Self-Shielding Gyroscopic Radiosurgery-A First Clinical Experience, Case Series, and Dosimetric Comparison.
Self-shielding gyroscopic radiosurgery (GRS) represents a technical innovation in the field of stereotactic radiosurgery. GRS does not require a radiation vault and is optimized for radiosurgical treatments. Reports on its usage are limited. We describe the first clinical experience of GRS at our institution to assess the application of GRS in the treatment of cranial tumors. Moreover, we perform a dosimetric comparison to robotic radiosurgery (RRS) with vestibular schwannoma (VS) GRS patients. Patients who were treated with GRS between July and November 2021 were included. Patient, tumor, and dosimetric characteristics were retrospectively summarized and analyzed. Forty-one patients with 48 intracranial tumors were included. Tumor entities mostly comprised VS, brain metastases, and meningiomas. The median prescription dose and isodose line were 13.5 Gy and 50.0% for benign neoplasia versus 20 Gy and 60.0% for malignant tumors, respectively. The mean planning target volume was 1.5 cubic centimeters. All patients received a single-fraction treatment without encountering any technical setup difficulties. Treatment plan comparisons with RRS revealed comparable plan characteristics, dose gradients, and organs at risk doses. Significant differences were detected concerning the new conformity index and number of monitor units per treatment (both P < 0.01). This case series provides more evidence on the usage of self-shielding GRS in the management of cranial tumors. Dosimetric comparisons for VS cases revealed mostly equivalent dosimetric characteristics to RRS. Further clinical and physical analyses for GRS are underway.


Pharmacogenetic study of apolipoprotein E, cholesteryl ester transfer protein and hepatic lipase genes and simvastatin therapy in Brazilian subjects.
In recent years, one of the focuses of genetic investigation in cardiology has been to identify the genetic factors associated with variable response to statin treatment. Polymorphisms in apolipoprotein E (APOE), cholesteryl ester transfer protein (CETP) and hepatic lipase (LIPC), proteins with major roles in lipid metabolism and homeostasis have been shown associated with lipid-lowering drugs response. One hundred forty-six hypercholesterolemic patients of European descent were prospectively enrolled and treated with simvastatin 20 mg per day for over 6 months. Ninety-nine subjects completed the 6-month follow-up. Plasma lipids and lipoproteins were measured before and throughout the study. APOE (E*2, E*3 and E*4), LIPC-250A > G and CETP TaqIB genotypes were determined by PCR and restriction mapping. After a 6-month follow-up, no differences among genotypes in the percentage variation in lipid and lipoprotein concentrations for APOE and LIPC SNPs were observed. After adjustment for covariates, CETP B2B2 homozygotes showed a greater HDL-cholesterol increase compared to B1B2 and B1B1 subjects (14.1% vs. 1.7% and 1.3%, P < 0.05, respectively). Our study demonstrates that individual plasma HDL-cholesterol response to simvastatin is mediated, in part, by the CETP gene locus, with the B2 homozygotes having more benefit in HDL-C improvement than carriers of B1 allele.


Comorbid psychopathology and everyday functioning in a brief intervention study to reduce khat use among Somalis living in Kenya: description of baseline multimorbidity, its effects of intervention and its moderation effects on substance use.
Migration and khat use were found to correlate with high rates of psychopathology. In this paper we aimed for assessing baseline multimorbidity and its interactions with a Brief Intervention. In the RCT, 330 male Somali khat users were assigned to treatment conditions (khat use is a predominantly male habit). The ASSIST-linked BI for khat users was administered. Using the TLFB Calendar, the PHQ-9, a Somali short version of the PDS and parts from the CIDI, khat use and comorbidity was assessed. With a regression analysis we tested for the influence of comorbidity and with mixed effect models group differences over time in sleep duration, khat use-time and everyday functioning. We found high rates of baseline multimorbidity: 51% (N = 168) for depression, 22% (N = 74) for PTSD and 23% (N = 73) for khat-psychotic symptoms. Depression and khat-psychotic symptoms, but not PTSD symptoms decreased without group differences. Khat use-time decreased and functional time increased with significant time × group interactions (p ≤ 0.046). Depression and PTSD did not influence therapy success but in participants without comorbid psychopathology, more khat use reduction after the intervention was found (p = 0.024). Somali khat users in Kenya are highly burdened by multimorbidity of depression, PTSD and khat-psychotic symptoms. The main effects for time and differences in healthy vs. mentally ill khat users indicate potential of unspecific support and the specific need for mental health care in combination with substance abuse treatment. The increase of everyday functioning promises more options for alternative activities, preventing excessive use and addiction.


Circularly Polarized Luminescence Designed from Molecular Orbitals: A Figure-Eight-Shaped [5]Helicene Dimer with D2 Symmetry.
Although many chiral molecules exhibiting circularly polarized luminescence (CPL) have been reported recently, few molecular design guidelines are known for increasing the dissymmetry factor for CPL (glum). We demonstrate that a figure-eight-shaped molecule with D2 symmetry has excellent chiroptical properties (Φf = 0.08, |glum| = 1.5 × 10-2), which are attributed to the parallel arrangement of μ and m as well as a good |μ|/|m| ratio.


[Species affiliation of staphylococci isolated in purulent infections].
The microflora was studied of the clinical material taken from those patients presenting with different pyo-septic diseases. It has been ascertained that a key role in the etiology of the above diseases must be referred to gramme-positive micro-organisms--to coagulase-negative staphylococci among their number. Of these, S. haemolyticus and S. epidermidis were found with high frequency.


Characteristics of punctate inner choroidopathy complicated by choroidal neovascularisation on Multispectral Imaging in comparison with other imaging modalities.
To describe the characteristics seen on multispectral imaging (MSI) in patients with punctate inner choroidopathy (PIC) and choroidal neovascularisation (CNV) and compare the findings with current standard multimodal imaging techniques. This is a retrospective observational case series of 10 patients with PIC complicated by CNV that underwent multimodal retinal imaging examinations. Twelve eyes of 10 patients were included. CNV was identified in 11 of the 12 eyes (91.7%) by MSI with nodular or trunk-like hyperreflectance on retinal oxy/deoxyhemoglobin map. MSI revealed choroidal vasculature around CNV in 91.7% eyes and pathological changes including retinal pigment epithelial atrophy and melanin disruption of punctate lesions in all eyes. MSI helps in noninvasively detecting CNV in PIC patients and observing associated changes in choroidal vasculature. This imaging technique is also a promising tool for better tracking pathological changes of PIC lesions complementary to current standard multimodal imaging modalities.


Wild-type and 'a' epitope variants in chronic hepatitis B virus carriers positive for hepatitis B surface antigen and antibody.
This study aims to examine the genomic variants of the 'a' epitope in chronic hepatitis B virus (HBV) carriers positive for both hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs). Eighteen HBV carriers were studied. Hepatitis B virus (HBV) DNA was extracted and the 'a' epitope region was amplified and sequenced. Eighteen Chinese asymptomatic HBV carriers were studied. There were 13 patients who were positive for both HBsAg and anti-HBs. Of these, one patient had only wild-type HBV, three had a viral mixture, and five had only 'a' epitope variant HBV. Of the three patients with a viral mixture, all had variants in the less conserved region (123-137). Of the five patients with pure HBsAg mutants, three had variants in the less conserved region while two had variants in the highly conserved region. In this study with a limited number of patients, the serum alanine aminotransferase (ALT) levels were higher in patients with wild-type HBV, compared with those with either 'a' epitope variants or a viral mixture consisting of wild type and variants. Eight of the nine (89%) patients positive for both HBsAg and anti-HBs harbored an 'a' epitope variant. The lower ALT levels seen in patients who had either pure 'a' epitope variant or a mixture of wild type and mutants suggest that a closer monitoring of these 'a' epitope variants should be required, as patients carrying these infectious viral strains may remain asymptomatic.


Can VISION 2020 be implemented in rural government settings? Findings from two programmes in Tanzania.
To generate information on essential components and the cost recovery potential of VISION 2020 programmes in rural Africa. We took a structured approach to planning, training, implementation and supervision of programmes in Singida and Mara regions, Tanzania involving both government and non-government partners. Extensive mentoring was provided to monitor activities and costs. Annual numbers of patients receiving eye care increased sevenfold, cataract surgeries by a factor of 2.6 and spectacles dispensed by a factor of 16. Running costs were shared; the government provided 40-60%, non-government organisations (NGOs) 25-45%, and patient fees 15%. Comprehensive eye care can be delivered with cooperation among partners. However, continued coordination and cooperation from government and NGOs are critical to reach VISION 2020 goals.


Internal vertical shortening for the correction of diffuse or segmental postoperative blepharoptosis.
In a series of 18 patients operated on because of postoperative eyelid contour abnormalities or small to moderate amounts of diffuse blepharoptosis, a technique of internal vertical shortening produced consistently reliable results. A cosmetically acceptable result was achieved in 17 of 18 patients (95%); only one of 18 (5%) showed no improvement. In cases of overcorrected upper eyelid retraction secondary to thyroid ophthalmopathy, 11 of 11 patients had cosmetically acceptable results. In those with blepharoptosis or eyelid contour abnormalities secondary to other causes, six of seven patients (84%) had cosmetically acceptable results. In our technique of internal vertical shortening, a predetermined amount of conjunctiva and overlying scar tissue or levator aponeurosis is removed. The resection uses a posterior approach to remove tissue from the superior tarsal border upward.


Nationwide improvement of rectal cancer treatment outcomes in Norway, 1993-2010.
The Norwegian Rectal Cancer Project was initated in 1993 with the aims of improving surgery, decreasing local recurrence rates, improving survival, and establishing a national rectal cancer registry. Here we present results from the Norwegian Colorectal Cancer Registry (NCCR) from 1993 to 2010. A total of 15 193 patients were diagnosed with rectal cancer in Norway 1993-2010, and were registered with clinical data regarding diagnosis, treatment, locoregional recurrences and distant metastases. Of these, 10 796 with non-metastatic disease underwent tumour resection. The results were stratified into five time periods, and the treatment outcomes were compared. Recurrence rates are presented for the 9785 patients who underwent curative major resection (R0/R1). Among all 15 193 patients, relative five-year survival increased from 54.1% in 1993-1997 to 63.4% in 2007-2010 (p < 0.001). Among the 10 796 patients with stage I-III disease who underwent tumour resection, from 1993-1997 to 2007-2010, relative five-year survival improved from 71.2% to 80.6% (p < 0.001). An increasing proportion of these patients underwent surgery at large-volume hospitals; and 30- and 100-day mortality rates, respectively, decreased from 3.0% to 1.4% (p < 0.001) and from 5.1% to 3.0% (p < 0.011). Use of preoperative chemoradiotherapy increased from 6.5% in 1993 to 39.0% in 2010 (p < 0.001). Estimated local recurrence rate after major resection (R0/R1) decreased from 14.5% in 1993-1997 to 5.0% in 2007-2009 (p < 0.001), and distant recurrence rate decreased from 26.0% to 20.2% (p < 0.001). Long-term outcomes from a national population-based rectal cancer registry are presented. Improvements in rectal cancer treatment have led to decreased recurrence rates of 5% and increased survival on a national level.


