A highly contorted push-pull naphthalenediimide dimer and evidence of intramolecular singlet exciton fission.
Singlet fission is a process by which two molecular triplet excitons are generated subsequent to the absorption of one photon. Molecules that enable singlet fission have triplet state energy at least half of the bright singlet state energy. This stringent energy criteria have challenged chemists to device new molecular and supramolecular design principles to modulate the singlet-triplet energy gap and build singlet fission systems from a wide range of organic chromophores. Herein, we report for the first time intramolecular singlet fission in the seminal naphthalenediimide (NDI) scaffold constrained in a push-pull cyclophane architecture, while individually the NDI chromophore does not satisfy the energy criterion. The challenging synthesis of this highly contorted push-pull cyclophane is possible from the preorganized pincer-like precursor. The special architecture establishes the shortest co-facial NDI⋯NDI contacts (3.084 Å) realized to date. Using broadband femtosecond transient absorption, we find that the correlated T-T pair forms rapidly within 380 fs of photoexcitation. Electronic structure calculations at the level of state-averaged CASSCF (ne,mo)/XMCQDPT2 support the existence of the multi-excitonic T-T pair state, thereby confirming the first example of singlet exciton fission in a NDI scaffold.


In vivo measurement of absolute tissue iodine content by fluorescence excitation.
A method based on the measurement of fluorescent and transmitted photons has been developed for the quantitative determination of stable iodine concentrations in tissues. The results are independent of the thickness of the material surrounding the measuring site. The method yields an accuracy of better than 3% for both Ge semiconductor and NaI(TI)detector arrangements.


Unpacking the 'process of sustaining'-identifying threats to sustainability and the strategies used to address them: a longitudinal multiple case study.
Although sustainability remains a recognised challenge for Quality Improvement (QI) initiatives, most available research continues to investigate sustainability at the end of implementation. As a result, the learning and continuous adjustments that shape sustainability outcomes are lost. With little understanding of the actions and processes that influence sustainability within QI initiatives, there is limited practical guidance and direction on how to enhance the sustainability of QI initiatives. This study aims to unpack the 'process of sustaining', by exploring threats to sustainability encountered throughout the implementation of QI Initiatives and identifying strategies used by QI teams to address these threats over time. A longitudinal multiple case study design was employed to follow 4 QI initiatives over a 3-year period. A standardised sustainability tool was used quarterly to collect perceptions of sustainability threats and actions throughout implementation. Interviews (n=38), observations (32.5 h), documentary analysis, and a focus group (n=10) were conducted to enable a greater understanding of how the process of sustaining is supported in practice. Data were analysed using the Consolidated Framework for Sustainability (CFS) to conduct thematic analysis. Analysis identified five common threats to sustainability: workforce stability, improvement timelines, organisational priorities, capacity for improvement, and stakeholder support. Each of these threats impacted multiple sustainability constructs demonstrating the complexity of the issues encountered. In response to threats, 12 strategies to support the process of sustaining were identified under three themes: engagement (five strategies that promoted the development of relationships), integration (three strategies that supported initiatives to become embedded within local systems), and adaptation (four strategies that enhanced understanding of, and response to, emergent conditions and contextual needs). Sustaining improvements from QI initiatives requires continuous investment in relationships, resilience to integrate improvements in local systems, and flexibility to understand emergent conditions. Findings provide practitioners, funders, and researchers with a better understanding of, and preparation for, the threats associated with sustaining improvements from QI initiatives and offer insight into specific actions that can be taken to mitigate these risks. This learning can be used to inform future initiative design and support, to optimise the sustainability of healthcare improvements. Not applicable.


Patient outcomes using revised guidance NHS Continuing Care Eligibility Criteria, Scotland (CEL 2008).
To determine the efficacy of selection of patients for NHS (Scotland) continuing care using revised guidance eligibility criteria, CEL (2008). On September 2009, a census was conducted of 632 patients, distributed over 10 hospital sites in NHS Lanarkshire Older People's Directorate, to identify those patients who had future care needs assessed using revised NHSS CEL (2008) eligibility criteria during the previous 3 months. These patients were then assigned to one of four categories: (1) eligible for NHS continuing care; (2) likely destination care home; (3) likely discharge home with complex care package; and (4) outcome uncertain. 'Frailty' was recorded in a sub-group of patients using Rockwood's frailty index. The index records frailty on a scale 0-1, a higher score indicating greater frailty. Outcomes were recorded at 2-monthly intervals for 1 year. Patients undergoing acute assessment and/or specialist rehabilitation, those admitted before 1 April 2009 and already accepted for NHS continuing care and those with a planned discharge date were excluded. Two hundred and eleven patients were identified as meeting the criteria for allocation to one of the four categories. Mortality at 1 year was as follows: NHS continuing care 40/45 (89%), likely Care Home destination 39/81 (48%), likely home discharge 22/61 (35%), outcome uncertain 13/24 (54%). Mean frailty scores were: NHS continuing care 0.4, likely care home 0.34, likely discharge home 0.29; p=0.0002 (ANOVA). Re-admission rates were high, 60% once and 40% twice or more, in patients discharged from hospital. The revised guidance on Eligibility for NHS Continuing Care in Scotland, CEL (2008), is useful in identifying the frailest patients with complex needs and limited survival. However, hospital re-admission rates and mortality are high in all patients considered for eligibility to NHS continuing care in whom the guidance is applied.


Angiotensin II modulates the cardiovascular responses to microinjection of NPY Y1 and NPY Y2 receptor agonists into the nucleus tractus solitarii of the rat.
The aim of this work was to investigate the modulation of the cardiovascular effects of neuropeptide Y (NPY) in the nucleus tractus solitarii (NTS) by angiotensin II (Ang II) and to determine the NPY receptor subtype involved in this modulation. Anesthesized Sprague-Dawley rats received microinjections in the NTS of Ang II (threshold and ED(50) doses) with NPY Y(1) agonist Leu(31)Pro(34)NPY and NPY Y(2) agonist NPY(13-36) (threshold and ED(50) doses). The changes in mean arterial pressure (MAP) and heart rate (HR) recorded in the femoral artery were analyzed during 60 min after the microinjections. The injection of threshold doses of Ang II, Y(1) agonist or Y(2) agonist alone did not produce any change in cardiovascular parameters. However, the co-injections into the NTS of threshold doses of both Ang II and the Y(1) agonist elicited significant increases of MAP and HR of about 12 and 10%, respectively. The co-administration of threshold doses of Ang II with the Y(2) agonist also induced a significant vasopressor response. The vasodepressor and bradycardiac effect of an ED(50) dose of the Y(1) agonist was significantly counteracted (P<0.01) by a threshold dose of Ang II. The vasopressor effect elicited by an ED(50) dose of the Y(2) agonist was significantly enhanced by a threshold dose of Ang II (P<0.01). No significant change of cardiovascular responses elicited by an ED(50) dose of Ang II was observed in the presence of threshold doses of the Y(1) agonist or of the Y(2) agonist. The present study gives functional evidences for a differential modulatory activity of Ang II on the cardiovascular responses mediated by Y(1) and Y(2) receptor subtypes, which may be of relevance for central cardiovascular regulation in the NTS.


