated the biochemical defect in control cells and exacerbated it in subject cells. C12orf62 is apparently restricted to the vertebrate lineage. It codes for a very small (6 kDa), uncharacterized, single-transmembrane protein that localizes to mitochondria and elutes in a complex of ∼110 kDa by gel filtration. COX I, II, and IV coimmunoprecipated with an epitope-tagged version of C12orf62, and 2D blue-native-polyacrylamide-gel-electrophoresis analysis of newly synthesized mitochondrial COX subunits in subject fibroblasts showed that COX assembly was impaired and that the nascent enzyme complex was unstable. We conclude that C12orf62 is required for coordination of the early steps of COX assembly with the synthesis of COX I.


[Economic management. Why economic regulation of prevention?].
There is much lip service but little practical every day behavior aiming at prevention. Instructors and practitioners or health promotion and health protection experience much less recognition than the healers of diseases. Infrastructure and training for prevention let much to be desired. Only a political action on a higher level can give preventive measures the weight they deserve. Economic mechanisms seem the most appropriate way of regulation.


Different clinical course of pallidal deep brain stimulation for phasic- and tonic-type cervical dystonia.
Dystonia has been treated well using deep brain stimulation at the globus pallidus internus (GPi DBS). Dystonia can be categorized as two basic types of movement, phasic-type and tonic-type. Cervical dystonia is the most common type of focal dystonia, and sequential differences in clinical outcomes between phasic-type and tonic-type cervical dystonia have not been reported. This study included a retrospective cohort of 30 patients with primary cervical dystonia who underwent GPi DBS. Age, disease duration, dystonia direction, movement types, employment status, relevant life events, and neuropsychological examinations were analyzed with respect to clinical outcomes following GPi DBS. The only significant factor affecting clinical outcomes was movement type (phasic or tonic). Sequential changes in clinical outcomes showed significant differences between phasic- and tonic-type cervical dystonia. A delayed benefit was found in both phasic- and tonic-type dystonia. The clinical outcome of phasic-type cervical dystonia is more favorable than that of tonic-type cervical dystonia following GPi DBS.


Visualization of actin polymerization and depolymerization cycles during polyamine-induced cytokinesis in living Amoeba proteus.
Microinjection of spermine induces cytokinesis of Amoeba proteus. Within 30--60 s after spermine injection cells form one, or less commonly, two cleavage furrows and within the following 4--10 min the constrictions are completed. The resulting nucleated cell parts show normal streaming and locomotion, whereas the non-nucleated cell parts remain stationary and later degenerate. The intracellular distribution of fully polymerization-competent fluorescently labelled muscle actin was followed by image intensification. Double injection experiments initially using labelled action and 30 min later spermine revealed a ring-like structure of enhanced fluorescence corresponding to the constricting cleavage furrow. Immediately after cleavage was completed, the ring disappeared. Electron microscopy of cells fixed during spermine-induced cytokinesis showed numerous well aligned actin and myosin filaments in the developing cleavage furrow. These filaments are a specialized manifestation of the cell cortex. The results demonstrate that cycles of actin and myosin polymerization and depolymerization and the parallel alignment of preexisting filaments (crosslinking) represent a basic mechanism in the generation of the motive force during cytokinesis.


Our human quest with the Black Hole.
Black holes are fundamental: They are where small and large scales meet, where the two main theories of physics clash, and where the finite and infinite come together. Furthermore, the explosion of twentieth century black hole science coincided with a shift in the phenomenology of the universe. We consider this philosophical turn towards cosmic mindfulness, and ask whether there are definite limits to our interaction with black holes, and if a human world could ever take direct advantage of the counterintuitive effects happening near a black hole's event horizon.


Total body bathing with 'Hibiscrub' (chlorhexidine) in surgical patients: a controlled trial.
Total body bathing with 'Hibiscrub' (chlorhexidine-detergent) solution was compared with non-medicated soap in 224 patients admitted for surgery. Some 9.6 per cent of patients were found to be nasal carriers of Staphylococcus aureus on admission but 17.3 per cent were colonized at some time during their inpatient stay. Skin colonization by Staph, aureus was only seen in four patients (2 per cent), three were cleared by 'Hibiscrub' bathing but carriage persisted in the other patient who used non-medicated soap. A greater reduction in the total bacterial count on the skin and in the perianal region was seen in patients using 'Hibiscrub'. An increase in the bacterial count was frequently seen in patients using non-medicated soap. Postoperative staphylococcal wound infection occurred in nine patients (4-0 per cent) but nasal or skin carriage was only present in two patients. Although there was no difference in the rates of infection using 'Hibiscrub' or ordinary soap, pre-operative bathing with 'Hibiscrub' may be beneficial as there is a greater reduction in the total bacterial count. The use of non-medicated soap is of dubious value and may even increase the numbers of bacteria on the skin.


AIE-active polysiloxane-based fluorescent probe for identifying cancer cells by locating lipid drops.
Comparing with normal cells, Lipid droplets (LDs) of cancer cells show lower polarity and less quantity, which can be utilized as a marker for cancer diagnosis. However, the investigation of LDs in living cancer cells is restricted by the lack of effective molecular tools. Herein, we first reported a novel polysiloxane-based polymer fluorescent polar probe TR-1 with AIE properties, which realized the possibilities for locating LDs. It can aggregate in the LDs of cancer cells and show a stronger fluorescent signal to conduct cancer diagnosis. Moreover, the excellent photostability of TR-1 enable stable fluorescence to exhibit in cancer cells during effective time.


Exposure to ionizing radiation causes long-term increase in serum estradiol and activation of PI3K-Akt signaling pathway in mouse mammary gland.
Exposure to ionizing radiation is an established risk factor for breast cancer. Radiation exposure during infancy, childhood, and adolescence confers the highest risk. Although radiation is a proven mammary carcinogen, it remains unclear where it acts in the complex multistage process of breast cancer development. In this study, we investigated the long-term pathophysiologic effects of ionizing radiation at a dose (2 Gy) relevant to fractionated radiotherapy. Adolescent (6-8 weeks old; n = 10) female C57BL/6J mice were exposed to 2 Gy total body γ-radiation, the mammary glands were surgically removed, and serum and urine samples were collected 2 and 12 months after exposure. Molecular pathways involving estrogen receptor-α (ERα) and phosphatidylinositol-3-OH kinase (PI3K)-Akt signaling were investigated by immunohistochemistry and Western blot. Serum estrogen and urinary levels of the oncogenic estrogen metabolite (16αOHE1) were significantly increased in irradiated animals. Immunostaining for the cellular proliferative marker Ki-67 and cyclin-D1 showed increased nuclear accumulation in sections of mammary glands from irradiated vs. control mice. Marked increase in p85α, a regulatory sub-unit of the PI3K was associated with increase in Akt, phospho-Akt, phospho-BAD, phospho-mTOR, and c-Myc in irradiated samples. Persistent increase in nuclear ERα in mammary tissues 2 and 12 months after radiation exposure was also observed. Taken together, our data not only support epidemiologic observations associating radiation and breast cancer but also, specify molecular events that could be involved in radiation-induced breast cancer.