Production of scleroglucan from Sclerotium rolfsii MTCC 2156.
Scleroglucan, a neutral homopolysaccaride consisting of a linear chain of beta-D-(1-3)-glucopyranosyl and beta-D-(1-6)-glucopyranosyl groups, was produced by pure culture fermentation from Sclerotium rolfsii MTCC 2156 by submerged culture. Fermentation process was optimized in two steps. In the first step, one-factor-at-a-time method was used to investigate the effects of medium constituents such as carbon and nitrogen sources. In the second step, concentration of medium components was optimized using an L16-orthogonal array method. In all, 10 different carbon sources and eight different nitrogen sources were evaluated. Maximum yield of 16.58 g/l was obtained in a medium containing sucrose as a carbon source and sodium nitrate and yeast extract as nitrogen source.


The insertion domain of the duck hepatitis B virus core protein plays a role in nucleocapsid assembly.
Synthesis of hepadnaviral DNA is dependent upon both the viral DNA polymerase and the viral core protein, the subunit of the nucleocapsids in which viral DNA synthesis takes place. In a study of natural isolates of duck hepatitis B virus (DHBV), we cloned full-length viral genomes from a puna teal. One of the clones failed to direct viral DNA replication in transfected cells, apparently as a result of a 3 nt inframe deletion of histidine 107 in the core protein. Histidine 107 is located in the center of a predicted helical region of the "insertion domain", a stretch of 45 amino acids which appears to be at the tip of a spike on the surface of the nucleocapsid. The mutation was introduced into a well-characterized strain of DHBV for further analysis. Core protein accumulated in cells transfected with the mutant DHBV but was partially degraded, suggesting that it was unstable. Assembled nucleocapsids were not detected by capsid gel electrophoresis. Interestingly, the mutant protein appeared to form chimeric nucleocapsids with wild-type core protein. The chimeric nucleocapsids supported viral DNA replication. These results suggest that the insertion domain of the spike may play a role either in assembly of stable nucleocapsids, possibly in formation of the dimer subunits, or in triggering nucleocapsid disintegration, required during initiation of new rounds of infection.


Arthroscopic Removal of Extra-Articular Foreign Bodies From the Shoulder: Inside-Out Technique.
Arthroscopic shoulder surgery can be performed for retrieval of bullets and retained metallic fragments in the glenohumeral and subacromial spaces. Previous case reports and case series have demonstrated the effectiveness of an arthroscopic approach over an open procedure, as it is less invasive, allows for improved inspection and documentation of the joint surfaces and periarticular structures, and potentially leads to a faster recovery. An arthroscopic approach for extracting foreign bodies from both the quadrilateral space and the posterior extra-articular space by first accessing the glenohumeral space has yet to be described. This inside-out technique may afford surgeons the potential for improved visualization and less morbidity compared with a traditional open posterior approach. We report a technique for an arthroscopic inside-out approach for removal of extra-articular foreign bodies retained in either the quadrilateral space or the posterior extra-articular space.


Inhibition of cellular transition from G1-resting to G1-prereplicative phase by aminonucleoside of puromycin.
Human embryonic lung fibroblasts (IMR-90 and WI-38) were arrested in the G1 phase of the cell cycle by serum deprivation and high population density. Within 1 hr after the addition of medium containing fresh serum, these cells showed an increase in rRNA synthesis. The inclusion of 100 micrograms per ml aminonucleoside of puromycin (AMS) in the fresh medium eliminated the serum stimulation of rRNA synthesis and prevented the cells from making the G1-resting phase to G1-prereplicative phase transition. AMS also prevented the synthesis of HnRNA normally found within 10 hr after serum stimulation. Serum-stimulated RNA synthesis in starved, SV-40 transformed fibroblasts (WI-38-VA-13 cells) was inhibited, but not completely prevented, by AMS indicating that transformed cells may produce specific RNA's that are not AMS-sensitive and that may be responsible for the failure of transformed cells to be arrested in G1.


[Prenatal intestinal volvulus: A life-threatening event with good long-term outcome].
To describe the outcome of neonates with prenatal intestinal volvulus. All neonates with prenatal intestinal volvulus managed in our institution between May 2004 and December 2010 were retrospectively studied. All neonates with prenatal or neonatal diagnosis of prenatal intestinal volvulus were included. We analyzed age at diagnosis, fetal ultrasound (US) scan and magnetic resonance imaging (MRI) findings, clinical signs at birth, surgical findings, management, and postoperative outcome. Ten neonates with prenatal intestinal volvulus were identified. Prenatal US scans or MRI demonstrated evidence of meconium peritonitis in one fetus and bowel dilatation in 2 others. The mean gestational age at birth was 36 weeks (range, 31-38 weeks) and the mean birth weight was 2811g (range, 2050-3700g). One premature neonate developed respiratory distress and required ventilatory support at birth. In 7 neonates, clinical examination showed distended abdomen and emesis, whereas plain abdominal radiographs showed intestinal obstruction. All neonates underwent surgery and all had normal intestinal rotation, except one with total intestinal volvulus secondary to malrotation. Other causes of volvulus were suspected in 4 neonates: mesenteric defect (n=1), intestinal atresia (n=2) and narrow mesentery (n=1). Detorsion of total volvulus, ileostomy, or intestinal resection with primary anastomosis was performed in 2, 5, and 3 neonates, respectively. One patient with total intestinal volvulus secondary to malrotation died, whereas all other neonates survived. In one patient, the postoperative course was complicated by intestinal dysmotility of the distal small bowel requiring a secondary jejunoileostomy. Stoma closure was subsequently performed at 1 year of age with good outcome. One patient developed angiocholitis treated successfully with antibiotics. Median time to initiate enteral feeds was 7 days (range, 4-16 days) and all patients were subsequently weaned from parenteral nutrition. Median duration of parenteral nutrition was 29 days (range, 6-667 days). None of the patients had cystic fibrosis. Unlike postnatal volvulus, most prenatal volvulus occurs without malrotation. Although prenatal volvulus is a life-threatening condition, our results suggest that good long-term outcome can be achieved in most cases.


Characterization of a rat liver protein carboxyl methyltransferase involved in the maturation of proteins with the -CXXX C-terminal sequence motif.
We have utilized S-farnesyl-Leu-Ala-Arg-Tyr-Lys-Cys as a methyl-accepting substrate to characterize a membrane-bound C-terminal protein methyltransferase from rat liver. We have localized the activity to the microsomal fraction and show that the bulk of the enzyme fractionates by density gradient centrifugation with glucose-6-phosphatase, a marker of the endoplasmic reticulum, and not with 5'-nucleotidase, a marker of the plasma membrane, or galactosyl:N-acetylglucosamine transferase, a marker of the Golgi apparatus. This methyltransferase appears to form an integral part of the membrane structure. Its activity is markedly affected by a variety of detergents used to solubilize membrane proteins in their native form. All activity is lost when membranes are treated with seven different detergents at a concentration of 1% (w/v). The activity is inhibited by N-ethylmaleimide, although it can be protected against inactivation with its substrate S-adenosyl-L-methionine, or its product S-adenosyl-L-homocysteine. Finally, we find that 5'-methylthioadenosine, a substrate analogue reported to be an inhibitor of this activity in other studies, is not an effective inhibitor in vitro.


Hashimoto's thyroiditis: a possible risk factor for lung cancer among Japanese women.
To study the epidemiologic association between Hashimoto's thyroiditis and malignancies, autopsy protocols (1959--1974) were examined at the Tokyo University Hospital. The study cases were classified according to major cause of death, including breast and lung cancer. The relationship between thyroid changes and breast cancer was not significant; however, a significant association between thyroid alteration and lung cancer was identified. This finding suggested that Hashimoto's thyroiditis and related changes could be one of the risk factors for lung cancer among Japanese women.


Reperfusion-induced arrhythmias: do free radicals play a critical role?
This article assesses whether oxygen-derived free radicals are one of the molecular causes of life-threatening arrhythmias that arise upon reperfusion of the ischemic myocardium. Evidence supporting this proposition has been obtained from studies of the effects of free radical scavengers and antioxidants, free radical generating systems, inhibition of various sources of free radicals and studies investigating the formation of free radicals and their products during early reperfusion. It has been hypothesized that free radical formation causes localised membrane damage to the sarcolemma that results in focal alterations in transmembrane ionic fluxes, particularly potassium. These changes in ionic fluxes may then lead to electrophysiological abnormalities that culminate in ventricular arrhythmias.


Treatment of rectovaginal fistulas that has failed previous repair attempts.
The purpose of this study was to assess results of treatment of rectovaginal fistulas (excluding pouch vaginal fistulas) that have failed previous attempts at repair. A retrospective chart review of all patients presenting with nonhealing rectovaginal fistula was performed. Twenty eight patients with persistent fistulas were identified. In 18 patients the fistula was classified as simple, and in 10 the fistula was complex. Fourteen fistulas were secondary to obstetric injury, five were caused by Crohn's disease, and nine patients had miscellaneous etiologies for their fistulas. Of patients with persistent simple fistulas, 13 (72 percent) of the fistulas healed, 5 after advancement flaps, 5 following sphincteroplasty, and 3 after coloanal anastomoses. Of persistent complex fistulas, only four of ten (40 percent) healed, one following sphincteroplasty, one with coloanal anastomosis, and two after gracilis transposition. A total of 23 advancement flaps were done in 17 patients with five fistulas healing (29 percent). Sphincteroplasty and fistulectomy was successful in six of seven patients (86 percent). Coloanal anastomosis resulted in healing of four of six patients (67 percent) in whom it was attempted. Gracilis muscle transfer was successful in two of two patients (100 percent). Persistent rectovaginal fistula presents a difficult management problem. Choice of operation must be tailored to the underlying pathology and type of repair previously done. Advancement flap repair is generally not recommended for persistent complex fistulas or for simple fistulas that have failed a previous advancement flap repair.


