Long-term oncological outcomes in robotic gastrectomy versus laparoscopic gastrectomy for gastric cancer: a meta-analysis.
Robotic gastrectomy (RG) has been a new technical alternative for gastric cancer. However, the long-term oncological outcomes of RG still should be further evaluated. In this meta-analysis, the long-term oncological outcomes of RG and laparoscopic gastrectomy (LG) are compared. Comprehensive searches from various databases are compared in February 2017 to identify that the oncological outcomes of RG and LG are evaluated in gastric cancer patients. The pooled oncological outcomes of the overall survival (OS), disease-free survival (DFS), and the recurrence rate were performed by adopting the meta-analysis to calculate the hazard ratio (HR) or the odds ratio with 95% confidence intervals (CIs). Five studies that concern retrospective design and prospective data collection and involve 1614 patients were included. All the five studies evaluated OS. Two studies evaluated DFS, while four studies reported the recurrence rate or recurrence cases in RG and LG groups with the long-term follow-up. The pooled analysis showed no significant difference in OS and DFS between RG and LG, without significant between-study heterogeneity. Besides, the recurrence rate between RG and LG had no significant difference without heterogeneity. RG could provide comparable long-term oncological outcomes as well as LG for the treatment of gastric cancer. OS, DFS, and the recurrence rate by the long-time follow-up of RG were comparable with LG. Generally speaking, more randomized clinical trials and a larger patient cohort with longer follow-up are still essential to further demonstrate the value of the robotic surgery for gastric cancer.


Macropinocytosis in Phagocyte Function and Immunity.
Phagocytes play critical roles in the maintenance of organismal homeostasis and immunity. Central to their role is their ability to take up and process exogenous material via the related processes of phagocytosis and macropinocytosis. The mechanisms and functions underlying macropinocytosis have remained severely understudied relative to phagocytosis. In recent years, however, there has been a renaissance in macropinocytosis research. Phagocytes can engage in various forms of macropinocytosis including an "induced" form and a "constitutive" form. This chapter, however, will focus on constitutive macropinocytosis and its role in the maintenance of immunity. Functions previously attributed to macropinocytosis, including antigen presentation and immune surveillance, will be revisited in light of recent revelations and emerging concepts will be highlighted.


Successful treatment of high congenital dislocated hips in older children by open reduction, pelvic and femoral osteotomy with external fixator stabilization (average 8.2 years of age).
A new technique using a hinged external fixator to stabilize an open reduction with pelvic and femoral osteotomies has been developed for treating high-dislocated hips in older children with developmental dislocated hip (DDH). This technique was performed in 11 patients (12 hips) at a mean age of 8.2 years. At follow up, radiographic results showed no redislocation/subluxation and clinical results demonstrated 11 hips as excellent/good and only one hip as poor from persistent stiffness. In conclusion, this new technique produces acceptable results in the treatment of older children with high dislocation of the hip from DDH.


[Hysteroscopy in the diagnosis of endometrial carcinoma].
To determine the diagnostic value of hysteroscopy in endometrial cancer. 216 patients underwent hysteroscopy and endometrial biopsy. A comparison was made between hysteroscopic impression and histological examination. Sensitivity of hysteroscopy for diagnosing of endometrial cancer was 83.33%, specificity was 99.04%, positive predictive value was 71.42% and negative predictive value was 99.52%. Hysteroscopy was found to have a very important role in the diagnosis of endometrial cancer.


A 14-year-old girl who regained normal vision after bilateral visual impairment following hot water injury to the eyes.
A 14-year-old girl presented with bilateral visual impairment following hot water injury to the eyes. The patient was admitted for a week and managed with guttae tropicamide 0.5% 8 h, diclofenac sodium 0.1% 4 h, and fluoroquinolone 0.3% 6 h and ointment chloramphenicol 8 h. Also, the patient was managed with capsule doxycycline 100 mg 12 h for 10 days, tablet cataflam 50 mg 12 h for 7 days and intramuscular tetanus toxoid 0.5 mg stat and dermacine cream for facial scald. The visual acuities improved from 3/60 (right eye) and 6/24 (left eye) to 6/6 in both eyes. There were resolutions of facial/eye pain, tearing, photophobia, lid edema, blepharospasm, and conjunctival hyperemia. There was complete healing of facial wounds and corneal ulcers. She was discharged from hospital on the 7th day of admission. Prompt presentation, degree of scald sustained, and appropriate medical intervention enhanced visual recovery and wound healing in the patient.


Depinning Transition of a Domain Wall in Ferromagnetic Films.
We report first principle numerical study of domain wall (DW) depinning in two-dimensional magnetic film, which is modeled by 2D random-field Ising system with the dipole-dipole interaction. We observe nonconventional activation-type motion of DW and reveal the fractal structure of DW near the depinning transition. We determine scaling functions describing critical dynamics near the transition and obtain universal exponents establishing connection between thermal softening of pinning potential and critical dynamics. We observe that tuning the strength of the dipole-dipole interaction switches DW dynamics between two different universality classes, corresponding to two distinct dynamic regimes characterized by non-Arrhenius and conventional Arrhenius-type DW motions.


An alternative method for the determination of uric acid in serum.
A novel fluorometric method for the determination of uric acid based on the coupled reactions of uric acid with uricase and peroxidase to form highly fluorescent 2,2'dihydroxy-3,3'-dimethoxy-biphenyl-5,5'-diacetic acid is described. The calibration curve was constructed from a series of standard uric acid solutions vs. the corresponding relative fluorescence. It was linear up to 15 mg/dl (0.9 mmol/l). The serum or plasma samples must be deproteinated with (absolute) ethanol before assay and its uric acid content can be obtained from the calibration curve. This method is rather simple, having good precision and accuracy. High level ascorbic acid in the sample falsely elevates uric acid concentration. Comparison of the results obtained on the patient sera with a colorimetric phosphotungstate method and a standard enzymatic spectrophotometric method gave coefficients of correlation of 0.908 and 0.986, respectively.


Plant structure and the searching efficiency of coccinellid larvae.
| 1. To determine the effect of plant structure on the searching efficiency of Coccinella septempunctata L. larvae, their functional response on pea and bean plants was compared. 2. The attack coefficient a was lower on pea than on bean plants. 3. This was not due to a difference in the coincidence of prey distribution and predator searching effort, but was due to larvae falling off the smooth leaves of pea plants significantly more frequently than off bean plants. 4. It was concluded that plant structure is an important factor in determining the quality of a habitat for coccinellids.


Influence of wastewater effluents on the bioaccumulation of volatile methylsiloxanes in the St. Lawrence River.
The bioaccumulation of cyclic volatile methylsiloxanes (D3 to D6) as well as linear siloxanes (L3 to L5) was studied in a food web in the St. Lawrence River downstream of the effluent of the municipal wastewater treatment plant in Montreal, Canada. For most species, differences in δ15N in fish and prey showed a clear separation of individual fish feeding in food webs influenced by the wastewater plume from those feeding outside the plume. Cyclic siloxanes were detected in all biotic samples from the individuals identified as feeding in the effluent plume. Siloxane D5 accounted for more than 80% of the total siloxanes. Linear siloxane L5 was also abundant in walleye and gull eggs. Total siloxane concentrations in suspended sediments were 17.3 times higher than in surface sediments in the region of the river in the effluent plume. Caged freshwater mussels (Elliptio sp.), placed in the effluent plume, bioaccumulated 43 times more total siloxanes than PBDEs in 30 days, demonstrating how readily siloxanes are taken up in biota and what a significant component of the contaminant body burden they can account for. The sediment-biota accumulation factors (BSAF) for total siloxanes (∑ D3 to D6 and L3 to L5) showed values of 65.4, 27.8, 9.9 and 6.4 for walleye, northern pike, yellow perch and round goby respectively.


The effect of topiramate on cognitive fMRI.
Topiramate (TPM) is known to cause language impairment in healthy volunteers and patients with epilepsy. We assessed the effects of TPM on functional language networks in both patients with focal epilepsies and healthy controls using functional magnetic resonance imaging (fMRI). We obtained fMRI data in 24 controls and 35 patients with frontal lobe epilepsy using a simple verbal fluency (VF) paradigm. Eight of the 35 patients were treated with TPM in polytherapy. We compared cognitive task related activations and de-activations in patients taking TPM with patients taking other AEDs and healthy controls. In a longitudinal pilot study with VF-fMRI paradigm, we studied two patients with focal epilepsies twice, prior to starting and on stable doses of TPM, two patients twice, before and after tapering TPM completely and two healthy controls twice, before and after single doses of 200mg TPM. Cross sectional analyses of VF-fMRI showed a reduction in the task-related deactivation of the default mode network (DMN) in patients taking TPM. The longitudinal study corroborated these findings as both chronic administration and a single dose of TPM were associated with impaired categorical verbal fluency and disruption of task-related deactivations. Similar neuropsychological and fMRI findings in patients and healthy controls indicate a specific effect of TPM in default mode network areas that may be essential components of the language network. Our preliminary data suggest a mechanism by which TPM impairs cognitive processing during language function and highlights the sensitivity of fMRI to detect the effects of AEDs on cognitive brain networks.


Inhibitory Effects of P2Y12 Receptor Antagonist on PAR1- and PAR4-AP-Induced Platelet Aggregation in Patients with Stroke or TIA.
The inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-activating peptide (AP)-induced platelet aggregation have not been fully elucidated. The present study aimed to investigate the inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-AP-induced platelet aggregation using platelet-rich plasma (PRP) from individuals including patients with stroke or transient ischemic attack (TIA). PRP was given to 10 healthy individuals pretreated in vitro with cangrelor, then stimulated with adenosine diphosphate (ADP), PAR4-AP, or PAR1-AP. Moreover, 20 patients were enrolled from 148 consecutive patients with acute ischemic stroke or TIA admitted to our institute between December 2017 and April 2019. PRP obtained from each patient before and >7 days after initiation of clopidogrel was similarly stimulated with these agonists. Platelet aggregation was measured using an automatic coagulation analyzer in all participants. In healthy individuals, ADP- and PAR4-AP-induced platelet aggregations were significantly inhibited depending on the cangrelor concentration in vitro, while PAR1-AP-induced platelet aggregation was slightly inhibited. In patients with stroke or TIA, clopidogrel inhibited ADP-induced platelet aggregation at all concentrations, and significantly inhibited PAR4-AP-induced platelet aggregation at 50 µmol/L of PAR4-AP (p<0.05), especially in 5 patients who showed high reactivity to PAR4-AP. PAR1-AP-induced platelet aggregation was also slightly inhibited. We showed significant inhibitory effects on PAR4-AP-induced platelet aggregation by clopidogrel in patients with stroke or TIA who had high reactivity to PAR4-AP.