A quantitative study of the slow decline of chlorophyll a fluorescence in isolated chloroplasts.
A detailed study of the photo-induced decline in chlorophyll a fluorescence intensity (Kautsky phenomenon) in coupled isolated chloroplasts from a high level (P) to a low stationary level (S) is presented. 1. A linear relationship between P leads to S quenching and intrathylakoid H+ concentration was found. When the light-induced proton gradient was abolished by uncoupling, the fluorescence emission at room temperature was lowered proportionally to increased H+ concentration in the medium. 2. Fluorescence spectra at -196 degrees C of samples frozen at the P and S states showed no significant differences in the Photosystem I/Photosystem II ratio of fluorescence emission. Furthermore, freezing to -196 degrees C reversed the P leads to S quenching. This indicates that the P leads to S quenching is not related to an increase of spillover of excitation energy from Photosystem II to Photosystem I. 3. When Mg2+ was added to thylakoids suspended in a medium free of divalent cations, the inhibition of spillover required lower Mg2+ concentrations (half saturation at 0.6 mM). Increased proton concentration in the medium also inhibited spillover. 4. The results are interpreted in terms of two sites of Mg2+ and H+ effects on excitation deactivation in Photosystem II. One site is located on the outer face of the thylakoid membrane; action of both Mg2+ and H+ at this side diminishes spillover. The second site is located on the inner face of the membrane; as Mg2+ is displaced there by protons, a non-photochemical quenching of Photosystem II fluorescence is induced, which is manifested by the P leads to S decline.


Routine use of HbA1c amongst inpatients hospitalised with decompensated heart failure and the association of dysglycaemia with outcomes.
Diabetes is an independent risk factor for development of heart failure and has been associated with poor outcomes in these patients. The prevalence of diabetes continues to rise. Using routine HbA1c measurements on inpatients at a tertiary hospital, we aimed to investigate the prevalence of diabetes amongst patients hospitalised with decompensated heart failure and the association of dysglycaemia with hospital outcomes and mortality. 1191 heart failure admissions were identified and of these, 49% had diabetes (HbA1c ≥ 6.5%) and 34% had pre-diabetes (HbA1c 5.7-6.4%). Using a multivariable analysis adjusting for age, Charlson comorbidity score (excluding diabetes and age) and estimated glomerular filtration rate, diabetes was not associated with length of stay (LOS), Intensive Care Unit (ICU) admission or 28-day readmission. However, diabetes was associated with a lower risk of 6-month mortality. This finding was also supported using HbA1c as a continuous variable. The diabetes group were more likely to have diastolic dysfunction and to be on evidence-based cardiac medications. These observational data are hypothesis generating and possible explanations include that more diabetic patients were on medications that have proven mortality benefit or prevent cardiac remodelling, such as renin-angiotensin system antagonists, which may modulate the severity of heart failure and its consequences.


Early-Onset Posterior Capsule Opacification: Incidence, Severity, and Risk Factors.
To evaluate the incidence, severity, and risk factors of early-onset posterior capsule opacification (PCO) following uneventful phacoemulsification and intraocular lens (IOL) implantation. Patients with cataracts who underwent phacoemulsification and IOL implantation surgery for 3 months from September 2019 to April 2020 were enrolled. All the subjects completed a comprehensive ocular examination. Retroillumination images of the posterior capsule were obtained using a slit lamp with imaging system, and PCO was graded by two ophthalmologists. Univariate and multivariate logistic regression analyses were performed to assess the risk factors for PCO. A total of 1039 subjects were enrolled, with mean age 66.68 ± 11.43 years and 42.06% were male. The incidence of early-onset PCO in the 3 months after cataract surgery was 29.93%, and PCO of grade 3 and grade 4 was present in 31 patients (2.98%). Patients with complicated cataract had a higher incidence of PCO than age-related cataract, especially for patients with previous pars plana vitrectomy (PPV) surgery (P < 0.001). Moreover, the incidence of PCO increased with the deficiency of capsulorhexis-IOL overlap (P < 0.001). Multivariate logistic regression also showed that previous PPV surgery (OR 2.664, P = 0.003) and incomplete capsulorhexis-IOL overlap were risk factors for PCO (180-360° overlap: OR 2.058, P < 0.001; < 180° overlap: OR 5.403, P < 0.001). Larger capsulorhexis and PPV surgery history contribute to the occurrence of early-onset PCO, indicating that primary posterior continuous curvilinear capsulorhexis can be considered during cataract surgery for patients with PPV history.


Anti-oxidation activity of the crude polysaccharides isolated from Polygonum cillinerve (Nakai) Ohwi in immunosuppressed mice.
Polygonum cillinerve (Nakai) Ohwi is commonly used in China for over 2000 years. Previous research has shown that the crude polysaccharides extracted from Polygonum cillinerve (Nakai) Ohwi (PCCP) have the scavenging free radicals and anti-tumor activities in vitro. In present study, PCCP were further approached the perspective of their anti-oxidation in immunosuppressed mice. ICR mice were treated firstly with cyclophosphamide (CY, 150 mg/kg), 1 day later, treated with different dosages of PCCP or saline solution once daily for 21 days. Twenty-four hours later for the last drug administration, the animals were weighed, and then killed by decapitation. The liver, spleen, and thymus indices were investigated, and the biochemical parameters were evaluated for various tissues (liver, heart, and kidney). The administration of PCCP with gavage was able to overcome the cyclophosphamide-induced immunosuppression, and significantly to raise the TOC, CAT, SOD, and GSH-Px level. It also raised the liver, spleen, and thymus indices, and decreased the MDA level in mice. PCCP possess the pronounced free radical-scavenging and antioxidant activities, and could play an important role in the prevention of oxidative damage in immunological system.


Standardizing terms for tribocorrosion-associated adverse local tissue reaction in total hip arthroplasty.
Recognizing and adopting standardized terms for adverse local tissue reaction associated with tribocorrosion in total hip arthroplasty are essential for clear scientific discourse and clinical communication. Our goal was to develop terms that can be broadly applied to characterize the local tissue response to tribocorrosion debris, based on current evidence regarding the etiology of this failure mode and its consequences. The proposed standardized terms will improve the understanding and interpretation of analytical tests, advance diagnostic and treatment algorithms, and reduce confusion in research by maintaining consistent nomenclature.