In vivo and in vitro studies of anticancer actions of alpha-TEA for human prostate cancer cells.
Vitamin E analog, 2,5,7,8-tetramethyl-2R-(4R,8R, 12-trimethyltridecyl) chroman-6-yloxyacetic acid, referred to as alpha-TEA induces apoptosis in a variety of human cancer cells in cell culture and reduces tumor burden and metastases in preclinical animal models of breast and ovarian cancer. The goal of this study was to determine in vivo anticancer efficacy of alpha-TEA against human prostate cancer cells and identify mechanisms of action. A PC-3-GFP xenograft model was used to assess the effects of alpha-TEA formulated in liposomes and administered orally on tumor burden and metastases. Tumor tissue was examined by immunohistochemical staining for percentage of cells undergoing apoptosis by TUNEL or cell proliferation by Ki-67. In vitro analyses of mechanisms employed western immunoblotting to examine effects of alpha-TEA-treatments in LNCaP and PC-3-GFP cells on levels of pro-survival and pro-death factors. Functional significance was determined using ectopically expressed constitutively active forms, inhibitors, or siRNA. alpha-TEA significantly reduced tumor burden and metastases, increased apoptosis and decreased proliferation of tumor cells (P < 0.05). alpha-TEA treatment of both LNCaP and PC-3-GFP cells in vitro reduced levels of pAkt1, pAkt2; FOXO1, c-FLIP(L) and survivin. Constitutively active Akt1, Akt2, c-FLIP or survivin reduced alpha-TEA-induced apoptosis. PI3K inhibitor enhanced apoptosis. Constitutively active FOXO1 enhanced alpha-TEA induced Fas ligand expression; whereas, FOXO1 siRNA reduced alpha-TEA induced Fas ligand expression. alpha-TEA is an effective anticancer agent for human prostate cancer cells. Downregulation of pro-survival and upregulation of pro-death factors play roles in alpha-TEA-induced apoptosis.


Molecular characterization of mu class glutathione-S-transferase from disk abalone (Haliotis discus discus), a potential biomarker of endocrine-disrupting chemicals.
The present study has reported the cloning, expression, and characterization of a mu class glutathione S-transferase (GST) gene, HdGSTM1, identified from disk abalone (Haliotis dicus discus) cDNA library. HdGSTM1 encodes a polypeptide of 215 amino acids with a calculated molecular mass of 25 kDa. The recombinant HdGSTM1 exhibited a relatively low activity of 0.172+/-0.01 mumol/min/mg protein toward 1-chloro-2, 4-dinitrobenzenel (CDNB), and 0.114+/-0.03 mumol/min/mg protein toward ethacrynic acid (ECA). Kinetic analysis with respect to glutathione and CDNB gave a K(m) value of 0.734+/-0.053 mM and 2.721+/-0.236 mM, respectively. HdGSTM1 had an optimum temperature of 35 degrees C and an optimum pH of 8.0. It also showed stability in a wide range of temperatures and pH. Modeling structure analysis revealed that the low catalytic activity of HdGSTM1 was caused by the improper residues in key active sites. The transcripts of HdGSTM1 were detected in all five examined organs, with the highest levels in gills and gonads. After 48 h waterborne exposure of three model endocrine-disrupting chemicals (PAH, PCB, and TBT), the expression of HdGSTM1 was significantly induced in both gill and digestive tract tissues through semi-quantitative RT-PCR examination, suggesting good biomarker potentials.


Communication between organ donor families and recipients: a definitely controversial subject.
In transplant centers, few topics are more controversial than communication between organ donor families (ODF) and recipients (RE). The Organ Procurement Organizations and transplant centers have felt obliged to protect the confidentiality and interests of ODF and RE. However, some authors have reported favorable effects of contact between ODF and RE. This study sought to investigate the current situation of the communication between ODF and RE from the viewpoint of transplanted patients (n = 50) and waiting transplant patients (n = 50) at a Brazilian University Hospital, ODF (n = 10), physicians from transplant centers (n = 50), as well as the opinion of the general population of a Brazilian city (n = 100). This work was developed as a survey whose questions related to the issue of communication between ODF and RE. The results showed that the majority of transplanted patients (82%) and patients awaiting transplant (60%) wanted to meet ODF to express their gratitude for receiving the organ. Likewise, ODF (67%) wanted to have a meeting with recipients, which allowed them to confirm the benefit of their donation. The general population was also favorable (66%) to ODF and RE communication. In contrast, the physicians (74%) were opposed to the ODF and RE contact. They affirmed that direct contact could lead to serious emotional conflicts or attempts of material involvement. One believes that decisions concerning the contact between ODF and RE would have to be determined by the involved parties. The transplant team could analyze the requests case by case, but ODF and RE must have the right to make the final decision.


Electrification of New Zealand transport: Environmental impacts and role of renewable energy.
New Zealand's goal to be carbon neutral by 2050 has led to the development of strategic policies and schemes to encourage the use of electric vehicles (EVs). However, most studies are focused on the greenhouse gas emissions of EVs while limited studies are available on their other potential environmental impacts. Using life cycle assessment (LCA), the environmental impacts of EV adoption, specifically the battery electric vehicle (BEV), were assessed to determine the future environmental challenges for New Zealand. Due to 87.1 % share of renewable sources of electricity generation in New Zealand in 2022, EV adoption has demonstrated its strong potential to reduce the CO2 emission of the transport sector. Results showed that lithium-ion battery (LIB), including production and disposal, is the major contributor to the environmental impacts of BEV adoption. The direct environmental impacts of BEV in New Zealand range from 0.34 % to 42.5 % across its life cycle. The results are sensitive to the assumptions of the driving range and number of LIB replacements where they could increase up to 34.5 % per km and up to 48.9 % per replacement of LIB on environmental impacts, respectively. Scenario analysis also showed that when the renewable energy share in electricity production is increased to 100 %, the environmental impacts of the BEV life cycle could be reduced by up to 14.5 % while it could decrease by up to 69.6 % in New Zealand. Additionally, reusing the spent LIB for other purposes would have the least environmental impacts on disposal among the options considered in the study. Therefore, New Zealand would benefit the most from BEV adoption by generating 100 % electricity from renewable sources, and developing policies and schemes to repurpose LIB at its end of life.


Evolutionary steps in the design and biofunctionalization of the additively manufactured sub-periosteal jaw implant 'AMSJI' for the maxilla.
The purpose of this prospective registry case-series study was to determine the biological, mechanical, and aesthetic improvements made to the additively manufactured sub-periosteal jaw implant (AMSJI) after timed installation. A total of nine patients received maxillary AMSJIs in three sessions over a 2-year period. Architectural changes, topological optimization, and amendments to biofunctionalization were performed after each phase through the use of computer-aided design, finite element analysis, and growing clinical experience. Biological improvements included sandblasting (large grit alumina) and acid-etching; increased hydrophilicity by plasma surface activation; deletion of the crestal connecting struts; relocation of the anterior post in front of the anterior part of the basal loop; protection of the Schneiderian membrane from fixation screw penetration; high polishing of the posts; major platform switch with equigingival connections; the use of removable posts that require local anaesthesia and do not inflict major biological damage; scaffolding for secondary stability; and the provision of an incision guide. Mechanical improvements included the creation of a generic design based on finite element analysis and the resulting topological optimization, a shortening of the wings, and a reduction in the number of fixation screws. Aesthetic improvements included relocation of the anterior post, as described above, and pink anodization of the posts.


Individualized optimization of colistin loading doses.
Colistin remains one of the few available options for the treatment of infections caused by resistant bacteria. Pharmacokinetic (PK) studies have been successful in estimating the appropriate colistin methanesulfonate (CMS) dose to achieve a target colistin concentration. Currently, there is a consensus that the dose of CMS should vary according to the patient renal function since CMS is mainly eliminated by renal route. For this same reason, the loading dose should vary according to the patient's renal capacity; however, this is not the current clinical practice. In this study we develop a framework to determine two key parameters for the loading dose regimen: (1) the optimal dose according to the characteristics (renal function and weight) of the patient; (2) the waiting time before the maintenance dose. Based on a previous PK model, our framework allows a fast parameter sweep so as to select optimal loading dose and waiting time minimizing the deviation between the plasma concentration and a target value. The results showed that patients presenting low creatinine clearance (CrCL) should receive a lower CMS loading dose with longer interval to start maintenance treatment to avoid nephrotoxic colistin concentrations. In cases of high CrCL, the dose should be higher and the interval to the next dose shorter to avoid subtherapeutic concentrations. Optimization of the loading dose should considerably improve colistin therapy, as the target concentration is reached more quickly, without reaching toxic values.


Impact of COVID-19 on electroconvulsive therapy practice across Canadian provinces during the first wave of the pandemic.
Electroconvulsive therapy (ECT) is a procedural treatment that is potentially life-saving for some patients with severe psychiatric illness. At the start of the global coronavirus disease 2019 (COVID-19) pandemic, ECT practice was remarkably disrupted, putting vulnerable individuals at increased risk of symptom exacerbation and death by suicide. This study aimed to capture the self-reported experiences of psychiatrists based at healthcare facilities across Canadian provinces who were delivering ECT treatments during the first phase of the COVID-19 pandemic (i.e., from mid-March 2020 to mid-May 2020). A multidisciplinary team of experts developed a survey focusing on five domains: ECT unit operations, decision-making, hospital resources, ECT procedure, and mitigating patient impact. Responses were collected from psychiatrists providing ECT at 67 ECT centres in Canada, grouped by four geographical regions (Ontario, Quebec, Atlantic Canada, and Western Canada). Clinical operations of ECT programs were disrupted across all four regions - however, centres in Atlantic Canada were able to best preserve outpatient and maintenance care, while centres in Western Canada were able to best preserve inpatient and acute care. Similarly, Atlantic and Western Canada demonstrated the best decision-making practices of involving the ECT team and clinical ethicists in the development of pandemic-related guidelines. Across all four regions, ECT practice was affected by the redeployment of professionals, the shortage of personal protective equipment, and the need to enforce social distancing. Attempts to introduce modifications to the ECT delivery room and minimize bag-valve-mask ventilation were consistently reported. All four regions developed a new patient prioritization framework, and Western Canada, notably, aimed to provide ECT to only the most severe cases. The results suggest that ECT provision was disproportionately affected across different parts of Canada. Possible factors that could explain these interregional differences include population, distribution of urban vs. rural areas, pre-pandemic barriers in access to ECT, number of cases, ability to control the spread of infection, and the general reduction in physicians' activities across different areas of health care. Studying these factors in the future will inform how medical centres should respond to public health emergencies and pandemic-related circumstances in the context of procedural treatments.