The cytosolic chaperonin CCT associates to cytoplasmic microtubular structures during mammalian spermiogenesis and to heterochromatin in germline and somatic cells.
Spermiogenesis, the haploid phase of spermatogenesis, is characterised by a dramatic cytodifferentiation of spermatids. The two major steps, nuclear shaping and cytoplasmic reorganisation of the organelles, rely on an extensive remodelling of the microtubule cytoskeleton. Folding of alpha- and beta-tubulin is mediated by the cytoplasmic chaperonin containing TCP-1 (CCT), highly expressed in testis. We studied CCT cellular distribution throughout spermatogenesis by immunofluorescence and immunoelectron microscopy. We unveil two main cytoplasmic localisations for CCT: at the centrosome and at the microtubules of the manchette, a structure unique to male germ cells. Both structures are essential for spermatid differentiation and may require CCT function. Although CCT is essentially cytoplasmic, a few reports suggest that a subset may have a nuclear localisation. We demonstrate that in the nucleus of germline and somatic cells, part of CCT associates to heterochromatin. In interphase cells, CCT seems generally confined to constitutive heterochromatin. Nevertheless, in condensing nucleus of future spermatozoon, it is also associated with chromatin undergoing compaction. Finally, in fully-condensed mitotic chromosomes, CCT is located all along the chromosomes. Our finding that CCT is associated with constitutive heterochromatin and to compacting chromatin raises the possibility that it may be implicated in maintenance and remodelling of heterochromatin.


A physiological approach to surgical treatment of progressive early idiopathic scoliosis.
The results of previous clinical and experimental studies have provided accumulated evidence for the role of rib asymmetry in the pathogenesis of idiopathic scoliosis (IS). Moreover, it has been shown that scoliosis induced in rabbits can be corrected by elongation or growth stimulation of ribs on the side of the convexity. Taking these observations into consideration, a 7-year-old girl with right convex thoracolumbar IS was operated upon by 2-cm shortening of three concave ribs. The preoperative coronal Cobb angle was 46 degrees and the sagittal angle was 55 degrees. Twenty-seven months after the operation the curves were reduced to 21 degrees and 35 degrees, or by 54 and 36%, respectively. It is concluded that new, easy to perform and harmless interventions on the ribs may have vast implications for the overall treatment of young patients with early progressive, thoracic, IS.


Abdominal wall partitioning (the accordion effect) for reconstruction of major defects: a retrospective review of 10 patients.
Ten patients underwent abdominal wall reconstruction using the technique of abdominal wall partitioning. All defects were closed in the midline by approximating fascia to fascia with the assistance of a general surgeon. One patient had skin grafted small bowel. Five patients had chronically infected mesh and previous failed attempts at repair. Four patients had large ventral hernias following gastric reduction operations and massive weight loss. No defect in any dimension was less than 20 cm. All patients had secure abdominal wall repair by reconstruction of a midline anchor for the abdominal wall musculature. One patient was lost to follow-up after 3 weeks. The average follow-up time for the remaining nine patients was 18.6 months (range, 6 months to 4.7 years). One patient required readmission to the hospital for management of a limited area of skin necrosis. Two patients had minor wound infections, and three patients had subcutaneous seromas, all of which were managed on an outpatient basis. One patient developed a 2 x 2-cm subxiphoid hernia recurrence. Technical details include subcutaneous undermining of the abdominal skin to the anterior axillary lines bilaterally, mobilization of the viscera to expose the white lines of Toldt bilaterally, and parallel, parasagittal, staggered releases of the transversalis fascia, transversalis muscle, external oblique fascia, external oblique muscle, and rectus fascia. These multiple releases allow expansion and translation of the abdominal wall by an accordion-like effect. This accordion-like effect allows closure of abdominal wall defects that are substantially larger than what can be closed with current techniques.


The Journey and Barriers to Treatment of Patients With Renal Nutcracker Syndrome.
To better understand renal nutcracker syndrome (NCS) from a patients' perspective starting at presentation and followed through to diagnosis and management METHODS: This descriptive study was conducted on a national level via a self-selected online survey distributed via river sampling by a post on the Facebook Page 'Renal Nutcracker Syndrome Support Group.' Of the 22 responses collected, 95.5% were female and 91% self-identified as White. 43% experienced symptoms as teenagers and 62% were diagnosed as young adults. Prior to receiving a definitive diagnosis, over half of the respondents were worked up for kidney stones (57%) and ovarian cysts (48%) and saw at least 10-15 providers. Nearly 80% experienced constant pain throughout the day. Pain management included prescription oral pain relievers (38%), prescription patches (29%), and physical therapy (19%). Surgical procedures included nephrectomy with auto transplant (38%), left renal vein transposition (10%), and laparoscopic extravascular stent placement (10%). Respondents had high healthcare utilization for management of NCS. Nearly 30% were unable to work and had filed for disability. Awareness of NCS should increase among healthcare providers of all specialties to improve quality of care to those living with NCS. It is crucial to keep NCS within the differential diagnosis in patients presenting with gross hematuria and unusual abdominal and/or flank pain.


Evolution of Liver Transplantation in Kazakhstan: Two-Era Experience of a Single Center, the First Report.
Liver transplantation has been performed in Kazakhstan since 2011. The present study aimed to analyze the outcomes of the most experienced liver transplant center in Kazakhstan. Between December 2011 and December 2018, 131 liver transplantations were performed at A.N. Syzganov's National Scientific Center of Surgery. The clinical data of 88 adult patients who underwent living donor liver transplantations from December 2011 to December 2017 were analyzed. The patients were divided into 2 cohorts based on the periods in which the procedure was performed: the early era (2011-2014; n = 25) and the late era (2015-2017; n = 63). The clinical course and outcomes were retrospectively reviewed. There were significant differences in the characteristics of the recipients. The patients who were treated during the late era had significantly better survival rates compared with the early era (1 year, 90.5%; 3 year, 79.6%; vs 1 year, 67.7%; 3 year 63.3%; P < .05). Right lobe grafts were used significantly more frequently during the late era (P < .05), while splenectomy was indicated significantly less frequently (P < .05). We also noted a decrease in the complication rate, including early postoperative mortality (P < .05). Over the past 7 years, the liver transplant program has been established, and the operative techniques used in living donor liver transplant have changed dramatically. Patient survival has been improving with increased experience.


Yolk sac volume assessed by three-dimensional ultrasonography using the VOCAL method.
Establish normative data for yolk sac volume (YSV) at 7-10 weeks of gestation assessed by transvaginal three-dimensional ultrasonography (3D-US) using the VOCAL method and analyze its correlation with gestational age (GA) and crown-rump length (CRL). A cross-sectional study involving 62 normal pregnancies was performed to assess YSV from 7 to 10 weeks of gestational age. An endocavitary volumetric transducer (3D5-8EK) was used for all measurements. The VOCAL (Virtual Organ Computer-aided AnaLysis) method with a 30 degrees rotation angle was used for volumetric calculations. Regression models were constructed to analyze the correlation between YSV and GA or CRL The mean, standard deviation, median, minimum and maximum values were calculated for each gestational age. There was a poor correlation between YSV and GA or CRL. The quadratic regression was the model that best expressed the correlation between these variables: R2=0.188 for GA and R2=0.203 for CRL. The mean YSV went from 0.063 cm(3) (95% CI: 0.047; 0.080) at 7 weeks to 0.164 cm3 (95% CI 0.095; 0.232) at 10 weeks. Reference limits were generated for first trimester YSV using 3D-US. There was a poor correlation between YSV and GA or CRL.