High frequency of antibodies to Hantaan virus and hepatitis C virus in chronic haemodialysis patients. Coincidence or cross-reaction?
To address the question of whether there is any coincidence or cross-reaction between hepatitis C virus (HCV) and Hantaan virus (both RNA arboviruses), as well as to assess the frequency of antibodies to the above viruses amongst chronic haemodialysis patients in our region. Collection of serum samples from consecutive unselected chronic haemodialysis patients. A tertiary referral center (University Hospital). One hundred and fourteen chronic haemodialysis patients were investigated for the presence of antibodies to HCV (anti-HCV) and Hantaan virus disease (anti-HVD). Eleven unselected non-haemodialysis patients with well-defined haemorrhagic fever with renal syndrome (HFRS) were also investigated for the anti-HCV antibodies comprising the disease control group. None. The utility of an anti-HVD positive test in chronic haemodialysis patients. Seventeen patients (14.9% 95% confidence interval [CI] 8.4-21.4%) were anti-HCV positive, whereas 15 (13.2%, 95% CI 6.9-19.3%) were anti-HVD positive. An anti-HCV positive test was confirmed by recombinant immunoblot assay (RIBA II) in 88.2%. The presence of anti-HCV antibodies was not associated with transfusions but with the longer duration of haemodialysis (62.8 +/- 29.8 vs. 31.2 +/- 29.3 months, P < 0.001). Anti-HVD antibodies were not associated with transfusions or with the duration of haemodialysis. Three patients were positive for both anti-HCV and anti-HVD antibodies. None of the 11 patients with well-defined HFRS had anti-HCV antibodies. Chronic haemodialysis patients are a high risk group for HCV infection in association with the duration of haemodialysis and, at least for our geographical area, these patients have to be examined for anti-HVD antibodies especially when a definite causative agent for chronic renal failure is not found. The HVD and HCV infection are not exceptional amongst haemodialysis patients in our region, whereas the possibility of a cross-reaction between these two RNA arboviruses is rather excluded as there was no evidence of HCV infection amongst the patients with well-defined HFRS.


Non-A, non-B chronic hepatitis is chronic hepatitis C: a sensitive assay for detection of hepatitis C virus RNA in the liver.
To study the role of hepatitis C virus in non-A, non-B chronic hepatitis, 49 liver biopsy samples from 40 patients with non-A, non-B chronic hepatitis and 9 control patients were analyzed by complementary DNA/polymerase chain reaction. Two segments of the HCV genome, one in the nonstructural region and the other in the noncoding region, were amplified by two sets of primer pairs. With use of the nonstructural region primers, hepatitis C virus RNA was detected in 24 (60%) of 40 patients with non-A, non-B chronic hepatitis. Of these 40 patients, RNA was detected in 19 (70%) of 27 patients positive for antibody to hepatitis C virus and in 5 (38%) of 13 patients negative for antibody to hepatitis C virus. However, with the noncoding region primers, hepatitis C virus RNA was detected in 38 (95%) of 40 patients with non-A, non-B chronic hepatitis. Of these patients, the RNA was detected in 26 (96%) of 27 patients positive for antibody to hepatitis C virus and also in 12 (92%) of 13 patients positive for antibody to hepatitis C virus. Hepatitis C virus RNA was not detected in any of the control patients. Sequence analysis showed homology between our samples and the prototype to be only 66% to 77% in the nonstructural region but 99% to 100% in the noncoding region. We conclude that almost all patients with non-A, non-B chronic hepatitis in Japan are currently infected with hepatitis C virus, regardless of the presence or absence of antibody to hepatitis C virus.(ABSTRACT TRUNCATED AT 250 WORDS)


Evolutionary consequences of polyploidy in prokaryotes and the origin of mitosis and meiosis.
The origin of eukaryote-specific traits such as mitosis and sexual reproduction remains disputable. There is growing evidence that both mitosis and eukaryotic sex (i.e., the alternation of syngamy and meiosis) may have already existed in the basal eukaryotes. The mating system of the halophilic archaeon Haloferax volcanii probably represents an intermediate stage between typical prokaryotic and eukaryotic sex. H. volcanii is highly polyploid, as well as many other Archaea. Here, we use computer simulation to explore genetic and evolutionary outcomes of polyploidy in amitotic prokaryotes and its possible role in the origin of mitosis, meiosis and eukaryotic sex. Modeling suggests that polyploidy can confer strong short-term evolutionary advantage to amitotic prokaryotes. However, it also promotes the accumulation of recessive deleterious mutations and the risk of extinction in the long term, especially in highly mutagenic environment. There are several possible strategies that amitotic polyploids can use in order to reduce the genetic costs of polyploidy while retaining its benefits. Interestingly, most of these strategies resemble different components or aspects of eukaryotic sex. They include asexual ploidy cycles, equalization of genome copies by gene conversion, high-frequency lateral gene transfer between relatives, chromosome exchange coupled with homologous recombination, and the evolution of more accurate chromosome distribution during cell division (mitosis). Acquisition of mitosis by an amitotic polyploid results in chromosome diversification and specialization. Ultimately, it transforms a polyploid cell into a functionally monoploid one with multiple unique, highly redundant chromosomes. Specialization of chromosomes makes the previously evolved modes of promiscuous chromosome shuffling deleterious. This can result in selective pressure to develop accurate mechanisms of homolog pairing, and, ultimately, meiosis. Emergence of mitosis and the first evolutionary steps towards eukaryotic sex could have taken place in the ancestral polyploid, amitotic proto-eukaryotes, as they were struggling to survive in the highly mutagenic environment of the Early Proterozoic shallow water microbial communities, through the succession of the following stages: (1) acquisition of high-frequency between-individual genetic exchange coupled with homologous recombination; (2) acquisition of mitosis, followed by rapid chromosome diversification and specialization; (3) evolution of homolog synapsis and meiosis. Additional evidence compatible with this scenario includes mass acquisition of new families of paralogous genes by the basal eukaryotes, and recently discovered correlation between polyploidy and the presence of histones in Archaea. This article was reviewed by Eugene Koonin, Uri Gophna and Armen Mulkidjanian. For the full reviews, please go to the Reviewers' comments section.


Injectable shear-thinning sodium alginate hydrogels with sustained submucosal lift for endoscopic submucosal dissection.
Endoscopic submucosal dissection (ESD) is one of the most effective approaches for the minimally invasive treatment of early gastrointestinal cancers. Submucosal injections help safely and successfully remove lesions during ESD by elevating the mucosa and separating the submucosal muscle layer. Herein, we report dynamic injectable sodium alginate hydrogels (ISAHs) with shear-thinning for ESD surgery, which were easily fabricated by the sulfhydryl group of GSH-modified sodium alginate (SA-GSH) reacting with the aldehyde group of oxidized sodium alginate (OSA) at room temperature. ISAHs have advantageous self-healing abilities and antioxidant activity. Additionally, according to an in vitro test on porcine colorectal submucosal lifting, the submucosal elevation heights created by ISAHs were 13 % -18 % greater than those created by commercial ESD solutions (0.4 w/v% sodium hyaluronate). These properties and biocompatibility were confirmed in vitro and in vivo experiments. ISAHs will hopefully become a novel submucosal injectable hydrogel to assist ESD surgery.