Synthesis of antibodies and immunoglobulins bearing recipient allotypic markers and donor idiotypic specificities in irradiated rabbits grafted with allogeneic cells from hyperimmune donors.
Irradiated rabbits were grafted with a mixture of bone marrow, lymph node and spleen cells from donors hyperimmunized against TMV. Recipient and donors were characterized by different a allotypic specificities. Antibodies synthesized in the recipients display allotypic markers from the recipients but idiotypic specificities cross-reactive with those of donor antibodies. The results show that the differentiation of new host B cells is influenced by the presence of donor memory cells and are interpreted in the light of network concepts.


Effect of an intravenous gammaglobulin preparation on the opsonophagocytic activity of preterm serum against coagulase-negative staphylococci.
Recent reports have described cases of septicaemia caused by coagulase-negative staphylococci in preterm neonates, mainly due to the use of artificial intravenous devices. It was of interest to examine if intravenous immunoglobulin therapy, known to be effective in group B streptococcal infections of neonates, had a similar beneficial effect in coagulase-negative staphylococcal infections. Opsonophagocytosis of coagulase-negative staphylococci by normal polymorphonuclear leukocytes in the presence of cord blood serum supplemented with the commercial IgG preparation 'Sandoglobulin' was investigated, using luminol-dependent chemiluminescence. It was found that with two different coagulase-negative staphylococcal strains, Sandoglobulin had a concentration-dependent enhancing effect on the chemiluminescent response. This effect was demonstrated in the presence of native as well as inactivated cord blood serum and in the presence of sera from preterm infants (28-33 weeks). It is concluded that intravenous Sandoglobulin therapy may be effective in the treatment of preterm infants with severe coagulase-negative staphylococcal infections.


Participant views and experiences of participating in HIV research in sub-Saharan Africa: a qualitative systematic review.
Human immunodeficiency virus clinical trials are increasingly being conducted in sub-Saharan Africa. There is a tension between the pressure to increase levels of research participation and the need to ensure informed consent and protection of participants' rights. Researchers need to be aware of the particular ethical issues that underpin Human immunodeficiency virus research conduct in low income settings. This necessitates hearing from those who have participated in research and who have direct experience of the research process. This review aimed to synthesize and present the best available evidence in relation to Human immunodeficiency virus research participation in sub-Saharan Africa, based on the views and experiences of research participants. The review included studies whose participants were current or former adult Human immunodeficiency virus research participants from sub-Saharan African countries. Views, experiences, attitudes, understandings, perceptions and perspectives of Human immunodeficiency virus research participants in sub-Saharan Africa. Types of studies: This review considered studies that focused on qualitative data, including, but not limited to, designs such as phenomenology, ethnography, grounded theory, action research and feminist research. A three-step search strategy was utilized. Seven databases (CINAHL, Ovid MEDLINE (R) 1946, ASSIA, PsychInfo, Web of Science, EMBASE, and African Index Medicus) were searched with no limitation to years of publication, followed by hand searching of reference lists. Only studies published in the English language were considered. Methodological quality was assessed using the Qualitative Assessment and Review Instrument developed by the Joanna Briggs Institute. Qualitative findings were extracted using the Joanna Briggs Institute Qualitative Assessment and Review Instrument. Qualitative research findings were pooled using a pragmatic meta-aggregative approach and the Joanna Briggs Institute Qualitative Assessment and Review Instrument software. Twenty-one studies were included in the review. One hundred and thirty-six findings were extracted from included studies and clustered into 14 categories based on similarities in meaning. These were further synthesized into five synthesized findings, set out below; i) Individuals are motivated to participate in Human immunodeficiency virus research due to a range of perceived benefits for themselves and others. ii) Participation in research can be associated with considerable fear and uncertainty. iii) Participation in Human immunodeficiency virus research is strongly influenced by social relationships (e.g. support or disapproval of family or friends) and social-economic and domestic factors (such as time or finances). iv). The meanings of research programs and processes are constructed within a context of existing lay beliefs, experiences and social relations associated with Human immunodeficiency virus and biomedical interventions in general. This means that local people may understand research and its processes very differently to health professionals. v) Participants' research experiences and their continued participation in Human immunodeficiency virus research are influenced by the research clinic context and the nature of their interactions with research staff. Individuals are generally willing to participate in Human immunodeficiency virus research. However their understanding of the process can be limited, and the experience may may cause anxiety or have negative consequences. Furthermore longer-term participation may become problematic due to socio-economic pressure or social commitments. The review suggests a need to develop better ways to explain research processes and to support participants, when/if they encounter problems. There is also a need to engage better with communities in order to educate them about HIV research programs. All the included studies focused on experiences around research enrolment and participation (retention); however there is a complete evidence gap on experiences of trial closure.


The lung function score and its components as predictors of overall survival and chronic graft-vs-host disease after allogeneic stem cell transplantation.
To retrospectively assess if the modified lung function score (LFS) and/or its components, forced expiratory volume within the first second (FEV1) and diffusion capacity for carbon monoxide corrected for hemoglobin level (cDLCO), predict overall survival (OS) and chronic graft-vs-host-disease (cGvHD). We evaluated 241 patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the University of Regensburg Transplant Center between June 1998 and July 2005 in relation to their LFS, FEV1 and cDLCO, before and after HSCT. Decreased OS after allo-HSCT was related to decreased pre-transplantation values of FEV1<60% (P=0.040), cDLCO<50% of predicted value (P=0.025), and LFS≥III (P=0.037). It was also related to decreased FEV1 at 3 and 12 months after HSCT (P<0.001 and P=0.001, respectively) and increased LFS at 3 and 12 months after HSCT (P=.028 and P=0.002, respectively), but not to changes of cDLCO. A higher incidence of cGvHD was related to decreased FEV1 at 6, 12, and 18 months (P=0.069, P=0.054, and P=0.009, respectively) and increased LFS at 12 months (P=0.002), but not to changes in cDLCO. OS was related to both LFS and FEV1, but cGvHD had a stronger relation to FEV1 than to cDLCO or LFS. FEV1 alone offered more information on the outcome after allo-HSCT than LFS or cDLCO, suggesting limited value of LFS for the patients' assessment after allo-HSCT.


An estimation of the heritability of phototaxis in Daphnia magna Straus.
The phototactic responses of four clones of Daphnia magna were experimentally analysed. Broad-sense heritability of this behavioural character was estimated through an analysis of variance, and it was very high under the standardised experimental conditions of this study.


Evolution of osmoregulatory patterns and gill ion transport mechanisms in the decapod Crustacea: a review.
Decapod crustaceans exhibit a wide range of osmoregulatory patterns and capabilities from marine osmoconformers to brackish and freshwater hyperregulators to terrestrial hyporegulators. The principal gill salt transport mechanisms proposed to underlie the ability of the better-known taxa to occupy these specific habitats are examined here. Traditional thinking suggests that a graduated series of successively stronger adaptive mechanisms may have driven the occupation of ever more dilute osmotic niches, culminating in the conquest of freshwater and dry land. However, when habitat and osmoregulatory parameters are analyzed quantitatively against the phylogenies of the taxa examined, as illustrated here using a palaemonid shrimp clade, their association becomes questionable and may hold true only in specific cases. We also propose a putative evolution for gill epithelial ion pump and transporter arrangement in a eubrachyuran crab clade whose lineages occupy distinct osmotic niches. By including the systematics of these selected groups, this review incorporates the notion of a protracted time scale, here termed 'phylophysiology', into decapod osmoregulation, allowing the examination of putative physiological transformations and their underlying evolutionary processes. This approach assumes that species are temporally linked, a factor that can impart phylogenetic structuring, which must be considered in comparative studies. Future experimental models in decapod osmoregulatory physiology should contemplate the phylogenetic relationships among the taxa chosen to better allow comprehension of the transformations arising during their evolution.


HIV risk behavior profiles among men who have sex with men interested in donating blood: Findings from the Assessing Donor Variability and New Concepts in Eligibility study.
Individual risk assessment allows donors to be evaluated based on their own behaviors. Study objectives were to assess human immunodeficiency virus (HIV) risk behaviors in men who have sex with men (MSM) and estimate the proportion of the study population who would not be deferred for higher risk HIV sexual behaviors. Cross-sectional survey and biomarker assessment were conducted in eight U.S. cities. Participants were sexually active MSM interested in blood donation aged 18-39 years, assigned male sex at birth. Participants completed surveys during two study visits to define eligibility, and self-reported sexual and HIV prevention behaviors. Blood was drawn at study visit 1 and tested for HIV and the presence of tenofovir, one of the drugs in oral HIV pre-exposure prophylaxis (PrEP). Associations were assessed between HIV infection status or HIV PrEP use and behaviors, including sex partners, new partners, and anal sex. A total of 1566 MSM completed the visit 1 questionnaire and blood draw and 1197 completed the visit 2 questionnaire. Among 1562 persons without HIV, 789 (50.4%) were not taking PrEP. Of those not taking PrEP, 66.2% reported one sexual partner or no anal sex and 69% reported no new sexual partners or no anal sex with a new partner in the past 3 months. The study found that questions were able to identify sexually active, HIV-negative MSM who report lower risk sexual behaviors. About a quarter of enrolled study participants would be potentially eligible blood donors using individual risk assessment questions.


[Improving access to kidney transplantation for highly sensitized patients: What place for IL-6 pathway blockade in desensitization protocols?]
Desensitization allows kidney transplantation for HLA highly sensitized subjects. Due to the central role of IL-6 in immunological response, tocilizumab (monoclonal antibody directed against IL-6 receptor) could probably improve desensitization efficacy. Pubmed systematic review by using MeSH terms: tocilizumab, clazakizumab, interleukin-6 blockade, kidney transplantation, kidney graft and desensitization. IL-6 plays a role in humoral response (plasmocyte differentiation induced by lymphocyte T, IL-21 secretion) as well as in cellular response (differentiation of LT Th17 rather than T reg). In desensitization field, tocilizumab was first studied as second-line treatment after failing of standard-of-care (apheresis, rituximab ± IgIV). Recent study showed that tocilizumab as a monotherapy attenuated anti-HLA antibodies rates but was not sufficient to allow transplantation. However, lymphocyte immunophenotyping showed that tocilizumab hindered B cells maturation. Thereby, tocilizumab could improve long-term efficacy of desensitization, by limiting the anti-HLA rebound and so avoiding antibody-mediated rejection. This hypothesis is supported by a recent study which used clazakizumab (monoclonal antibody directed against IL-6) in association with standard-of-care. In that study, clazakizumab was continued after kidney transplantation. Results were encouraging because 9/10 patients were transplanted and there was no donor-specific antibody at 6 months post-transplantation. IL-6 pathway blockade as a monotherapy fails to desensitize HLA highly sensitized kidney transplant candidates. In association with standard-of-care, it does not seem to significatively improve kidney allograft access (short-term efficacy) vs. standard-of-care only. However, it could improve long-term prognosis of HLA incompatible transplantation by orienting the response towards a tolerogenic profile, by hindering B-cell maturation and, thereby, avoiding DSA rebounds after transplantation. This hypothesis needs to be proven by further studies.