Behavioral effects of intrahippocampal injections of clonidine, yohimbine and salbutamol in the rat.
Intrahippocampal injections of adrenergic drugs, clonidine (an alpha 2-agonist), yohimbine (an alpha 2-antagonist), and salbutamol (a beta 2-agonist) were performed in the awake rat. The injection of a high dose of clonidine caused a depression in locomotion in the open-field. Yohimbine partially antagonized the clonidine-induced hypomotility. The intrahippocampal injection of salbutamol had no effect on ambulatory behavior of the rat. These results suggest that the role played by the anterodorsal hippocampus in modifying behavior in novel situations is dependent on the specific sub-population of adrenoceptors that is stimulated.


Where children and adolescents drown in Queensland: a population-based study.
This retrospective population-based study examined drowning location by the site of immersion for both fatal and non-fatal drowning events in Queensland. Drowning location is not routinely collected, and this study used data linkage to identify drowning sites. The resulting enhanced quality data quantify drowning incidence for specific locations by geographic region, age group and by severity for the first time. Linked data were accessed from the continuum of care (prehospital, emergency, hospital admission and death data) on fatal and non-fatal drowning episodes in children aged 0-19 years in Queensland for the years 2002-2008 inclusive. Drowning locations ranked in order of overall incidence were pools, inland water, coastal water, baths and other man-made water hazards. Swimming pools produced the highest incidence rates (7.31/100,000) for overall drowning events and were more often privately owned pools and in affluent neighbourhoods. Toddlers 0-4 years were most at risk around pools (23.94/100,000), and static water bodies such as dams and buckets-the fatality ratios were highest at these 2 locations for this age group. Children 5-14 years incurred the lowest incidence rates regardless of drowning location. Adolescents 15-19 years were more frequently involved in a drowning incident on the coast shoreline, followed by inland dynamic water bodies. Linked data have resulted in the most comprehensive data collection on drowning location and severity to date for children in the state of Queensland. Most mortality and morbidity could have been prevented by improving water safety through engaged supervision around pools and bath time, and a heightened awareness of buckets and man-made water hazards around the farm home for young children. These data provide a different approach to inform prevention strategies.


[Identification of Functionally Significant Polymorphic Variants in miRNA Genes in Carotid Atherosclerosis].
miRNAs are vital molecules of gene expression. They are involved in the pathogenesis of various common diseases, including atherosclerosis, its risk factors, and its complications. A detailed characterization of the spectrum of functionally significant polymorphisms of miRNA genes in patients with advanced carotid atherosclerosis is an important research task. We analyzed miRNA expression and exome sequencing data of carotid atherosclerotic plaques of male patients (n = 8, 66-71 years of age, 67-90% degree of carotid artery stenosis). For further study and analysis of the association between the rs2910164 polymorphism of the MIR146A gene and advanced carotid atherosclerosis, we recruited 112 patients and 72 relatively healthy Slavic residents of Western Siberia. A total of 321 and 97 single nucleotide variants (SNVs) were detected in the nucleotide sequences of pre- and mature miRNAs in carotid atherosclerotic plaques. These variants were located in 206 and 76 miRNA genes, respectively. Integration of the data of exome sequencing and miRNA expression revealed 24 SNVs of 18 miRNA genes that were processed to mature form in carotid atherosclerotic plaques. SNVs with the greatest potential functional significance for miRNA expression predicted in silico were rs2910164:C>G (MIR146A), rs2682818:A>C (MIR618), rs3746444:A>G (MIR499A), rs776722712:C>T (MIR186), rs199822597:G>A (MIR363). The expression of miR-618 was lower in carotid atherosclerotic plaques of patients with the AC rs2682818 genotype of the MIR618 gene compared with the CC genotype (log2FC = 4.8; p = 0.012). We also found an association of rs2910164:C (MIR146A) with the risk of advanced carotid atherosclerosis (OR = 2.35; 95% CI: 1.43-3.85; p = 0.001). Integrative analysis of polymorphisms in miRNA genes and miRNA expression is informative for identifying functionally significant polymorphisms in miRNA genes. The rs2682818:A>C (MIR618) is a candidate for regulating miRNA expression in carotid atherosclerotic plaques. The rs2910164:C (MIR146A) is associated with the risk of advanced carotid atherosclerosis.


Fetal hydrocephalus--prenatal treatment.
From January 1986 to January 2001, 85 cases of hydrocephalus were referred to the Pediatric Neurosurgery and Fetal Medicine Sections of the São Paulo Federal University and the Santa Joana Maternity Hospital in São Paulo, Brazil. Thirty-nine of these cases concerned fetuses ranging from 24 to 32 weeks' gestation, who underwent intrauterine treatment. The hydrocephalus etiologies consisted of: aqueduct stenosis (18 cases), intraventricular hemorrhage (8 cases), Dandy-Walker malformation (4 cases), Chiari type II (4 cases), and other diverse etiologies (5 cases). Twenty fetuses underwent repeated cephalocentesis: 18 received a ventriculo-amniotic shunt and in 1 case endoscopic third ventriculostomy was performed. The follow-up period varied between 1 and 14 years (median 5 years). Out of 39 patients, 26 have been considered as normal (IQ above 70), 6 have mild or moderate handicaps (IQ from 35 to 70), and 7 are severely handicapped (IQ below 35). After birth, 38 patients underwent ventriculoperitoneal shunting with low-pressure valves. In the absence of chromosomopathies, when the gestational age ranges between 24 and 32 weeks, progressive fetal hydrocephalus of a non-infectious origin can obtain benefit from intraventricular decompression performed during the fetal period. New methods of diagnosis and treatment should be developed, especially in those countries where interruption of gestation is not permitted by law, for the benefit of those families who, due to social or religious factors, do not accept abortion.


The effect of preventive use of hydrolyzed protein formula milk on gastrointestinal diseases and physical development of premature infants: A protocol for systematic review and meta-analysis.
Because of the controversy in clinical nutritional support therapy of hydrolyzed protein formula milk and standard preterm infant formula (SPIF) in premature infants. In this study, the effectiveness and safety of preventive use of hydrolyzed protein formula milk in reducing gastrointestinal diseases and promoting physical development of premature infants are scientifically evaluated by systematic evaluation. To help find the suitable nutritional support for premature infants. To search the database of Chinese and English by computer: SinoMed, CNKI, WanFang Data, VIP, PubMed, EMbase and The Cochrane Library, and to collect randomized controlled trials on the application of hydrolyzed protein formula milk in nutritional support treatment of premature infants compared with SPIF. The retrieval time limit is from the establishment of each database to September 1, 2020. Two authors independently completed the paper search, and sorting out the main outcome indicator and secondary outcome indicator in the selected literature, and the data are statistically analyzed by Review Manager software (RevManV.5.3.0) and STATA 13.0. This study will provide a high-quality evidence on the effects of hydrolyzed protein formula milk on gastrointestinal diseases and physical development of premature infants. At present, the clinicians are controversial about the safety and effectiveness of hydrolyzed protein formula milk and SPIF in the nutritional support therapy of premature infants. This study will compare the effectiveness and safety of these 2 nutritional support methods, and make a comprehensive analysis of the influence of hydrolyzed protein formula milk on gastrointestinal diseases and physical development of premature infants, and finally give a positive conclusion. DOI 10.17605/OSF.IO/UQD92.