Reconstruction of the Occipital and Parietal Congenital Defect with 3D Custom-Made Titanium Prosthesis: A Case Report with Four and a Half Years of Follow-Up and a Brief Review of Literature.
Management of patients with congenital skull defects requires a multidisciplinary approach. Considering the defect's location and size, brain protection, and the cosmetic outcome makes such reconstructions challenging. Due to limited resemblance to skull contour and donor site morbidity of autogenous bone grafts, alloplastic materials are widely used for skull reconstructions. Titanium alloys have proper strength values, low infection rates, favorable osseointegration property, and excellent marginal adaptability when manufactured by computer-aided design (CAD) and computer-aided manufacturing (CAM). A 13-year-old female patient presented with congenital defects at the superior third of occipital bone and posterior thirds of the bilateral parietal bones. On CT scan, the exact size and shape of the defect were determined. Using CAD/CAM, a 3D virtual model of the prosthesis was designed and then printed with titanium alloy (TiAl6V4) via additive manufacturing method. The prosthesis was placed on the defect in a total surgery time of only 90 minutes. On 4.5 years of follow-up, the contour of the skull was ideal and the skin over the defect and neurologic status was intact. Due to their biocompatibility and rigidity, custom-made titanium prostheses are promising options for reconstructing complex skull defects.


Superior haptic-to-visual shape matching in autism spectrum disorders.
A weak central coherence theory in autism spectrum disorder (ASD) proposes that a cognitive bias toward local processing in ASD derives from a weakness in integrating local elements into a coherent whole. Using this theory, we hypothesized that shape perception through active touch, which requires sequential integration of sensorimotor traces of exploratory finger movements into a shape representation, would be impaired in ASD. Contrary to our expectation, adults with ASD showed superior performance in a haptic-to-visual delayed shape-matching task compared to adults without ASD. Accuracy in discriminating haptic lengths or haptic orientations, which lies within the somatosensory modality, did not differ between adults with ASD and adults without ASD. Moreover, this superior ability in inter-modal haptic-to-visual shape matching was not explained by the score in a unimodal visuospatial rotation task. These results suggest that individuals with ASD are not impaired in integrating sensorimotor traces into a global visual shape and that their multimodal shape representations and haptic-to-visual information transfer are more accurate than those of individuals without ASD.


Duplication and deletion analysis by fluorescent real-time PCR-based genotyping.
Gene dosage determination is an increasingly important field for the study of genome variation and organization. In parallel, the advances in our understanding of the genetic basis of disease have produced an exponential increase in the demand for molecular diagnostic analyses. Although efforts have been spent on increasing both the accuracy and the throughput of the gene dosage analysis, the success has been limited. A large number of suitable methods has been proposed; most are based on quantitative real-time PCR or amplification of multiple targets. A new approach exploits the differences between fluorescent signals of SNP alleles in heterozygous samples to assess duplications. The SNP typing-dependent fluorescent signal allelic asymmetry is an intrinsic characteristic of a SNP typing assay and can lead to a simple and cost-effective gene dosage method. This strategy provides sufficient throughput and sensitivity for duplication analysis. There are advantages and disadvantages of real-time methodology when applying the approach to the molecular diagnostic field.


Neural Correlations Underlying Self-Generated Decision in the Frontal Pole Cortex during a Cued Strategy Task.
We have previously shown how the Frontal Pole cortex (FPC) neurons play a unique role in both the monitoring and evaluating of self-generated decisions during feedback in a visually cued strategy task. For each trial of this task, a cue instructed one of two strategies: to either stay with the previous goal or shift to the alternative goal. Each cue was followed by a delay period, then each choice was followed by a feedback. FPC neurons show goal-selective activity exclusively during the feedback period. Here, we studied how neural correlation dynamically changes, along with a trial in FPC. We classified the cells as goal-selective and not goal-selective (NS) and analyzed the time-course of the cross-correlations in 76 pairs of neurons from each group. We compared a control epoch with the feedback epoch and we found higher correlations in the latter one between goal-selective neurons than between NS neurons, in which the correlated activity dropped during feedback. This supports the involvement of goal-selective cells in the evaluation of self-generated decisions at the feedback time. We also observed a dynamic change of the correlations in time, indicating that the connections among cell-assemblies were transient, changing between internal states at the feedback time. These results indicate that the changing of the pattern of neural correlations can underlie the flexibility of the prefrontal computations.


A Nonconserved Histidine Residue on KRAS Drives Paralog Selectivity of the KRASG12D Inhibitor MRTX1133.
MRTX1133 is the first noncovalent inhibitor against the KRASG12D mutant that demonstrated specificity and potency in preclinical tumor models. Here, we used isogenic cell lines expressing a single RAS allele to evaluate the selectivity of this compound. In addition to KRASG12D, MRTX1133 showed significant activity against several other KRAS mutants as well as wild-type KRAS protein. In contrast, MRTX1133 exhibited no activity against both G12D and wild-type forms of HRAS and NRAS proteins. Functional analysis revealed that the selectivity of MRTX1133 toward KRAS is associated with its binding to H95 on KRAS, a residue that is not conserved in HRAS and NRAS. Reciprocal mutation of amino acid 95 among the three RAS paralogs resulted in reciprocal change in their sensitivity toward MRTX1133. Thus, H95 is an essential selectivity handle for MRTX1133 toward KRAS. Amino acid diversity at residue 95 could facilitate the discovery of pan-KRAS inhibitors as well as HRAS and NRAS paralog-selective inhibitors. The nonconserved H95 residue on KRAS is required for the selectivity of the KRASG12D inhibitor MRTX1133 and can be exploited for the development of pan-KRAS inhibitors.


Combination of a fusogenic glycoprotein, pro-drug activation and oncolytic HSV as an intravesical therapy for superficial bladder cancer.
There are still no effective treatments for superficial bladder cancer (SBC)/non-muscle invasive bladder cancer. Following treatment, 20% of patients still develop metastatic disease. Superficial bladder cancer is often multifocal, has high recurrences after surgical resection and recurs after intravesical live Bacillus Calmette-Guérin. Oncovex(GALV/CD), an oncolytic herpes simplex virus-1, has shown enhanced local tumour control by combining oncolysis with the expression of a highly potent pro-drug activating gene and the fusogenic glycoprotein. In vitro fusion/prodrug/apoptotic cell-based assays. In vivo orthotopic bladder tumour model, visualised by computed microtomography. Treatment of seven human bladder carcinoma cell lines with the virus resulted in tumour cell killing through oncolysis, pro-drug activation and glycoprotein fusion. Oncovex(GALV/CD) and mitomycin C showed a synergistic effect, whereas the co-administration with cisplatin or gemcitabine showed an antagonistic effect in vitro. Transitional cell cancer (TCC) cells follow an apoptotic cell death pathway after infection with Oncovex(GALV/CD) with or without 5-FC. In vivo results showed that intravesical treatment with Oncovex(GALV/CD) + prodrug (5-FC) reduced the average tumour volume by over 95% compared with controls. Our in vitro and in vivo results indicate that Oncovex(GALV/CD) can improve local tumour control within the bladder, and potentially alter its natural history.


