A new mini-triaxial cell for combined high-pressure and high-temperature in situ synchrotron X-ray microtomography experiments up to 400°C and 24 MPa.
A new experimental triaxial cell for in situ synchrotron X-ray micro-computed tomography aimed at imaging small samples of (6 mm × 19 mm) at high temperatures (up to 400°C) and pressures (up to 24 MPa confining) is presented. The system has flow-through capabilities, independent axial and radial pressure control, and has been developed and tested at the 8.3.2. beamline at the Advanced Light Source. The characteristics of this new experimental rig are described, along with the challenges, mainly concerning the combination of X-ray transparency with vessel strength at high temperature, and solutions found during the development stage. An experiment involving oil shale pyrolysis under subsurface conditions, highlighting the importance of a device able to operate in this pressure and temperature range, is also introduced. The availability of this cell enables an unprecedented range of experiments in the Earth Sciences, with a special focus on subsurface geothermal processes.


Novel mutations in the EXT1 gene in two consanguineous families affected with multiple hereditary exostoses (familial osteochondromatosis).
Multiple hereditary exostoses (HME) is an autosomal dominant developmental disorder exhibiting multiple osteocartilaginous bone tumors that generally arise near the ends of growing long bones. Here, we report two large consanguineous families from Pakistan, who display the typical features of HME. Affected individuals also show a previously unreported feature--bilateral overriding of single toes. Analysis using microsatellite markers for each of the known EXT loci, EXT1, EXT2, and EXT3 showed linkage to EXT1. In the first family, mutation analysis of the EXT1 gene revealed that affected individuals were heterozygous for an in-frame G-to-C transversion at the conserved splice donor site in intron 1. This mutation is predicted to disrupt splicing of the first intron and produce a frameshift that leads to a premature termination codon. In the second family, an insertion of an A in exon 8 is predicted to produce a frameshift at codon 555 followed by a premature termination, a further 10 codons downstream. In both families, an increased number of affected male subjects were observed. In affected females in family 2, phenotypic variability and incomplete penetrance were noted.


Postoperative pain treatment with transmuscular quadratus lumborum block and fascia iliaca compartment block in patients undergoing total hip arthroplasty: a randomized controlled trial.
Patients often suffer moderate or even severe pain after total hip arthroplasty; such pain seriously affects early postoperative recovery. This study aimed to investigate the analgesic efficacy of ultrasound-guided transmuscular quadratus lumborum block combined with fascia iliaca compartment block for elderly patients undergoing total hip arthroplasty. Fifty-four patients scheduled for total hip arthroplasty were included in this randomized controlled study. The patients were randomly assigned to receive only transmuscular quadratus lumborum block (group Q) or transmuscular quadratus lumborum block combined with fascia iliaca compartment block (group QF) with ultrasound guidance. Postoperatively in both groups, paracetamol 1 g was regularly administered at 6 h intervals and patient-controlled intravenous analgesia was administered. The primary outcome was cumulative sufentanil consumption via patient-controlled intravenous analgesia 24 h postoperatively. The secondary outcomes included pain degree, time to the first analgesic requirement, joint range of motion, quality of recovery, and the incidence of postoperative complications. Fifty patients were included, and their data were analyzed. The cumulative sufentanil consumption in group QF was significantly lower during the first 24 h after surgery than that in group Q, and the cumulative sufentanil consumption in group QF was reduced at 6-12 and 12-18 h after surgery. The postoperative pain intensity was lower in group QF than in group Q (linear mixed-effects model, the main effect of treatment: P < 0.001). Compared with group Q, group QF had higher quality of recovery and joint range of movement. The time to the first analgesic requirement was longer in group QF than in group Q (log-rank, P < 0.001). There was no statistically significant difference in complications postoperatively between the two groups. Our study provides a multimodal, opioid-sparing analgesic regimen for elderly patients undergoing total hip arthroplasty. The combination of transmuscular quadratus lumborum block and fascia iliaca compartment block provides a significant advantage for early postoperative functional recovery. Further studies are required to confirm the minimum effective dose. The study was registered on the 21st December 2020 (retrospectively registered) on the Chinese Clinical Trial Registry: ChiCTR2000038686 .


A novel cold-adapted and glucose-tolerant GH1 β-glucosidase from Exiguobacterium antarcticum B7.
A novel GH1 β-glucosidase (EaBgl1A) from a bacterium isolated from Antarctica soil samples was recombinantly overexpressed in Escherichia coli cells and characterized. The enzyme showed unusual pH dependence with maximum activity at neutral pH and retention of high catalytic activity in the pH range 6 to 9, indicating a catalytic machinery compatible with alkaline conditions. EaBgl1A is also a cold-adapted enzyme, exhibiting activity in the temperature range from 10 to 40°C with optimal activity at 30°C, which allows its application in industrial processes using low temperatures. Kinetic characterization revealed an enzymatic turnover (Kcat) of 6.92s(-1) (cellobiose) and 32.98s(-1) (pNPG) and a high tolerance for product inhibition, which is an extremely desirable feature for biotechnological purposes. Interestingly, the enzyme was stimulated by up to 200 mM glucose, whereas the commercial cocktails tested were found fully inhibited at this concentration. These properties indicate EaBgl1A as a promising biocatalyst for biotechnological applications where low temperatures are required.


Use of a levonorgestrel-releasing intrauterine device in the treatment of adenomyosis associated heavy menstrual bleeding.
To evaluate the effects of a levonorgestrel-releasing intrauterine device in the treatment of adenomyosis associated with heavy menstrual bleeding. The retrospective study was conducted at a tertiary referral hospital in Izmir, Turkey, and comprised data on adenomyosis patients who were implanted with a levonorgestrel-releasing intrauterine device for heavy menstrual bleeding between December 2004 and January 2008. After the insertion of the device, all patients were followed up by transvaginal ultrasonography and serum haemoglobin levels and menstrual patterns were determined at the 6th and 12th month. Data was analysed using SPSS 10. The mean age of the 42 women in the study was 43.2 +/- 0.8 years. At the sixth month, amenorrhoea, oligomenorrhoea, spotting and regular menstrual flow were 9.5% (n = 4), 7% (n = 3), 19% (n = 8), and 64% (n = 27), respectively. At the 12th month, the same parametres were 9.5% (n = 4), 7% (n = 3), 12% (n = 5), and 71% (n = 30), respectively. Haemoglobin levels had increased and endometrial thickness had decreased, and these differences were statistically significant (p < 0.001). The easy-to-use levonorgestrel-releasing intrauterine device can be added to the treatment options as a well-tolerated alternative in cases where a woman who has completed her fertility and does not request a hysterectomy has anaemia associated with adenomyosis.


Facial plexiform neurofibroma.
Facial plexiform neurofibroma is a relatively rare manifestation of Von Recklinghausen's neurofibromatosis. Two patients with extensive facial tumor involvement are presented, each having undergone wide local resection after multiple previous local excisions had failed to control the tumor and its locally deforming and destructive effects. A discussion of the problem, its etiology, pathogenesis, natural history, prognosis and suggested treatment is presented.


[Japanese Society of Hematology conflict of interest management in medical research].
In March 2017, considering the recent social trend, the Japanese Association of Medical Sciences (JAMS) officially announced the "JAMS Conflicts of Interest (COI) Management Guideline" and the "JAMS Guidance on Criteria for Qualification to Practice Guideline." In response to this announcement, the Japanese Society of Internal Medicine partially revised and announced the "Common Guideline on the Policy of COI in Medical Research," including the "COI Management to Practice Guideline" and the "Treatment Guideline," for its affiliated societies in September 2017. To ensure consistency with the Japanese Society of Internal Medicine, the Japanese Society of Hematology (JSH) has adopted and implemented the "Common Guideline of the Policy of COI in Medical Research of JSH," which matches that of the Japanese Society of Internal Medicine, and revised "Bylaws Concerning Conflict of Interest Policy in Clinical Research of JSH" to "Disclosure of COI in Conferences or Official Journals of JSH." Clinical Trials Act came into effect in April 2018, and the Japanese Ministry of Health, Labour, and Welfare has published "Guidance on COI Management according to Clinical Trials Act."


Absolute Quantification of Plasma MicroRNA Levels in Cynomolgus Monkeys, Using Quantitative Real-time Reverse Transcription PCR.
RT-qPCR is one of the most common methods to assess individual target miRNAs. MiRNAs levels are generally measured relative to a reference sample. This approach is appropriate for examining physiological changes in target gene expression levels. However, absolute quantification using better statistical analysis is preferable for a comprehensive assessment of gene expression levels. Absolute quantification is still not in common use. This report describes a protocol for measuring the absolute levels of plasma miRNA, using RT-qPCR with or without pre-amplification. A fixed volume (200 µL) of EDTA-plasma was prepared from the blood collected from the femoral vein of conscious cynomolgus monkeys (n = 50). Total RNA was extracted using commercially available system. Plasma miRNAs were quantified by probe-based RT-qPCR assays which contains miRNA-specific forward/reverse PCR primer and probe. Standard curves for absolute quantification were generated using commercially available synthetic RNA oligonucleotides. A synthetic cel-miR-238 was used as an external control for normalization and quality assessment. The miRNAs that showed quantification cycle (Cq) values above 35 were pre-amplified prior to the qPCR step. Among the 8 miRNAs examined, miR-122, miR-133a, and miR-192 were detectable without pre-amplification, whereas miR-1, miR-206, and miR-499a required pre-amplification because of their low expression levels. MiR-208a and miR-208b were not detectable even after pre-amplification. Sample processing efficiency was evaluated by the Cq values of the spiked cel-miR-238. In this assay method, technical variation was estimated to be less than 3-fold and the lower limit of quantification (LLOQ) was 102 copy/µL, for most of the examined miRNAs. This protocol provides a better estimate of the quantity of plasma miRNAs, and allows quality assessment of corresponding data from different studies. Considering the low number of miRNAs in body fluids, pre-amplification is useful to enhance detection of poorly expressed miRNAs.