Development of dual gradient column in liquid chromatography.
The dual gradient column, in which both the chemical property of the stationary phase and the flow velocity in the mobile phase are heterogeneous longitudinally along the column, is developed to obtain the mobile phase gradient-like elution in an isocratic condition. Here, the step-wise dual gradient columns were prepared by connecting an inlet column (I.D. 50 microm, packed with ODS) serially to an outlet column (I.D. 100-200 microm, packed with the mixture of ODS and C1 [9:1]). The retention behavior of alkylbenzenes was able to be controlled in the dual gradient column depending on the variation in the flow velocity. Moreover, the change in retention behavior induced by the flow velocity variation for the dual gradient columns was quite different from that by the variation in organic modifier content of the mobile phase in isocratic elution for a single gradient column and can induce the similar effect with an ordinary gradient elution in a mobile phase composition.


Endovascular repair of distal arch aneurysm with double-chimney technique.
We report 2 cases of distal arch aneurysm treated by thoracic endovascular aneurysm repair (TEVAR) with the "double-chimney technique." This technique permitted the implantation of a thoracic stent graft in the ascending aorta over the arch branches while preserving perfusion of innominate and left common carotid arteries without debranching bypasses. The procedure is a feasible and less invasive treatment for distal arch aneurysm with a short proximal neck (<2 cm to the origin of the innominate artery) in patients at high risk when undergoing sternotomy and in emergent cases.


Liposome mediated delivery of retinoids and aromatic polyamidines: Effects on growth of tumor cell lines.
This paper describes the increase of antiproliferative activity toward tumor cell lines of liposome-delivered retinoids and aromatic polyamidines.


An exploratory cost-effectiveness analysis of a novel tissue valve compared with mechanical valves for surgical aortic valve replacement in subgroups of people aged 55-64 and 65+ with aortic stenosis in the UK.
Exploratory analysis to conceptualize and evaluate the potential cost-effectiveness and economic drivers of using a novel tissue valve compared with mechanical heart valves for surgical aortic valve replacement (SAVR) in people aged 55-64 and 65+ with aortic stenosis (AS) from a National Health Service (NHS) UK perspective. A decision-analytic model was developed using a partitioned survival model. Parameter inputs were obtained from published literature. Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted to explore the uncertainty around the parameters. The novel tissue valve was potentially associated with higher quality-adjusted life years (QALYs) of 0.01 per person. Potential cost savings were greatest for those aged 55-64 (£408) versus those aged 65+(£53). DSA indicated the results to be most dependent on relative differences in general mortality, procedure costs, and reoperation rates. PSA estimated around 75% of the iterations to be cost-effective at £20,000 per QALY for those aged 55-64, and 57% for those aged 65+. The exploratory analysis suggests that the novel tissue valve could be a cost-effective intervention for people over the age of 55 with AS who are suitable for SAVR in the UK.


Tumor and non-tumor liver angiogenesis is traced and evaluated by hepatic arterial ultrasound in murine models.
We studied the relationships between hepatic and mesenteric mean blood-flow velocities (mBFVs) measured by ultrasound imaging and (1) downstream tumor angiogenesis during liver metastasis induced by spleen injection of LS174 human colon cells overexpressing the antiangiogenic Netrin4 (LS174-NT4) or not (LS174-WT) and (2) downstream normal angiogenesis during hepatic regeneration after 50% hepatectomy. Liver volume and mBFVs were measured before and after surgery, at day 30 in the first model and at days 2, 7 and 16 in the second model. LS174-NT-4 vs. LS174-WT mice presented fewer metastases (25% vs. 90%, p < 0.001) and decreased hepatic mBFVs (16.5 ± 0.8 vs. 21.8 ± 1.4 cm s(-1), p < 0.01), without difference in mesenteric mBFVs. After partial hepatectomy, hepatic and mesenteric mBFVs increased at day 7, from 12.4 ± 1.7 and 11.8 ± 2.6 to 19.1 ± 1.8 and 17.5 ± 2.4 cm s(-1), respectively, (p < 0.01) then returned to baseline as liver volume. Duplex Doppler ultrasonography reliably assesses normal or tumor angiogenesis and may provide follow-up functional evaluation.


Malignant melanoma of the conjunctiva. Report of a case.
Malignant melanomas of the conjunctiva are extremely rare in children. The authors report an 11-year-old boy who had a nodule at the limbus in a pigmented area since early childhood. The lesion was excised and the diagnosis of atypical compound nevus was made. Five months later, the patient returned with multiple nodules in the bulbar and palpebral conjunctiva. One of the lesions was excised, and the diagnosis was malignant melanoma. He was lost for follow-up for 6 months; then he presented a large pigmented, vascularized mass protruding through the palpebral aperture. Results of systemic workup for metastatic disease were negative, and an exenteration was performed. A few months later, cervical lymphadenopathy developed followed by extensive metastatic disease.


An Inexpensive and Easy Ultrasound Phantom: A Novel Use for SPAM.
Ultrasound models, commonly referred to as "phantoms," are simulation tools for ultrasound education. Commercially produced phantoms are available, but there are "homemade" alternatives such as raw poultry and gelatin molds. Precooked, processed meat, better known as SPAM (Hormel Foods Corporation, Austin, MN), can be used as an ultrasound phantom to teach several ultrasound applications. It is a versatile, hygienic, and easily manipulated medium that does not require refrigeration or preparatory work and can be easily discarded at the end of use.


Clinical and roentgenological studies on malalignment disorders of the patello-femoral joint. Part I: Classification of patello-femoral alignments using dynamic sky-line view arthrography with special consideration of the mechanism of the malalignment disorders.
Dynamic sky-line view arthrography at 30, 60, and 90 flexion degrees was carried out on 1,242 knees of 621 cases who claimed trouble with at least one knee. The patient's age range was from 15 to 35 years. Alignment of the patello-femoral joint was classified into four groups; Grade I: The patello-femoral joint is congruent in all the three views. Grade II: The view taken at 30 degrees shows the joint space open in the medial facet but closed in the view at 60 degrees. Grade III: The medial interspace is open at 60 degrees but closed at 90 degrees. Grade IV: The medial joint space is open in all three views. Grade distribution of all cases studied was: Grade I, 62.1%; Grade II, 25.8%; Grade III, 6.7%; and Grade IV, 5.4%. Clinical disorders thus occur at high percentages in the groups of Grades III and IV. Based on this observation, the mechanism of the malalignment disorders of the patello-femoral joint is discussed.


February asthma outbreaks in NSW: a case control study.
To investigate individual factors associated with an asthma outbreak among children aged one to 14 years in Sydney in February 1999. A case control study was undertaken with cases (n=92) defined as all children admitted to Sydney Children's Hospital for asthma in February 1999. Unmatched controls (n=76) were all children admitted for asthma in the previous three months. We obtained information by a structured telephone survey of parents. Logistic regression analyses were used to determine odds ratios for risk factors for hospital admission. Mean age for hospital admission of 4.7 years for cases and 4.4 years for controls. The presence of one or more siblings reduced the risk of admission during an asthma outbreak (OR=0.59, 95% CI 0.37 to 0.93). Children with older siblings aged 10 to 14 years were also less likely to be admitted (OR=0.3, 95% CI 0.12 to 0.74). An age effect was observed. Other demographic, clinical and environmental characteristics, including smoking, were not associated with admission during the outbreak. The main findings of this study are the protective effect of siblings and an age-dependent effect in risk of hospital admission during an asthma outbreak. These findings are consistent with an infective cause of the outbreak. Children without siblings, particularly older siblings, appear to be at highest risk of hospital admission during an asthma outbreak. Environmental and other factors need to be examined to further explain the episodicity of such outbreaks and to determine means of predicting and preventing future episodes.


Bioinformatic Prediction of Bulked Oligonucleotide Probes for FISH Using Chorus2.
Fluorescence in situ hybridization (FISH) provides great conveniences for detection and visualization of specific genomic segments. Oligonucleotide (Oligo)-based FISH further broadened the applications in plant cytogenetics researches. High-specific single-copy oligo probes are essential for successful oligo-FISH experiments. Here, we introduce the bioinformatic pipeline to design genome-scaled single-copy oligos and filter repeat-related probes with Chorus2 software. Robust probes are accessible for both well-assembled genome and species without a reference genome based on this pipeline.


The effect of supplemental feeding on home range size and activity patterns in the lizard Uta stansburiana.
There was no difference in home range size between supplementally fed and unfed lizards even though supplementally fed lizards gained significantly more body mass than did unfed lizards. A logistic growth model was fit to curves of accumulative home range size against days of observation for fed and unfed lizards. An analysis of these curves showed that supplementally fed lizards's home range estimates grew at a slower rate than did unfed lizards. Thus, fed lizards utilized the habitat at a slower rate than did unfed lizards. Moreover, the rate at which fed lizards utilized the habitat was linearly related to their increase in body mass. Supplementally fed male and unfed lizards of both sexes were equally active through the summer. On average, they were active on one out of every two days (49.4%), whereas, supplementally fed females were active on a significantly greater number of days (83.9%).


Investigating the feasibility of a hand-held photoacoustic imaging probe for margin assessment during breast conserving surgery.
Approximately 19 % of breast cancer patients undergoing breast conserving surgery (BCS) must return for a secondary surgery due to incomplete tumour removal. Our previous work demonstrated that the lower lipid content, characteristic of tumour tissue, was observed as regions of hypo-intense photoacoustic (PA) contrast. The goal of this work was to evaluate feasibility of a low-frequency, hand-held PA imaging probe for surgical margin assessment based on lipid content differences. Here, we describe (i) the design of a prototype hand-held PA imaging probe, (ii) the effect of limited-bandwidth on image contrast, (iii) accuracy towards hypo-intense contrast detection, (iv) the limited-view characteristics of the single sensor design, and (iv) early imaging results of an ex-vivo breast cancer specimen. The probe incorporates a single polyvinylidene fluoride acoustic sensor, a 1-to-4 optical fibre bundle and a polycarbonate axicon lens for light delivery. Imaging results on phantoms designed to mimic positive margins demonstrated the ability to detect gaps in optical absorption as small as 1 mm in width. Compared to images from a near full-view PAI system, the hand-held PAI probe had higher signal to noise ratio but suffered from negativity image artifacts. Lumpectomy specimen imaging showed that strong signals can be obtained from the fatty tissue. Taken together, the results show this imaging approach with a hand-held probe has potential for detection of residual breast cancer tissue during BCS; however, more work is needed to reduce the size of the probe to fit within the surgical cavity.