Epigenetic mechanisms of Strip2 in differentiation of pluripotent stem cells.
Significant evidence points to Strip2 being a key regulator of the differentiation processes of pluripotent embryonic stem cells. However, Strip2 mediated epigenetic regulation of embryonic differentiation and development is quite unknown. Here, we identified several interaction partners of Strip2, importantly the co-repressor molecular protein complex nucleosome remodeling deacetylase/Tripartite motif-containing 28/Histone deacetylases/Histone-lysine N-methyltransferase SETDB1 (NuRD/TRIM28/HDACs/SETDB1) histone methyltransferase, which is primarily involved in regulation of the pluripotency of embryonic stem cells and its differentiation. The complex is normally activated by binding of Krueppel-associated box zinc-finger proteins (KRAB-ZFPs) to specific DNA motifs, causing methylation of H3 to Lysin-9 residues (H3K9). Our data showed that Strip2 binds to a DNA motif (20 base pairs), like the KRAB-ZFPs. We establish that Strip2 is an epigenetic regulator of pluripotency and differentiation by modulating DNA KRAB-ZFPs as well as the NuRD/TRIM28/HDACs/SETDB1 histone methyltransferase complex.


Adolescent urethral coitus: 2 cases and review of the literature.
Urethral coitus is a very rare finding in adolescent women. There are 26 reported cases in the literature, but only two were in adolescents. Urethral coitus has been most commonly described in women with müllerian anomalies and less commonly in other unusual clinical circumstances. We report 2 cases of adolescent women with known müllerian anomalies who were unknowingly engaging in urethral coitus; 1 adolescent with known vaginal agenesis and VACTERL association and one 16-year-old with an oblique vaginal septum and non-communicating functioning uterine horn. Both young women had significant urethral dilation at the time of examination under anesthesia. Urethral intercourse is rare but may have significant consequences. Ongoing follow-up, careful history, and physical examination in adolescent women with müllerian anomalies are important in order to avoid possible complications, particularly when they are contemplating sexual activity. A history of urinary incontinence, dyspareunia, and urinary tract infections in young women with müllerian anomalies should raise suspicion of urethral coitus. If possible, the müllerian anomaly should be corrected to allow vaginal intercourse and discontinuation of urethral coitus.


Stages of Drusen-Associated Atrophy in Age-Related Macular Degeneration Visible via Histologically Validated Fundus Autofluorescence.
To determine histologic correlates for stages of drusen-associated atrophy observed with fundus autofluorescence (FAF) and color fundus photography (CFP), of eyes with advanced age-related macular degeneration (AMD). Case study and clinicopathologic correlation. A white woman with AMD findings of inactive subretinal fibrosis (right eye) and untreated nonexudative type 1 macular neovascularization (left eye) was followed for 9 years before death at 90 years of age. Eyes preserved 6.25 hours after death were postfixed in osmium tannic acid paraphenylenediamine and were prepared for submicrometer epoxy resin sections (115 and 90 from the right and left eye, respectively), with 19 aligned to clinical B-scans. Drusen visible by CFP at the last visit were assigned to 4 stages of FAF: stage 1, isoautofluorescence; stage 2, mildly uniform hyperautofluorescence; stage 3, a ring of hyperautofluorescence around a center of the hypoautofluorescence; and stage 4, uniform hypoautofluorescence. Light microscopic morphologic features at known FAF stages, including druse size, druse contents, and changes in overlying retinal pigment epithelium (RPE), photoreceptors, and external limiting membrane (ELM). Histologic examination of 166 drusen demonstrated that stage 1 isoautofluorescent drusen were visible on CFP. Hyperautofluorescence in stage 2 corresponded to short photoreceptors and complete coverage by RPE. Hypoautofluorescence in stages 3 and 4 corresponded to different extents of RPE atrophy (RPE gap and no RPE, respectively). Of stage 4 drusen, 67% showed no outer nuclear layer (ONL) and an undetectable ELM. Stage 4 included a high proportion of refractile drusen (82%) with many calcific nodules, visible on CFP. We present the first direct clinicopathologic correlation for FAF imaging of drusen-associated atrophy. Our data support 4 FAF stages of drusen-associated atrophy. Stage 2 is the earliest detected stage in which loss of screening by photoreceptor photopigment contributes to uniform hyperautofluorescence. Stages 3 and 4 comport with incomplete RPE and outer retinal atrophy as defined by the Classification of Atrophy Meetings group. Loss of RPE, ONL, and ELM in stage 4 indicates that atrophy can begin over individual drusen. Findings will help the identification of new therapeutic approaches and clinical study end points.


Detection and quantification of Leishmania braziliensis in ectoparasites from dogs.
American cutaneous leishmaniasis (ACL) is a disease caused by different species of Leishmania protozoa, Leishmania braziliensis being the main species found in Brazil. In this study, two rural areas in Pernambuco, northeastern Brazil, where ACL is endemic, were selected. Genomic DNA was extracted from canine ectoparasites (ticks, fleas, and lice) and tested using a conventional PCR and a quantitative real time PCR. A total of 117 ectoparasites were collected, being 50 (42.74%) of them positive for L. braziliensis (in at least one PCR protocol), with a mean parasite load of 14.14 fg/μL. Furthermore, 46 (92.00%) positive ectoparasites were collected from positive dogs and 4 (8.00%) from negative ones. This study reports the detection of L. braziliensis DNA in ectoparasites, but does not prove their vector competence. Certainly, experimental transmission studies are necessary to assess their role, if any, in the transmission of Leishmania parasites to dogs.


Peripheral, synaptic and central neuronal transmission is affected in type 1 diabetes.
We hypothesized that adults with type 1 diabetes and severe polyneuropathy have alterations in neuronal transmission at different anatomical levels. The aims were to investigate upstream sensory neuronal activation in terms of peripheral, spinal, precortical, and cortical transmission. 48 participants with type-1 diabetes and polyneuropathy, and 21 age-matched healthy participants were included. Electrophysiological median nerve recordings were used to analyze peripheral transmission at Erb's point (P9-N11); spinal evoked potentials at Cv7 (P11-N14); subcortical evoked potentials at Oz (N14-P18); early cortical evoked potentials at CP5 (N20-P22); late cortical evoked potentials at C1 (N60-P80) and estimated cortical inter-peak latencies as measures of central conduction time. In comparison to healthy, the presence of diabetes prolonged peripheral transmission at P9 and N11 (+0.49 ms, p = .000; +0.47 ms, p = .04, respectively), early cortical evoked potentials at CP5: N20 (+2.41 ms, p = .003) and P22 (+5.88 ms, p = .001) and cortical potentials at C1: N60 (+39.08 ms, p = .001) and P80 (+54.55 ms, p = .000) and central conduction time. Decreased amplitudes were shown peripherally (-2.13 μV, p = .000), spinally (-0.57 μV, p = .005) and pre-cortically (-0.22 μV, p = .004). In both healthy and people with diabetes increased central conduction time were associated with decreased parasympathetic tone (ρ = -0.52, p = .027; ρ = -0.35, p = .047, respectively). Neuronal afferent transmission and brain responses were significantly impaired in diabetes and the presence of prolonged central conduction time is indicative of severe extensive neuronal damage. Trial registry number: EUDRA CT: 2013-004375-12; clinicaltrials.gov: NCT02138045.