Evaluation of electrical stimulation for ischemic wound therapy: a feasibility study using the lapine wound model.
Chronic wounds are a major secondary complication for many people with impaired mobility. Electrical stimulation (ES) has been recommended as a adjunctive therapy, however optimal treatment paradigms have not been established. Our group seeks to determine the basic mechanisms underlying ES wound therapy, an area where understanding is currently limited. A feasibility study was carried out to develop the Ahn/Mustoe lapine wound model for systematic investigation of the effects of electrical stimulation on ischemic wound therapy. A standardized surgical procedure incorporated a hybrid stimulation system comprising an implantable mini-stimulator and surface electrodes, with creation of repeatable ischemic wounds. Twenty mature male New Zealand white rabbits (3 kg weight) were employed to evaluate the effects of two empirically selected stimulation paradigms applied continuously for 7-21 days, using each animal as its own control. Outcomes measures included transcutaneous blood gas levels, histology, total RNA content and analysis of alpha2 (I) collagen (COL-I), type IV collagen (COL-IV), alpha1 (V) collagen (COL-V), and vascular endothelial growth factor (VEGF) expression using real-time quantitative PCR. All markers for stimulated wounds showed increased activity relative to non-stimulated control wounds between 7 and 14 days following injury, with peak activity at 14 days. By 21 days post-injury, all activity had returned to near baseline level. VEGF and COL-IV levels were found to be significantly higher for pattern A (110 mus pulse width) compared to pattern B (5 mus pulse width) at 14 days, implying that pattern A may be more effective at promoting angiogenesis. All wounds were fully re-epithelialized by 10 days post-injury. Both COL-I and COL-V showed statistically significant (P < 0.05) increased activity between day 7 and day 14 for pattern A, potentially indicating a continued effect on matrix remodeling. The early closure of all wounds implies that the rabbit ear model may not be valid for chronic wound studies.


Mutagenicity testing of amniotic fluid from diabetic women, with special reference to their smoking habits.
Amniotic fluid from 16 diabetic and 78 healthy women at term was tested for capacity to cause mutations in Salmonella typhimurium bacterial tester strain TA98 (Ames test). Diabetes as well as heavy smoking increased the mutagenic activity of amniotic fluid. The difference between groups of diabetics and controls was significant in both nonsmokers and women who had smoked more than 5 cigarettes the last 48 h before delivery. It seems plausible that metabolic disturbances, perhaps enhanced by a lowered oxygenation, in some instances could produce mutagenic compounds. Mutagenic activity in amniotic fluid may be one of the factors underlying the increased incidence of congenital malformations in the offspring of diabetic women. Early mutations could cause such developmental errors in the embryos, and possibly also in future generations by damage to germ cells. Heavy smoking alone also caused an increase in mutagenic activity in term amniotic fluid. Our findings reflected an enhancing effect of smoking in diabetes. A pregnant diabetic woman who smoked would thus further endanger her already jeopardized pregnancy.


Corni fructus scavenges hydroxy radicals and decreases oxidative stress in endothelial cells.
Corni fructus has been used as a tonic, analgesic, and diuretic in Korean herbal medicine. The present investigation was undertaken to evaluate the antioxidative effect of corni fructus and its capacity to protect cells against oxidative damage. The radical scavenging activity of corni fructus extracts was measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH), and the antioxidant activity was determined by measuring the peroxide value in a linoleic acid emulsion system. In addition, human umbilical vein endothelial cells (HUVECs) were treated with corni fructus extracts and incubated with H(2)O(2) to investigate protection against apoptosis induction. Both ethanol and water extracts of corni fructus produced higher DPPH radical scavenging activity than hexane, chloroform, and ethyl acetate extracts. Strong antioxidative activities of both water and ethanol extracts were observed in an emulsion system containing linoleic acid and phosphate buffer. The incubation of HUVECs with the addition of ethanol extract significantly decreased H(2)O(2)-initiated damage of endothelial cells, but the water extract did not. The pretreatment with ethanol extract, but not with water extract, significantly decreased apoptotic damage of the H(2)O(2)-treated HUVECs and kept the morphological normality. This study demonstrates that corni fructus is a potent antioxidant substance, and suggests that further investigation is needed to characterize the difference between extract types and to identify its antioxidant compounds.


Effect of cholesterol diet on reproductive function in male albino rats.
The present study was carried out to investigate the effect of cholesterol diet (400 mg/kg body weight) for 60 days on gonadal function in albino rats. The study was conducted in the Animal House Unit at Jordan University of Science and Technology, School of Medicine, Irbid, Jordan between October 2003 and February 2004. Adult male and female albino rats of Sprague Dawley strain were raised under controlled temperature and light. Male rats were divided into: a) control group--rats receiving vehicle (olive oil) for 60 days and treatment group--rats receiving cholesterol diet for a reproductive cycle. Animals were weighed and autopsied 24 hours after the last dose. Biochemical and histological approaches were used to assess fertility in both groups. The treatment caused significant reduction (p < or = 0.001) in sperm motility and density in cauda epididymides and testes. A significant reduction (p < or = 0.001) in epithelial cell height of caput, cauda and seminal vesicle was also observed. In the treated group, there was a significant reduction (p<0.001) in seminiferous tubules diameter and Leydig cell nuclear diameter. Spermatocytes (primary and secondary) were significantly decreased (p < or = 0.01) and spermatids were significantly reduced (p < or = 0.001) in the treatment group. Whereas, the number of degenerating Leydig cells (interstitial cells) increased significantly (p < or = 0.001). Serum biochemistry reveals significant increase (p<0.001) in cholesterol and triglyceride levels. The intragastric administration of cholesterol diet to male rats for 60 days significantly reduced the number of females impregnated by these males. However, the number of implantations and number of viable fetuses were significantly (p<0.01) decreased in female rats impregnated by males that ingested cholesterol. On the other hand, the number of resorptions was significantly (p<0.01) increased in females impregnated by males that ingested cholesterol. The histometry and histology of reproductive organs confirm these results. Hyperlipidemia can cause alteration in the biochemistry and histometry of reproductive organs and can cause inhibition of spermatogenesis via the Leydig cell.


Cervical spinal epidural arteriovenous fistula with coexisting spinal anterior spinal artery aneurysm presenting as subarachnoid hemorrhage--case report.
Hemorrhagic presentation of spinal epidural arteriovenous fistulas (AVFs) is rare in patients with cervical spinal vascular lesions. The present report describes a patient with cervical spine epidural AVFs associated with anterior spinal artery aneurysm at the same vertebral level presenting with subarachnoid hemorrhage. A 54-year-old man presented with sudden onset of headache. Computed tomography of the head showed subarachnoid hemorrhage. Diagnostic angiography revealed an epidural AVF located at the C1-2 level that was fed mainly by the dorsal somatic branches of the segmental arteries from the radicular artery and anterior spinal artery. This AVF drained only into the epidural veins without perimedullary venous reflux. Further, there was a 4-mm anterior spinal artery aneurysm in the vicinity of the fistula that was thought to be the cause of the hemorrhage. Endovascular transarterial fistulas embolization from the right radicular artery was performed to eliminate the AVF and to reduce hemodynamic stress on the aneurysm. No new symptoms developed after the treatment and discharged without neurological deficits. The aneurysm was noted to be reduced in size after the treatment and totally disappeared by 1 year later, according to follow-up angiography. Anterior spinal artery aneurysm from a separate vascular distribution may coexist with spinal epidural AVFs. In the setting of spinal subarachnoid hemorrhage, comprehensive imaging is indicated to rule out such lesions.


The new approaches on sustainable wildlife of Amik Lake.
Turkey has been on a crucial routes of the migrating birds. These birds have been coming from Istanbul-Camlica hills and through Artvin-Borcka to the homeland. And the migrating birds turn to the Africa continent over Syria by passing Hatay-Belen. During the mmigration, the birds use the location of Amik Lake as a watery land for temporary settlement. The Amik Lake which should have been protected as a watery land for birds according to Ramsar Agreement that Turkey signed, was caused to dry ten years ago. There weren't only negative effects on the wildlife by drying but also soil degraded and productivity decreased though the aim was to improve agriculture and contributions to local developments on the Amik Lake dry land. During the last two decades, it was known that one of the birds, which is called Anhinga rufa extincted as a cause of drying ot Amik Lake. In this study, some results that emerged as a cause of drying of Amik Lake were presented.


Reflections on retinoscopy.
It has often been stated that static retinoscopy findings are not affected by the examiner's refractive correction. To what extent this statement remains true is the subject of this statement remains true is the subject of this paper. The basic principle of retinoscopy is the Foucault test. In this test, a knife edge placed on the principal axis of an optical system (S) intercepts a bundle of rays coming out of (S). Depending on the position of the knife edge, various distributions of light and shadow can be observed on the anterior surface of (S). In retinoscopy it is either the entrance pupil of the examiner or the peephole of the instrument that plays the role of the knife edge. Therefore, any change in conditions that bring about a change in the "knife-edge-pupil" position will result in errors in static retinoscopy. Nevertheless, calculations show that these errors do not become significant under usual clinical conditions of static retinoscopy.


The effect of obesity on recurrence pattern in early breast cancer patients.
Obesity is a well known risk factor for breast cancer recurrence and poor prognosis. We studied the effect of body mass index (BMI) on recurrence pattern in early breast cancer patients. This retrospective cross-sectional study analyzed the data of 2731 early stage breast cancer patients. Patients who had metastatic disease at the time of diagnosis and with unknown BMI values were excluded from study (N=276). Patients were classified into three BMI categories: normal body weight, overweight, and obese. The recurrent/metastatic sites of patients were grouped in 8 categories: local, contralateral, lymph node, bone, lung, liver, brain and others. The association between first relapse site of early breast cancer patients and BMI categories were evaluated. The median patient age was 48 years (range 18-92). The median follow up time was 40 months (range 1-284). During follow-up, 469 (17.1%) patients developed recurrence and/or metastasis. Of 2455 total patients, 853 (34.6%) were classified as having normal weight, 898 (36.2%) were overweighted and 704 (29.2%) were obese. In the whole patient group no relation between metastatic sites and BMI groups was noticed. The first primary metastatic sites were also not associated with BMI groups in pre and postmenopausal subpopulations. In obese patients, disease free survival (DFS) was shorter compared to normal weighted patients, but the difference was not significant. There was no significant difference between site-specific DFS in relation to BMI categorization. Obese and overweighted patients had significantly shorter overall survival (OS) compared to the normal-weight group (p=0.003). Although obesity had no effect on recurrence pattern of early breast cancer patients, obese early breast cancer patients had shorter OS compared to their normal-weight counterparts.