First Expert Evaluation of a New Steerable Catheter in an Isolated Beating Heart.
In previous studies we developed two mechanical prototypes of steerable catheters: the Sigma, which uses joysticks to actuate two steerable tip segments, and the Epsilon, which has a handle that is an enlarged version of the tip. In this study, we present a first performance evaluation of the prototypes in the cardiac environment. The evaluation was carried out by an expert user, an electrophysiologist with over 20 years of experience, to obtain insight in clinically relevant factors. Two experiments were conducted. In the first experiment, the Sigma was used in a passive beating heart setup connected to pumps with a saline solution and camera visualization, and compared with the expert's past experience with conventional steerable catheters. In the second experiment, the Sigma was used in an active beating heart setup with blood perfusion through the coronary arteries and echo visualization, and compared with the Epsilon prototype. The prototype was evaluated through questionnaires on task performance, catheter usability, and workload. After each of the experiments, the catheter characteristics were evaluated via a survey and followed by an in-depth interview. The expert user found the passive beating heart setup to more successful than the active beating heart setup for the purpose of this experiment, with insightful visualization while the heart was in beating condition. The steerability of the prototypes was experienced as useful and clinically relevant. Based on the questionnaires and interview we were able to identify future design improvements and developments for the steerable catheter prototypes.


Relationship among anogenital distance, adrenal gland volume, and penile length and width at 22-36 weeks of pregnancy.
The subject of current work was to determine the relationship of fetal ultrasonographic biomarkers, including anogenital distance (AGD), adrenal gland volume, and penile length and width in mothers with male fetuses at 22-36 weeks of gestation for the assessment of the effect of fetal adrenal gland producing androgens on the male anogenital structures that are exposed to androgen effects as anogenital region and penis. This study is a prospective cross-sectional study conducted in our hospital's outpatient perinatal care unit. One hundred and seventy pregnant women with a male fetus aged 22-36 weeks of gestation were included in the study. The fetal adrenal gland length, width, and depth for the calculation of adrenal volume, AGD, and penile length and width were measured for each participant. The Pearson coefficients were calculated to assess the correlation among these parameters. The adrenal gland volume had a meaningful, positive moderate relationship with both the AGD (r=0.60) and penile length and width (r=0.57 and r=0.59, respectively; p<0.001). The AGD had a positive, strong correlation with the penile length and width (r=0.74 and r=0.76, respectively; p<0.001). The fetal adrenal gland as one of the androgen sources of the fetus is an influencer of the development of the anogenital and penile region. The findings of the current study support that the adrenal gland considerably affects the masculinization of male fetuses, since there were remarkable correlations among the AGD, adrenal gland volume, and penile length and width.


Practical aspects of Boersch phase contrast electron microscopy of biological specimens.
Implementation of physical phase plates into transmission electron microscopes to achieve in-focus contrast for ice-embedded biological specimens poses several technological challenges. During the last decade several phase plates designs have been introduced and tested for electron cryo-microscopy (cryoEM), including thin film (Zernike) phase plates and electrostatic devices. Boersch phase plates (BPPs) are electrostatic einzel lenses shifting the phase of the unscattered beam by an arbitrary angle. Adjusting the phase shift to 90° achieves the maximum contrast transfer for phase objects such as biomolecules. Recently, we reported the implementation of a BPP into a dedicated phase contrast aberration-corrected electron microscope (PACEM) and demonstrated its use to generate in-focus contrast of frozen-hydrated specimens. However, a number of obstacles need to be overcome before BPPs can be used routinely, mostly related to the phase plate devices themselves. CryoEM with a physical phase plate is affected by electrostatic charging, obliteration of low spatial frequencies, and mechanical drift. Furthermore, BPPs introduce single sideband contrast (SSB), due to the obstruction of Friedel mates in the diffraction pattern. In this study we address the technical obstacles in detail and show how they may be overcome. We use X-ray photoelectron spectroscopy (XPS) and Auger electron spectroscopy (AES) to identify contaminants responsible for electrostatic charging, which occurs with most phase plates. We demonstrate that obstruction of low-resolution features is significantly reduced by lowering the acceleration voltage of the microscope. Finally, we present computational approaches to correct BPP images for SSB contrast and to compensate for mechanical drift of the BPP.


Left atrial structural and mechanical remodelling in heart failure with reduced ejection fraction.
In patients with heart failure with reduced ejection fraction (HFrEF), an association between left atrial (LA) dilatation and dysfunction is expected, but the degree of coexistence of the two abnormalities and their relative prognostic role is not known. A total of 626 HFrEF patients formed the study population. All of them underwent a comprehensive echocardiographic evaluation. LA maximal volume was indexed to body surface area (LAVi); LA function was assessed using strain analysis during the reservoir phase: peak atrial longitudinal strain (PALS) analysis. Study primary endpoint was overall mortality or hospitalization for worsening heart failure. Four groups of patients were included in this study according to LAVi (≤34 or >34 mL/m2 ) and PALS (≤23% or >23%); 61 (10%) patients had normal LA volume and function (Group 1), 58 (9%) had LA dilatation but normal function (Group 2), 100 (16%) had normal volume but abnormal function (Group 3), and 407 (65%) had enlarged left atrium and abnormal function (Group 4). PALS was associated with primary endpoint in patients with both normal-size [Groups 1 and 3: hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.88-0.96; P = 0.0006] and dilated left atria (Groups 2 and 4: HR 0.93, 95% CI 0.91-0.96; P < 0.0001). In contrast, LAVi was associated with the primary endpoint in patients with abnormal LA function (Groups 3 and 4: HR 1.018, 95% CI 1.011-1.024; P < 0.00001) but not in those with normal PALS (Groups 1 and 2: HR 1.023, 95% CI 0.99-1.057; P = 0.1). Left atrial dilatation and dysfunction frequently but not invariably coexist. PALS emerged as a significant prognostic parameter in HFrEF even in the absence of LA dilation.


Inhibin A and B in peri- and postmenopause.
The aim of the study was to investigate the origin of inhibin A and B during the last years of the reproductive age and after menopause by measuring their levels in the ovarian and peripheral venous blood. The study population consisted of 43 women, aged 42-69 years (mean 50), who underwent hysterectomy with ovarian removal for a benign disease. A total of 24 of them were in follicular phase, 11 in luteal phase, and eight were postmenopausal. Peripheral and ovarian venous blood was collected for measurement of inhibin A and B. In addition, sex steroid hormone and gonadotropin levels were measured. Ovarian venous inhibin B correlated significantly with ovarian estradiol secretion (r = 0.5, P = 0.001). The levels of inhibin B were significantly higher in the ovarian vein than in the peripheral vein (P = 0.006). The highest inhibin B concentrations were detected in the mid-proliferative (mid-follicular) phase (median 31.6 pg/ml range 25.9-47.9). In postmenopausal women, inhibin B was not detectable. No correlation between FSH and ovarian inhibin B was found. Inhibin A rose rapidly in late proliferative (late follicular) phase (median 28.5, range < 2-51.8) and dominated in the circulation throughout the luteal phase (median 20.9, range 8.8-60). For inhibin A, no concentration gradient existed between the ovarian and peripheral vein. Unlike inhibin B, inhibin A was detectable in ovarian and peripheral blood in postmenopausal women. A significant negative correlation between ovarian and peripheral inhibin A and FSH was found (r = -0.386, P = 0.015; r = -0.345, P = 0.034, respectively). Inhibin B correlates with ovarian estradiol secretion and seems to reflect follicular function. Inhibin A dominates in circulation during the luteal phase but is detectable at low concentrations both in follicular phase and even in postmenopause. Our findings suggest that inhibin A may play a role in FSH suppression in the female reproduction. In addition to the ovary, there may be extragondal source(s) of inhibin A.


[Vaccination, a public health tool].
Vaccination remains a major public health tool, the only one that has enabled the eradication of an infectious disease, smallpox. In this fight, biotechnological innovations point to considerable progress in the development of new vaccines. However, whatever technical progress is made, the impact of a vaccination program will depend on its performance and on the support of the population.


High density lipoprotein levels in children of young men with ischaemic heart disease.
This study was designed to assess HDL levels in children of young men with IHD, compared with children of asymptomatic men. Like their fathers, sons of patients with heart disease, had significantly lower HDL cholesterols than controls. This difference was independent of fasting triglycerides, obesity, diet or physical activity, and was the only "coronary risk factor" in this young age group.


[Establishment and Implementation of Humanistic Nursing Care in Ophthalmic Ward].
To discuss the role of humanistic nursing care in improving the nursing quality and patients' degree of satisfaction in ophthalmic ward. A mode of humanistic nursing care was established, hospital environment was improved and work flow was arranged in details. Nurses received professional training of humanistic care skills. By using multiple educational approaches, nursing care with responsibility system can be delivered in a continuous and seamless manner. The measures of humanistic nursing care were fully implemented. The nurses' communication ability was improved and the nurses worked more actively. The quality of nursing and patients' degree of satisfaction (99%) were equally significantly improved. No mistake occurred and no complaint was received from the patients. Proper application of humanistic care in clinical nursing provides high-quality nursing for patients.


Regulation of mitochondrial fusion and division.
In many organisms, ranging from yeast to humans, mitochondria fuse and divide to change their morphology in response to a multitude of signals. During the past decade, work using yeast and mammalian cells has identified much of the machinery required for fusion and division, including the dynamin-related GTPases--mitofusins (Fzo1p in yeast) and OPA1 (Mgm1p in yeast) for fusion and Drp1 (Dnm1p) for division. However, the mechanisms by which cells regulate these dynamic processes have remained largely unknown. Recent studies have uncovered regulatory mechanisms that control the activity, assembly, distribution and stability of the key components for mitochondrial fusion and division. In this review, we discuss how mitochondrial dynamics are controlled and how these events are coordinated with cell growth, mitosis, apoptosis and human diseases.


Rhizoglyphus robini, a pest mite of saffron, is unable to resist extracellular ice formation.
The saffron mite, Rhizoglyphus robini Claparède (Acari, Astigmata: Acaridae), is one of the most important pests of saffron-producing regions in Iran. It causes yellowing and decreases saffron growth, and finally it destroys the bulbs. In this research, the cold tolerance and supercooling point (SCP) of the saffron mite were measured in three populations and two temperature regimes. Our results showed that the mean SCP of the saffron mite was approximately -14.6 °C without significant difference among the populations. On the contrary, acclimation of the mites significantly decreased their SCP to a mean of approximately -16.5 °C. Exposure of the mites for 24 h to 0 and -2.5 °C had no significant effect on the survival of the mites but when the mites were exposed to -5.0 °C for 24 h, survival of the three populations reached the lowest level of roughly 60%. By 24-h exposure to -7.5 °C, survival of the mites was almost negligible. As a large proportion of mortality was observed above the SCP, and LT50 > SCP, it can be inferred that the saffron mite is likely a chill-susceptible species. This suggests that the saffron mite lacks the ability to withstand extracellular ice formation. Overall, the results of the current study suggest no significant physiological differences between populations of the saffron mite.