Management Challenge of Rhino-Orbito-Cerebral Mucormycosis in Covid 19 Era: A Prospective Observational Study.
Mucormycosis is an uncommon but a fatal fungal infection that usually affects patients with altered immunity. The Rhizopus Oryzae is most common type and responsible for nearly 60% of mucormycosis cases in humans and also accounts for 90% of the Rhino-orbital-cerebral (ROCM) form. Our aim and objective was to study, the site of mucormycosis in nose and paranasal sinuses, adjacent site like orbit palate or intracranial involvement, co-morbid condition and management to be done in confirm mucormycosis patients. The most common sinuses involved are the ethmoid, maxillary followed by the frontal and sphenoid sinus. Diabetes mellitus is often associated with mucormycosis of the paranasal sinuses, as is corona virus infection; uncontrolled diabetes further increases the risk. Intra-orbital involvement is common, but intracranial involvement is rare. Extensive steroid and broad-spectrum antibiotic use for Covid-19 management may cause or exacerbate fungal disease. All the patients required surgical intervention along with medical treatment.


High-pressure thermal conductivity and compressional velocity of NaCl in B1 and B2 phase.
Sodium chloride (NaCl) is an important, commonly used pressure medium and pressure calibrant in diamond-anvil cell (DAC) experiments. Its thermal conductivity at high pressure-temperature (P-T) conditions is a critical parameter to model heat conduction and temperature distribution within an NaCl-loaded DAC. Here we couple ultrafast optical pump-probe methods with the DAC to study thermal conductivity and compressional velocity of NaCl in B1 and B2 phase to 66 GPa at room temperature. Using an externally-heated DAC, we further show that thermal conductivity of NaCl-B1 phase follows a typical T-1 dependence. The high P-T thermal conductivity of NaCl enables us to confirm the validity of Leibfried-Schlömann equation, a commonly used model for the P-T dependence of thermal conductivity, over a large compression range (~ 35% volume compression in NaCl-B1 phase, followed by ~ 20% compression in the polymorphic B2 phase). The compressional velocities of NaCl-B1 and B2 phase both scale approximately linearly with density, indicating the applicability of Birch's law to NaCl within the density range we study. Our findings offer critical insights into the dominant physical mechanism of phonon transport in NaCl, as well as important data that significantly enhance the accuracy of modeling the spatiotemporal evolution of temperature within an NaCl-loaded DAC.


Purpura fulminans localising to a recent burn injury.
The development of progressive, severe skin changes (purpura fulminans) is a serious complication of septicaemia, particularly meningococcal septicaemia. Purpura fulminans almost invariably leads to some full thickness skin loss and may lead to limb amputation. The pathophysiology may involve microemboli, endotoxins and direct bacterial damage to the vessels. We describe a case of purpura fulminans, probably as a result of meningococcal septicaemia, localising to a recent, healed burn with complete resolution. We can find no other record of the skin manifestations of meningococcal septicaemia localising to a previous injury.


Biomarkers of Response and Resistance to Immunotherapy in Microsatellite Stable Colorectal Cancer: Toward a New Personalized Medicine.
Immune Checkpoint Inhibitors (ICIs) are well recognized as a major immune treatment modality for multiple types of solid cancers. However, for colorectal cancer (CRC), ICIs are only approved for the treatment of Mismatch-Repair-Deficient and Microsatellite Instability-High (dMMR/MSI-H) tumors. For the vast majority of CRC, that are not dMMR/MSI-H, ICIs alone provide limited to no clinical benefit. This discrepancy of response between CRC and other solid cancers suggests that CRC may be inherently resistant to ICIs alone. In translational research, efforts are underway to thoroughly characterize the immune microenvironment of CRC to better understand the mechanisms behind this resistance and to find new biomarkers of response. In the clinic, trials are being set up to study biomarkers along with treatments targeting newly discovered immune checkpoint molecules or treatments combining ICIs with other existing therapies to improve response in MSS CRC. In this review, we will focus on the characteristics of response and resistance to ICIs in CRC, and discuss promising biomarkers studied in recent clinical trials combining ICIs with other therapies.


Multi-targeted hybrids based on HDAC inhibitors for anti-cancer drug discovery.
Multi-targeted hybrids combine two drugs in a single molecule to have greater medicinal effects than its individual components. Recently, a number of anti-cancer drug candidates such as CUDC-101 (Curis) have been designed based on linking properly two selected pharmacophores endowed with activity against different therapeutic targets.


Inhibition of plasminogen activator inhibitor-1: antibody fragments and their unique sequences as a tool for the development of profibrinolytic drugs.
Physiological inhibition of plasminogen activator inhibitor-1 (PAI-1) might improve the prevention and treatment of various cardiovascular diseases. To date, a variety of monoclonal antibodies that neutralize PAI-1 have been generated. The current study presents the cloning, expression and characterization of four single-chain variable fragments (i.e. scFv-33B8, scFv-33H1F7, scFv-35A5 and scFv-55F4C12) from the corresponding PAI-1 neutralizing monoclonal antibodies. Surprisingly, affinity constants of scFv-33B8, scFv-33H1F7 and scFv-55F4C12 for PAI-1 (KA = 1.4 +/- 0.2 x 1010 m-1, 3.7 +/- 0.1 x 109 m-1, 1.0 +/- 0.2 x 109 m-1, respectively) were only 2- to 4-fold lower compared to those of the respective monoclonal antibodies (MAs). In contrast, scFv-35A5 exhibited a 6250-fold decrease in affinity (KA = 3.2 +/- 0.8 x 106 m-1 vs. 2.0 +/- 0.8 x 1010 m-1 observed for MA-35A5) with a concomitant absence of functional effects on PAI-1 activity. Evaluation of the dose-response curves of the PAI-1 neutralizing effect of the other scFvs revealed a shift towards slightly higher concentrations (in line with the small decrease in affinity) eventually resulting in a similar maximum effect as the corresponding MAs (i.e. 92 +/- 2%, 34 +/- 3% and 66 +/- 5% PAI-1 inhibition for scFv-33B8, scFv-33H1F7 and scFv-55F4C12, respectively). In conclusion, the sequence information of the scFvs allows to humanize MAs with PAI-1 inhibiting properties whereas the scFv constructs serve as an excellent starting point for structure based drug design, both aiming at the reduction of cardiovascular diseases.


Demographic and clinical characteristics of patients who recommence clozapine following therapy interruptions.
The proportion of patients who recommence clozapine after cessation, the time taken to resume clozapine post-cessation, and distinguishing demographic and clinical characteristics of this group have been poorly researched. We evaluated these in the current study. We retrospectively extracted selected demographic and clinical variables and clozapine treatment interruption and recommencement data up to December 2018 of a cohort of 458 patients who first commenced clozapine between 2006 and 2016. The study was conducted at three Australian health services. Of the 310 (69%) patients who had at least one interruption of clozapine treatment, 170 (54.8%) did not resume clozapine, and 140 (45.2%) recommenced it after the first interruption. More than half of those who recommenced did so within a month and 80% by 12 months. Cox regression analysis revealed that age was significantly associated with recommencement, with a 2% decrease in the likelihood of restarting after an interruption for each year later that clozapine was initially commenced (HR = 0.98 95%CI: 0.97, 0.997, p = 0.02). Those who ceased clozapine due to adverse effects were less likely to restart than those who ceased due to noncompliance (HR = 0.63 95%CI: 0.41, 0.97, p = 0.03). More time on clozapine prior to interruption increased the likelihood of restarting it, with each additional month on clozapine increasing this likelihood by 1% (HR = 1.01 95%CI: 1.01, 1.02, p < 0.001). If the distinguishing demographic and clinical characteristics of the group identified in this study are corroborated through further research, this could further validate the need to identify treatment resistance and commence clozapine early in people with schizophrenia and provide appropriate interventions to those more at risk of permanent discontinuation of clozapine.