[Benefits and effectiveness of recording somatosensory evoked potentials in surgery on the carotid artery].
Operative treatment of high-grade carotid stenosis is an established procedure. The question whether a temporary - either selective or routine - shunt is needed, is a matter of controversy, and the decision is based on a number of available monitoring procedures. Within the framework of quality assurance based on the regular collection of our own patient data, carotid thromboendarterectomy (TEA) with recording of somatosensory evoked potentials (SEP) was analysed for its effectiveness. Two non-randomised groups of patients were analysed retrospectively: Group I: 99 carotid TEAs with no recording of SEP (1.1.99-31.12.99); Group II: 139 carotid TEAs with SEP recording (1.1.01-31.12.01). These two groups were unselected in terms of procedure, as also with regard to age, sex, stage or degree of carotid stenosis or surgeon, and were homogeneously distributed. A comparison was made of anaesthesia and operating times, shunt rate and the outcome of the two groups. Additionally, the two subgroups surgery with no shunt, and surgery with shunt, and the subgroups thromboendarterectomy with patchplasty (TEA) and eversion endarterectomy (EEA), were analysed. A temporary shunt was employed in 41 (41.4 %) of the patients in Group I (no SEP recording) and in 16 (11.5 %) of those in Group II (SEP recording). The average operating time in Group II was 11.4 min shorter (p < 0.001) than in Group I. The average carotid clamping time in Group II was significantly reduced (by 4.2 min; p < 0.001), while the duration of anaesthesia prior to skin incision was increased by an average of 18.3 min (p < 0.001), and the overall duration of anaesthesia by an average of 15.8 min (p < 0.001). A comparison of the subgroups surgery with no shunt and surgery with shunt revealed - both in Group I and Group II - a significant prolongation of the anaesthesia time and operating time (p < 0.001). In both Groups I and II, the subgroup TEA revealed a significant prolongation of both the anaesthesia and operating times vis-à-vis EEA. The major stroke rate was 2.0 % in Group I and 1.4 % in Group II, and the minor stroke rate 3.0 in Group I and 3.6 % in Group II; no deaths were observed. A reduction in the shunt rate to 11 % (by means of SEP) significantly decreased the average operating time (incision - suture) and the clamping time, with identical outcome in Groups I and II. Despite a reduction in the average incision-suture time in Group II (with SEP recording), the average overall operating time (anaesthesia time) was significantly increased due to the greater technical effort required. Carotid TEA with a selective shunt as determined by SEP is a high-cost procedure with no demonstrable benefit. At a stroke rate < 5 % and a need for stratification into several groups in accordance with the AHA classification, it is not possible to achieve adequate patient recruitment for a randomised analysis of outcome of the individual monitoring procedures. Alternative procedures are the routine use of a shunt and operation under regional anaesthesia.


Modified U Slot Patch Antenna with Large Frequency Ratio for Vehicle-to-Vehicle Communication.
This paper presents a single-fed, single-layer, dual-band antenna with a large frequency ratio of 4.74:1 for vehicle-to-vehicle communication. The antenna consists of a 28 GHz inset-fed rectangular patch embedded into a 5.9 GHz patch antenna for dual-band operation. The designed dual-band antenna operates from 5.81 to 5.99 GHz (Dedicated Short Range Communications, DSRC) and 27.9 to 30.1 GHz (5G millimeter-wave (mm-wave) band). Furthermore, the upper band patch was modified by inserting slots near the inset feed line to achieve an instantaneous bandwidth of 4.5 GHz. The antenna was fabricated and measured. The manufactured prototype operates simultaneously from 5.8 to 6.05 GHz and from 26.8 to 31.3 GHz. Notably, the designed dual-band antenna offers a high peak gain of 7.7 dBi in the DSRC band and 6.38 dBi in the 5G mm-wave band.


Exebacase in Addition to Daptomycin against MRSA.
Exebacase is a lysin (cell wall hydrolase) with direct lytic activity against Staphylococcus aureus including methicillin-resistant S. aureus (MRSA). Time-kill analysis experiments illustrated bactericidal activity of exebacase-daptomycin against MRSA strains MW2 and 494. Furthermore, exebacase in addition to daptomycin (10, 6, and 4 mg/kg/day) in a two-compartment ex vivo pharmacokinetic/pharmacodynamic simulated endocardial vegetation model with humanized doses resulted in reductions of 6.01, 4.99, and 2.81 log10 CFU/g (from initial inoculum) against MRSA strain MW2.


Allogeneic Red Blood Cell Transfusion and Infectious Complications Following Pediatric Spinal Fusion: NSQIP-P Analysis.
Substantial bleeding occurs during spinal fusion surgery in the pediatric population, and many patients receive allogeneic red blood cell transfusion (ARBT) for the treatment of resulting perioperative anemia. ARBT is thought to increase vulnerability to postoperative infections following major surgical procedures, but studies of this relationship in children undergoing spinal fusion have yielded conflicting results. Patients who underwent spinal fusion before the age of 18 years were identified from the National Surgical Quality Improvement Program-Pediatric (NSQIP-P) 2016 to 2019 databases, along with patient and procedure-specific characteristics, transfusion events and volumes, and postoperative infectious complications such as wound-related infection, pneumonia, urinary tract infection (UTI), and sepsis. Multivariable logistic regression analyses provided adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the association between ARBT and each infection outcome and the overall risk of infection. Among 19,159 patients studied, 714 (3.7%) developed a total of 931 episodes of postoperative infection. In multivariable logistic regression analyses, perioperative ARBT was independently associated with postoperative pneumonia (aOR = 1.93, 95% CI = 1.40 to 2.68), UTI (aOR = 1.80, 95% CI = 1.19 to 2.73), sepsis (aOR = 1.58, 95% CI = 1.10 to 2.28), and the overall risk of infection (aOR = 1.40, 95% CI = 1.20 to 1.64). The risk of any postoperative infection increased in a dose-response fashion with transfusion volume. ARBT in pediatric spinal fusion is associated with significantly increased risks of postoperative pneumonia, UTI, and sepsis. The overall risk of postoperative infection increases with the volume transfused. Enhanced efforts to minimize perioperative anemia and ARBT should be considered as a means of improving patient outcomes. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Prevalence and factors predictive of intraocular fungal infection in patients with fungemia at an academic urban tertiary care center.
To report the prevalence and to identify factors predictive of intraocular infection in patients with fungemia receiving prophylactic antifungal therapy. A retrospective review of patients who received prophylactic antifungal therapy and a dilated fundus examination at an academic urban tertiary care center from 2000 to 2007. Basic demographic information, fungal species grown, antifungal agent(s) used, number of positive blood culture specimens, visual acuity, visual symptoms, and known risks of disseminated candidiasis were noted. Logistic regression analysis was used to determine the factors significantly associated with intraocular fungal infection. A total of 132 patients with positive fungemia culture were requested to have ophthalmology consults. The prevalence of ocular infection was 6.9% (N=9). All nine patients were infected with Candida species. Undergoing gastrointestinal (GI) surgery within the prior 6 months was significantly related to developing intraocular infection, with an odds ratio of 18.5 (95% confidence interval, 15.1-24.3; P=0.002). Having ≥3 positive fungal blood cultures was also a significant risk factor, with an odds ratio of 2.6 (95% confidence interval, 1.8-3.7; P=0.03). Among 40 patients having GI surgery, eight (20.0%) had intraocular fungal disease, compared with one of 92 patients (1.1%) not having GI surgery. Among 125 patients with a negative baseline examination result, two of 32 patients (6.3%), who had recent GI surgery, subsequently developed fungal ocular disease, compared with 0 of 93 patients (0%), who did not have recent GI surgery. Recent GI surgery and higher numbers of positive fungal blood culture specimens may be predictive of candida ocular infections. Normal baseline fundoscopy examination results in patients with such risks may require repeat evaluations to detect delayed manifestations.


A novel multicolor immunofluorescence method using heat treatment.
We describe a novel method for immunofluorescent detection of multiple antigens in a single paraffin-embedded tissue section. We hypothesized that if fluorescent dyes are resistant to heat treatment, then thermal inactivation of immunoglobulins during antigen detection procedures might make it possible to use multicolor immunofluorescence detection even if the primary antibodies are from the same species. We found that several fluorescent dyes, including fluorescein isothiocyanate (FITC), Cy3 and Cy5, were resistant to heating at 90 degrees Celsius for 15 min, whereas the antigenicities of the primary antibodies were lost completely. This novel method, which uses heat treatment between staining steps, has great advantages for multicolor immunofluorescence because unlabeled primary antibodies from the same species can be used. Therefore, by using this method not only 3 unlabeled mouse monoclonal antibodies but also 3 unlabeled rabbit antisera can be used as primary antibodies for multicolor immunofluorescence.


Patent ductus arterious and increased conjugated bilirubin in the second week after birth are independent risk factors for necrotizing enterocolitis in preterm infants: an observational study.
Neonatal necrotizing enterocolitis (NEC) is a common critical illness of the gastrointestinal system in neonatal intensive care units with complex causes. We want to explore effects of serum-conjugated bilirubin on the occurrence of NEC in preterm infants. A retrospective study of clinical case data of premature infants from 2017 to 2020 in the Department of pediatrics of the First Affiliated Hospital of Nanjing Medical University was conducted. Among these, 41 were diagnosed with NEC. After screening, 2 cases were excluded because of incomplete data. Propensity-matching score (PSM) was performed according to the ratio of 1:2(2 preterm infants in the NEC group were not matched), and finally, 37 cases were in the NEC group (average time to diagnosis was 18.9 days), and 74 cases in the non-NEC group. We compared the difference between the NEC and non-NEC groups in early serum-conjugated bilirubin and total bilirubin levels (time points: the first day of birth, 1 week after birth, 2 weeks after birth). (1) The changing trend of conjugated bilirubin was different between the two groups(F = 4.085, P = 0.019). The NEC group's serum-conjugated bilirubin levels gradually increased ([Formula: see text] ± s:12.64±2.68; 17.11±4.48; 19.25±11.63), while the non-NEC group did not show a continuous upward trend ([Formula: see text] ± s:13.39±2.87; 15.63±3.75; 15.47±4.12). (2) Multiple analyses showed that patent ductus arteriosus(PDA) (odds ratio[OR] = 5.958, 95%confidence interval[CI] = 2.102 ~ 16.882) and increased conjugated bilirubin in the 2nd week (OR = 1.105, 95%CI = 1.013 ~ 1.206) after birth were independent risk factors for NEC. The body had already experienced an elevation of conjugated bilirubin before the occurrence of NEC. The change of early conjugated bilirubin may be an important factor in the occurrence of NEC.


Entry to β-alkoxyacrylates via gold-catalyzed intermolecular coupling of alkynoates and allylic ethers.
The first gold-catalyzed intermolecular coupling of alkynoates and allylic ethers invoking alkoxy addition and [3,3]-sigmatropic rearrangement as the key mechanism has been developed. Remarkably, the reaction showed complete chemoselectivity toward the pathway initiated by the alkoxy addition to alkynes. This unprecedented reactivity led to a new access to diversely substituted β-alkoxyacrylates in a highly efficient manner.