Overview of inherited metabolic disorders causing cardiovascular disease.
Inherited metabolic disorders contribute importantly to adverse cardiovascular outcomes and affect all tissue types. This review summarizes some of the more important aspects. In the venous system, heterozygosities for the factor V Leiden and prothrombin 20210G > A mutations are common and occur in 4% and 1%, respectively, of caucasians. They confer a 2- to 3- fold increase in risk of venous, but not arterial, thrombosis. Marfan syndrome affects the systemic circulation and has a population prevalence of about 1 in 4000. The more than 200 mutations responsible are in the fibrillin-1 gene (15q21.1) and mediate the characteristic skeletal, lens and aortic changes. There are two potentially lethal inherited disorders of cardiac conduction, the long QT and Brugada syndromes. The prevalence for each is about 1 in 10,000. On the other hand, autosomal dominant hypertrophic cardiomyopathies are relatively common, at 1 in 500, but with variable penetrance. Mutations are in the sarcomere proteins and more than 140 are known. Hypertrophic cardiomyopathy may be confused with Fabry disease, for which effective treatment is now available. Mutations in several genes have been shown to produce dilated cardiomyopathy in the young, but there is as yet no specific treatment. In fatty acid oxidation disorders, arrhythmias and cardiomyopathy occur during acute decompensation. An important recently established cause of cardiomyopathy is carnitine transporter defect; it is treated effectively with oral carnitine. The autosomal dominant arrhythmogenic right ventricular dysplasia occurs with a prevalence of about 1 in 15,000 and presents with arrythmias and a dilated right ventricle. The mutations responsible have been mapped to chromosomes 1, 2, 10 and 14. Lysosomal storage disorders, the Ehlers-Danlos syndrome and other connective-tissue disorders affect cardiac valves and vessels. In addition to the relatively common inherited lipoprotein disorders familial hypercholesterolaemia and familial combined hyperlipidaemia, an important dominantly inherited lipid variable contributing to coronary risk is lipoprotein(a). The gene is localized to chromosome 6 and there is full expression in childhood. Elevated lipoprotein(a) levels contribute to the occurrence and severity of early-onset coronary disease and add to the already enhanced risk in patients with familial hypercholesterolaemia.


Three-in-one customized bioink for islet organoid: GelMA/ECM/PRP orchestrate pro-angiogenic and immunoregulatory function.
Islet organoids open up new strategies for diabetes treatment and pancreatic tissue engineering. Digital light processing (DLP) bioprinting has been extensively applied to the construction of organoids due to its ability to provide precisely patterned scaffolds with fast printing time while specific tailored bioink is indispensable for islet organoid. Customized bioinks that meet different needs were created and frequently applied based on gelatin methacryloyl (GelMA) mixed with other ingredients. Decellularized extracellular matrix (ECM) retains many organic specific structural and functional components and is widespread utilized to reconstruct the native niche like environment. However, considerable cytokines and growth factors were inevitably lost during the decellularized process, while platelet rich plasma (PRP) contains a string of growth factors which often exerted pro-angiogenic role. Therefore, a customized specific bioink for constructing islet organoid based on GelMA, pancreatic ECM and PRP was prepared in our research. In vitro, tube formation assay, CD31 immunofluorescence and relative mRNA expression of vascular genes indicated that the bioink with distinctively promote angiogenesis potential. Macrophages polarization was also conducted, which exhibited superior expression of CD206 (M2 marker) and inferior expression of iNOS (M1 marker). 3D printed organoids maintain the activity of mouse islet β-cells (MIN6) with enhanced glucose sensitivity. In vivo, the results of CD31, CD206 and iNOS immunofluorescence were consistent with that in vitro. In summary, we prepared and characterized specific custom-made bioink with orchestrating immune-regulation response indicated by abundant M2-polarized macrophages, attenuated inflammation, and promoted angiogenesis, which provides an underlying bioink for the fabrication of 3D printed islet organoid.


A qualitative description of receiving a diagnosis of clefting in the prenatal or postnatal period.
This study investigated the experience of receiving a diagnosis of clefting in the prenatal or postnatal period. Open-ended interviews were conducted with 20 parents of children with cleft lip with or without cleft palate. Interviews were transcribed and analyzed using a qualitative descriptive approach with an emphasis on thematic analysis. Common themes emerged from participants' responses regarding the delivery of the diagnosis, preparation for the birth of their child, advantages and disadvantages of prenatal diagnosis, use of the Internet, views on abortion and genetic testing, among other issues. All participants in the prenatal group indicated they were satisfied they learned of the cleft before the birth of their child. Some participants in the postnatal group would rather have received the diagnosis prenatally, while others were content with learning of the diagnosis in the delivery room. Greater awareness of the parental experience of the timing of receiving a cleft diagnosis may assist health care professionals in providing care for these families.


The postnatal development and growth of the human lung. I. Morphometry.
The lungs of 7 children (age: 26 days to 5 years 4 months) who died from non-respiratory causes were morphometrically investigated by means of light and electron microscopy. For analysis, the set of data was supplemented with results obtained previously on 8 normal adult lungs using similar quantitative techniques (Gehr et al., 1978). The results allowed us to distinguish two phases of postnatal lung development and growth, the first phase lasting from birth to about 18 months and the second phase from then to adulthood. The first phase was characterized by an overproportionate volume increase in the O2-transporting media, air and blood, at the expense of the parenchymal tissue compartment. In the second phase, the volumetric composition of the lung did not change further because there was proportionate growth of all lung compartments. The growth curves for the airspace and capillary surface areas were not biphasic: they increased in direct proportion to lung volume from birth to adulthood, indicating a steady increase in the air-blood interface complexity during the entire growth period. As a consequence of the differences in growth paces between the various structural lung components in early childhood, the morphometric parameters showed large variations in their overall growth rates between birth and adulthood. Thus, the parenchymal tissue components increased by a factor of 15, lung volume and the gas-exchange surface areas between 20 and 25 times (in parallel to body mass), and, finally, the O2-transporting media, air and blood, more than 30 times. The morphometrically determined pulmonary diffusing capacity for O2 (DLO2) scaled with body mass to the power of 1.15, a value significantly different from 1. This relative improvement with age of the gas exchange function per unit body mass is due mainly to an overproportionate growth of the capillary blood compartment.