Use of anchorchip-time-of-flight spectrometry technology to screen tumor biomarker proteins in serum for small cell lung cancer.
The purpose of this study is to discover potential biomarkers in serum for the detection of small cell lung cancer (SCLC). 74 serum samples including 30 from SCLC patients and 44 from healthy controls were analyzed using ClinProt system combined with matrix-assisted laser desorption/ionization time-of-flight masss spectrometry (MALDI-TOF-MS). ClinProt software and genetic algorithm analysis selected a panel of serum markers that most efficiently predicted which patients had SCLC. The diagnostic pattern combined with 5 potential biomarkers could differentiate SCLC patients from healthy persons, with a sensitivity of 90%, specificity of 97.73%. Remarkably, 88.89% of stage I/II patients were accurately assigned to SCLC. Anchorchip-time-of-flight spectrometry technology will provide a highly accurate approach for discovering new biomarkers for the detection of SCLC.


Development of a framework with specific reference to exit-level outcomes for the education and training of South African undergraduate physiotherapy students.
The aim of the study was to develop a framework for undergraduate programmes for the education and training of physiotherapists in South Africa. The research comprised a literature survey, interviews with United Kingdom physiotherapy educators and departmental workshops in South Africa. The Delphi technique was employed as research method to evaluate the proposed framework. The measuring instrument was a questionnaire comprising of amongst others, statements related to exit-level outcomes, which were rated on a five-point rating scale. Two rounds of the Delphi technique were required before acceptable consensus was reached and a framework for the development of a physiotherapy education and training programme was compiled. The framework has been designed as a benchmark for the development of innovative physiotherapy curricula in South Africa. This paper provides information of the exit-level outcomes specified in the framework.


Studies on histamine H2 receptors coupled to cardiac adenylate cyclase. Effects of guanylnucleotides and structural requirements for agonist activity.
In particulate preparations from guinea-pig ventricle, histamine in the concentration range 10(-6)--10(-3) M caused a 3--5fold stimulation of adenylate cyclase activity which was dependent on the presence of GTP. The effects of fourteen analogs of histamine were examined on this cyclase preparation. Five of the compounds studied proved to be partial agonists relative to histamine while nine others had essentially the same intrinsic activity as histamine. The intrinsic activities of the partial agonists were increased by GppNHp to the extent that dimaprit, which was a partial agonist in the presence of GTP, became a full agonist in the presence of GppNHp. The relative potencies of the full agonists as activators of the cyclase were found to correlate with the relative potencies on physiologically defined H2 receptor systems. Activation of the cyclase by histamine, as well as by several of the agonist analogs, including dimaprit and tolazoline, was completely blocked by the H2 antagonist cimetidine, but was not affected by pharmacologically relevant concentrations of the H1 antagonist mepyramine, the beta-blocker alprenolol, or the alpha-blocker phentolamine. The results suggest that all the agonists studied probably interact with a common H2 receptor site on the cardiac muscle cell leading to activation of adenylate cyclase. The accompanying increase in cyclic AMP is presumably responsible for the chronotropic and inotropic effects of histamine and related compounds on cardiac muscle.


A primary amoebic meningoencephalitis case associated with swimming in seawater.
This case report describes a 62-year-old male fisherman who presented with persistent vomiting, headache, and behavior changes. Despite initial antibiotic and corticosteroid treatment, his condition worsened, leading to coma and subsequent death. Macro-genome sequencing of cerebrospinal fluid (CSF) revealed the presence of Naegleria fowleri infection, which had been missed during initial laboratory tests. The patient's exposure history included sea-swimming near Zhoushan Island.


Antigen processing and intracellular traffic of antigens and MHC molecules.
Antigen processing leads to binding of antigenic peptides to major histocompatibility complex (MHC) molecules, and these peptide-MHC complexes are recognized by T cells. The class I and class II MHC antigen processing pathways employ different mechanisms and patterns of intracellular transport that allow the two classes to bind and present peptides from different subcellular compartments, determining the source and nature of peptides to be presented.


[Bilateral amaurosis after spinal trauma].
This article presents the case of a 72-year-old male patient who suffered severe trauma of the spinal column. The patient developed persistent, bilateral, complete blindness after prolonged emergency neurosurgical treatment in a prone position. A bilateral surgical posterior ischemic optic neuropathy (PION) was diagnosed, which is a rare but severe complication of prolonged non-ocular surgery with circulatory stress. The massive, mostly bilateral, irreversible visual loss up to complete blindness leads to severe and permanent impairment of affected patients.


Pandemics, policy, and pluralism: A Feyerabend-inspired perspective on COVID-19.
We analyse insufficient epistemic pluralism and associated problems in science-based policy advice during the COVID-19 pandemic drawing on specific arguments in Paul Feyerabend's philosophy. Our goal is twofold: to deepen our understanding of the epistemic shortcomings in science-based policy during the pandemic, and to assess the merits and problems of Feyerabend's arguments for epistemic pluralism as well as their relevance for policy-making. We discuss opportunities and challenges of integrating a plurality of viewpoints from within and outside science into policy advice thus contributing to discussions about normative issues concerning evidence and expertise in policy-making.


Mutations in the cell-binding motif of lam-3/laminin α reveal hypercontraction behavior and defective sensitivity to levamisole in Caenorhabditis elegans.
The amino acid sequence Arg-Gly-Asp (RGD) is a cell-binding motif for extracellular matrix proteins. Initially found in fibronectin, the RGD motif is also found in LAM-3/laminin α chain in C. elegans. Laminin, a heterotrimeric glycoprotein, is a significant component of the basement membrane. Mutations in laminin subunits disrupt the extracellular matrix hence inhibit cell adhesion. This study aims to characterize the function of the RGD motif in lam-3/laminin α. Two mutations, lam-3 RGE and lam-3 ΔRGD, were generated. Our analysis of the mutants revealed that the RGD motif is involved in the motility of animals, suggesting that the cell-laminin interaction plays a role in regulating body contraction.


Alcohol-induced drowsiness and vigilance performance.
Detection of signals in a visual vigilance task decreased significantly after drinking 1.2 g of alcohol per kg. Two mechanisms for the detection decrement are discussed.


Neovascular age-related macular degeneration presenting at extremities of age: a comparative study.
To compare the characteristics and response to treatment between patients with NVAMD presenting at the extremities of the AMD age spectrum. Fifty-four eyes of 47 patients were included in this retrospective study, divided by age at NVAMD presentation under 65 (n = 15) or over 85 (n = 39) years. All patients were initially treated with 3 monthly bevacizumab injections, followed by a PRN protocol. Clinical parameters and OCT characteristics were recorded and analyzed at presentation, after the initial 3 monthly injections and at 1 year. At presentation, patients in the young group had significantly higher rates of subretinal fluid (p = 0.005), a polypoidal choroidal vasculopathy-like pattern (p < 0.01) and a history of smoking (p = 0.004). Submacular hemorrhage and pigment epithelial detachments were more common in young patients, and intraretinal fluid was more common in elderly patients (all with borderline statistical significance). VA improved significantly more in the younger patients at 3 months and 1 year (p = 0.001 and 0.002, respectively), despite similar treatment protocols and mean number of injections. Bilateral involvement at baseline was more common in elderly patients (p = 0.008). The differences in OCT characteristics between groups remained throughout the study period. There are considerable differences in the clinical manifestations and response to treatment between NVAMD patients at the extremities of the AMD age spectrum. Different pathophysiological, systemic, and genetic factors may play a role in such patients.


Increased levels of circulating oxidized mitochondrial DNA contribute to chronic inflammation in metabolic syndrome, and MitoQ-based antioxidant therapy alleviates this DNA-induced inflammation.
Here, the aim was to investigate the role of circulating oxidized mitochondrial DNA (ox-mtDNA) in metabolic syndrome (MetS)-associated chronic inflammation and evaluate the effect of Mito-Quinone (MitoQ)-based antioxidant therapy on inflammation. A total of 112 MetS patients and 111 healthy control individuals (HCs) were recruited. Peripheral blood was collected, and mononuclear cells (PBMCs) were separated. In a preclinical study, MitoQ, a mitochondrial-targeted antioxidant, was administered to Sprague-Dawley (SD) rats fed a high-fat diet (HFD). In vitro, H2O2- or MitoQ-treated HUVECs served as the oxidative or antioxidative cell models to detect the cell-free ox-mtDNA level. Plasma or cell-free ox-mtDNA levels were measured by qPCR. Additionally, THP-1 cells were incubated with plasma cell-free DNA (cfDNA) from MetS patients and HCs or cell-free ox-mtDNA to detect TLR9-NF-κB pathway activation. Plasma ox-mtDNA levels and TLR9 expression levels in PBMCs were increased in MetS patients. In vivo, HFD-fed rats showed elevated plasma ox-mtDNA and TLR9 expression levels in cardiac-residing immune cells, but MitoQ administration attenuated these increases. In vitro, a significant lower level of cell-free ox-mtDNA was detected in MitoQ-treated cells, compared with H2O2-treated cells. Coincubation of plasma cfDNA from MetS patients or cell-free ox-mtDNA and THP-1 cells increased TLR9-NF-κB p65 expression, and promoted IL-1β, IL-6 and IL-8 secretion in THP-1 cells. In conclusion, increased circulating ox-mtDNA contributes to chronic inflammation in MetS by activating the TLR9-NF-κB pathway. MitoQ-based antioxidant therapy effectively alleviates inflammation by reducing ox-mtDNA release.


Fibronectin involvement following herpes simplex infection of cultured rat astrocytes.
To evaluate the potential impact of a strongly neurotropic virus on the matricial fibronectin (FN) of a given neural cell type, first subculture of rat astrocytes were inoculated with either a low (0.1-0.5) or a high MOI (10-100) of Herpes simplex virus-type 1 (HSV-1). Infected samples, as well as matched controls, were harvested from 12 to 72 h post-inoculation and processed for extracellular FN labeling by the peroxidase-antiperoxidase (PAP) method. Following low MOI, multinucleated cell formation and syncytial development drastically modified peripheral FN, since the typical loose network was largely replaced by a patch-like appearance. At high MOI, when viral action caused further cytoplasmic retraction leading to rounded or stellate cells, the FN pattern was remarkably altered, even with total FN loss around highly retracted cells. It may be concluded that a virus such as HSV-1, capable of modifying astrocyte morphology, induces a redistribution or loss of pericellular FN.