Venous Valvuloplasty.
The technical feasibility of surgical correction of abnormal venous valves is now established. In times past, it was generally thought that surgery inside the veins would be fraught with a virtual certainty of failure due to thrombosis of the vein. This has turned out to be not true. In 1968 the first venous valvuloplasty was done and since then hundreds more have been reported from surgeons in America and Europe with a very rare incidence of post-operative thrombosis. The operation is done today by any vascular surgeon who has taken the time to study the details of technique that are necessary to achieve a successful repair.


Differential effects of Bifidobacterium pseudolongum strain Patronus and metronidazole in the rat gut.
In the luminal contents of metronidazole-treated rats, there was a dominant Bifidobacterium species. A strain has been isolated, its 16S rRNA gene has been sequenced, and the strain has been named Bifidobacterium pseudolongum strain Patronus. In this study, using an experimental model of healthy rats, the effects of metronidazole treatment and B. pseudolongum strain Patronus administration on the luminal and mucosa-associated microbiota and on gut oxidation processes were investigated. Metronidazole treatment and the daily gavage of rats with B. pseudolongum strain Patronus increased the numbers of bifidobacteria in cecal contents and in cecal mucosa-associated microbiota compared with those in control rats. Metronidazole reduced the colonic oxidative damage to proteins. This is the first evidence that B. pseudolongum strain Patronus exerts an effect on a biomarker of oxidative damage by reducing the susceptibility to oxidation of proteins in the colon and the small bowel. Antioxidant effects of metronidazole could be linked to the bifidobacterial increase but also to other bacterial modifications.


Characteristics of arterial stiffness in very low birth weight premature infants.
Premature birth is a factor of increased blood pressure in adulthood. Little is known about the physiologic characteristics of the arterial bed in neonates. The aim of this study was to characterize in vivo the arterial compliance in neonates and its maturation profile in very low birth weight (VLBW) premature infants. A group of stable, VLBW premature infants was compared with a control group of near term neonates. The abdominal aortic wall distensibility coefficient (DC) and whole-body arterial compliance (WBAC) were determined using specifically designed noninvasive methods, based on ultrasonic measurements in combination with synchronous, beat-to-beat recording of aortic pulse pressure (PP). On the fifth day of life, WBAC and the CD were lower in VLBW premature infants than in controls. Furthermore, WBAC and the DC remained unchanged in VLBW premature infants 7 wk after birth. In conclusion, VLBW premature infants are characterized as early as the fifth day of life by high arterial stiffness, which persists when they reach their theoretical term. It can be speculated that early alteration of arterial elastic properties may pave the way for long-term elevation of arterial pressure in VLBW premature infants.


Nonmyeloablative allogeneic hematopoietic cell transplants: any role for rheumatoid arthritis?
Recent studies have suggested limited efficacy of high dose cyclophosphamide and autologous stem cell transplant as a treatment for severe rheumatoid arthritis. Preclinical data and anecdotal evidence from human transplants suggest that greater efficacy and possible cures might be achieved through use of allogeneic transplants. Newer less intensive methods of allogeneic transplantation have been introduced that reduce morbidity and mortality of the procedure. This article reviews the possible role of the so-called nonmyeloablative transplants in the treatnent of RA.


Endothelial cell adhesiveness is a function of environmental lighting and melatonin level.
The endothelial layer regulates the traffic of cells and substances between the blood and tissues and plays a central role in the mounting of an inflammatory response. We have recently shown that inhibition of the nocturnal melatonin surge during the mounting of an inflammatory response primes endothelial cells to a highly reactive state, increasing the expression of adhesion molecules and inducible nitric oxide synthase (iNOS) as well as the in vitro adherence of leukocytes. Here, we investigated whether physiological variations in the plasma melatonin levels owing to the light/dark environmental cycle could also prime the reactive state of endothelial cells. Cultured endothelial cells (16-20 days) obtained from rats killed during the daytime adhere more neutrophils, expressed more adhesion molecules and iNOS, and had a higher content of the transcription factor nuclear factor kappa B (NF-kB) translocated to the nuclei. We also evaluated the expression of 84 genes (using real-time PCR array) related to the innate inflammatory response and observed a higher expression of 19 genes in cultures obtained during the daytime. In addition, the only gene that was highly expressed in cells obtained from rats killed during nighttime was one that encodes a protein that negatively modulates inflammatory response. In conclusion, the daily rhythm of melatonin also primes the ability of endothelial cells to adhere to neutrophils. This new approach for evaluating the influence of the donor on cells maintained in culture should have applications for the standardization of cell banks.


Effects of ghrelin on activation of Akt1 and ERK1/2 pathways during in vitro maturation of bovine oocytes.
The purpose of this study was to investigate the possible molecular pathways through which ghrelin accelerates in vitro oocyte maturation. Bovine cumulus-oocyte complexes (COCs), after 18 or 24 h maturation in the absence or the presence of 800 pg ml-1 of acylated ghrelin were either assessed for nuclear maturation or underwent in vitro fertilization in standard media and putative zygotes were cultured in vitro for 8 days. In a subset of COCs the levels of phosphorylated Akt1 and ERK1/2 (MAPK1/3) were assessed at the 0th, 6th, 10th, 18th and 24th hours of in vitro maturation (IVM). At 18 and 24 h no difference existed in the proportion of matured oocytes in the ghrelin-treated group, while in the control group more (P < 0.05) matured oocyte were found at 24 h. Oocyte maturation for 24 h in the presence of ghrelin resulted in substantially reduced (P < 0.05) blastocyst yield(16.3%) in comparison with that obtained after 18 h (30.0%) or to both control groups (29.3% and 26.9%, for 18 and 24 h in maturation, respectively). Ghrelin-treated oocytes expressed lower Akt1 phosphorylation rate at the 10th hour of IVM, and higher ERK1/2 at the 6th and 10th hours of IVM compared with controls. In cumulus cells, at the 18th and 24th hours of IVM Akt1 phosphorylation rate was higher in ghrelin-treated oocytes. Our results imply that ghrelin acts in a different time-dependent manner on bovine oocytes and cumulus cells modulating Akt1 and ERK1/2 phosphorylation, which brings about acceleration of the oocyte maturation process.


An 88.8-kb Novel Deletion of 19q13.2 Encompassing the ATP1A3 Gene Detected by Array CGH in a Patient with Delayed Psychomotor Development, Generalized Hypotonia and Macrocephaly.
Many neurodevelopmental disorders are caused by the presence of CNVs. Chromosome microarray technology is widely used to accurately detect CNVs. We report the case of a male, aged 3 years, presenting with delayed psychomotor development, generalized hypotonia, encephalopathy, delayed myelination in the central nervous system, and poor motor coordination. The array CGH revealed an interstitial deletion of chromosome 19q13.2 with a size of 88.8 kb involving 3 OMIM genes: RABAC1, ARHGEF1, and ATP1A3. Heterozygous mutations in the ATP1A3 gene are associated with delayed psychomotor development, alternating hemiplegia of childhood type 2 (AHC2), dystonia type 12, and cerebellarataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome, also called CAPOS syndrome. The phenotypic expression of partial ATP1A3 deletion is, however, poorly described in the literature. The deletion was confirmed by MLPA, and we identified a hitherto undescribed novel deletion of exons 3b-21 of the ATP1A3 gene. Our data suggest that the deletion of the ATP1A3 gene is a causative factor of the AHC2 phenotype in the patient.


The role of membrane destabilisation and protein dynamics in BAM catalysed OMP folding.
The folding of β-barrel outer membrane proteins (OMPs) in Gram-negative bacteria is catalysed by the β-barrel assembly machinery (BAM). How lateral opening in the β-barrel of the major subunit BamA assists in OMP folding, and the contribution of membrane disruption to BAM catalysis remain unresolved. Here, we use an anti-BamA monoclonal antibody fragment (Fab1) and two disulphide-crosslinked BAM variants (lid-locked (LL), and POTRA-5-locked (P5L)) to dissect these roles. Despite being lethal in vivo, we show that all complexes catalyse folding in vitro, albeit less efficiently than wild-type BAM. CryoEM reveals that while Fab1 and BAM-P5L trap an open-barrel state, BAM-LL contains a mixture of closed and contorted, partially-open structures. Finally, all three complexes globally destabilise the lipid bilayer, while BamA does not, revealing that the BAM lipoproteins are required for this function. Together the results provide insights into the role of BAM structure and lipid dynamics in OMP folding.


Morphoproteomic study of primary pleural angiosarcoma of lymphangioendothelial lineage: a case report.
An unusual case of bilateral primary pleural angiosarcoma with an immunophenotype of lymphangioendothelial lineage is described. Pleural angiosarcoma is a highly malignant neoplasm for which there is currently no standard of care. A comprehensive immunophenotypic characterization established a lymphangioendothelial lineage. A morphoproteomic analysis was also performed to identify the proteins and corresponding molecular pathways activated in the patient's tumor. The information derived from the morphoproteomic studies provides insight into the biology of the tumor and may be useful in formulating therapeutic alternatives.


Crystal structure of the mobile metallo-β-lactamase AIM-1 from Pseudomonas aeruginosa: insights into antibiotic binding and the role of Gln157.
Metallo-β-lactamase (MBL) genes confer resistance to virtually all β-lactam antibiotics and are rapidly disseminated by mobile genetic elements in Gram-negative bacteria. MBLs belong to three different subgroups, B1, B2, and B3, with the mobile MBLs largely confined to subgroup B1. The B3 MBLs are a divergent subgroup of predominantly chromosomally encoded enzymes. AIM-1 (Adelaide IMipenmase 1) from Pseudomonas aeruginosa was the first B3 MBL to be identified on a readily mobile genetic element. Here we present the crystal structure of AIM-1 and use in silico docking and quantum mechanics and molecular mechanics (QM/MM) calculations, together with site-directed mutagenesis, to investigate its interaction with β-lactams. AIM-1 adopts the characteristic αβ/βα sandwich fold of MBLs but differs from other B3 enzymes in the conformation of an active site loop (residues 156 to 162) which is involved both in disulfide bond formation and, we suggest, interaction with substrates. The structure, together with docking and QM/MM calculations, indicates that the AIM-1 substrate binding site is narrower and more restricted than those of other B3 MBLs, possibly explaining its higher catalytic efficiency. The location of Gln157 adjacent to the AIM-1 zinc center suggests a role in drug binding that is supported by our in silico studies. However, replacement of this residue by either Asn or Ala resulted in only modest reductions in AIM-1 activity against the majority of β-lactam substrates, indicating that this function is nonessential. Our study reveals AIM-1 to be a subclass B3 MBL with novel structural and mechanistic features.