Dyskeratosis congenita: hematologic evaluation of a sibship and review of the literature.
Dyskeratosis congenita is a rare genodermatosis whose hematologic complications include pancytopenia of variable time of onset, a propensity for opportunistic infections, and neoplasia. A family in which the disorder segregated in 3 generations and involved 9 members is reported, and the hematologic data of the 46 previously reported cases are reviewed.


'Forgotten': a personal comment and communiqué on West Papuan refugees.
To raise awareness of the ongoing human rights violations of the Indigenous residents of West Papua and their mental health consequences. The author, herself a refugee from West Papua, provides a summary comment from a presentation to the Leadership in Mental Health: Island Nations course, based on personal experience in West Papua and Papua New Guinea, and a telephone survey of West Papuan refugees resident in Australia. A communiqué in solidarity from all course delegates was produced and is included. Human rights violations continue in West Papua, and the plight of its indigenous residents and West Papuan refugees in Papua New Guinea and Australia are dire and should not be 'forgotten'.


Tumor-targetable magnetoluminescent silica nanoparticles for bimodal time-gated luminescence/magnetic resonance imaging of cancer cells in vitro and in vivo.
Bimodal photoluminescence-magnetic resonance (MR) imaging technique has attracted tremendous attention due to its great potential in biomedical researches and clinical practices. Herein a novel multifunctional magnetoluminescent nanocomposite, FA-Gd-Tb@SiO2, was found to serve as an effective probe for bimodal time-gated luminescence/MR imaging of cancer cells in vitro and in vivo. The nanoprobe was designed by integrating a luminescent Tb3+ complex, a Gd(III)-based contrast agent and a tumor-targeting molecule, folic acid (FA), into a silica nanoparticle. The integration of these functional moieties allows the nanoprobe to be employed for specific imaging of cancer cells with background-free TGL and non-invasive MR imaging modes. In addition, the optical and magnetic properties were dramatically improved after implicating the newly synthesized nanoarchitecture. In vitro cellular TGL imaging demonstrated that the FA-Gd-Tb@SiO2 nanoprobe could recognize and accumulate in cancer cells overexpressing FA receptor. Furthermore, in vivo study revealed that the as-prepared nanoprobe was able to effectively enhance T1-weighted MR contrast and TGL intensity in tumor tissue, which might contribute to the precise detection and tracing of cancer cells, as well as diagnosis and therapy of tumor in clinical.


How Do We Best Educate Our Patients' Caregivers? Comparing the Efficacy of Print Versus Media-based Education Materials in Peripheral Nerve Catheter and Pain Pump Education.
Media-based educational materials (EMs) are becoming prominent. The purpose of this study was to compare print versus media-based EMs given to caregivers of pediatric and young adult patients undergoing surgery. We aimed to see whether print or media-based EMs lead to greater caregiver satisfaction, comfort, and preparedness for outpatient peripheral nerve catheter and pain pump management. We also assessed caregiver preference for EM modality. We hypothesized that media-based EMs would demonstrate greater overall efficacy and thus generate higher caregiver preference. Randomized control trial. After IRB approval, clinicaltrials.gov registration (17-0638), and informed consent, caregivers were randomized to either media or print-based EM groups. Caregivers reviewed their assigned EM and completed a standardized assessment of their comprehension. We assessed caregiver satisfaction, preparedness, and comfort level with the content on a 5-point Likert scale. On postoperative days 1 to 2, caregivers reported satisfaction, comfort, and preference for EM modality. An intent-to-treat analysis was used to compare the 2 groups. From our final cohort of 135 caregivers, we found no difference [P>0.05] in satisfaction, comfort level, level of preparedness, or discharge readiness scores between groups. After the caregivers were given both EMs, they were evenly split in their preference for print (49.6%) versus video (50.4%) based methods. We did not detect a significant difference in caregiver preference or feelings of preparedness between groups. Interestingly, a significant proportion of caregivers (25%) did not feel comfortable managing the peripheral nerve catheter and its pain pump at home. Future studies should work to improve caregiver comfort with educational content before patient discharge. Providers and institutions should feel comfortable providing both print and media-based patient and caregiver education. Caregiver education may be best suited based on caregiver preference of one EM modality versus the other. Level I.


Estrogen for the prevention of recurrent urinary tract infections in postmenopausal women: a meta-analysis of randomized controlled trials.
Recurrent urinary tract infections (rUTIs) are commonly encountered in postmenopausal women. Optimal non-antimicrobial prophylaxis for rUTIs is an important health issue. The aim of this study was to evaluate the use of estrogen in the prevention of rUTIs versus placebo. Eligible studies published up to December 2019 were retrieved through searches of MEDLINE, Embase, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews. We included randomized controlled trials of estrogen therapies versus placebo regarding the outcomes of preventing rUTIs. Changes in vaginal pH and estrogen-associated adverse events were also analyzed. Eight studies including 4702 patients (2367 who received estrogen and 2335 who received placebo) were identified. Five studies including 1936 patients evaluated the use of vaginal estrogen, which resulted in a significant reduction in rUTIs (relative risk, 0.42; 95% CI, 0.30-0.59). Three studies including 2766 patients evaluated the outcomes of oral estrogen in the prevention of UTIs and showed no significant difference in the number of rUTIs compared to treatment with placebo (relative risk, 1.11; 95% CI, 0.92-1.35). Two studies reviewed changes in vaginal pH and showed a lower pH (mean difference, -1.81; 95% CI, -3.10--0.52) after vaginal estrogen therapy. Adverse events associated with vaginal estrogen were reported, including vaginal discomfort, irritation, burning, and itching. There was no significance increase in the vaginal estrogen group (relative risk, 3.06; 95% CI, 0.79-11.90). Compared with placebo, vaginal estrogen treatment could reduce the number of rUTIs and lower the vaginal pH in postmenopausal women.


The Fanconi anemia core complex is required for efficient point mutagenesis and Rev1 foci assembly.
Fanconi anemia (FA) is a chromosome instability syndrome characterized by congenital abnormalities, cellular hypersensitivity to DNA crosslinking agents, and heightened cancer risk. Eight of the thirteen identified FA genes encode subunits of a nuclear FA core complex that monoubiquitinates FANCD2 and FANCI to maintain genomic stability in response to replication stress. The FA pathway has been implicated in the regulation of error-prone DNA damage tolerance via an undefined molecular mechanism. Here, we show that the FA core complex is required for efficient spontaneous and UVC-induced point mutagenesis, independently of FANCD2 and FANCI. Consistent with the observed hypomutability of cells deficient in the FA core complex, we also demonstrate that these cells are impaired in the assembly of the error-prone translesion DNA synthesis polymerase Rev1 into nuclear foci. Consistent with a role downstream of the FA core complex and like known FA proteins, Rev1 is required to prevent DNA crosslinker-induced chromosomal aberrations in human cells. Interestingly, proliferating cell nuclear antigen (PCNA) monoubiquitination, known to contribute to Rev1 recruitment, does not require FA core complex function. Our results suggest a role for the FA core complex in regulating Rev1-dependent DNA damage tolerance independently of FANCD2, FANCI, and PCNA monoubiquitination.