Interaction of the rumen fungus Orpinomyces joyonii with Megasphaera elsdenii and Eubacterium limosum.
The degradation and fermentation of microcrystalline cellulose were studied in monoculture of the polycentric anaerobic fungus Orpinomyces joyonii and in co-cultures with the rumen bacteria Megasphaera elsdenii and Eubacterium limosum. More than 25% of cellulose hydrolysis products (glucose and cellodextrins) were released by the fungus into the medium after 8 d of cultivation. These products were metabolized by bacteria in mixed cultures. In co-culture with the fungus M. elsdenii and E. limosum increased the extent of microcrystalline cellulose degradation by 10.12% and 7.96%, respectively. Biomass yield in co-cultures was increased by 89.9% and 59.4% for M. elsdenii and E. limosum. Y cellulose for fungus alone was 52.29 g dry matter mol-1 glucose. These values were 64.93 and 55.92 g mol-1 glucose unit in co-culture with M. elsdenii and E. limosum, respectively.


Prevalence of antimicrobial-resistant Cutibacterium isolates and development of multiplex PCR method for Cutibacterium species identification.
Cutibacterium species such as C. acnes, C. avidum, and C. granulosum are known anaerobic skin inhabitants and often cause surgical site infections. These species are genetically similar and are difficult to identify rapidly. In addition, their pathogenicity and antimicrobial resistance remain unknown. In this study, antimicrobial resistance in Cutibacterium isolates was studied and a multiplex PCR method for their identification was developed. A total of 497 C. acnes, 71 C. avidum, and 25 C. granulosum strains which were isolated from the acne pustule and infectious regions, were used. The antimicrobial resistance rates of C. acnes, C. avidum, and C. granulosum strains isolated from patients with acne vulgaris were higher than those of strains isolated from patients with infectious diseases. In particular, macrolide-clindamycin-resistant strains were isolated most frequently from all species. Among the resistant strains, strains with 23S rRNA mutations were the most common in C. acnes (24.3%, 71/292), whereas C. avidum and C. granulosum strains were most frequently found with erm(X). For the first time, a C. granulosum strain carrying pTZC1, which codes erm(50) and tet(W), was isolated from patients with acne vulgaris. Regarding the rapid identification of causative pathogens from infectious regions, three Cutibacterium species were identified with 100% sensitivity and specificity using multiplex PCR method. Our data showed that antimicrobial resistance differed among Cutibacterium species. The multiplex PCR method may contribute to the rapid detection of Cutibacterium species and selection of appropriate antimicrobial agents.


Multisensory integration in the superior colliculus: a neural network model.
Neurons in the superior colliculus (SC) are known to integrate stimuli of different modalities (e.g., visual and auditory) following specific properties. In this work, we present a mathematical model of the integrative response of SC neurons, in order to suggest a possible physiological mechanism underlying multisensory integration in SC. The model includes three distinct neural areas: two unimodal areas (auditory and visual) are devoted to a topological representation of external stimuli, and communicate via synaptic connections with a third downstream area (in the SC) responsible for multisensory integration. The present simulations show that the model, with a single set of parameters, can mimic various responses to different combinations of external stimuli including the inverse effectiveness, both in terms of multisensory enhancement and contrast, the existence of within- and cross-modality suppression between spatially disparate stimuli, a reduction of network settling time in response to cross-modal stimuli compared with individual stimuli. The model suggests that non-linearities in neural responses and synaptic (excitatory and inhibitory) connections can explain several aspects of multisensory integration.


Effect of angiotensin II on RNA synthesis by isolated nuclei.
Peptide hormones are known to bind to cell surface receptors as the first step in the generation of their effects on target tissues. However, it remains uncertain whether internalized hormone might also play a role in the production of longterm or trophic effects of peptide hormones. Because the peptide hormone angiotensin II appears to be internalized by target cells, we studied the effect of this peptide on isolated hepatic nuclei. At both 5 X 10(-7)M and 5 X 10(-9)M, angiotensin II significantly increased RNA synthesis. This effect was not mimicked by Sar1-Ala8-angiotensin II (saralasin) or the unrelated nonapeptide teprotide.


Decreases of cortical and thalamic glucose metabolism produced by parietal cortex stimulation in the rat.
Parietal cortex stimulation elicited focal decreases as well as increases of brain glucose metabolism in ipsilateral cortex, ipsilateral thalamus, and contralateral cortex of rats in a pattern resembling 'surround inhibition'. It is proposed that parietal stimulation activated inhibitory circuits which decreased cortical and thalamic glucose metabolism. This decrease of cerebral glucose metabolism is important for interpreting brain glucose metabolic studies particularly when metabolic changes do not correlate with changes of neuronal activity.


Elevated phosphorylation of estrogen receptor α at serine-118 in ovarian endometrioma.
To evaluate the phosphorylation of estrogen receptor α at serine-118 (phospho-ERα S118) in the endometrium, ovarian endometrioma, and deep infiltrating endometriosis (DIE). Experimental study. University-affiliated hospital and academic research laboratory. Twenty-five patients underwent a hysterectomy, 18 patients underwent surgical removal of ovarian endometrioma, and 6 patients underwent DIE. Tissue samples were obtained from patients who underwent surgical procedures. Immunostaining for phospho-ERα S118, ERα, or phosphorylated p44/42 mitogen-activated protein kinase (phospho-p44/42 MAPK) was performed to evaluate the endometrium with or without endometriosis, ovarian endometrioma, and DIE. For in vitro analysis, endometrial epithelial cells (Ishikawa cells) were stimulated with estradiol (E2) or tumor necrosis factor alpha (TNFα), and the expression levels of phospho-ERα S118 and phospho-p44/42 MAPK were evaluated via Western blotting. First, phospho-ERα S118 level was significantly higher in the glands and stroma of ovarian endometriosis samples than in those of endometrial and DIE samples. Second, colocalization of phospho-p44/42 MAPK and phospho-ERα S118 was observed in the glands of ovarian endometrioma. The proportions of cells strongly expressing phospho-p44/42 and phospho-ERα were 87% in phosphor-p44/42 MAPK-positive cells and 79% in phosphor-ERα-positive cells. Third, E2 stimulation significantly enhanced phospho-ERα S118 after 15 and 30 minutes in in vitro analysis using endometrial epithelial cells. Fourth, TNFα stimulation modestly but significantly enhanced phospho-ERα S118 after 15 and 30 minutes. Fifth, in Ishikawa cells, treatment with a p44/42 inhibitor (PD98059) significantly reduced phospho-ERα S118 by TNFα but not by E2. ERα-S118 phosphorylation was increased in ovarian endometriosis. Our findings may provide a new perspective for understanding the mechanism of increased ERα action in the pathophysiology of endometriosis.


Neuromuscular ultrasonography: quantifying muscle and nerve measurements.
Neuromuscular ultrasonography can be used both descriptively and quantitatively in the evaluation of patients with neuromuscular disorders. This article reviews the quantitative use of this technology, particularly measurements of the size and echogenicity of nerve and muscle, as a tool for assessing the severity, progression, and response of these tissues to therapeutic interventions. Neuromuscular ultrasonography has several features, including portability and noninvasiveness, that make it an attractive research tool for advancing the diagnosis and treatment of neuromuscular disorders.


Mood and anxiety disorders among inpatients of a university hospital in Turkey.
The aim of the study was to assess the prevalence of mood and anxiety disorders among inpatients and the relationship between sociodemographic factors, medical illnesses and treatments. In the present study, we selected 650 inpatients from all clinics except psychiatry and pediatrics in a general hospital by a simple random sampling method. Based on the exclusion criteria, 57 patients were excluded. Mood and anxiety disorders were determined by means of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Of the participants, 226 (37.5%) had a psychiatric disorder, 87 (14.4) had a mood disorder and 146 (24.2%) had an anxiety disorder. The most common specific diagnoses were not otherwise specified as anxiety disorder (9.5%), major depression (8.6%) and generalized anxiety disorder (7.6%). While the overall prevalence was highest in the hematology clinic (60.0%), it was lowest in the clinic of infectious diseases (22.7%). Logistic regression analysis indicated that the independent factors associated with psychiatric disorders were being of the female gender and a personal history of psychiatric disorders. In conclusion, results of the present study suggest that mood and anxiety disorders were frequently observed among inpatients, particularly in female patients and those with an individual history of psychiatric disorder. Successful treatment of these disorders may positively contribute to the course of the disease in inpatients. However, this assumption should be confirmed by further studies.


RhoA/ROCK I signalling downstream of the P2Y13 ADP-receptor controls HDL endocytosis in human hepatocytes.
Cell surface receptors for high-density lipoprotein (HDL) on hepatocytes are major partners in the regulation of cholesterol homeostasis. We have previously demonstrated on human hepatocytes that apolipoprotein A-I binding to an ectopic F(1)-ATPase stimulates the production of extracellular ADP that activates a P2Y(13)-mediated high-density lipoprotein (HDL) endocytosis pathway. However, P2Y(13)-dependent signalling pathway has never been described yet. The current study demonstrates a major role of cytoskeleton reorganization in F(1)-ATPase/P2Y(13)-dependent HDL endocytosis under the control of the small GTPase RhoA and its effector ROCK I. Indeed human hepatocytes (HepG(2) cells) stimulated by ADP or AR-C69931MX (both P2Y(13) agonists) showed a high specific activation of RhoA; in addition, inhibition of Rho proteins by C3 exoenzyme impairs HDL endocytosis whereas a constitutively active form of RhoA stimulates HDL endocytosis at the same level as under F(1)-ATPase/P2Y(13) activation. Pharmacological inhibition of ROCK activity decreased HDL endocytosis following stimulation by apoA-I (F(1)-ATPase ligand), ADP or AR-C69931MX and specific siRNA ROCK I extinction prevented the stimulation of HDL endocytosis without effect of ROCK II extinction. The functional involvement of ROCK I downstream F(1)-ATPase/P2Y(13) was confirmed by the strong enrichment of the membrane fraction in ROCK I and by the requirement of actin polymerization in hepatocyte HDL endocytosis. These results allow the identification of the molecular events downstream P2Y(13) receptor activation for a better understanding of hepatocyte HDL endocytosis, the latest step in reverse cholesterol transport.