An evidence-based appraisal of complementary and alternative medicine strategies for the management of hypertension.
: Hypertension is a major risk factor for cardiovascular disease and all-cause mortality. Numerous antihypertensive medications and lifestyle changes have proven effective for the reduction of blood pressure (BP). Over the past few decades, the emergence of complementary and alternative medicine (CAM)-based strategies to lower BP have broadened the therapeutic armamentarium for hypertension. CAM is defined as a group of heterogeneous medical treatments that are used to enhance the effect of standard therapy, or, conversely, are implemented as an alternative to standard practice. The available body of evidence does substantiate the BP-lowering effects of certain CAM-based therapies in individuals with and without established hypertension. Collectively, alternative strategies for BP reduction have undergone less rigorous testing than traditional BP-lowering strategies and the lack of robust clinical data has greatly hampered the broad-scale adoption of CAM therapies into clinical practice. Despite these limitations, CAM-based therapies for the reduction of BP require consideration as they could offer substantial public health benefits given the high prevalence of hypertension in the general population. This article reviews some of the most promising CAM-based therapies for the reduction of BP and cardiovascular outcomes based on the current literature.


Novel plasmid-mediated beta-lactamase from Escherichia coli that inactivates oxyimino-cephalosporins.
A highly cephem-resistant Escherichia coli strain, FP1546, isolated from the fecal flora of laboratory dogs previously administered beta-lactam antibiotics was found to produce a beta-lactamase, FEC-1, of 48-kilodalton size and pI 8.2. FEC-1 hydrolyzed cefuroxime, cefotaxime, cefmenoxime, and ceftriaxone, as well as the enzymatically less-stable antibiotics cephaloridine, cefotiam, and cefpiramide. Of the oxyimino-cephalosporins, ceftizoxime was fairly stable to FEC-1. FEC-1 differed notably from chromosomal E. coli cephalosporinase, especially in its broad-spectrum substrate profile and its high inhibition by clavulanic acid, sulbactam, and imipenem. A conjugation study revealed that FEC-1 was encoded by a 74-megadalton plasmid, pFCX1. This may be the first instance of a plasmid-mediated oxyimino-cephalosporinase from E. coli.


[Healthcare rights: an invitation for reflection].
This study focuses on changes and breaks in contemporary society relating to the right to healthcare as a universal value, in conformity with the guidelines provided by multilateral agencies and disseminated particularly since the 1990s. From the genesis of social rights and by tracing the interdependence between social and economic aspects of social citizenship in democratic capitalist countries, the study presents the two paradigms informing the approach to healthcare in the early 21st century: the full citizenship paradigm, according to which the right to healthcare is a universal value, and the paradigm of restricted social citizenship, according to which the right to healthcare is guided by the criterion of efficiency and economic rationalization. These propositions align with the health economy paradigm, which (i) defends focused resource allocation to attenuate poverty conditions, (ii) reduces the role of the state, (iii) recommends resource allocation to healthcare in association with social protection, and (iv) defines the market as the privileged regulator of healthcare actions.


The RiboPuromycylation Method (RPM): an Immunofluorescence Technique to Map Translation Sites at the Sub-cellular Level.
While isotopic labeling of amino acids remains the reference method in the field for quantifying translation rate, it does not provide any information on spatial localization of translation sites. The rationale behind developing the ribopuromycylation method (RPM) was primarily to map translation sites at the sub-cellular level while avoiding detection of newly synthesized proteins released from ribosomes. RPM visualizes actively translating ribosomes in cells via standard immunofluorescence microscopy in fixed and permeabilized cells using a puromycin-specific monoclonal antibody to detect puromycylated nascent chains trapped on ribosomes treated with a chain elongation inhibitor.


Psychosocial issues in the management and treatment of children and adolescents with asthma.
Asthma is one of the most common chronic childhood illness. Studies have reported higher incidence of psychosocial adaptation problems in children with asthma, particularly severe asthma, than children in the general population. Increased psychosocial problems in children with asthma have been ascribed to adverse developmental impact of having a chronic health problems, increased demands on the family and dysfunctional familial interactional patterns. Treatment models include education and self management training programs, family therapy, relaxation therapy and biofeedback. These programs have been found to produce improved adjustment, increased medication compliance and greater perceived self competence in managing symptoms and decreased use of medical services. It is concluded that children with asthma require a comprehensive management strategy that pays attention not only to physiological control of asthma symptoms but also emotional and behavioural problems of children and their families.


Laboratory evaluation of novaluron as a rodent feed-through insecticide against sand fly larvae (Diptera: Psychodidae).
Experiments were conducted to evaluate novaluron as a feed-through larvicide to control immature phlebotomine sand flies (Phlebotomus papatasi Scopoli) (Diptera: Psychodidae). The minimum effective concentration of novaluron against sand fly larvae fed hamster feces treated with novaluron, or feces of hamsters fed a diet containing novaluron, was 9.88 and 9.88 x 10(-1) mg/kg, respectively. Feces of novaluron-treated hamsters were held under conditions simulating the inside of a rodent burrow for up to 30 d, and all larvae that consumed these feces died before pupation; a significant reduction in treated larval survival relative to control was observed when the feces were aged for up to 150 d. Novaluron was shown to be effective as a feed-though larvicide when novaluron-treated food made up only a portion of the diet of hamsters. The results of this study suggest that novaluron could be effective as a rodent feed-through insecticide in a field setting.


Public awareness and use of 997 emergency medical service phone number during the COVID-19 pandemic.
Emergency medical services (EMSs) are an important element of the healthcare system as it provides an opportunity to respond to critical medical conditions and save people's lives. In Saudi Arabia, EMS is offered via the EMS phone number "997" and mobile application "Asefny". This was an observational cross-sectional survey study exploring public awareness and use of the EMS phone number during the COVID-19 pandemic in Saudi Arabia. A bivariate analysis was performed to investigate factors affecting awareness and use of the EMS phone number and to compare the EMS acceptance to transport and timelines of ambulance arrival between requests made via the "997" EMS phone number and the "Asefny" mobile application during the country's emergency lockdown. A total of 805 participants were included in the analysis, where 66% reported awareness of the EMS phone number and 75% of them accurately identified the nature of the service provided by dialing the number. The men who participated, those with a bachelor's degree, with children, and with chronic conditions were more aware of the EMS phone number compared to the other participants. Of the total sample, 46.7% used EMS phone numbers at least one time (ever users). During the COVID-19 lockdown, the EMS accepted to transport 87% of the calls made by 997 phone number and 56.2% of the mobile application requests (P < 0.00). The ambulance arrived in ≤ 8 min in 53.6% of the 997 phone calls and 35.5% of the Asefny mobile requests (P < 0.00). Findings showed commendable levels of awareness and the use of EMS phone numbers. However, the results suggest room for improvement by developing promotional and educational campaigns inspired by the factors identified as influential on both awareness and use. Mobile applications in EMS are promising to improve prehospital emergency service accessibility, which needs to be further investigated to assess its impact on the public health informatics experience.


Plasma proteins in fetal sheep brain: blood-brain barrier and intracerebral distribution.
1. Plasma proteins have been demonstrated to be present in early fetal sheep brain in amounts which cannot be accounted for by blood contamination. 2. The distribution of alpha-fetoprotein, albumin, fetuin, alpha 1-antitrypsin and transferrin has been studied by immunoassay of extracts from brain homogenates and by immunoperoxidase histochemistry of fetal brains between 37 and 125 days gestation (term is 150 days). 3. At 35 days gestation fetuin and albumin were quantitatively the most important proteins in fetal brain, both as estimated by extraction and by immunohistochemistry. Both of these proteins, and also alpha-fetoprotein and alpha 1-antitrypsin, declined considerably in amount by 60 days gestation. After 60 days the concentrations of albumin and alpha-fetoprotein were not significantly different from that due to blood contamination and only occasional cells could be demonstrated by immunohistochemistry. Fetuin and alpha 1-antitrypsin were present in reduced but significant amounts at least up to 125 days gestation. 4. The immunohistochemical results showed that considerable numbers of immature neurones were stained for some plasma proteins. Fetuin positive cells predominated both in terms of the larger number of cells which stained at 35-40 days gestation and in the persistence of positive cells up to 125 days gestation. Numerous cells in the neuroependymal layer and in several layers of the developing cortical plate were positive, especially early in gestation. Only a few transferrin or alpha 1-antitrypsin positive cells were observed. 5. Permeability of the blood-brain barrier to sheep or human serum albumin (labelled with 125I) was tested in 60 day fetal sheep by intravenous injection and estimation of brain radioactivity at 3 or 6 hr with allowance for blood contamination. Only a very small (but significant) penetration of protein was detected. Unlike penetration of protein into c.s.f. at the same age, it did not reach its natural steady state in brain. 6. It is concluded that the blood-brain barrier to protein is well developed in the immature fetal sheep but that developing neurones probably acquire certain plasma proteins directly from the c.s.f. when they are differentiating in the neuroependyma. The subsequent distribution of plasma protein positive cells in different brain regions is suggested to be due to the migration of developing neurones for the neuroependyma although the possibility of local synthesis of plasma proteins has not been excluded.


On the Importance of Electronic Symmetry for Triplet State Delocalization.
The influence of electronic symmetry on triplet state delocalization in linear zinc porphyrin oligomers is explored by electron paramagnetic resonance techniques. Using a combination of transient continuous wave and pulse electron nuclear double resonance spectroscopies, it is demonstrated experimentally that complete triplet state delocalization requires the chemical equivalence of all porphyrin units. These results are supported by density functional theory calculations, showing uneven delocalization in a porphyrin dimer in which a terminal ethynyl group renders the two porphyrin units inequivalent. When the conjugation length of the molecule is further increased upon addition of a second terminal ethynyl group that restores the symmetry of the system, the triplet state is again found to be completely delocalized. The observations suggest that electronic symmetry is of greater importance for triplet state delocalization than other frequently invoked factors such as conformational rigidity or fundamental length-scale limitations.