Immunohistochemical localization of substance P in anencephalic human fetus spinal cord.
The distribution of substance P (SP) in human anencephalic fetus spinal cord has been studied with the indirect immunofluorescence technique. The SP-like immunoreactivity was detected within plexuses of fibres localized in the superficial layers of the dorsal grey including the marginal zone and substantia gelatinosa, and also the dorsal funicular grey. The other spinal cord areas were devoid of SP-like immunoreactivity. Comparison with normal fetus spinal cord reveals that in both normal and anencephalic fetuses the dorsal SP-patterns are comparable. This study indicates that in human fetus spinal cord most of the SP-fibres dorsally localized, occur even if the brain itself does not develop.


Preliminary experiences with a single-patient trials service in general practice.
To pilot a single-patient trials (SPTs) service in general practice, designed to improve decision-making about long-term medications for chronic conditions. 12-week within-patient, randomised, double-blind, placebo-controlled, crossover comparison of ibuprofen with paracetamol for osteoarthritis, involving three pairs of two-week treatment periods for each participating patient. Patients attending an academic general practice with a clinical diagnosis of osteoarthritis, with pain of at least a month's duration severe enough to warrant consideration of long-term non-steroidal anti-inflammatory drug (NSAID) use. Pain and stiffness; measures of overall arthritis compared with previous fortnight; preference for NSAID at the end of each two-week treatment period; use of escape analgesia; side effects; and management changes as a result of the SPTs. Eight of 14 patients completed SPTs. One was a clear responder to NSAIDs, five were non-responders, and two were indefinite. Of the five who were using NSAIDs' before the SPT, two continued and three ceased using them. Clinically useful information assisted decision-making for all eight participants. Medication management changed for six. Single-patient trials can be successfully implemented in general practice and might be a valuable method for GPs to identify patients who respond to medication for chronic stable conditions such as osteoarthritis, in which individual response to medication is variable.


Plasma osteopontin levels are predictive of disease stage in patients with transitional cell carcinoma of the bladder.
To measure plasma levels of osteopontin in patients with transitional cell carcinoma (TCC) of the bladder, and to determine if osteopontin levels relate to disease stage. Blood samples were collected from 72 consecutive patients with TCC. Clinical data were obtained from medical record reviews. Patients were divided into subgroups based on disease status (active vs inactive) and clinical and pathological stage of TCC (tumour, nodes and metastases staging system). Osteopontin levels were measured using an enzyme-linked immunosorbent assay. Plasma osteopontin levels were higher in patients with active TCC than in controls (P = 0.035). Plasma osteopontin levels were not significantly different between patients with active and inactive TCC, but were higher in patients with metastases than in patients with active, clinically organ-confined TCC (P = 0.021). Plasma osteopontin levels increase with tumour stage in TCC of the bladder. These findings suggest that larger, more extended studies on plasma osteopontin levels in patients with TCC are warranted.


Ultrasound-Guided Neuraxial Anesthesia.
There has been a recent surge of interest in clinical applications of ultrasound, which has revolutionized acute pain management. This review is to summarize the current status of ultrasound utilization in neuraxial anesthesia, the most common type of regional anesthesia. Ultrasound-assisted and ultrasound-guided neuraxial anesthesia has improved clinical accuracy and patient safety through landmark identification including proper vertebral level and midline, as well as via measurements on neuraxial space. Direct needle or catheter visualization during the entire procedure has not yet been achieved consistently. The recent introduction of ultrasound into neural anesthesia has clinical performance benefits and patient safety implications, with documented improvement on overall efficacy with higher first attempt success rate as well as less needle pass. More controlled studies are needed for the overall impact of ultrasonography in neuraxial anesthesia in obstetric and non-obstetric patients.


[Brånemark method for preparation of titanium implants integrating with bone. Literature review].
On the basis of a literature survey the Branemark method of preparing implants integrating with bone is presented considering preoperative management, two-step surgical intervention and prosthetic treatment. The results obtained as yet are presented.


18 F-Fluoromisonidazole positron emission tomography/CT-guided volumetric-modulated arc therapy-based dose escalation for hypoxic subvolume in nasopharyngeal carcinomas: A feasibility study.
The purpose of this study is to investigate the feasibility of a simultaneously integrated boost to the hypoxic subvolume of nasopharyngeal carcinomas (NCPs) under the guidance of 18 F-fluoromisonidazole (FMISO) positron emission tomography (PET)/CT using volumetric-modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) techniques. Eight patients with NPC were treated with simultaneous integrated boost-IMRT (treatment plan named IMRT70) with dose prescriptions of 70 Gy, 66 Gy, 60 Gy, and 54 Gy to the gross tumor volume (GTV), positive neck nodes, the planning target volume (PTV), and the clinically negative neck, respectively. Based on the same datasets, experimental plans with the same dose prescription plus a dose boost of 14 Gy (an escalation of 20% of the prescription dose) to the hypoxic volume target contoured on the pretreatment 18 F-FMISO PET/CT imaging were generated using IMRT and VMAT techniques, respectively (represented by IMRT84 and VMAT84). Two or more arcs (approximately 2-2.5 arcs, totally rotating angle <1000 degrees) were used in VMAT plans and 9 equally separated fields in IMRT plans. Dosimetric parameters, total monitor units, and delivery time were calculated for comparative study of plan quality and delivery efficiency between IMRT84 and VMAT84. In experimental plans, hypoxic target volumes successfully received the prescribed dose of 84 Gy in compliance with other dose constraints with either the IMRT technique or the VMAT technique. In terms of the target coverage, dose homogeneity, and organs at risk (OAR) sparing, there was no statistically significant difference between the actual treatment plan of IMRT70 and experimental plans. The total monitor unit of VMAT84 (525.7 ± 39.8) was significantly less than IMRT70 (1171.5 ± 167; P = .001) and IMRT84 (1388.3 ± 151.0; P = .001) per fraction, with 55.1% and 62.1% reduction. The average machine delivery time was 3.5 minutes for VMAT plans in comparison with approximately 8 minutes for IMRT plans, resulting in a reduction factor of 56.2%. For experimental plans, the 3D gamma index average was over 98.0% with no statistical significant difference when a 3%/3 mm gamma passing rate criteria was used. With the guidance of 18 F-FMISO PET/CT imaging, dose escalation to hypoxic zones within NPC could be achieved and delivered efficiently with the VMAT technique in comparison with the IMRT technique.


Differentiation of serum-free embryoid bodies from human induced pluripotent stem cells into networks.
Three-dimensional aggregation cultures allow for complex development of differentiated human induced pluripotent stem cells. However, this approach is not easily amenable to live-cell imaging and electrophysiological applications due to the thickness and the geometry of the tissue. Here, we present an improvement on the traditional aggregation method by combining the use of cell culture inserts with serum-free embryoid bodies (SFEBs). The use of this technique allows the structures to maintain their three-dimensional structure while thinning substantially. We demonstrate that this technique can be used for electrophysiological recodings as well as live-cell calcium imaging combined with electrical stimulation, akin to organotypic slice preparations. This provides an important experimental tool that can be used to bridge 3-D structures with traditional monolayer approaches used in stem cell applications.


Micro RNA-550a interferes with vitamin D metabolism in peripheral B cells of patients with diabetes.
The pathogenesis of diabetes is to be further investigated. Vitamin D3 (VitD3) can improve diabetes. Micro RNAs (miR) are involved in regulating cell activities. This study tests a hypothesis that miR-550a interferes with the metabolism of VitD3 in peripheral B cells. In this study, blood samples were collected from patients with diabetes and healthy persons. The B cells were isolated from the blood samples to be treated with tumor necrosis factor (TNF)-α. The B cells were then collected and analyzed for the expression of miR-550a and cyp27b1. The results showed that B cells from healthy subjects were capable of converting VitD metabolite calcidiol to calcitriol, which was impaired in B cells collected from diabetic patients. The diabetic patients showed lower bone mineral density than that in healthy subject. The miR-550a was negatively correlated with bone mineral density and the Levels of cyp27b1 in peripheral B cells of patients with diabetes. In vitro study showed that TNF-α increased miR-550a expression and inhibited the expression of cyp27b1 in B cells. miR-550a mediated the effects of TNF-α on inducing chromatin remodeling at the cyp27b1 gene locus. In conclusion, miR-550a mediates the TNF-α-induced suppression of cyp27b1 expression in peripheral B cells of patients with diabetes, which can be blocked by inhibition of miR-550a.


Choosing the hospital information system: a nursing perspective.
If computerization of patient care information is to be successful, nurses must be involved in the process from the beginning. This article describes the process used by a committee in choosing a hospital information system and the roles of the nurses who served on the committee.


Principles of Whole-Genome Amplification.
Modern molecular biology relies on large amounts of high-quality genomic DNA. However, in a number of clinical or biological applications this requirement cannot be met, as starting material is either limited (e.g., preimplantation genetic diagnosis (PGD) or analysis of minimal residual cancer) or of insufficient quality (e.g., formalin-fixed paraffin-embedded tissue samples or forensics). As a consequence, in order to obtain sufficient amounts of material to analyze these demanding samples by state-of-the-art modern molecular assays, genomic DNA has to be amplified. This chapter summarizes available technologies for whole-genome amplification (WGA), bridging the last 25 years from the first developments to currently applied methods. We will especially elaborate on research application, as well as inherent advantages and limitations of various WGA technologies.


Chondromyxoid fibroma of the maxilla.
A case of chondromyxoid fibroma of the anterior maxilla arising in a 38-year-old Japanese woman is presented. Review of the literature reveals 16 cases of CMF of the jaws, of which only 3 were in the maxilla. Curettage and subsequent 5 year followup showed no evidence of recurrence.