Pharmacokinetics of orally and intravenously administered cyclosporine in pre-kidney transplant patients.
The pharmacokinetics of cyclosporine (CSA) and four metabolites were evaluated in eight hemodialysis subjects awaiting renal transplantation to compare metabolic patterns with those observed in post-transplant patients and normal volunteers. Each subject received a single 4-mg/kg intravenous and a single 10-mg/kg oral dose separated by a 1-week washout period. Blood samples were collected before and at .5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, and 24 hours after CSA dosing. Cyclosporine blood, plasma, and metabolite (M17, M1, M18, M21) levels were determined by high-pressure liquid chromatography. Mean (+/- standard deviation) CSA blood clearance was .47 +/- .15 L/hour/kg, steady-state volume of distribution (Vss) was 1.9 +/- .5 L/kg, and mean residence time (MRT) was 4.4 +/- 1.8 hours after intravenous dosing. With plasma, mean clearance was .70 +/- .31 L/hour/kg, Vss was 2.4 +/- 1.2 L/kg, and MRT was 3.7 +/- 2.2 hours. Cyclosporine bioavailability (F) averaged 24 +/- 11 and 24 +/- 15%, using blood and plasma, respectively. Values for clearance and Vss were approximately 30 to 100% greater than comparable estimates in healthy volunteers, but F and MRT were not altered to this extent. These changes might be explained on the basis of decreased protein binding in uremic patients. The area under the curve ratio for M17 and M1 to CSA increased an average of 1.7- and 3.9-fold, respectively, after oral dosing compared with intravenous administration, indicating increased conversion during first-pass metabolism.


Degradation of bisphenol-A (BPA) in the presence of reactive oxygen species and its acceleration by lipids and sodium chloride.
In this study, (1) change in bisphenol-A (BPA) leached from polycarbonate (PC) tube to water samples at 37 degrees C, (2) effect of reactive oxygen species (ROS) produced by Fenton reaction on BPA recovery and thiobarbituric acid (TBA) value with or without generally existing environmental substances such as alcohol, lipids and NaCl, were investigated. Amounts of BPA leached from PC tube to water samples containing lipids possessing unsaturated fatty acid with high TBA values were significantly lower than the amount of BPA to water only, and addition of NaCl to lipid containing water further decreased BPA concentration. The result indicates that BPA could be degraded by lipoperoxides formed by auto-oxidation of lipid, and NaCl plays an important role in BPA degradation. In the presence of ROS, BPA recovery was the lowest in water and addition of EtOH increased in both BPA recovery and TBA value, suggesting that EtOH could play a role as scavenger of ROS on the oxidative BPA degradation. Furthermore, the higher the concentration of lipid and/or NaCl, the lower the BPA recovery and TBA value. Physiologically and environmentally important concentrations of NaCl could enhance oxidative degradation of BPA in the presence of ROS.


Targeting the lung epithelium after intravenous delivery by directed evolution of underexplored sites on the AAV capsid.
Advances in adeno-associated virus (AAV) engineering have provided exciting new tools for research and potential solutions for gene therapy. However, the lung has not received the same tailored engineering as other major targets of debilitating genetic disorders. To address this, here we engineered the surface-exposed residues AA452-458 of AAV9 capsid proteins at the three-fold axis of symmetry and employed a Cre-transgenic-based screening platform to identify AAV capsids targeted to the lung after intravenous delivery in mice. Using a custom image processing pipeline to quantify transgene expression across whole tissue images, we found that one engineered variant, AAV9.452sub.LUNG1, displays dramatically improved transgene expression in lung tissue after systemic delivery in mice. This improved transduction extends to alveolar epithelial type II cells, expanding the toolbox for gene therapy research for diseases specific to the lung.


Robot-assisted thymectomy is superior to transsternal thymectomy.
Complete thymectomy is the procedure of choice in the treatment of thymomas and in treating selected patients with myasthenia gravis. Transsternal thymectomy is the gold standard for most patients. Robot-assisted thymectomy has emerged as an alternative to open transsternal surgery. The goal of this study was to compare perioperative outcomes in patients who underwent transsternal or robot-assisted thymectomy. We performed a retrospective review of all patients who underwent robot-assisted or transsternal thymectomy at our institution from February 2001 to February 2010. Data are presented as mean ± SD. Significance was set as P < 0.05. Fifty patients underwent either transsternal (n = 35) or robot-assisted (n = 15) thymectomy. Patient demographics and the incidence of myasthenia gravis were similar between groups. There were no intraoperative complications or conversions to open surgery in the robot-assisted group. Intraoperative blood loss was significantly higher in the transsternal group (151.43 vs. 41.67 ml, P = 0.01). There were 20 postoperative complications and 1 postoperative death in the transsternal group and 1 postoperative complication in the robot-assisted group (P = 0.001). Hospital length of stay was 4 days (range 2-27 days) in the transsternal group and 1 day (range 1-7 days) in the robot-assisted group (P = 0.002). Robot-assisted thymectomy is superior to transsternal thymectomy, reducing intraoperative blood loss, postoperative complications, and hospital length of stay. Further investigation of the long-term oncologic results in thymoma patients and long-term remission rates in patients with myasthenia gravis who underwent robot-assisted thymectomy is warranted.


FAO/INFOODS food composition database for biodiversity.
Nutrient content can vary as much between different varieties of the same foods, as they do among different foods. Knowledge of varietal differences can therefore mean the difference between nutrient adequacy and inadequacy. The FAO/INFOODS food composition database for biodiversity has been developed with analytical data for foods described at the level of variety, cultivar and breed, and for underutilized and wild foods. It contains 6411 food entries and values for 451 components together with the bibliographic references and other information. The database is in MS Excel format and can be downloaded free-of-charge from the INFOODS website http://www.fao.org/infoods/biodiversity/index_en.stm. It is intended to annually publish new editions, making these data available for national and regional food composition databases. This database could be used to raise the awareness, promote and investigate food biodiversity and help to better estimate nutrient intakes.


WWOX inhibition by Zfra1-31 restores mitochondrial homeostasis and viability of neuronal cells exposed to high glucose.
Diabetes has been associated with an increased risk of cognitive decline and dementia. However, the mechanisms underlying this association remain unclear and no effective therapeutic interventions exist. Accumulating evidence demonstrates that mitochondrial defects are a key feature of diabetes contributing to neurodegenerative events. It has also been demonstrated that the putative tumor suppressor WW domain-containing oxidoreductase 1 (WWOX) can interact with mitochondria in several pathological conditions. However, its role in diabetes-associated neurodegeneration remains unknown. So, this study aimed to evaluate the role of WWOX activation in high glucose-induced neuronal damage and death. Our experiments were mainly performed in differentiated SH-SY5Y neuroblastoma cells exposed to high glucose and treated (or not) with Zfra1-31, the specific inhibitor of WWOX. Several parameters were analyzed namely cell viability, WWOX activation (tyrosine 33 residue phosphorylation), mitochondrial function, reactive oxygen species (ROS) production, biogenesis, and dynamics, autophagy and oxidative stress/damage. The levels of the neurotoxic proteins amyloid β (Aβ) and phosphorylated Tau (pTau) and of synaptic integrity markers were also evaluated. We observed that high glucose increased the levels of activated WWOX. Interestingly, brain cortical and hippocampal homogenates from young (6-month old) diabetic GK rats showed increased levels of activated WWOX compared to older GK rats (12-month old) suggesting that WWOX plays an early role in the diabetic brain. In neuronal cells, high glucose impaired mitochondrial respiration, dynamics and biogenesis, increased mitochondrial ROS production and decreased mitochondrial membrane potential and ATP production. More, high glucose augmented oxidative stress/damage and the levels of Aβ and pTau proteins and affected autophagy, contributing to the loss of synaptic integrity and cell death. Of note, the activation of WWOX preceded mitochondrial dysfunction and cell death. Importantly, the inhibition of WWOX with Zfra1-31 reversed, totally or partially, the alterations promoted by high glucose. Altogether our observations demonstrate that under high glucose conditions WWOX activation contributes to mitochondrial anomalies and neuronal damage and death, which suggests that WWOX is a potential therapeutic target for early interventions. Our findings also support the efficacy of Zfra1-31 in treating hyperglycemia/diabetes-associated neurodegeneration.


Heterogeneity of amino acid transport in horse erythrocytes: a detailed kinetic analysis of inherited transport variation.
1. Thoroughbred horses were divisible into five distinct amino acid transport subgroups on the basis of their erythrocyte permeability to L-alanine, measured uptake rates ranging from 5 to 625 mumol l cells-1 h-1 (0.2 mM-extracellular L-alanine, 37 degrees C). 2. Erythrocytes from animals belonging to the lowest L-alanine permeability subgroup (5-15 mumol l cells-1 h-1) (transport-deficient type) exhibited slow nonsaturable transport of this amino acid. In contrast, cells from horses of the four transport-positive subgroups possessed additional high-affinity (apparent L-alanine Km (Michaelis constant) congruent to 0.3 mM) and/or low-affinity (apparent L-alanine Km congruent to 13 mM) Na+-independent transport routes selective for L-neutral amino acids of intermediate size. The two transporters, designated systems asc1 and asc2, respectively, also possessed a significant affinity for dibasic amino acids. 3. Amino acid transport activity in horse erythrocytes behaved as if controlled by three co-dominant alleles (s, h and l), where s is a silent allele, and h and l code for the functional presence of systems asc1 and asc2, respectively. 4. At physiological temperature, system asc1 operated preferentially in an exchange mode. In contrast, system asc2 did not participate in exchange reactions at 37 degrees C, but did exhibit significant trans-acceleration at 25 degrees C. 5. Reduction of the incubation temperature also resulted in dramatic decreases in apparent Km and Vmax for L-alanine uptake by system asc2, whereas the effects of temperature on system asc1 were much less marked. At 5 degrees C the two transporters exhibited equivalent kinetic constants for L-alanine influx. L-Alanine uptake by transport-deficient cells was relatively insensitive to temperature. Influx by this route may represent the ground-state permeability of the lipid bilayer. 6. The effects of low temperature on system asc2 suggest a preferential impairment of the mobility of the unloaded carrier relative to that of the loaded transporter. Similarly, the different kinetic properties of systems asc1 and asc2 at physiological temperature are attributed to a difference in the mobilities of the empty carriers, this difference being minimized at 5 degrees C.