Optimal therapy for rare disorders and genetic diseases: ethical and political challenges.
Almost 40 years have passed since pediatrician-pharmacologist Harry Shirkey coined the term 'therapeutic orphans'. His intent was to describe the plight of children deprived of appropriate drugs for the treatment of common conditions and of adequate information to support effective prescribing. Awareness has since grown of the extent to which children are denied information to support optimal drug prescribing, and legislation has now been introduced in the US and the European Community to foster expanded therapeutic investigation in pediatrics. It has also been recognized that the therapeutic orphan concept may be applied more widely in a context that goes well beyond pediatrics to include, not just a patient population which has been orphaned, but also diseases and rare disorders for which effective therapeutic interventions may be lacking.


Mitochondrial Genetics Regulate Breast Cancer Tumorigenicity and Metastatic Potential.
Current paradigms of carcinogenic risk suggest that genetic, hormonal, and environmental factors influence an individual's predilection for developing metastatic breast cancer. Investigations of tumor latency and metastasis in mice have illustrated differences between inbred strains, but the possibility that mitochondrial genetic inheritance may contribute to such differences in vivo has not been directly tested. In this study, we tested this hypothesis in mitochondrial-nuclear exchange mice we generated, where cohorts shared identical nuclear backgrounds but different mtDNA genomes on the background of the PyMT transgenic mouse model of spontaneous mammary carcinoma. In this setting, we found that primary tumor latency and metastasis segregated with mtDNA, suggesting that mtDNA influences disease progression to a far greater extent than previously appreciated. Our findings prompt further investigation into metabolic differences controlled by mitochondrial process as a basis for understanding tumor development and metastasis in individual subjects. Importantly, differences in mitochondrial DNA are sufficient to fundamentally alter disease course in the PyMT mouse mammary tumor model, suggesting that functional metabolic differences direct early tumor growth and metastatic efficiency.


Severe autoimmune hemolytic anemia associated with IgM warm auto-antibodies in primary Sjögren's syndrome.
Primary Sjögren's syndrome is an autoimmune disorder involving mainly salivary and lachrymal glands. However, many extraglandular symptoms have also been reported. Although leucocytopenia and lymphocytopenia are frequently observed in hematological disorders, autoimmune hemolytic anemia is rarely reported. We experienced a case of primary Sjögren's syndrome developing severe autoimmune hemolytic anemia. The patient's red blood cells showed spontaneous agglutination in saline at room temperature, and immunoglobulin M (IgM) was detected on the surface of red blood cells by flow cytometry, indicating that autoimmune hemolytic anemia was caused by warm reactive IgM antibodies. Immediate corticosteroid therapy resulted in a dramatic recovery. We report a first case of severe autoimmune hemolytic anemia caused by warm reactive IgM antibodies in primary Sjögren's syndrome.


Asymmetric Ruthenium-Catalyzed Carbonyl Allylations by Gaseous Allene via Hydrogen Auto-Transfer: 1° vs 2° Alcohol Dehydrogenation for Streamlined Polyketide Construction.
Iodide-bound ruthenium-JOSIPHOS complexes catalyze the redox-neutral C-C coupling of primary alcohols 2a-2r with the gaseous allene (propadiene) 1a to form enantiomerically enriched homoallylic alcohols 3a-3r with complete atom-efficiency. Using formic acid as reductant, aldehydes dehydro-2a and dehydro-2c participate in reductive C-C coupling with allene to deliver adducts 3a and 3c with comparable levels of asymmetric induction. Deuterium labeling studies corroborate a mechanism in which alcohol dehydrogenation triggers allene hydroruthenation to form transient allylruthenium-aldehyde pairs that participate in carbonyl addition. Notably, due to a kinetic preference for primary alcohol dehydrogenation, chemoselective C-C coupling of 1°,2°-1,3-diols occurs in the absence of protecting groups. As illustrated by the synthesis of C7-C15 of spirastrellolide B and F (7 vs 17 steps), C3-C10 of cryptocarya diacetate (3 vs 7 or 9 steps), and a fragment common to C8'-C14' of mycolactone F (1 vs 4 steps) and C22-C28 marinomycin A (1 vs 9 steps), this capability streamlines type I polyketide construction.


Mortality Rates After the First Diagnosis of Psychotic Disorder in Adolescents and Young Adults.
Individuals with psychotic disorders have increased mortality, and recent research suggests a marked increase shortly after diagnosis. To use population-based data to examine overall and cause-specific mortality after first diagnosis of a psychotic disorder. This cohort study used records from 5 integrated health systems that serve more than 8 million members in 5 states. Members aged 16 through 30 years who received a first lifetime diagnosis of a psychotic disorder from September 30, 2009, through September 30, 2015, and 2 comparison groups matched for age, sex, health system, and year of diagnosis were selected from all members making an outpatient visit (general outpatient group) and from all receiving a first diagnosis of unipolar depression (unipolar depression group). First recorded diagnosis of schizophrenia, schizoaffective disorder, mood disorder with psychotic symptoms, or other psychotic disorder in any outpatient, emergency department, or inpatient setting. Death within 3 years after the index diagnosis or visit date, ascertained from health system electronic health records, insurance claims, and state mortality records. A total of 11 713 members with first diagnosis of a psychotic disorder (6976 [59.6%] men and 4737 [40.4%] women; 2368 [20.2%] aged 16-17 and 9345 [79.8%] aged 18-30 years) were matched to 35 576 outpatient service users and 23 415 members with a first diagnosis of unipolar depression. During the year after the first diagnosis, all-cause mortality was 54.6 (95% CI, 41.3-68.0) per 10 000 in the psychotic disorder group compared with 20.5 (95% CI, 14.7-26.3) per 10 000 in the unipolar depression group and 6.7 (95% CI, 4.0-9.4) per 10 000 in the general outpatient group. After adjustment for race, ethnicity, and preexisting chronic medical conditions, the relative hazard of death in the psychotic disorder group compared with the general outpatient group was 34.93 (95% CI, 8.19-149.10) for self-inflicted injury or poisoning and 4.67 (95% CI, 2.01-10.86) for other type of injury or poisoning. Risk of death due to heart disease or diabetes did not differ significantly between the psychotic disorder and the general outpatient groups (hazard ratio, 0.78; 95% CI, 0.15-3.96). Between the first and third years after diagnosis, all-cause mortality in the psychotic disorder group decreased from 54.6 to 27.1 per 10 000 persons and injury and poisoning mortality decreased from 30.6 to 15.1 per 10 000 persons. Both rates, however, remained 3 times as high as in the general outpatient group (9.0 per 10 000 for all causes; 4.8 per 10 000 for injury or poisoning). Increases in early mortality underscore the importance of systematic intervention for young persons experiencing the first onset of psychosis. Clinicians should attend to the elevated suicide risk after the first diagnosis a psychotic disorder.


Statistical Issues in Estimation of Adjusted Risk Ratio in Prospective Studies.
Binary outcomes are common in prospective studies such as randomized controlled trials and cohort studies. Logistic regression is the most popular regression model for binary outcomes. Logistic regression yields an odds ratio that approximates the risk ratio when the risk of outcome is low. A consensus has been reached in an extensive argument in much of the literature that the risk ratio is preferred over the odds ratio for prospective studies. To obtain a model-based estimate of risk ratios, log-binomial regression has been recommended. However, this model may fail to converge and many methods have been provided as an alternative in these situations. In this paper, we discuss the methods to obtain adjusted risk ratios in settings with independent and clustered data and we will review the results of comparisons between these methods based on simulation studies, especially a large simulation study which was conducted by the authors. We use hypothetical examples to show how log-Poisson regression with modified standard errors can be used to estimate risk ratio in practice using popular statistical software. The potential misinterpretation of odds ratios should be considered by researchers, especially when the risk of the outcome is high. When researchers want to estimate the effect of exposure or intervention by controlling potential covariates, the misinterpretation of odds ratios can be avoided using regression models that can estimate risk ratios instead of logistic regression. The log-Poisson regression with modified standard errors can be considered to estimate risk ratios in both independent and clustered data settings.


Anal carcinoma: incidence and effect of cumulative infections.
Human papilloma virus (HPV) causes anal condyloma that is a risk factor for anal carcinoma. The incidence and mechanism of invasive anal carcinoma in patients with anal condyloma are prospectively determined. From 1993 to 2002, 228 consecutive patients (164 HIV positive) with anal canal condylomas were included in the study, after curing of their lesions. They were asked to attend follow-up visits at 3- or 6-month intervals. We checked for anal co-infection with syphilis, gonococci, viruses (Epstein-Barr virus, cytomegalovirus, herpes simplex, HPV types), and quantified Langerhans' cells (LC) in anal mucosa at baseline and during follow up. We cured and analysed relapsed condylomas during follow up (3-112 months; median 26). Serum HIV loads and CD4 T-lymphocyte counts were determined at each visit and the densities of LC in consecutive specimens from patients with cancers were compared with that for a matched control group (n = 23). Analysis of 199 patients showed high-grade dysplasia (HGD) in 13.6% of patients, more in HIV-positive (16%) than in HIV-negative (6%) patients at baseline. During follow up, 3.5% (7/199; six HIV positive) patients developed invasive carcinoma after 13-108 months and 112 (56%) patients relapsed condylomas. HIV and anal co-infection were identified as independent risk factors (P < 0.01) for HGD and cancer: odd ratio (95% confidence interval) of 9.4 (2.4-37.4) and 3.67 (0.95-14.2), respectively. LC densities in anal mucosa were lower in patients with invasive carcinoma than in controls. The risk of invasive carcinoma in HPV-infected patients is increased by HIV and anal co-infection. Decreases in LC numbers in anal mucosa may favour this outcome.


Pathogenicity of Phyllosticta citricarpa Ascospores on Citrus spp.
Citrus black spot, caused by Phyllosticta citricarpa, is one of the most important fungal diseases in many citrus-growing regions with hot and humid summers. Ascospores and conidia are known to contribute to epidemic development of the disease. However, pathogenicity testing has never been done for pure ascospores produced from fully characterized P. citricarpa isolates, due to the inability to induce the sexual state in vitro. Recently, an in vitro mating technique was developed to readily produce pure P. citricarpa ascospores for use in host inoculation studies. To test the pathogenicity of P. citricarpa ascospores, we inoculated Troyer citrange leaves and Murcott tangor fruit with ascospores produced in vitro from characterized P. citricarpa isolates. Typical symptoms of citrus black spot occurred. Recovery of P. citricarpa isolates from symptomatic lesions and their characterization using genetic markers enabled us to identify recombinant genotypes among the isolates recovered from ascospore inoculations and, as such, fulfill Koch's postulates for ascospores. We have also identified Troyer citrange seedlings as a potential model system for citrus black spot inoculation studies, because it allows typical symptoms of citrus black spot to be expressed with a much shorter latent period than on fruit. This will facilitate future studies of epidemiological aspects of P. citricarpa ascospores relative to conidia and improve our understanding of the citrus black spot pathosystem. The susceptibility of Troyer citrange seedlings will also facilitate experimenting with disease management methods, aimed at reducing the impact of citrus black spot.