Major femoral vascular access complications after coronary diagnostic and interventional procedures: A Danish register study.
Vascular access complications after coronary angiography (CAG) and percutaneous coronary intervention (PCI) are known to increase morbidity, prolong hospitalization and raise hospital costs. Therefore, risk factor identification and improvement of safety strategies for vascular management are important. We aimed to assess the incidence of major vascular complications related to femoral access, and to identify potential risk factors. Over a period of six years, 23,870 index procedures (CAG) were performed in two centres, prospectively entered in the database and retrospectively analysed. Data was obtained from the Eastern Danish Heart Registry and cross-matched with data from the Danish Vascular Registry. Index procedures were defined as the first trans-femoral procedure. Demographic, procedural and mortality data, as well as information on access complications requiring surgery within 30 days were collected. Mortality data were collected for minimum 12 months. We identified 130 (0.54%) access complications requiring surgery; 65 pseudoaneurysms (0.28%), 46 arterial occlusions (0.19%), 15 hematomas (nine groin and six retroperitoneal hematomas) (0.06%), and 4 arterial dissections (0.02%). Risk factors for complications were left sided femoral access (OR 4.11 [2.29-7.37] p<0.001), peripheral arterial disease (PAD) (OR 2.42 [1.48-3.94] p<0.0001) and female sex (OR 2.22 [1.51-3.24] p<0.0001). Vascular complications related to femoral access in coronary diagnostic and interventional procedures are low (0.54%). Risk factors were left sided access, PAD, and female sex.


Isolation, molecular characterization, and phylogenetic analysis of porcine encephalomyocarditis virus strain HB10 in China.
Encephalomyocarditis virus (EMCV) can cause myocarditis, respiratory failure, reproductive failure, and mortality in pregnant sows, fetuses, and ablactating piglets. Diseases caused by EMCV currently affect the swine industry worldwide. A virus was isolated from organs of dead piglets that presented with acute myocarditis in northern China. The production of a specific cytopathic effect on susceptible cells and the results of hemagglutination inhibition (HI) assay, PCR, electron microscopy (EM), and sequencing indicated that the pathogen was EMCV; the strain was named HB10. Other pathogenic agents causing myocarditis and death were excluded as possible pathogenic agents. Phylogenetic analyses of the capsid coding region and the VP3/VP1 genes using the neighbour-joining method revealed that EMCV isolates cluster into two groups (groups 1 and 2) with two sub-clusters within group 1 (group 1a and b). HB10 belongs to group 1a, along with strains CBNU, GX0601, BJC3, NJ08, and BEL-2887A/91. Five strains isolated from Sus scrofa belong to group 2. The results of this and previous studies indicate that HB10 and other EMCV strains cause myocarditis of pigs in China.


Use of reverse diet kit as a treatment to regress atheroma in a known CAD patient: A case report.
The way people eat have changed rapidly across the globe and is one of the reasons for developing coronary artery disease (CAD). Atheroma is caused due to the accumulation of fatty deposits and scar tissue leading to the degeneration of the walls of the arteries, restriction of the circulation and a risk of thrombosis. This single case experimental study shows that regression in atheroma may be achieved by replacing the normal diet with a low calories diet used in the reverse diet kit. The patient complained of angina on minor exertion. Post admission the patient underwent a computed tomography angiogram (CT-angiogram) to measure the plaque volumes of left anterior descending artery (LAD), left circumflex artery (LXC) and right coronary artery (RCA) of the heart. The patient was monitored for 12 weeks with the administration of reverse diet as a treatment method. The change in weight, blood pressure and heart rate was monitored every week. After 12 weeks, CT-angiogram was performed again. There was a 7.3 kg decrease in weight along with normalization of blood pressure (BP). A 92.8 mm3 regression of the total atheroma volume was observed. The diet provided may help in reducing atheroma burden in this CAD patient.


Factors associated with county-level mental health during the COVID-19 pandemic.
The objective of this study is to determine county-level factors associated with anxiety, depression, and isolation during the coronavirus disease 2019 (COVID-19) pandemic. This study used daily data from 23,592,355 respondents of a nationwide Facebook-based survey from April 2020 to July 2021, aggregated to the week-county level to yield 212,581 observations. Mental distress prevalences were modeled using weighted linear mixed-effects models with a county random effect. These models revealed that weekly percentages of mental distress were higher in counties with higher unemployment rates, populations, and education levels; higher percentages of females, young adults, individuals with a medical condition, and individuals very worried about their finances and COVID-19; and lower percentages of individuals who were working outside the home, living with children, without health insurance, and Black. Anxiety peaked in April 2020, depression in October 2020, and isolation in December 2020. Therefore, United States counties experienced the mental health effects of the pandemic differently dependent upon their characteristics, and mental distress prevalence varied across time.


COVID-19 in Switzerland real-time epidemiological analyses powered by EpiGraphHub.
Here we present the design and results of an analytical pipeline for COVID-19 data for Switzerland. It is applied to openly available data from the beginning of the epidemic in 2020 to the present day (august 2022). We analyzed the spatio-temporal patterns of the spread of SARS-CoV2 throughout the country, applying Bayesian inference to estimate population prevalence and hospitalization ratio. We also developed forecasting models to characterize the transmission dynamics for all the country's cantons taking into account their spatial correlations in COVID incidence. The two-week forecasts of new daily hospitalizations showed good accuracy, as reported herein. These analyses' raw data and live results are available on the open-source EpiGraphHub platform to support further studies.


Structural and functional changes in soil bacterial communities by drifting spray application of a commercial red seaweed extract as revealed by metagenomics.
Kappaphycus alvarezii seaweed extract (KSWE) is known to enhance crop productivity and impart stress tolerance. Close to one quarter of foliar spray applied to maize falls on the soil, either as drift or from leaf as drip. It was hypothesized that the drift spray would profoundly influence soil microbes under stress. An experiment was conducted with five treatments, with or without KSWE application at critical stages of maize grown under soil moisture stress and compared with an irrigated control. An Illumina platform was employed for the analysis of the V3-V4 region of 16S rRNA gene from the soil metagenome. A total of 345,552 operational taxonomic units were generated which were classified into 55 phyla, 152 classes, 240 orders, 305 families and 593 genera. Shannon's index and Shannon's equitability indicated increased soil bacterial diversity after multiple KSWE applications under conditions of abiotic duress. The abundance of the genera Alicyclobacillus, Anaerolinea, Bacillus, Balneimonas, Nitrospira, Rubrobacter and Steroidobacter decreased (49-79%) under drought imposed at the V5,10 and 15 stages of maize over the irrigated control, while it significantly improved when followed by KSWE application under drought. Flavobacterium, Nitrosomonas, Nitrosovibrio, Rubrobacter genera and several other bacterial taxa which are important for plant growth promotion and nutrient cycling were found to be enriched by KSWE application under drought conditions. Treatments having enriched microbial abundance due to KSWE application under stress recorded higher soil enzymatic activities and plant cob yield, suggesting the contribution of altered soil ecology mediated by KSWE as one of the reasons for improvement of yield.