Postoperative functional voice changes after conventional open or robotic thyroidectomy: a prospective trial.
To use objective and subjective voice function analysis to compare outcomes in patients who had undergone conventional open thyroidectomy or robotic thyroidectomy. The study involved 88 consecutive patients who underwent thyroid surgery between May 2009 and December 2009; 46 patients underwent a conventional open thyroidectomy, and 42 underwent a robotic thyroidectomy. Auditory perceptual evaluation was used to make subjective assessments of voice function, and videolaryngostroboscopy, acoustic voice analysis with aerodynamic study, electroglottography, and voice range profile were used to make objective assessments. Each assessment was made before surgery, and at 1 week and 3 months after surgery. The conventional open and robotic thyroidectomy groups were similar in terms of age, gender ratio, and disease profile. We found that 18 (20.5%) of the 88 patients showed some level of voice dysfunction at 1 week after surgery; that the dysfunction resolved by 3 months after surgery in all cases; and that it was not permanent according to postoperative videolaryngostroboscopy. The conventional open and robotic thyroidectomy groups were found to have similar levels of dysfunction at 1 week after surgery, except for jitter, which was greater in the robotic group. For both groups, any such dysfunction spontaneously resolved by 3 months after surgery, and there were no significant differences between the groups in terms of any voice function parameter. Voice dysfunction was present after both open and robotic thyroidectomy (without any evident laryngeal nerve injury). However, function subsequently normalized to preoperative levels at 3 months after surgery in both groups. Voice function outcomes after robotic thyroidectomy are similar to those after conventional open thyroidectomy.


Draft genome sequence of the virulent strain 01-B526 of the fish pathogen Aeromonas salmonicida.
Aeromonas salmonicida is an important fish pathogen, mainly of salmonids. This bacterium causes a disease named furunculosis, which is particularly detrimental for the aquaculture industry. Here, we present the draft genome sequence of A. salmonicida 01-B526, a strain isolated from a brook trout that is more virulent than A. salmonicida reference strain A449, for which a genome sequence is available.


Suppression of ovarian function by LHRH and its analogues in pregnant rats.
1. LHRH and its analogues, when infused continuously at the doses that inhibit ovum implantation, reduced serum concentration of progesterone in pregnant rats. The progesterone concentration fell between Days 3 and 4 of pregnancy in rats treated with LHRH and Analogue I (Des-Gly10-LHRH-ethylamide), but fell between Days 4 and 5 in rats treated with Analogue II [Des-Gly10-(D-Ala6)-LHRH-ethylamide]. 2. Ovarian LH/hCG receptor levels were markedly reduced in rats treated with LHRH and its analogues in the first week of pregnancy. 3. Continuous infusion of LH to pregnant rats did not reduce the serum concentration of progesterone even with the highest dose that inhibited implantation. Interruption of pregnancy by LH appears to be due to excessive secretion of estrogen as indicated by uterine swellings, presence of large follicles in the ovaries, and absence of free blastocysts in the uterine lumen. Thus, the antifertility effects of LHRH and its analogues were not reproduced by LH administration.


Persistent post-enteritis diarrhoea.
Clinical, biochemical, and gastroenterological data have been examined im 48 patients in two age groups, one under 12 months of age, the other between 12 and 30 months with persistent post-enteritis diarrhoea. In these patients, the illness consisted of chronic diarrhoea which followed acute enteritis. It brought about a mild malabsorption syndrome with impairment of growth, particularly in infants under one year of age. Chronic inflammation with mucosal damage due to alteration of the intestinal microflora by inappropriate diets and therapy seemed to be the cause of persistent diarrhoea in these patients.


Persistent HIV-controllers are more prone to spontaneously clear HCV: a retrospective cohort study.
HIV-controllers have the ability to spontaneously maintain viraemia at low or undetectable levels in the absence of antiretroviral treatment. Furthermore, HIV-controllers seem to have a superior capacity to spontaneously clear hepatitis C virus (HCV) compared to non HIV-controllers. Some of these subjects eventually lose HIV-controller status (transient controllers), whereas some HIV-controllers show a persistent natural HIV control (persistent controllers). We aimed to analyse whether persistent controllers have superior capacity to spontaneously clear HCV compared to transient controllers. We recruited HIV-controllers from January 1981 up to October 2016 with available antibodies to HCV (anti-HCV) data (n = 744). Factors associated with HIV spontaneous control in relation to HCV status were analysed in persistent and transient HIV-controllers with anti-HCV positive (n = 202 and n = 138 respectively) in comparison with 1700 HCV positive non HIV-controllers recruited from January 1981 up to March 2018, bivariate and multivariate analyses, following a logistic regression model, were applied. In addition, the factors related to the loss and time to lose HIV-controller status were explored (n = 744) using Log rank test and Kaplan-Meier curves, in this case the multivariate analysis consisted in a Cox regression model. A higher frequency of HCV spontaneous clearance was found in persistent HIV-controllers (25.5%) compared to non-controllers (10.2%). After adjusting for potential confounders, as sex, age, HIV transmission risk, CD4+ T-cell nadir and time of follow-up, HCV clearance was independently associated with persistent HIV spontaneous control (p = 0.002; OR (95% CI) = 2.573 (1.428 to 4.633)), but not with transient spontaneous control (p = 0.119; 1.589 (0.888 to 2.845)). Furthermore, persistent HIV-controllers were more likely to spontaneously clear the HCV in comparison with transient controllers (p = 0.027; 0.377 (0.159 to 0.893). Finally, not to lose or lengthen the time of losing this control was independently associated with HCV spontaneous clearance (p = 0.010; 0.503 (0.297 to 0.850). This study shows an association between spontaneous persistent HIV-control and HCV spontaneous clearance. The study findings support the idea of preserved immune mechanisms in persistent HIV control implicated in HCV spontaneous clearance. These results highlight persistent HIV-controllers but not transient controllers as a good model of functional HIV cure.


Retrospective genetic analysis of SAT-1 type foot-and-mouth disease outbreaks in southern Africa.
In areas where foot-and-mouth disease (FMD) is endemic in wildlife hosts, such as the Kruger National Park (KNP) in South Africa, control measures are in place that ensure that potentially infected antelope and buffalo do not come into close contact with domestic animals. In South Africa several SAT-1 outbreaks occurred nearly simultaneously in cattle and impala between 1971-1981. Phylogenetic analysis based on partial 1D gene nucleotide sequencing indicated that several of these outbreaks were linked and it is probable that disease spread from the intermediary impala antelope host to cattle in close proximity. Evidence was found for the involvement of viruses from a single KNP genotype in precipitating outbreaks in impala over a 10-year period. In addition, several unrelated outbreaks affecting cattle and impala occurred within a single year. Characterisation of outbreak strains from Botswana similarly revealed that a single genotype affected different species over a 10-year period and that transboundary spread of SAT-1 virus occurred on at least one occasion. This retrospective analysis of outbreak strains has clearly demonstrated that FMD control policies that address the role of antelope as intermediaries in disease transmission are crucial as these wildlife species play an important role in disease dissemination.


An Argument for an Ecosystemic AI: Articulating Connections across Prehuman and Posthuman Intelligences.
As an art collective Cesar & Lois develops projects that examine sociotechnical systems, attempting to challenge anthropocentric technological pathways while linking to intelligences sourced in biological circuitry. As artists we imagine new configurations for what we understand as (social, economic, technological) networks and intelligences. With this ecosystemic approach we consider the possibility of an artificial intelligence (AI) that supports well-being in a broad sense, accommodating relationships across different layers of living worlds and involving local and global communities of all kinds. This thinking is grounded in research by theorists across disciplines, including communications and media theory, microbiology, anthropology, decolonial studies, social ecology, sociology and environmental psychology. At a time when human beings and their ecosystems face grave threats due to climate change and a global pandemic, we are rethinking the basis for our AIs, and for the resulting decision-making on behalf of societies and ecosystems. Creative projects by Cesar & Lois provide alternative conceptual models for thinking across networks, reframing the artists' and potentially viewers' understanding of what motivates and shapes societies. Referencing a series of artworks and the theories that underpin them, this article envisages a sociotechnical framework that takes into account ecosystems and challenges the philosophical orientations that guide society. Degenerative Cultures is an artwork in which the artists overlap microbiological organisms, AI and human systems as a speculative restructuring of networks across human and nonhuman entities. The push for ecosystemic technologies and intelligences is linked to the expansion of community to include planetary constituents, such as nonhuman beings and environments. The artists posit that such ecosystemic networks would be capable of taking into account the planet's human societies as well as nonhuman species and their environments, broadening the concept of community well-being and shifting the technological architecture to meet the complex needs of the planet and its constituent parts. The experimental series, [ECO]nomic Revolution, layers Physarum polycephalum, or slime mold, over the mapped demographics of human cities. The species polycephalum references multi-brains, and implies a decentralized logic, which for the non-neurological microbiological network translates to the sharing of nutrients and regulated growth across a culture. Assuming a perspective based in the arts, this proposition imagines a shift from the dominant conceptions of AI as an individual intelligence and frames it as part of a network that necessarily includes ecosystems. We envision the creation of sociotechnical systems that could be modeled on networked lifeforms that have optimized themselves across millions of years, like the organism Physarum polycephalum, which occurs globally in moist environments, or like those microbial populations within and outside of human bodies, whose percussive biological processing interacts with and alters many layers of lifeforms. We argue that an environmentally responsive intelligence based on relationships across living systems potentially serves a broad community composed of diverse human populations, nonhuman beings and ecosystems.


Further characterization and immunochemical studies on the carbohydrate specificity of jackfruit (Artocarpus integrifolia) lectin.
The lectin from jackfruit (Artocarpus integrifolia) seeds has been purified by Rivanol (6,9-diamino-2-ethoxyacridine lactate) treatment. The specific activity, molecular weights of parent lectin and its subunit, its glycoprotein nature, and hemagglutination-inhibition assays suggest that this preparation is identical to that obtained by affinity chromatography on melibiose-agarose adsorbent (Ahmed, H., and Chatterjee, B. P. (1986) in Lectins, Biology, Biochemistry, Clinical Biochemistry (Bøg-Hansen, T. C., and van Driessche, E., eds) Vol. 5, pp. 125-133, Walter de Gruyter, New York). The lectin strongly agglutinates human and several animal erythrocytes. The lectin contains five isolectins of pI values 7.1, 6.85, 5.5, 5.3, and 5.1. It is thermally stable and loses its activity above 75 degrees C. The hemagglutinating activity remains unchanged in the presence of bivalent cations viz., Ca2+, Mg2+, Mn2+, etc. It is a metalloprotein. The lectin retains its activity by dialysis with acetic acid followed by EDTA. It agglutinates Ehrlich ascites cells. Equilibrium dialysis of lectin with melibiose and quenching of fluorescence of 4-methylumbelliferyl-alpha-D-galactopyranoside by the lectin show that homotetrameric jackfruit lectin has two sugar-binding sites. The lectin precipitates well several galactomannans and glycoproteins having terminal D-Gal-alpha-(1----6)- or D-Gal-beta-(1----3)-D-GalNAc residues. It hardly or does not precipitate polysaccharides having terminal D-Gal-alpha-(1----3) residues. Quantitative precipitin-inhibition studies using various haptens suggest that the -OCH2- group at C-1 and -OH groups at C-4 and partially at C-6 in the alpha-glycoside of D-galactose configuration are important for lectin-sugar interaction.