Immunolocalization of basement membrane molecules in the stroma of salivary gland pleomorphic adenoma.
In order to determine the participation of basement membrane molecules in formation of its characteristic stroma, 30 cases of salivary gland pleomorphic adenoma were examined by immunohistochemical staining for type IV collagen, laminin, heparan sulfate proteoglycan, and entactin. The stroma was histopathologically classified into four types: hyaline, fibrous, myxoid, and chondroid. Immunohistochemically, type IV collagen and laminin were more intensively localized in hyaline, fibrous and chondroid types of stroma, whereas heparan sulfate proteoglycan was more prominent in myxoid areas. The results suggest that the stroma contains these basement membrane components, which are possibly biosynthesized by epithelial tumor cells, and that histological variety of the stroma depends on proportion of local contents of each basement membrane molecule.


The involvement of BDNF, NGF and GDNF in aging and Alzheimer's disease.
Aging is a normal physiological process accompanied by cognitive decline. This aging process has been the primary risk factor for development of aging-related diseases such as Alzheimer's disease (AD). Cognitive deficit is related to alterations of neurotrophic factors level such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and glial cell-derived neurotrophic factor (GDNF). These strong relationship between aging and AD is important to investigate the time which they overlap, as well as, the pathophysiological mechanism in each event. Considering that aging and AD are related to cognitive impairment, here we discuss the involving these neurotrophic factors in the aging process and AD.


Palliative endoscopic treatment of malignant esophageal stenosis using a Häring prosthesis.
The aim of this work was to analyze the outcome of 78 cases of esophageal cancer for which the endoscopic placement of a Häring prosthesis was chosen as a palliative method of treatment. The average length of hospitalization was 10 days and the average survival time was 90.8 days. The postinsertion mortality rate was 6% and there were 44 complications. The best indications are carcinoma of the lower two thirds of the esophagus, neoplastic mediastinitis and esophageal fistulae.


Novel Ehrlichia sp. detected in Magellanic penguins (Sphenicus magellanicus) and in the seabird tick Ixodes uriae from Magdalena Island, southern Chile.
Ehrlichia spp. are obligatory intracellular microorganisms that infect hematopoietic, endothelial or blood cells of mammals. Ticks are the only vectors of these agents in nature. To date, the role of birds and their associated ticks as reservoirs of ehrlichiae remains almost unexplored. In this study, we performed a molecular screening for bacteria of Anaplasmataceae family in samples of spleen (n = 72) and lung (n = 17), recovered from 72 carcasses of Magellanic penguins (Spheniscus magellanicus) in Brazil and Chile. One apparently unengorged tick (Ixodes uriae) was also collected while wandering upon one of the carcasses and submitted to molecular analyses as well. Through conventional and nested PCR protocols three genes (16S rRNA, dsb and groEL) of a new Ehrlichia sp. were partially characterized upon organs of three penguins and in the tick coming from Magdalena Island (Chile). First matches after BLASTn comparisons showed that our sequences share 99.4% (16S rRNA), 94.6% (groEL) and 79.3% (dsb) of identity with "Candidatus Ehrlichia ornithorhynchi", Ehrlichia sp. NS101 and Ehrlichia canis CCZ, respectively. Matrixes of genetic distance including other representatives of the Ehrlichia genus point a 99.4%, 94.0%, and 80.0% of identity with 16S rRNA, groEL and dsb genes from Ehrlichia sp. It25, Ehrlichia sp. NS101, and Ehrlichia chaffeensis San Louis, respectively. A Bayesian phylogenetic analysis of Anaplasmataceae 16S rRNA gene places the detected Ehrlichia sp. into a group with Ehrlichia sp. BAT and Ehrlichia sp. Natal. Although depicting different topologies, Bayesian unrooted phylogenetic trees constructed for groEL and dsb genes position this Ehrlichia sp. into well-supported branches, which reinforces the finding of a new taxon. For the moment, any pathogenic effect of this new Ehrlichia sp. on penguins is still unknown. However, this fact becomes important to assess from a conservation point of view since populations of Magellanic penguins are currently threatened and in an ongoing decrease.


[Processes maps in public health organizations: the experience of the Galician Department of Public Health].
To design the processes map of the Galician Department of Public Health, we performed document reviews, held meetings and interviewed persons in charge of programs and departments to identify the processes carried out. The processes were classified into strategic, key and support processes. We defined 4 levels of disaggregation and management and staff were kept informed throughout the process. At level 0, we included 4 key processes that defined the organization's mission. At level 1, 5 strategic, 5 support and 10 key processes were defined. The key processes at level 2 identified the health programs' services. A processes map was obtained by consensus and was then approved by management and staff as a first step in implanting a process management system to improve the organization's performance.


Effect of lipoprotein(a) levels on long-term outcome in octogenarians with coronary artery disease after drug-eluting stent implantation.
High levels of lipoprotein(a) [Lp(a)] are linked to adverse cardiovascular events. The significance of Lp(a) for the survival of octogenarians with coronary artery disease (CAD) after drug-eluting stent (DES) insertion is, however, not known. The purpose of the study is to investigated the connection between Lp(a) and outcome in octogenarians with CAD after DES implantation. We retrospectively enrolled a total of 506 consecutive octogenarians with CAD and DES implantation in our institution between January 2015 to August 2018. Two patient groups were established: a low group with plasma Lp(a) lower than 50 mg/dL (n = 408) and a high group with values above 50 mg/dL (n = 98). After following up for a median of 31.53 ± 8.22 months, Kaplan-Meier curves indicated that poorer outcome censored for major cardiovascular events (MACE), myocardial infarction (MI), and target vessel revascularization (TVR) in the high group relative to the low group (log-rank test p = 0.001, p = 0.008, and p < 0.001, respectively). High Lp(a) independently predicted MACE (hazard ratio (HR) 1.90; 95% confidence interval (CI) 1.28-2.84; p = 0.002), MI (HR 2.74; 95% CI 1.23-6.11; p = 0.014), and TVR (HR 3.65; 95% CI 1.99-6.69; p < 0.001) after covariate adjustment. High Lp(a) was also significantly related to poor long-term outcome in octogenarians with CAD after DES implantation.


Recurrence of circulating anti-glomerular basement membrane antibody three years after immunosuppressive treatment and plasma exchange.
A patient with auto-antibody mediated Goodpasture's syndrome was successfully treated with cytotoxic drugs, steroids and plasma exchange. After an absence of three years, circulating anti-glomerular basement membrane antibodies reappeared, and linear IgG staining of the glomeruli was shown by immunofluorescent studies. Renal function did not change and there was no evidence of pulmonary hemorrhage. Antibody levels then fell spontaneously over the succeeding 18 months.


Oxidative stress-induced DNA damage and DNA repair mechanisms in mangrove bacteria exposed to climatic and heavy metal stressors.
Bacteria thriving in the mangrove ecosystem are major drivers of elemental cycles. Climate change and environmental stressors (heavy metals) influence the performance of these microorganisms, thereby affecting the biogeochemical cycle. The present study reports the genotoxic effect of climatic and heavy metal stressors on mangrove bacteria and their adaptation strategies. Comparative analysis between two bacterial strains, Bacillus stercoris GST-03 and Pseudomonas balearica DST-02 isolated from the Bhitarkanika mangrove ecosystem, Odisha, India, showed cellular injuries in response to various stressors as evident by declined growth, elevated levels of reactive oxygen species (ROS) and resulted DNA damage. B. stercoris GST-03 showed more tolerance towards acidic pH, whereas P. balearica DST-02 showed higher tolerance towards UV exposure and heavy metals (Lead and Cadmium). The adaptation strategies of the strains revealed a significant role of GST in ROS scavenging activity and the involvement of Nucleotide excision repair or SOS response pathways. However, irreparable DNA damage was observed at pH 9 and 200 ppm Cd in B. stercoris GST-03, and at pH 4, 1000 ppm of Pb and 200 ppm of Cd in P. balearica DST-02. The current findings provide a broad overview of bacterial response and adaptability concerning future climate and environmental changes.


Monovalent ions and water dipoles in contact with dipolar zwitterionic lipid headgroups-theory and MD simulations.
The lipid bilayer is a basic building block of biological membranes and can be pictured as a barrier separating two compartments filled with electrolyte solution. Artificial planar lipid bilayers are therefore commonly used as model systems to study the physical and electrical properties of the cell membranes in contact with electrolyte solution. Among them the glycerol-based polar phospholipids which have dipolar, but electrically neutral head groups, are most frequently used in formation of artificial lipid bilayers. In this work the electrical properties of the lipid layer composed of zwitterionic lipids with non-zero dipole moments are studied theoretically. In the model, the zwitterionic lipid bilayer is assumed to be in contact with aqueous solution of monovalent salt ions. The orientational ordering of water, resulting in spatial variation of permittivity, is explicitly taken into account. It is shown that due to saturation effect in orientational ordering of water dipoles the relative permittivity in the zwitterionic headgroup region is decreased, while the corresponding electric potential becomes strongly negative. Some of the predictions of the presented mean-field theoretical consideration are critically evaluated using the results of molecular dynamics (MD) simulation.


Suppression of the endogenous luteinizing hormone surge by the gonadotrophin-releasing hormone antagonist Cetrorelix during ovarian stimulation.
Surges of luteinizing hormone (LH) that result in luteinization but occur prematurely with respect to the diameter of the leading follicle, prevent attempts to induce multiple follicular maturation for in-vitro fertilization (IVF) in a significant number of women. We examined the possibility of blocking premature LH surges by the administration of Cetrorelix, a potent antagonist of gonadotrophin-releasing hormone (GnRH), in a study including 20 patients, some of whom had previously shown premature LH surges. All patients were treated with human menopausal gonadotrophins (HMG) starting on day 2. From day 7 until the induction of ovulation by human chorionic gonadotrophin (HCG) the GnRH antagonist Cetrorelix was given daily. HCG was injected when the dominant follicle had reached a diameter of > or = 18 mm and oestradiol concentration was > 300 pg/ml for each follicle having a diameter of > 15 mm. Oocyte collection was performed 36 h later by transvaginal ultrasound puncture, followed by IVF and embryo transfer. The hormone profiles of these patients and the results of IVF and embryo transfer are comparable to those treated with GnRH agonists and HMG. However, less time and especially less HMG is needed in comparison to patients stimulated with a long agonist protocol. Hence, treatment with Cetrorelix proved to be much more comfortable for the patient. In this study we showed that combined treatment with gonadotrophins and the GnRH antagonist Cetrorelix is a promising method for ovarian stimulation in patients who frequently exhibit premature LH surges and therefore fail to complete treatment.