Improving Randomized-Controlled Trials in Foot and Ankle Orthopaedics: The Need to Include Sociodemographic Patient Data.
The representation of sociodemographic data within randomized-controlled trials (RCT) regarding foot and ankle surgery is undefined. The purpose of this study was to determine the incidence of sociodemographic data being reported in contemporary foot and ankle RCTs. Randomized-controlled trials within the PubMed database from 2016 to 2021 were searched and the full text of 40 articles was reviewed to identify sociodemographic variables reported in the manuscript. Data regarding race, ethnicity, insurance status, income, work status, and education were collected. Race was reported in the results in 4 studies (10.0%), ethnicity in 1 (2.5%), insurance status in 0 (0%), income in 1 (2.5%), work status in 3 (7.5%) and education in 2 (5.0%). In any section other than the results, race was reported in 6 studies (15.0%), ethnicity in 1 (2.5%), insurance status in 3 (7.5%), income in 6 (15.0%), work status in 6 (15.0%), and education in 3 (7.5%). There was no difference in sociodemographic data by journal (P = .212), year of publication (P = .216), or outcome study (P = .604). The overall rate of sociodemographic data reported in foot and ankle RCTs is low. There was no difference in the reporting of sociodemographic data between journal, year of publication, or outcome study. Level II.


Janus "nano-bullets" for magnetic targeting liver cancer chemotherapy.
Tumor-targeted delivery of anti-cancer drugs with controlled drug release function has been recognized as a promising strategy for pursuit of increased chemotherapeutic efficacy and reduced adverse effects. Development of magnetic nanoparticulates as delivery carriers to accommodate cytotoxic drugs for liver cancer treatment has evoked immense interest with respect to their convenience in biomedical application. Herein, we engineered multifunctional Janus nanocomposites, characterized by a head of magnetic Fe3O4 and a body of mesoporous SiO2 containing doxorubicin (DOX) as "nano-bullets" (M-MSNs-DOX). This nanodrug formulation possessed nanosize with controlled aspect-ratio, defined abundance in pore structures, and superior magnetic properties. M-MSN-DOX was determined to induce selective growth inhibition to the cancer cell under magnetic field rather than human normal cells due to its preferable endocytosis by the tumor cells and pH-promoted DOX release in the interior of cancer cells. Ultimately, both subcutaneous and orthotropic liver tumor models in mice have demonstrated that the proposed Janus nano-bullets imposed remarkable suppression of the tumor growth and significantly reduced systematic toxicity. Taken together, this study demonstrates an intriguing targeting strategy for liver cancer treatment based on a novel Janus nano-bullet, aiming for utilization of nanotechnology to obtain safe and efficient treatment of liver cancer.


Pharmaceuticals on a sewage impacted section of a Mediterranean River (Llobregat River, NE Spain) and their relationship with hydrological conditions.
Mediterranean rivers are characterized by a high flow variability, which is strongly influenced by the seasonal rainfall. When water scarcity periods occur, water flow, and dilution capacity of the river is reduced, increasing the potential environmental risk of pollutants. On the other hand, floods contribute to remobilization of pollutants from sediments. Contamination levels in Mediterranean rivers are frequently higher than in other European river basins, including pollution by pharmaceutical residues. Little attention has been paid to the transport behavior of emerging contaminants in surface waters once they are discharged from WWTP into a river. In this context, this work aimed to relate presence and fate of emerging contaminants with hydrological conditions of a typical Mediterranean River (Llobregat, NE Spain). River fresh water samples were collected twice a week over a period of 5 weeks at three sampling points. Sixty-six pharmaceutical compounds belonging to different therapeutical classes were analyzed by LC-MS/MS. Positive and negative correlations between the concentrations of the target analytes and hydrological variables like river flow and dissolved organic matter were observed pointing out the relevance of different hydrological phenomena like dilution effects or sediment re-suspension. Sensitivity calculations showed that the majority of compounds were sensitive to flow variations.


Prognostic role of the ratio of natural killer cells to regulatory T cells in patients with multiple myeloma treated with lenalidomide and dexamethasone.
Despite advances in treating newly diagnosed multiple myeloma (NDMM), a biomarker-driven personalized approach remains an unmet need. A combination of lenalidomide and dexamethasone (RD) is a widely available chemotherapeutic option for NDMM. We aimed to find a circulating immune cell-based biomarker to predict prognosis following RD in patients with NDMM. Clinical data and peripheral blood samples of 71 consecutive NDMM patients treated with RD were retrospectively analyzed. Peripheral blood samples were taken at the time of diagnosis. Immune cell populations, including natural killer (NK) cells, T cells, and their subpopulations, were identified by flow cytometry. In univariable analysis, four variables, including low expression (third or lower quartile) of NK cells, high expression (first or greater quartile) of regulatory T (Treg) cells, female sex, and lambda light chain type, could be plausible factors in predicting poor progression-free survival (PFS). With use of the ratio of NK cells to Treg cells (NK/Treg) as a biomarker, the median PFS of patients with low NK/Treg (less than first quartile, n = 18) was significantly inferior to that of patients with high NK/Treg (first or greater quartile, n = 53): 19.8 months versus 57.3 months, p = 0.047. In multivariable analysis, low NK/Treg was significantly associated with poor PFS (hazard ratio: 2.877, 95% confidence interval: 0.001-1.009, p = 0.048), even after adjusting for other confounding factors. NK/Treg at the time of diagnosis might be a useful immune cell biomarker for clinical decision-making for the use of RD in NDMM. Further investigations are needed to improve outcomes of NDMM patients based on the understanding of the role of NK/Treg.


Use of a latissimus dorsi flap for treatment of infection in a neuropathic shoulder joint.
Case report. To demonstrate the difficulties that can be encountered in diagnosis and treatment of an infected neuropathic shoulder in a paraplegic man. Spinal cord injury center in Germany. Ultimately, radical debridement and transplantation of a latissimus dorsi muscle flap. Successful treatment of the infection, partial weight bearing, and limited restriction of range of motion in the affected shoulder. The latissimus dorsi muscle flap can resolve the infection of a neuropathic shoulder.


Protein expression pattern distinguishes different lymphoid neoplasms.
To identify proteins associated with the histological subtypes of lymphoid neoplasms, we studied the proteomes of 42 cell lines from human lymphoid neoplasms including Hodgkin's lymphoma (HL; four cell lines), B cell malignancies (19 cell lines), T cell malignancies (16 cell lines), and natural killer (NK) cell lymphoma (three cell lines). The protein spots were sequentially selected by (i) Wilcoxon or Kruskal-Wallis tests to find the spots whose intensity was significantly (p <0.05) different among the cell line groups, (ii) by statistical-learning methods to prioritize the spots according to their contribution to the classification, and (iii) by unsupervised classification methods to validate the classification robustness by the selected spots. The selected spots discriminated (i) between HL cells and other cells, (ii) between the cells from B cell malignancies, T cell malignancies, and NK cell lymphoma cells, and (iii) between HL cells and anaplastic large cell lymphoma cells. Among the 31 informative protein spots, MS identified 24 proteins corresponding to 23 spots. Previous reports did not correlate these proteins to lymphocyte differentiation, suggesting that a proteomic study would identify the novel mechanisms responsible for the histogenesis of lymphoid neoplasms. These proteins may have potential as differential diagnostic markers for lymphoid neoplasms.


Are host control strategies effective to eradicate tick-borne diseases (TBD)?
Ticks are responsible for spreading harmful diseases including Lyme disease and tick-borne encephalitis. Understanding tick population dynamics and predicting risk of tick-borne disease insurgence helps to design preventive actions against the disease spread. Using a compartmental model describing the pathogen transmission among ticks and hosts, we study the influence of host-targeted tick control strategies with chemical insecticides on tick population and disease transmission dynamics. Our analysis shows that in areas with rapid-growing population of ticks, host-targeted controls using chemical insecticides may enhance disease persistence and even turn a disease-free area to a disease endemic area. Therefore, the complex dynamics of pathogen spread among ticks and hosts should be carefully examined when designing tick control strategies.