Over-expression of Zip-13 mRNA in kidney and lung during dietary zinc deficiency in Wistar rats.
Zinc is an essential nutrient for all organisms, which is involved in the function of numerous key enzymes in metabolism. Two gene families have been identified involved in zinc homeostasis. ZnT transporters reduce intracellular zinc while Zip transporters increase intracellular zinc. Previous studies in our laboratory have shown that Zip-1, ZnT-1, Zip-2 and LIV-1 mRNA are associated with zinc level in established human breast cancer in nude mice model. In this study, six zinc transporters: ZnT-1, ZnT-2, ZnT-4, Zip-1, Zip-8 and Zip-13 were chosen. We aim to determine the relation between zinc transporters and zinc level in kidney and lung of Wistar rats. Eighteen Wistar rats were randomly divided into three groups: normal group, zinc-deficiency group and pair-fed group. After 22 days, the rats were killed and organs samples were taken, then zinc transporters mRNA were detected by RT-PCR. Compared with the normal group, Zip-13 shows an up-regulation (P < 0.05) in zinc-deficiency group both in kidney and lung, and Zip-8 was significantly lower (P < 0.05) in zinc-deficiency group in kidney.


Rapid in vivo induction of HIV-specific CD8+ cytotoxic T lymphocytes by a 15-amino acid unmodified free peptide from the immunodominant V3-loop of GP120.
Efforts to generate a vaccine to prevent infection by human immunodeficiency virus (HIV) have focused on inducing neutralizing antibodies. However, cytotoxic T-lymphocyte (CTL) responses are a major immune defense mechanism required for recovery from many different virus infections. Since CTL epitopes can be defined by short synthetic peptides, we searched for HIV peptides that elicit a viral-specific CTL response in mice. We have developed a new method for screening CTL-inducing peptides involving a single injection into the footpad of mice to prime CTLs in the draining popliteal lymph node of mice within 10 days. Our results demonstrate that a 15-amino acid peptide (aa 315-329) derived from the V3 loop of HIV gp120 caused a rapid induction of peptide-specific and gp160-specific CD8-positive CTLs. Lysis of targets is specific since cells preincubated with unrelated peptides are resistant to lysis as are cells of a different MHC haplotype pretreated with the cognate peptide. Pretreatment of restimulated node cells with complement plus anti-CD8 but not anti-CD4 removed the lytic activity. We also successfully induced in vivo CTL activity with unmodified synthetic peptides from the influenza and Sendai virus nucleoproteins, indicating general applicability of our method for rapid screening of CTL epitopes. Because HIV replication has been reported by several labs to occur mainly in lymph nodes of infected patients, the rapid induction of HIV-specific CTLs in proximal lymph nodes by unmodified peptides emphasizes the physiological significance of our findings toward vaccine and therapeutic approaches.


Effects of low-dose aspirin and heparin on the pregnancy outcome in women with antiphospholipid syndrome.
The purpose of this study was to compare the use of low-dose aspirin alone versus prednisone and low-dose aspirin versus heparin and low-dose aspirin in the treatment of the antiphospholipid antibody syndrome in pregnant women. A prospective, single-center randomized trial included 14 patients who were alternately assigned to treatment. Each patient had a history of recurrent miscarriage diagnosed with antiphospholipid syndrome. 5 accepted the treatment of aspirin alone, 5 accepted the combination treatment of aspirin + prednisone, and 4 accepted the combination therapy of aspirin + heparin. Data were compared by the One-way ANOVA test using IBM SPSS stats 19. There were no significant differences in patient outcome data, obstetric complications, and gestational age at delivery in live births between the 3 groups (P > 0.05). However, treatment with aspirin + heparin increased neonatal weight (P < 0.05). Our data demonstrate the non-superiority one on each other of the three different regimens, except in terms of neonatal weight when aspirin + heparin were used. These findings raise questions about the need for therapies such as heparin and corticosteroids for women with antiphospholipid antibody syndrome, especially in resource-limited settings similar to Syria.


AMN107, a novel aminopyrimidine inhibitor of p190 Bcr-Abl activation and of in vitro proliferation of Philadelphia-positive acute lymphoblastic leukemia cells.
Previous studies have shown that patients with Bcr-Abl-positive acute lymphoblastic leukemia (ALL) either have primary disease that is refractory to imatinib mesylate or develop disease recurrence after an initial response. The authors investigated the effects of a newly designed Bcr-Abl inhibitor, AMN107, by comparing its in vitro inhibitory potency on p190 Bcr-Abl ALL cell lines with that of imatinib. In two Philadelphia (Ph)-positive ALL cell lines, AMN107 was found to be 30-40 times more potent than imatinib in inhibiting cellular proliferation. AMN107 was also more effective than imatinib in inhibiting phosphorylation of p190 Bcr-Abl tyrosine kinase in cell lines and primary ALL cells. The inhibition of cellular proliferation was associated with the induction of apoptosis in only one of the cell lines. No activity was observed in cell lines lacking the BCR-ABL genotype. The results of the current study suggest the superior potency of AMN107 compared with imatinib in Ph-positive ALL and support clinical trials of AMN107 in patients with Ph-positive ALL.


New cyclic somatostatin analogues containing a pyrazinone ring: importance of Tyr for antiproliferative activity.
Novel somatostatin analogues containing a pyrazinone ring, compounds 1 and 2, exhibited good antiproliferative activity on A431 tumor cells. To increase antitumor activity and binding affinity on somatostatin receptors (SSTRs), we substituted Tyr in the critical sequence, Tyr-D-Trp-Lys, with more hydrophobic aromatic residue. The substituted compounds dramatically lost antitumor activity, indicating that Tyr residue was an essential residue.


Effects of vitamin supply on spontaneous and chemically induced mutagenesis in human cells.
Chromosome aberrations in donor peripheral blood lymphocyte culture were evaluated before, 14 and 30 days after treatment with a vitamin/mineral complex. Treatment with the complex had no effect on spontaneous level of aberrant cells. The number of chromosome aberrations induced by dioxidine or cadmium chloride in vitro at the G2 stage decreased on days 14 and 30 of treatment with the complex.


Simple and sensitive liquid chromatographic method with fluorimetric detection for the analysis of gamma-amino-n-butyric acid in human urine.
A simple and sensitive liquid chromatographic method is described for the analysis of gamma-amino-n-butyric acid (GABA) in human urine. GABA is increased in the urine of cancer patients and could be used as a biomarker in the diagnosis and treatment of related patients. The method is based on derivatizing GABA with a fluorescent reagent (naproxen acyl chloride) for transforming the non-chromophoric GABA to a derivative with chromophoric and fluorophoric properties. The resulting derivative is highly responsive to a fluorimetric detector (lambda(ex)=230 nm, lambda(em)=350 nm). The lower quantitation of the method is attainable at 100 nM GABA with a detection limit about 10nM (S/N=3 with 20 microL injected). Application of the method to the analysis of GABA in the urine of patients with ovarian and uterine cancer was demonstrated.


An atlas of amyloid aggregation: the impact of substitutions, insertions, deletions and truncations on amyloid beta fibril nucleation.
Multiplexed assays of variant effects (MAVEs) guide clinical variant interpretation and reveal disease mechanisms. To date, MAVEs have focussed on a single mutation type-amino acid (AA) substitutions-despite the diversity of coding variants that cause disease. Here we use Deep Indel Mutagenesis (DIM) to generate a comprehensive atlas of diverse variant effects for a disease protein, the amyloid beta (Aβ) peptide that aggregates in Alzheimer's disease (AD) and is mutated in familial AD (fAD). The atlas identifies known fAD mutations and reveals that many variants beyond substitutions accelerate Aβ aggregation and are likely to be pathogenic. Truncations, substitutions, insertions, single- and internal multi-AA deletions differ in their propensity to enhance or impair aggregation, but likely pathogenic variants from all classes are highly enriched in the polar N-terminal region of Aβ. This comparative atlas highlights the importance of including diverse mutation types in MAVEs and provides important mechanistic insights into amyloid nucleation.


Chelation in metal intoxication. XXIX: Alpha-mercapto-beta-aryl acrylic acids as antidotes to mercury (II) toxicity.
alpha-Mercapto-beta-(2-furyl) acrylic acid (MFA), alpha-mercapto-beta-(phenyl) acrylic acid (MPA), alpha-mercapto-beta-(2-hydroxyphenyl) acrylic acid (MHA), alpha-mercapto-beta-(4-methoxyphenyl) acrylic acid (MMA), beta-1,2-phenylene di-alpha-mercapto acrylic acid (1, 2-PDMA) and beta-1, 4-phenylene di-alpha-mercapto acrylic acid (1, 4-PDMA) enhanced faecal excretion and reduced liver, spleen and blood burden of inorganic mercury when administered (0.5 m mol/kg, in two split doses) 24 hr after Hg (II) (1 mg/kg) in rats. MFA, MPA, MHA, and MMA were also effective in lowering renal Hg mainly from the cytosol, without any significant increase in urinary excretion of Hg. The results indicate that all the mono-mercapto acrylic acids including MFA were more effective than di-mercapto acrylic acids and act through the mechanism characteristic of thiol chelators, that is, mobilization of Hg as their complexes, contrary to the reported observation that MFA acts through the induction of metallothionein.


Temporary diplopia upon hyoscine-N-butyl bromide administration: case report.
Hyoscine-N-butyl bromide is a widely used antispasmodic belonging to the belladonna alkaloid class of semisynthetic quaternary ammonium compounds. These compounds exert a spasmolytic action on the smooth muscles of the bile-gastrointestinal tract, genitourinary tract, salivary glands (xerostomia), and also on the visual apparatus - in particular, the irido-ciliary complex. As a consequence, they provoke collateral effects such as mydriasis and accommodation disturbances. We report the case of a 23-year-old woman who complained of not only "dry mouth" but also "cloudy vision" and a "diplopia", both of temporary type, 2 hours after oral administration of hyoscine-N-butyl bromide.


Implementation approaches to improve environmental sustainability in operating theatres: a systematic review.
Operating theatres consume large amounts of energy and consumables and produce large amounts of waste. There is an increasing evidence base for reducing the climate impacts of healthcare that could be enacted into routine practice; yet, healthcare-associated emissions increase annually. Implementation science aims to improve the systematic uptake of evidence-based care into practice and could, therefore, assist in addressing the environmental impacts of healthcare. The aim of this systematic search with narrative synthesis was to explore what implementation approaches have been applied to reduce the environmental impact of operating theatre activities, described by implementation phases and methodologies. A search was conducted in EMBASE, PubMed, and CINAHL, limited to English and publication since 2010. In total, 3886 articles were retrieved and 11 were included. All were in the exploratory phase (seven of 11) or initial implementation phase (four of 11), but none were in the installation or full implementation phase. Three studies utilised a recognised implementation theory, model, or framework in the design. Four studies used interprofessional education to influence individuals' behaviour to reduce waste, improve waste segregation, or reduce anaesthetic gases. Of those that utilised behaviour change interventions, all were qualitatively successful in achieving environmental improvement. There was an absence of evidence for sustained effects in the intervention studies and little follow-up from studies that explored barriers to innovation. This review demonstrates a gap between evidence for reducing environmental impacts and uptake of proposed practice changes to deliver low-carbon healthcare. Future research into 'greening' healthcare should use implementation research methods to establish a solid implementation evidence base. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42022342786.