Within-season increase in parental investment in a long-lived bird species: investment shifts to maximize successful reproduction?
In nest-building species predation of nest contents is a main cause of reproductive failure and parents have to trade off reproductive investment against antipredatory behaviours. While this trade-off is modified by lifespan (short-lived species prioritize current reproduction; long-lived species prioritize future reproduction), it may vary within a breeding season, but this idea has only been tested in short-lived species. Yet, life history theory does not make any prediction how long-lived species should trade off current against future reproductive investment within a season. Here, we investigated this trade-off through predator-exposure experiments in a long-lived bird species, the brown thornbill. We exposed breeding pairs that had no prior within-season reproductive success to the models of a nest predator and a predator of adults during their first or second breeding attempt. Overall, parents reduced their feeding rate in the presence of a predator, but parents feeding second broods were more risk sensitive and almost ceased feeding when exposed to both types of predators. However, during second breeding attempts, parents had larger clutches and a higher feeding rate in the absence of predators than during first breeding attempts and approached both types of predators closer when mobbing. Our results suggest that the trade-off between reproductive investment and risk-taking can change in a long-lived species within a breeding season depending on both prior nest predation and renesting opportunities. These patterns correspond to those in short-lived species, raising the question of whether a within-season shift in reproductive investment trade-offs is independent of lifespan.


Antibioprophylaxis in Prevention of Endophthalmitis in Intravitreal Injection: A Systematic Review and Meta-Analysis.
Despite endophthalmitis being the most feared complication, antibioprophylaxis remains controversial in intravitreal injections. Therefore, we conducted a systematic review and meta-analysis on the effects of antibioprophylaxis in intravitreal injections in the prevention of endophthalmitis. The PubMed, Cochrane Library, Embase and Science Direct databases were searched for studies comparing groups with and without antibiotics in intravitreal injection, with the use of the following keywords: "antibiotic*", "endophthalmitis" and "intravitreal injection*". To be included, studies needed to specify number of participants and number of endophthalmitis within each group (with and without antibiotics). We conducted meta-analysis on the prevalence of clinical endophthalmitis including both culture-proven and culture negative samples. Nine studies were included. A total of 88 incidences of endophthalmitis were reported from 174,159 injections (0.051% i.e., one incidence of endophthalmitis for 1979 injections). Specifically, 59 incidences of endophthalmitis were reported from 113,530 injections in the group with antibiotics (0.052% or one incidence of endophthalmitis for 1924 injections) and 29 incidences of endophthalmitis from 60,633 injections in the group without antibiotics (0.048% or one endophthalmitis for 2091 injections). Our meta-analysis did not report a significant difference in the prevalence of clinical endophthalimitis between the two groups with and without topical antibiotics: the odds ratio of clinical endophthalimitis was 0.804 (CI95% 0.384-1.682, p = 0.56) for the antibiotic group compared with the group without antibiotics. In conclusion, we performed the first large meta-analysis demonstrating that antibioprophylaxis is not required in intravitreal injections. Strict rules of asepsis remain the only evidence-based prophylaxis of endophthalmitis. The results support initiatives to reduce the global threat of resistance to antibiotics.


Earthquake exposure, adverse childhood experiences, and psychosocial functioning in Chilean children: A longitudinal study.
The impact of an 8.8 magnitude Chilean earthquake on elementary school students' psychosocial functioning was assessed along with exposure to adverse childhood experiences (ACEs). Skills for Life, a national school-based mental health program in Chile, routinely assesses first- and third-grade students' psychosocial functioning and classroom adaptation. Students (N = 19,627) were screened before (2009) and after (2011) the 2010 earthquake with parent- and teacher-report measures and with a parent-report of four ACEs (family psychopathology, child chronic illness, family social isolation, father absence). Earthquake exposure was categorized as mild, moderate, or severe for Chile's 15 regions. Multilevel models analyzed the unadjusted and adjusted impacts of earthquake exposure and ACEs on functioning while clustering for school- and district-level effects. In covariate-adjusted models, earthquake exposure and three ACEs were significantly associated with worsened psychosocial functioning; earthquake exposure and all four ACEs were significantly associated with worsened classroom adaptation. New family psychopathology, B = 1.90, p < .001; chronic illness, B = 2.25, p < .001; and severe earthquake impact, B = 1.29, p < .001, held the strongest negative effects on psychosocial well-being. Moderate, B = 3.04, p = .011, and severe earthquake exposure, B = 2.53, p = .047, and new family psychopathology, B = 1.99, p < .001, were associated with the worst classroom functioning 1-year postdisaster. Findings suggest that both exogenous and home-based stressors can have significant consequences for children's psychosocial functioning and classroom adaptation, and routine screening helps quantify how individual students are affected by chronic versus acute stressors.


Levels of Catecholamines in the Plasma of Patients with Cardiopulmonary Arrest.
So far, there remains a controversy regarding the efficacy of epinephrine (Ep) in patients with cardiopulmonary arrest (CPA). In this study, we evaluated the importance of the plasma levels of catecholamines prior to the administration of Ep in patients with CPA. Patients with out-of-hospital cardiac arrest (OHCA) who were transferred to Gunma University Hospital were enrolled prospectively between July 2014 and July 2017. The levels of catecholamines [Ep, norepinephrine (NEp), and dopamine] and vasopressin (antidiuretic hormone) in the plasma were measured using blood samples of cardiogenic patients with OHCA not treated with Ep. Patients were divided into two groups: the return of spontaneous circulation [ROSC (+) ] group and the no return of spontaneous circulation [ROSC (-) ] group. The plasma levels of these agents and the conditions of resuscitation were compared between these two groups. 48 patients with cardiogenic CPA had not been treated with Ep prior to obtaining the blood samples. The ROSC (+) and ROSC (-) groups included 14 and 34 patients, respectively. The frequency of prehospital defibrillation was significantly higher in the ROSC (+) group. However, the prehospital resuscitation time was significantly shorter in the ROSC (+) group. Moreover, the levels of Ep and NEp in the plasma were significantly lower in the ROSC (+) group. The increased levels of Ep in the plasma may not be associated with the acquisition of ROSC in patients with cardiogenic CPA.


[Results of bone marrow scintigraphy in hematological diseases].
Bone marrow scintigraphy was performed in 40 patients with haematological disorders (lymphomas, multiple myeloma, myeloid leukaemia, panmyelopathy and others). Routine skeletal scintigraphy was available for comparison in 18 patients. In agreement with the literature it became evident that marrow scintigraphy can show infiltrations of the bone marrow in haematological disorders earlier than skeletal scintigraphy. Hot lesions were caused by reactive proliferation of the bone marrow such as may occur with acute inflammatory joint diseases, osteomyelitis, fracture healing or other entities. Marrow imaging demonstrated reliably the actual distribution of the functioning bone marrow, a characteristic that is important for diagnosis and staging, especially in myeloproliferative diseases.


The effect of parental smoking on lung function and development during infancy.
While the adverse effects of parental smoking on respiratory health during childhood are well recognized, its potential impact on early lung development is less clear. This review summarizes current evidence on the effect of parental smoking on lung function during infancy. It is difficult to separate the effects of pre- and postnatal exposure, since the majority of mothers who smoke in pregnancy (currently around 30% worldwide) continue to do so thereafter. Nevertheless, measurements undertaken prior to any postnatal exposure have consistently demonstrated significant changes in tidal flow patterns in infants whose mothers smoked in pregnancy. While there is, as yet, no convincing evidence from studies in human infants that smoking during pregnancy is associated with increased airway responsiveness at birth, many studies have demonstrated a reduction in forced expiratory flows (on average by 20%) in infants exposed to parental smoking. While maternal smoking during pregnancy remains the most significant source of such exposure and is likely to be responsible for diminished airway function in early life, continuing postnatal tobacco smoke exposure will increase the risk of respiratory infections, the combination of both being responsible for the two- to fourfold increased risk of wheezing illnesses observed during the first year of life in infants whose parents smoke. These findings emphasize the need to keep infants in a smoke-free environment both before and after birth, not least because of growing awareness that airway function in later life is largely determined by that during foetal development and early infancy.


[Lymphotherapy of early postoperative period in intraocular cataract correction].
Potentialities of lymphotropic method of drug administration for arresting inflammation after intraocular cataract correction were studied in 60 patients aged 48-63 years. Extracapsular cataract extraction with implantation of posterior-chamber Alexeev's intraocular lens (IOL) was carried out in all of them. Patients with complications of surgery and a history of inflammations in the operated eye were not included in the study. For assessing lymphotherapy effect on drug concentration in the blood, bloodflow aggregation gradient in the bulbar conjunctiva venules was estimated in the operated on eye. The data indicate that lymphotherapy is an effective method for treating early postoperative inflammations after IOL implantation, shortening the treatment terms in comparison with traditional therapy.


High surface recombination velocity limits Quasi-Fermi level splitting in kesterite absorbers.
Kelvin Probe Force Microscopy, Photoluminescence imaging and numerical simulations are used to study the surfaces of Cu2ZnSnSe4 absorber layers. In particular, the effect of NH4OH and annealing under ambient conditions is investigated. We observe drastic changes in the measured quasi Fermi-level splitting (QFLs) after chemical cleaning of the absorber surface with NH4OH, which is traced back to a removal of the surface inversion. Air annealing recovers surface inversion, which reduces the recombination current at the surface. Annealing above 200 °C leads to a permanent change in the work function which cannot be modified by NH4OH etching anymore. This modification makes the QFLs insensitive to surface cleaning and explains why air annealing in Cu2ZnSnSe4 is important. From numerical simulations we find that a large surface recombination velocity needs to be present in order to describe the experimental observations.


Contaminants in commercial dapsone.
Three contaminants commonly found in commercial dapsone were identified as 2,4'-sulfonylbis(benzeneamine), 4-(phenylsulfonyl)benzeneamine, and 4-(4'-chlorophenylsulfonyl)benzeneamine. The identities were based on the spectral analysis and unambiguous synthesis of each compound. Solvent-free, pure dapsone was prepared by recrystallization from chloroform.