Thoracic electrical impedance and fluid balance during aortic surgery.
Indices of fluid balance were evaluated during and after aortic surgery in 16 consecutive patients. Thoracic electrical impedance (TI), heart rate (HR), central venous (CVP), pulmonary artery mean (PAMP), pulmonary wedge (PWP) and mean arterial (MAP) pressure as well as fourteen arterial and venous blood gas variables were followed. Consistent with a reduction of T1 by 4.2 (-5.2 to 9.2) Ohm (median and range) during the operation, fluid balance was in excess of 1.8 (-0.1 to 3.3) 1 when evaporation was not taken into account, and it remained elevated by 1.3 (0.0 to 5.4) 1 on the first postoperative morning. The HR, MAP and PWP remained stable, while CVP and PAMP decreased by 6 (-2 to 13) and 6 (-1 to 22) mmHg, respectively. Of the determined variables only TI revealed a meaningful correlation to fluid balance (rho = -0.41; P < 0.01). Haemoglobin concentrations increased in proportion to the administered packed erythrocytes, while arterial oxygen saturation, pH and base excess decreased in proportion to the excess fluid. The results indicate that while central venous and pulmonary artery mean pressures gave the impression of a volume deficit, the positive fluid balance was mirrored by thoracic electrical impedance, and that even a minor increase of fluid balance may affect pulmonary function in patients subjected to aortic surgery.


Late Kidney Effects of Nephron-Sparing vs Radical Nephrectomy for Wilms Tumor: A Systematic Review and Meta-Analysis.
We compare differences in long-term kidney function between patients undergoing either radical nephrectomy (RN) or nephron-sparing surgery (NSS) in unilateral and bilateral Wilms tumor (WT), respectively. A systematic search was performed in September 2020. Comparative studies were evaluated according to Cochrane collaboration recommendations. Assessed long-term (>1-year postoperative) outcomes included chronic kidney disease, hypertension and glomerular filtration rate, among others. Odds ratio and mean difference with 95% confidence interval were extrapolated from available data for quantitative synthesis. Random-effects meta-analysis and meta-regression were performed according to study design and techniques. The systematic review was prospectively registered on PROSPERO (CRD42020205378). A total of 23 studies describing 293 cases of unilateral WT and 386 cases of bilateral WT were included in the qualitative synthesis. Overall effect estimates demonstrate that patients undergoing RN have significantly increased odds of developing abnormal kidney function (OR 4.29, 95% CI 1.02, 18.00) and lower estimated glomerular filtration rate at long-term followup (mean difference -8.99, 95% CI -16.40, -1.58) compared to those undergoing NSS. In bilateral WT, patients undergoing RN with contralateral NSS have higher odds of developing abnormal kidney function (OR 3.82, 95% CI 1.76, 8.33) and hypertension (OR 5.81, 95% CI 1.31, 25.68) compared to bilateral NSS. Current evidence is low quality but suggests that NSS for unilateral and bilateral WT may be associated with better kidney function or blood pressure at late followup. Further research to investigate sources of heterogeneity is recommended.


From Jenner to genes--the next generation of virus vaccines.
Vaccination has played a major role in the control of many virus diseases affecting man and animals. Two kinds of vaccines are in use: (i) attenuated vaccines, which infect the host without causing disease and (ii) killed vaccines, which consist of large amounts of virus particles that have been inactivated by either physical or chemical agents under conditions that ensure retention of their antigenic properties. Despite the success of vaccination there is still a need for products that are safer and more effective. Even more important, there are diseases for which 'conventional' vaccines are not available. New approaches that will ultimately solve these problems have been provided by the detailed analysis of viruses at the molecular level. Thus we are now beginning to understand virulence in molecular terms and particularly rapid advances have been made with poliovirus, holding out the promise of a completely avirulent attenuated vaccine. With killed vaccines, the major advance has come from the recognition that the immune response to most viruses is determined by a single protein. By identifying the genes coding for these proteins it has become possible to express them in large quantities not only in a variety of cells, but also in virus vectors that can be grown in vitro and in vivo. Moreover, in some instances, fragments of immunogenic proteins, small enough to be synthesized chemically, have been shown to be protective. The rapid pace of these conceptual and technological advances leads the author to the expectation that viruses and antigens that are defined in precise chemical terms will form the basis of the vaccines of the future.


Neuroprotective effect of crocin on acrylamide-induced cytotoxicity in PC12 cells.
Acrylamide (ACR) is a potent neurotoxic in human and animal models. In this study, the effect of crocin, main constituent of Crocus sativus L. (Saffron) on ACR-induced cytotoxicity was evaluated using PC12 cells as a suitable in vitro model. The exposure of PC12 cells to ACR reduced cell viability, increased DNA fragmented cells and phosphatidylserine exposure, and elevated Bax/Bcl-2 ratio. Results showed that ACR increased intracellular reactive oxygen species (ROS) in cells and ROS played an important role in ACR cytotoxicity. The pretreatment of cells with 10-50 μM crocin before ACR treatment significantly attenuated ACR cytotoxicity in a dose-dependent manner. Crocin inhibited the downregulation of Bcl-2 and the upregulation of Bax and decreased apoptosis in treated cells. Also, crocin inhibited ROS generation in cells exposed to ACR. In conclusion, our results indicated that pretreatment with crocin protected cells from ACR-induced apoptosis partly by inhibition of intracellular ROS production.


An association between environmental factors and the IVS4+44C>A polymorphism of the DMT1 gene in age-related macular degeneration.
Age-related macular degeneration (AMD) is an ocular disease affecting macula - the central part of the retina, resulting in the degeneration of photoreceptors and retinal epithelium and causing severe central vision impairment. The pathophysiology of the disease is not completely known, but a significant role is attributed to genetic factors. The contribution of oxidative stress in AMD as a trigger of the degenerative process is well-established. Iron ions may act as a source of reactive oxygen species; therefore, maintaining iron homeostasis is important for redox balance in the organism. Diversity in iron homeostasis genes may counterpart in unbalanced redox state, and thus be involved in AMD pathophysiology. In this work, we searched for an association between some single nucleotide polymorphisms in the divalent metal transporter 1 (DMT1) gene intronic IVS4+44C>A (rs224589) and 3'-UTR c.2044T>C (rs2285230) and environmental factors and AMD. Genotyping was performed using the PCR-RFLP method. DNA was obtained from 436 AMD patients and 168 controls. We did not find any association between the genotypes of the two polymorphisms and AMD occurrence. However, we observed that AMD patients living in a rural environment and having the CC genotype of the IVS4+44C>A polymorphism had an increased risk of AMD, while individuals with the CA genotype or the A allele had a decreased risk of the disease. Moreover, in male AMD patients the C allele increased the risk of the disease, while the AA genotype decreased it. These results suggest that the VS4+44C>A polymorphism of the DMT1 gene may interact with place of living and gender to modulate the risk of AMD.


Lectin expression in carcinoid tumours of the gastrointestinal tract.
The binding of peroxidase-conjugated Dolichos biflorus (DBA), Triticum vulgaris (WGA), Canavalia ensiformis (Con A), Arachis hypogaea (PNA), Lotus tetragonolobus, and Bandeiraea simplicifolia I (BSAI) to gastrointestinal carcinoid tumours was studied. The results indicate that carcinoid tumour cells express certain carbohydrates similar to those present in the adjacent surface epithelium. The differences in the lectin-binding properties of carcinoid tumours of different sites of the gastrointestinal tract are closely related to the regional differences in the lectin binding of adjacent surface epithelium. These observations therefore form a useful basis for further studies in the application of lectin histochemistry to elucidate the histogenesis of carcinoid tumours.


Mechanism of transport enhancement of LHRH through porcine epidermis by terpenes and iontophoresis: permeability and lipid extraction studies.
The purpose of this study was to investigate the effect of 5% terpenes (i.e., limonene, carvone, thymol, and cineole)/ethanol (EtOH) and iontophoresis on the in vitro permeability of luteinizing hormone releasing hormone (LHRH) through the porcine epidermis and biophysical changes in the stratum comeum (SC) lipids by fourier transform infrared (FT-IR) spectroscopy. Methods. The porcine epidermis was pretreated with enhancer for 2 h. The permeability measurement system included Franz diffusion cells, Ag/AgCl electrodes, and SCEPTOR iontophoretic power source. FT-IR spectroscopy was performed to assess the possible contribution of lipid extraction to the transport enhancement of LHRH. Terpenes in combination with EtOH significantly (p < 0.05) increased the flux of LHRH in comparison with the control (epidermis which was not enhancer treated). Iontophoresis further enhanced (p < 0.05) the flux of LHRH through terpenes/EtOH treated epidermis in comparison with their passive permeability. Reversibility studies showed that the post-recovery passive flux of LHRH through 5% limonene in EtOH/iontophoresis treated epidermis was significantly (p < 0.05) decreased but did not significantly recover to the baseline flux (i.e., flux through control epidermis). The SC treated with terpenes/ EtOH showed a decrease in peak heights and areas for both asymmetric and symmetric C-H stretching absorbances in comparison to untreated SC. A greater percent decrease in peak heights and areas was obtained by limonene/EtOH. However, treatment of the SC with terpenes/EtOH followed by iontophoresis did not further decrease the percentage of peak height and area over and above terpene/EtOH suggesting that iontophoresis alone does not cause SC lipid extraction. Terpenes/EtOH increased LHRH permeability by enhancing the extraction of the SC lipids. Iontophoresis synergistically enhanced the permeability of LHRH through terpenes/EtOH treated epidermis. Thus, terpenes can be used as chemical enhancers in combination with iontophoresis to enhance the transdermal delivery of peptides such as LHRH.


Orthopedic aspects of musculoskeletal disease in the lower extremities.
The elderly patient may be significantly benefited by careful evaluation and treatment of lower extremity disease. A great deal of emphasis must be given to preoperative planning to assure the most predictable outcome of any treatment program. Arthritis about the major joints has been revolutionized joint replacement surgery and fracture treatment has undergone many changes in the elderly. Most elderly patients can undergo surgical intervention.