Biocompatible green technology principles for the fabrication of food packaging material with noteworthy mechanical and antimicrobial properties-- A sustainable developmental goal towards the effective, safe food preservation strategy.
Biocompatible, eco-friendly, highly economical packaging methods should be needed as conventional packaging is known to cause undesirable effects. As food packaging is the major determining factor of food safety, the selection or methods of packaging materials plays a pioneering role. With this scope, modern food technology seeks unique sustainable approaches for the fabrication of package materials with notable desired properties. The principles, features, and fabrication methodology of modern food packaging are briefly covered in this review. We extensively revealed improved packaging (nanocoating, nanolaminates, and nano clay), active packaging (antimicrobial, oxygen scavenging, and UV barrier packaging), and intelligent/smart packaging (O2 indicator, CO2 indicator, Time Temperature Indicator, freshness indicator, and pH indicator). In particular, we described the role of nanomaterials in the fabrication of packaging material. Methods for the evaluation of mechanical, barrier properties, and anti-microbial assays have been featured. The present studies suggest the possible utilization of materials in the fabrication of food packaging for the production, utilization, and distribution of safe foods without affecting nutritional values.


[Primary Gougerot-Sjogren syndrome. Spontaneous one-year course of clinical, biological and histological signs].
The natural clinical course of primary Sjögren's syndrome was followed in 8 patients to identify the concomitant functional, clinical, biological, scintigraphic and histological manifestations of the disease. The diagnosis of primary Sjögren's syndrome was made on the basis of functional signs (ocular or salivary sicca syndrome) and 2 positive tests among the 3 objective ocular tests (Schirmer's test, break-up time, Rose Bengale). Work-up included recording of functional and clinical signs, ophthalmologic examination and laboratory tests at diagnosis and every 3 months for 12 months. Scintigraphy of the salivary glands was performed together with a biopsy at diagnosis and at 12 months. No one parameter varied significantly over a 1 year period demonstrating the lack of need for renewed examinations for diagnosis or regular follow-up. This is the first report providing a homogeneous series studied by one team over a determined period of time. It demonstrates that clinical, biological and anatomic criteria for primary Sjögren's syndrome do not show any correlation between functional signs and objective ocular tests.


A systematic review of leukocyte telomere length and age in adults.
To provide a systematic review of the relationship between age and leukocyte telomere length (LTL) in adults. Relevant studies were identified by a systematic search of Medline, EMBASE and ISI Web of Knowledge databases. Key data, such as age and LTL, were extracted from the studies along with correlation coefficients and yearly attrition rates where available. Obtained data were used to calculate weighted means and correlation coefficients. Overall, 124 cross-sectional studies and 5 longitudinal studies were identified. A statistically significant inverse correlation between mean age and mean LTL across cross-sectional studies was observed for both absolute (r=-0.338, p<0.0001) and relative LTL (r=-0.295, p=0.0088). From mean LTL and ages, a yearly telomere loss of 24.7 base pairs (BP)/year was estimated by weighted linear regression. Weighted means of within study correlation of age and TL and yearly telomere loss rate estimates from cross-sectional studies were also in a similar order of magnitude (-0.380 and 21.91 BP/year). The few longitudinal studies reported somewhat higher mean telomere loss rates (between 32.2 and 45.5 BP/year). While a decrease of LTL with age is out of question, data on variation of the decrease according to sex, age and other potential determinants especially from longitudinal data are still sparse.


Dominance and inheritance patterns of mobility and death feigning in beetle strains selected for moving activity.
Reciprocal crossing of different strains is a suitable method to investigate the dominance and inheritance of a focal trait. Herein, we performed reciprocal crossing among strains of Tribolium castaneum exhibiting a genetically high (H strain) and low (L strain) moving activity and investigated the related heritable factors in the F1 and F2 generations. We also evaluated death-feigning behavior, which negatively responded to artificial selection for moving activity in T. castaneum. The results obtained for the F1 generation suggest that low moving activity and short duration of death feigning were dominant. In the F2 generation, movement and death feigning exhibited continuous segregation. The distribution of each trait value in the F2 generation differed from that in the parental generation, and no individuals transgressing the distribution of trait values in the parental generation emerged in the F2 generation. These results suggest that the genetic correlation between movement and death-feigning behavior is controlled in a polygenic manner. Moreover, the examination of the proportions of both behaviors (high vs. low moving activity and long vs. short death-feigning duration) in the F1 generation revealed that the two behaviors may be controlled by the maternal genotype, suggesting that the gene(s) that control movement and death feigning are located on the sex chromosome in T. castaneum.


Comparison of survival and embryonic development in human oocytes cryopreserved by slow-freezing and vitrification.
To compare the survival, fertilization, early embryonic development, and meiotic spindle assembly and chromosome alignment in frozen-thawed human oocytes after slow-freezing and vitrification. A randomized study. A university-affiliated assisted reproductive center. Donated extra eggs from women undergoing assisted reproduction treatment. A total of 605 mature oocytes were divided into a slow-freezing group and a vitrification group for cryopreservation. After frozen-thawing, the oocyte survival rate, spindle assembly, and chromosome alignment were compared. The surviving oocytes were inseminated by intracytoplasmic sperm injection, and the rate of fertilization and embryo development were also compared in two groups. The oocyte survival rate was statistically significantly lower in the slow-freezing group (75 out of 123, 61.0%) than the vitrification group (268 out of 292, 91.8%). The fertilization rate was the same for both groups, but the cleavage rate of zygotes was statistically significantly different between two groups: (slow-freezing, 25/46 (54.4%) versus vitrification, 142 out of 182 (78.0%). There was a considerable difference in the percentage of high-quality embryos between slow-freezing and vitrification groups: 6 out of 25 (24.0%) versus 60 out of 142 (42.3%), respectively. The percentage of blastocyst development was statistically significantly higher in the vitrification group (47 out of 60, 33.1%) than in the slow-freezing group (3 out of 25, 12.0%). There was a much higher percentage of oocyte abnormalities in terms of spindle assembly and chromosome alignment in the slow-freezing group (25 out of 64, 39.1%) compared with the vitrification group (11 out of 62, 17.7%). Vitrification is superior to the slow-freezing method, leading to improved oocyte survival rate, fertilization, and embryonic development in vitro. These results may be related to vitrified human oocytes incurring less damage to spindle integrity and chromosome alignment.


Phosphorus nuclear-magnetic-resonance studies of the transition-state analogue complex of creatine kinase.
31P nuclear-magnetic-resonance spectra of MgADP bound to creatine kinase in the presence of creatine NO3- ions show that there are two non-identical forms of the bound nucleotide. The sites have different affinities for the nucleotide. MgADP at the high-affinity site is in slow exchange (k less than 125s-1 at 27 degrees C) with free MgADP.


Comparative evaluation of hepatotoxic and nephrotoxic effects of aroclors 1221 and 1254 in female rats.
Polychlorinated biphenyls (PCBs) are persistent environmental pollutants. This study compared effects of two PCB mixtures, Aroclors 1221 (A1221) and 1254 (A1254) on serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), urea, creatinine and uric acid in female rats. Histopathological changes in the liver and kidney were also examined. A group of adult Wistar rats served as controls. Groups II and III were subcutaneously injected with A1221 and A1254 at 10 mg/kg every other day for 6 weeks. At the end of this period, all animals were decapitated and blood samples were collected. Serum urea, creatinine, uric acid, ALT, AST and ALP levels were determined. Liver and kidney were collected for histopathological examination. They were fixed in formaldehyde and processed for light microscopy. Both A1221 and 1254 significantly elevated serum ALT (p < 0.05) and AST (p < 0.01) levels compared to the control group. Serum ALP values were significantly increased by A1221 (p < 0.05), but they were unaffected in the A1254 group. Treatment with both A1221 and A1254 significantly increased serum levels of urea (p < 0.05), creatinine (p < 0.01) and uric acid (except in the A1221 group; p < 0.005). Distinct histopathological changes including renal corpuscular atrophy, peritubular vascular congestion and dilated cortical tubules, sinusoidal dilatation, congestion and mononuclear cell infiltration were observed. These findings suggest that PCBs may cause nephrotoxicity and hepatotoxicity in female rats.