Fractionation and characterization of human small nuclear ribonucleoproteins containing U1 and U2 RNAs.
Human small nuclear ribonucleoproteins (snRNPs) containing U1 and U2 snRNAs have been isolated from cultured cells by nonimmunological methods. The U1 snRNP population remained immunoprecipitable by systemic lupus erythematosis anti-RNP and anti-Sm antibodies throughout fractionation and contained polypeptides of molecular weights corresponding to those defined as U1 snRNP polypeptides by immunoprecipitation of crude extracts. The purified assemblies contained U1 RNA and nine snRNP polypeptides of molecular weights 67,000 (P67), 30,000 (P30), 23,000 (P23), 21,500 (P22), 17,500 (P18), 12,300 (P12), 10,200 (P10), 9,100 (P9), and 8,500 (P8). P67, P30, and P18 were unique to U1 snRNPs. The U2 snRNP population remained immunoprecipitable by the systemic lupus erythematosis anti-Sm antibody throughout fractionation. The purified U2 assemblies contained six polypeptides of molecular weights corresponding to those defined by immunoprecipitation to be common to U1 and U2 snRNPs including P23, P22, P12, P10, P9, and P8. In addition, U2 snRNPs contained a unique polypeptide of 27,000 Da.


[Assessing the experience of practice placement nurse tutors].
Focused for many years on the quality of the supervision of student nurses during their practice placements, the teams of the American Hospital of Paris carried out an original survey around the new nurse training reference framework, questioning nurse tutors and young frontline professionals.


Neuroprognostication.
Patients with severe acute brain injury are left incapacitated, critically ill, and unable to make their own medical decisions. Surrogate decision-makers must make life-or-death decisions for patients and rely on clinicians' prognostication for guidance. No guidelines currently exist to guide clinicians in how to prognosticate; hence, neuroprognostication is still considered an "art" leaving room for high variability. This review examines the current literature on prognostication in neurocritical care, identifies ongoing challenges that exist in the field, and provides suggestions for future research with the goal to ameliorate variability and focus on scientific and patient-centered, rather than artistic approaches to prognostication.


A rhodamine-based dual chemosensor for the naked-eye detection of Hg2+ and enhancement of the fluorescence emission for Fe3.
A novel fluorescent chemosensor based on trimesoyl chloride-rhodamine (TR) was successfully synthesized. Rising chromogenic and fluorogenic spectral enhancements could be observed in trimesoyl chloride-rhodamine (TR) probes when Hg2+ and Fe3+ were added, respectively. TR has shown selectivity for Hg2+ and Fe3+ with high sensitivity due to metal ion complexation induced photophysical "turn-on" signaling responses. The detection limit towards Hg2+ was 2.46 × 10-8 M as determined by the 3σ method. At the same time, fluorogenic spectral enhancements were observed in TR, which exhibits a superior sensitive and selective recognition towards Fe3+ with 4.11 × 10-8 M of the detection limit. The test strips were used for colorimetric and simple detection towards Hg2+, which might finally enable the advancement of the Hg2+ sensor in the field of on-site detection.


Deletion of the myeloid endothelin-B receptor confers long-term protection from angiotensin II-mediated kidney, eye and vessel injury.
The endothelin system may be an important player in hypertensive end-organ injury as endothelin-1 increases blood pressure and is pro-inflammatory. The immune system is emerging as an important regulator of blood pressure and we have shown that the early hypertensive response to angiotensin-II infusion was amplified in mice deficient of myeloid endothelin-B (ETB) receptors (LysM-CreEdnrblox/lox). Hypothesizing that these mice would display enhanced organ injury, we gave angiotensin-II to LysM-CreEdnrblox/lox and littermate controls (Ednrblox/lox) for six weeks. Unexpectedly, LysM-CreEdnrblox/lox mice were significantly protected from organ injury, with less proteinuria, glomerulosclerosis and inflammation of the kidney compared to controls. In the eye, LysM-CreEdnrblox/lox mice had fewer retinal hemorrhages, less microglial activation and less vessel rarefaction. Cardiac remodeling and dysfunction were similar in both groups at week six but LysM-CreEdnrblox/lox mice had better endothelial function. Although blood pressure was initially higher in LysM-CreEdnrblox/lox mice, this was not sustained. A natriuretic switch at about two weeks, due to enhanced ETB signaling in the kidney, induced a hypertensive reversal. By week six, blood pressure was lower in LysM-CreEdnrblox/lox mice than in controls. At six weeks, macrophages from LysM-CreEdnrblox/lox mice were more anti-inflammatory and had greater phagocytic ability compared to the macrophages of Ednrblox/lox mice. Thus, myeloid cell ETB receptor signaling drives this injury both through amplifying hypertension and by inflammatory polarization of macrophages.


Automatic implantable cardioverter-defibrillator: patient survival, battery longevity and shock delivery analysis.
The automatic implantable cardioverter-defibrillator (AICD) has been shown to reduce the mortality rate of patients with malignant ventricular tachyarrhythmias. This report describes experience with implantation of 36 automatic implantable cardioverter-defibrillators (AID-B and AID-BR models) in 22 persons over a 44 month patient follow-up period (mean 19.6 months). There were five deaths: two patients died suddenly 22 and 29 months, respectively, after their second implant, one died of congestive heart failure, one died of respiratory failure and one died of catheter sepsis. Although 11 (50%) of the 22 patients never received a countershock for a ventricular tachyarrhythmia and are still alive, the other 11 received one or more spontaneous countershocks. Nine patients (41%) experienced spurious shocks during the follow-up period. Assuming that the first shock for presumed ventricular tachyarrhythmia prevented death, the hypothetical cumulative survival of patients at 42 months would have been 34 +/- 14.1% in the absence of an automatic implantable cardioverter defibrillator rather than the actual survival rate of 59 +/- 16.8%. The cumulative device survival of the 36 AID-B units was 92 +/- 5.62% at 15 months but diminished to 37 +/- 14.4% by 20 months. No unit lasted longer than 22 months. There were 12 battery depletions. The number of shocks emitted did not influence unit longevity. The manufacturer's elective replacement indicator is of uncertain validity. Six units remained active 7 to 17 months after surpassing their replacement indicator. The automatic implantable cardioverter-defibrillator prolongs the life of many patients with otherwise intractable arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)


Experience of Women in IR in the Arab World: Survey by the Pan Arab Interventional Radiology Society.
We report our assessment of the experience of female interventional radiologists in different Arab countries based on an online questionnaire that was sent to 57 female interventional radiologists in 5 Arab countries. These interventional radiologists were identified from the Pan Arab Interventional Radiology Society database and through personal communications. The survey included items related to demographics, social status, and the professional challenges of interventional radiologists, with a response rate of 93%. Forty-five percent of respondents were between 31 and 45 years of age. Interventional radiology practice represented 25%-50% of work time for 51% of respondents, and the main challenges reported were related to radiation exposure, balancing family/work life, and the male-dominated interventional radiology community.


Fluorescence polarization-based assays for detecting compounds binding to inactive c-Jun N-terminal kinase 3 and p38α mitogen-activated protein kinase.
Two fluorescein-labeled pyridinylimidazoles were synthesized and evaluated as probes for the binding affinity determination of potential kinase inhibitors to the c-Jun N-terminal kinase 3 (JNK3) and p38α mitogen-activated protein kinase (MAPK). Fluorescence polarization (FP)-based competition binding assays were developed for both enzymes using 1-(3',6'-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)-3-(4-((4-(4-(4-fluorophenyl)-2-(methylthio)-1H-imidazol-5-yl)pyridin-2-yl)amino)phenyl)thiourea (5) as an FP probe (JNK3: Kd = 3.0 nM; p38α MAPK: Kd = 5.7 nM). The validation of the assays with known inhibitors of JNK3 and p38α MAPK revealed that both FP assays correlate very well with inhibition data received by the activity assays. This, in addition to the viability of both FP-based binding assays for the high-throughput screening procedure, makes the assays suitable as inexpensive prescreening protocols for JNK3 and p38α MAPK inhibitors.


Glutathione reductase is essential for host defense against bacterial infection.
Glutathione reductase (Gsr) catalyzes the reduction of glutathione disulfide to glutathione, a major cellular antioxidant. We have recently shown that Gsr is essential for host defense against the gram-negative bacteria Escherichia coli in a mouse model of sepsis. Although we have demonstrated that Gsr is required for sustaining the oxidative burst and the development of neutrophil extracellular traps, the role of Gsr in other phagocytic functions remains unclear. It is also unclear whether Gsr-deficient mice exhibit host defense defects against gram-positive bacteria. In this study, we characterized the effects of Gsr deficiency on the innate immune responses to a gram-positive bacterium, group B Streptococcus, and to the gram-negative bacterial cell wall component lipopolysaccharide (LPS). We found that, like E. coli, group B Streptococcus resulted in a substantially more robust cytokine response and a markedly higher morbidity and mortality in Gsr-deficient mice than in wild-type mice. The increased morbidity and mortality were associated with greater bacterial burden in the Gsr-deficient mice. Interestingly, Gsr-deficient mice did not exhibit a greater sensitivity to LPS than did wild-type mice. Analysis of the neutrophils of Gsr-deficient mice revealed impaired phagocytosis. In response to thioglycollate stimulation, Gsr-deficient mice mobilized far fewer phagocytes, including neutrophils, macrophages, and eosinophils, into their peritoneal cavities than did wild-type mice. The defective phagocyte mobilization is associated with profound oxidation and aggregation of ascitic proteins, particularly albumin. Our results indicate that the oxidative defense mechanism mediated by Gsr is required for an effective innate immune response against bacteria, probably by preventing phagocyte dysfunction due to oxidative damage.


Modulation by naltrexone of stress-induced changes in humoral immune responsiveness and gastric mucosal integrity in rats.
The effects of restraint stress (RS) and the opioid antagonist, naltrexone, were evaluated on humoral immune responsiveness and gastric mucosal integrity in rats. RS for 24 h, but not 6 h, attenuated both the primary (PAR) and secondary antibody response (SAR) to sheep red blood cells (SRBC) after a single exposure to the stressor. Naltrexone (1 or 5 mg/kg) dose-dependently aggravated the effects of RS on anti-SRBC antibody titre in both PAR and SAR studies. Further, in rats sensitized with SRBC, RS (24 h), in addition to lowering the humoral antibody response, also induced gastric mucosal lesions. Both these responses were further aggravated with naltrexone pretreatment. These results are discussed in light of interactions between immune and visceral responses, and their regulation by endogenous opioids, during RS.


Factors associated with difficulty in crossing the culprit lesion of acute myocardial infarction.
In percutaneous coronary intervention (PCI) to the culprit lesion of acute myocardial infarction (AMI), unsuccessful guidewire crossing causes immediate poor outcomes. It is important to determine the factors associated with unsuccessful guidewire crossing in AMI lesions. The purpose of this study was to find factors associated with difficulty in crossing the culprit lesion of AMI. We defined the difficult group when the guidewire used to cross the culprit lesion was a polymer jacket type guidewire or a stiff guidewire. We included 937 patients, and divided those into the non-difficult group (n = 876) and the difficult group (n = 61). Proximal reference diameter was significantly smaller in the difficult group than in the non-difficult group (p < 0.001), and degree of calcification was severer in the difficult group than in the non-difficult group (p < 0.001). In the multivariate stepwise logistic regression analysis, proximal reference diameter [odds ratio (OR) 0.313, 95% confidence interval (CI) 0.185-0.529, p < 0.001)], previous PCI (OR 3.065, 95% CI 1.612-5.830, p = 0.001), moderate-severe calcification (OR 4.322, 95% CI 2.354-7.935, p < 0.001), blunt type obstruction (OR 12.646, 95% CI 6.805-23.503, p < 0.001), and the presence of collateral to the culprit lesion (OR 2.110, 95% CI 1.145-3.888, p = 0.017) were significantly associated with difficulty in crossing the culprit lesion. In conclusion, previous PCI, calcification, blunt type obstruction, and the presence of collateral were associated with difficulty in crossing the culprit lesion, whereas proximal reference diameter was inversely associated with difficulty. Our study provides a reference to recognize the difficulty in crossing the culprit lesions of AMI for PCI operators, especially junior operators.


Affinity based and molecularly imprinted cryogels: Applications in biomacromolecule purification.
The publications in macro-molecularly imprinted polymers have increased drastically in recent years with the development of water-based polymer systems. The macroporous structure of cryogels has allowed the use of these materials within different applications, particularly in affinity purification and molecular imprinting based methods. Due to their high selectivity, specificity, efficient mass transfer and good reproducibility, molecularly imprinted cryogels (MICs) have become attractive for researchers in the separation and purification of proteins. In this review, the recent developments in affinity based cryogels and molecularly imprinted cryogels in protein purification are reviewed comprehensively.


Quantitative in vivo assessment of arginine utilization and nitric oxide production in endotoxemia.
Until recently no methods were available to quantitate nitric oxide (NO) production in vivo. The advent of stable isotope techniques has allowed quantitation of NO production in different animal models and human disease states. In vivo NO production was assessed with the use of stable isotope labeled arginine. Enrichments of metabolites were measured by liquid chromatography-mass spectrometry (LC-MS). Knock-out mice were used to assess the influence of knocking out inducible NOS (iNOS) or constitutively expressed NOS (cNOS) on arginine-NO metabolism. Pig models were used to assess the role of individual organs on arginine-NO fluxes. In mice under basal conditions cNOS mediates half of the NO production. After endotoxin challenge NO production doubles as a result of iNOS induction and cNOS-mediated NO production is downregulated. In larger animal models (pig) whole body NO production is augmented after endotoxin challenge, largely resulting from NO production in liver, intestine and kidney. Arginine supplementation increases NO production in pigs in liver, intestine and kidney both in the basal state and after endotoxin challenge. Stable isotope techniques employing LC-MS allow in vivo assessment of NO production in small and large animal models and in patients. This allows definition of the role that iNOS and cNOS-mediated NO production play in several disease states.


Tenebrio molitor (Coleoptera: Tenebrionidae) as an alternative host to study fungal infections.
Models of host–pathogen interactions are crucial for the analysis of microbial pathogenesis. In this context, invertebrate hosts, including Drosophila melanogaster (fruit fly), Caenorhabditis elegans (nematode) and Galleria mellonella (moth), have been used to study the pathogenesis of fungi and bacteria. Each of these organisms offers distinct benefits in elucidating host–pathogen interactions. In this study,we present a newinvertebrate infection model to study fungal infections: the Tenebrio molitor (beetle) larvae. Here we performed T. molitor larvae infection with one of two important fungal human pathogens, Candida albicans or Cryptococcus neoformans, and analyzed survival curves and larva infected tissues.We showed that increasing concentrations of inoculum of both fungi resulted in increased mortality rates, demonstrating the efficiency of the method to evaluate the virulence of pathogenic yeasts. Additionally, following 12 h post-infection, C. albicans formsmycelia, spreading its hyphae through the larva tissue,whilst GMS stain enabled the visualization of C. neoformans yeast and theirmelanin capsule. These larvae are easier to cultivate in the laboratory than G. mellonella larvae, and offer the same benefits. Therefore, this insect model could be a useful alternative tool to screen clinical pathogenic yeast strainswith distinct virulence traits or different mutant strains.


Three cases of angiomyolipoma: diagnostic imaging by contrast-enhanced ultrasonography.
We used contrast-enhanced ultrasound using the Sonazoid microbubble contrast agent to diagnose three cases of hepatic angiomyolipoma, which is a rare benign tumor. Some characteristic findings are obtained in the early vascular phase, for example fork-like tumor vessels. However, a variety of findings are seen after the early vascular phase because of microbubbles circulating the vascular enriched tumor.


Endogenous growth factors as cosmeceuticals.
Research into the pathophysiology of photodamaged skin has revealed correlations with certain aspects of acute and chronic wound healing. In wound healing, growth factors accumulate at the wound site and interact synergistically to initiate and coordinate wound healing. To review the effects of topical growth factors in wound healing and their potential use in treating photodamaged skin. A mixture of multiple growth factors derived from human fibroblasts was applied topically to 14 patients twice daily for 60 days to stimulate the remodeling phase of wound healing. A total of 78.6% of patients with photodamaged skin showed clinical improvement at 60 days. New collagen formation increased by 37%, and epidermal thickening increased by 27%. These data, as well as other studies of growth factors in wound healing, demonstrate positive cosmetic and clinical outcomes of topical application of growth factors for the treatment of photodamaged skin.


Correlates of Lifetime and Past Month Vape Use in a Sample of Canadian University Students.
This study examines correlates of lifetime (ie, ever vaped) and past month vape use among students aged 17 to 19 years, 20 to 25 years, and 26+ years from Western University in London, Ontario. The secondary objective is to assess lifetime and past month vape use among students not of legal age to purchase vaping products in Ontario (ie, those 17 to 18 years only). Using Qualtrics, a cross-sectional survey was sent via email to all students at Western University (N = 38 442), assessing their current and past risk-taking behaviors, mental health, sociodemographic characteristics, as well as questions pertaining to their family structure and socioeconomic background during childhood. Students were asked if they had ever vaped in their lifetime and about past month vape use. Logistic regression models were used to assess correlates of lifetime and past month vape use. The sample consisted of 2626 university students. Compared to those ages 26+ years, teenage university students were 10 times more likely to have vaped in the past month and males were twice as likely as females to have vaped. Alcohol use doubled the odds of vaping in the past month, whereas cigarette, cannabis, or cocaine use approximately tripled the odds. Students who reported many sexual partners were far more likely to have vaped in the past month. Vape use is more common among teenage university students, males, those who drink alcohol, smoke, use cannabis or cocaine, and who report many sexual partners.


Genetic Diagnosis Impacts Medical Management for Pediatric Epilepsies.
Evidence of the impact of genetic diagnosis on medical management in individuals with previously unexplained epilepsy is lacking in the literature. Our goal was to determine the impact of genetic diagnosis on medical management in a cohort of individuals with early-onset epilepsy. We performed detailed phenotyping of individuals with epilepsy who underwent clinical genetic testing with an epilepsy panel and/or exome sequencing at Boston Children's Hospital between 2012 and 2019. We assessed the impact of genetic diagnosis on medical management. We identified a genetic etiology in 152 of 602 (25%) individuals with infantile- or childhood-onset epilepsy who underwent next-generation sequencing. Diagnosis impacted medical management in at least one category for 72% of patients (110 of 152) and in more than one category in 34%. Treatment was impacted in 45% of individuals, including 36% with impact on antiseizure medication choice, 7% on use of disease-specific vitamin or metabolic treatments, 3% on pathway-driven off-label use of medications, and 10% on discussion of gene-specific clinical trials. Care coordination was impacted in 48% of individuals. Counseling on a change in prognosis was reported in 28% of individuals, and 1% of individuals had a correction of diagnosis. Impact was documented in 13 of 13 individuals with neurotypical development and in 55% of those with epilepsy onset after age two years. We demonstrated meaningful impact of genetic diagnosis on medical care and prognosis in over 70% of individuals, including those with neurotypical development and age of epilepsy onset after age two years.


Use of potentiometric detection in (ultra) high performance liquid chromatography and modelling with adsorption/desorption binding kinetics.
Observation of a potentiometric sensor's response behaviour after injection in flow injection analysis at different concentrations allowed studying "on" and "off" kinetics of the analyte's adsorption/diffusion behaviour. The alkaloid metergoline was mostly used as an example. k(on) and k(off) rate constant values were measured, and the association constant K(ass), and ΔG values of the analyte-surface interaction were calculated with an adsorption-based model which proved to be fully applicable. k(on) increased by decreasing the sensor dimensions, while koff was unaffected by miniaturization. Increasing acetonitrile concentrations in the running buffer increased k(off), while k(on) was unaffected. The experimentally determined ΔG values of the analyte-surface interaction showed a linear relation to the response of the sensor, in mV. This knowledge was applied to optimize the potentiometric detection of plant alkaloids in (U)HPLC. Sub-micromolar detection limits were obtained with the potentiometric detector/(U)HPLC combination. This is the first time that the response rates and the response itself can be modelled accurately for coated wire potentiometric sensors, and it is the first application of a potentiometric detector in UPLC.