RAD-seq derived genome-wide nuclear markers resolve the phylogeny of tunas.
Although species from the genus Thunnus include some of the most commercially important and most severely overexploited fishes, the phylogeny of this genus is still unresolved, hampering evolutionary and traceability studies that could help improve conservation and management strategies for these species. Previous attempts based on mitochondrial and nuclear markers were unsuccessful in inferring a congruent and reliable phylogeny, probably due to mitochondrial introgression events and lack of enough phylogenetically informative markers. Here we infer the first genome-wide nuclear marker-based phylogeny of tunas using restriction site associated DNA sequencing (RAD-seq) data. Our results, derived from phylogenomic inferences obtained from 128 nucleotide matrices constructed using alternative data assembly procedures, support a single Thunnus evolutionary history that challenges previous assumptions based on morphological and molecular data.


Neuroanatomical and neuropsychological features of elderly euthymic depressed patients with early- and late-onset.
Whether or not cognitive impairment and brain structure changes are trait characteristics of late-life depression is still disputed. Previous studies led to conflicting data possibly because of the difference in the age of depression onset. In fact, several lines of evidence suggest that late-onset depression (LOD) is more frequently associated with neuropsychological deficits and brain pathology than early-onset depression (EOD). To date, no study explored concomitantly the cognitive profile and brain magnetic resonance imaging (MRI) patterns in euthymic EOD and LOD patients. Using a cross-sectional design, 41 remitted outpatients (30 with EOD and 11 with LOD) were compared to 30 healthy controls. Neuropsychological evaluation concerned working memory, episodic memory, processing speed, naming capacity and executive functions. Volumetric estimates of the amygdala, hippocampus, entorhinal and anterior cingulate cortex were obtained using both voxel-based and region of interest morphometric methods. White matter hyperintensities were assessed semiquantitatively. Both cognitive performance and brain volumes were preserved in euthymic EOD patients whereas LOD patients showed a significant reduction of episodic memory capacity and a higher rate of periventricular hyperintensities compared to both controls and EOD patients. Our results support the dissociation between EOD thought to be mainly related to psychosocial factors and LOD that is characterized by increasing vascular burden and episodic memory decline.


Performance of anaerobic sequencing batch biofilm reactor submitted to different influent volume feeds and cycle time periods maintaining organic loading.
The stability and efficiency of an anaerobic reactor containing biomass immobilized on polyurethane foam were assessed. The reactor with mechanical stirring of 500 rpm and maintained at 30+/-1 degrees C treated synthetic wastewater with a concentration of approx 500 mg of chemical oxygen demand/L and was fed with different influent volumes and cycle times maintaining organic load. Operation was in batch mode with renewal of only part of the volume of wastewater to be treated; that is reactor discharge was not complete, but partial. The main operational characteristic investigated was the ratio of the volume of wastewater fed per cycle (VA) to the volume of wastewater in the reactor (VA) maintaining the same volumetric organic load. This way, operating flexibility could be verified in relation to the volume of treated wastewater at each cycle and the cycle time for the same organic load. The results indicated that the reactor was able to operate with different VA/Vu ratios with no significant loss in performance, thus allowing increased operational flexibility. For conditions in which VA was >or=50% of VA, removal efficiencies of filtered and nonfiltered organic matter were about 84 and 79%, respectively, whereas at conditions of higher initial influent dilution, these efficiencies were slightly lower, about 80 and 74%, respectively. At higher initial influent dilutions, it became difficult to maintain a constant reactor medium volume, owing to a high formation rate of viscous polymer-like material, likely of microbiologic origin.


COVID-19 Prognosis in Association with Antidepressant Use.
Various subtypes of severe acute respiratory syndrome coronavirus 2 and variations among immune systems in different ethnicities need to be considered to understand the outcomes of coronavirus disease 2019 (COVID-19). This study aimed to provide evidence for the association between the use of antidepressants and the severity of COVID-19. We used the National Health Information Data-COVID database. Patients with one or more prescriptions of any antidepressant were selected as the exposure group. Detailed analyses were performed to determine the type of medication associated with the prognosis. The use of selective serotonin reuptake inhibitors (SSRIs) was associated with a lower risk of severe outcomes of COVID-19, whereas the use of tricyclic antidepressants (TCAs) increased the risk of poor prognosis of COVID-19. Detailed analyses showed that escitalopram was significantly associated with better clinical outcomes, and nortriptyline was linked to more severe COVID-19 outcomes. This study revealed an association between antidepressants and COVID-19 prognosis. SSRIs were significantly associated with a lower risk of severe outcomes, whereas TCAs were related to the poor prognosis of COVID-19.


Promising effects of exosomes from menstrual blood-derived mesenchymal stem cells on endometriosis.
Endometriosis as a non-malignant gynecological disease leads to dysregulation of numerous cellular functions including apoptosis, angiogenesis, migration, proliferation, and inflammation. Accumulating evidence has shed light on the importance of endometrial stem cells within the menstrual blood which are involved in the establishment and progression of endometriotic lesions in a retrograde manner. According to the fact that the therapeutic benefits of mesenchymal stem cells are provided through paracrine functions, we used exosomes from menstrual blood-derived stem cells (MenSCs) for treating endometriotic stem cells to inhibit their lesion formation tendency. Menstrual blood samples from healthy and endometriosis women were collected. Isolated MenSCs by the density-gradient centrifugation method were characterized by flow cytometry. Secreted exosomes were isolated from healthy MenSCs (NE-MenSCs) and used to treat endometriotic cells (E-MenSCs). 72 h after treatment, different mechanisms and pathways including inflammation, proliferation, apoptosis, migration, and angiogenesis were analyzed using Real-Time PCR, ELISA, immunocytochemistry, annexin V/PI, and scratching assay. Exosome treatment significantly reduce the expression level of markers related to inflammation, proliferation, migration, and angiogenesis in E-MenSCs which are aberrantly expressed in endometriosis. Moreover, apoptosis was induced in E-MenSCs after treatment which was evaluated in both gene and protein levels. In this study, we give preliminary evidence for the potential of MenSCs-Exo in ameliorating endometriosis. Regarding our results, we suggest that after relevant clinical trial, MenSCs-derived exosomes can be considered as a better treatment option to improve endometriosis compared to common and conventional treatments and show their potential as a cell-free product in endometriosis repair.