Visual motion information modulates tactile roughness perception.
We perceive the roughness of an object through our eyes and hands. Many crossmodal studies have reported that there is no clear visuo-tactile interaction in roughness perception using static visual cues. One exception is that the visual observation of task-irrelevant hand movements, not the texture of task-relevant objects, can enhance the performance of tactile roughness discrimination. Our study investigated whether task-irrelevant visual motion without either object roughness or bodily cues can influence tactile roughness perception. Participants were asked to touch abrasive papers while moving their hand laterally and viewing moving or static sine wave gratings without being able to see their hand, and to estimate the roughness magnitude of the tactile stimuli. Moving gratings with a low spatial frequency induced smoother roughness perceptions than static visual stimuli when the visual grating moved in the direction opposite the hand movements. The effects of visual motion did not appear when the visual stimuli had a high spatial frequency or when the participants touched the tactile stimuli passively. These results indicate that simple task-irrelevant visual movement without object roughness or bodily cues can modulate tactile roughness perception with active body movements in a spatial-frequency-selective manner.


[Experience gained in the Pecica region (Arad) regarding the organizational aspects of the integration of antitubercular chemotherapy in the basic health network].
The present paper reports on the author's experience concerning certain organizational aspects in the closely surveyed treatment of tuberculosis following integration of this activity in the general health network. Emphasis is layed on the role of the general practitioner and ancillary staff who must work under the guidance of a specialist in pneumophyhisiology. The importance of personal motivation in the general health services and the role of health education of the patients is underlined.


Rickettsia sibirica isolation from a patient and detection in ticks, Portugal.
We report the first isolation of Rickettsia sibirica (strain mongolotimonae) from the blood of a patient and detection by polymerase chain reaction (PCR) of the rickettsia in a Rhipicephalus pusillus tick collected from a dead mongoose (Herpestes ichneumon) in the Alentejo region, Portugal. We describe also the first PCR detection of a new Rickettsia strain that is related to R. sibirica.


The Mediterranean Adequacy Index: further confirming results of validity.
Since dietary patterns can influence levels of major risk factors for chronic disease, various indexes or scores of overall diet quality have been proposed and related to risk factors for disease. The Mediterranean Adequacy Index (MAI) was developed to simply assess how close a diet is to the Healthy Reference National Mediterranean Diet (HRNMD), a healthful diet in which Mediterranean food patterns are inversely correlated with prevalence of risk factors for chronic disease. This report describes further evidence of MAI values for diets of population groups from different countries. MAI is obtained by dividing the food group intakes typical of a healthy reference Mediterranean diet, expressed in g/day, by the food group intakes not characteristic of a healthy Mediterranean diet. In this paper, the MAI was computed based on the diets of 23 population groups from Italy, Greece, U.S.A., Costa Rica, Chile, Spain, and Germany. High MAI values were recorded among working class men from southern Italy, and Seven Countries Study (SCS) men from the Greek islands, and the lowest among U.S.A. men and a control group of German women; surprisingly low values were recorded among Madrid men and women and participants from Spanish-speaking Latin American countries. The inversely significant correlation between the 16 SCS cohort diet MAI values and the 25-year coronary heart disease death rate previously observed was stable when an appropriate statistical analysis was used. Furthermore, MAI values of diets in elderly participants from 10 European countries followed for 10 years were inversely associated with total mortality. The above results further confirm the validity of MAI, indicating that it is as good as the most utilised indexes or scores proposed for adults in Europe.


Nasal reconstruction in surgery of the anterior skull base.
We sought to evaluate the effectiveness of a number of surgical maneuvers in nasal reconstruction of a diverse population of patients undergoing skull base surgery. Study design We conducted a retrospective review of a cohort of patients undergoing nasal reconstruction during surgery of the anterior skull base and craniovertebral junction. All patients undergoing skull base surgery and nasal reconstruction by the senior author (Y.D.) with a minimum follow-up of 12 months from 1997 to 2001 were evaluated. Preoperative and postoperative photographs and clinical evaluation were examined in detail with particular attention focused on the nasal complex. A total of 47 patients were evaluated for this study, including those who had undergone anterior craniofacial resections (n = 14), Le Fort osteotomies (n = 5), subcranial approaches (n = 10), maxillotomies (n = 8), and midfacial disassemblies (n = 10). Primary calvarial bone graft reconstruction of the anterior craniofacial group was facilitated with the use of positioning plates and resuspension of the upper lateral cartilages when available. In contradistinction to secondary bone grafting, dorsal grafts in this group extended to the native nasal bone length. A small overlay bone graft was thought to be necessary when the nasal root was osteotomized in conjunction with the orbital and/or maxillary segments to maintain dorsal height in the long term. Le Fort osteotomy patients require refixation of the septum to the anterior nasal spine region for stability. Use of the techniques outlined in this article appears to be associated with gratifying long-term nasal form in reconstruction of the anterior skull base.


Twitter and brachytherapy: An analysis of "tweets" over six years by patients and health care professionals.
Twitter may reflect attitudes underrepresented in traditional surveys. This study aimed to understand professionals' and patients' thoughts regarding brachytherapy on Twitter. Twitter was queried with "brachytherapy" to identify all tweets about patients' experiences from January 2012 to May 2017. A random sample of tweets by health care professionals containing "brachytherapy" was obtained using the first weekly tweet in the same interval. Consensus coding was used to categorize tweets as "patient" or "professional" based on content about receiving brachytherapy or self-identification as a health care professional. Tweets were analyzed for positive, neutral, or negative sentiment and recurrent themes using manual, iterative coding. Patient tweets were analyzed for whether they were shared before or after treatment and whether the patient, friends, or family had posted them. Professional tweets were analyzed to identify temporal theme changes. One hundred sixty-two patient tweets and 260 professional tweets were obtained from January 2012 to May 2017. On average, 2.5 patient tweets were shared monthly compared to 69 for providers. Among tweets by patients and professionals, 57% vs. 12% expressed positive sentiment, 21% vs. 3% negative sentiment, and 22% vs. 85% neutral sentiment, respectively. The most common patient and professional codes were "general sharing of experience/casual conversation" (32%) and "science" (21%), respectively. Patients tweeted less about brachytherapy than professionals and generally expressed favorable and negative sentiments regarding their radiation treatment experiences. Professionals tended to express neutral sentiment and focus on research. Opportunities exist for greater radiation oncologist engagement in this medium.


Use of in vitro bone models to screen for altered bone metabolism, osteopathies, and fracture healing: challenges of complex models.
Approx. every third hospitalized patient in Europe suffers from musculoskeletal injuries or diseases. Up to 20% of these patients need costly surgical revisions after delayed or impaired fracture healing. Reasons for this are the severity of the trauma, individual factors, e.g, the patients' age, individual lifestyle, chronic diseases, medication, and, over 70 diseases that negatively affect the bone quality. To investigate the various disease constellations and/or develop new treatment strategies, many in vivo, ex vivo, and in vitro models can be applied. Analyzing these various models more closely, it is obvious that many of them have limits and/or restrictions. Undoubtedly, in vivo models most completely represent the biological situation. Besides possible species-specific differences, ethical concerns may question the use of in vivo models especially for large screening approaches. Challenging whether ex vivo or in vitro bone models can be used as an adequate replacement for such screenings, we here summarize the advantages and challenges of frequently used ex vivo and in vitro bone models to study disturbed bone metabolism and fracture healing. Using own examples, we discuss the common challenge of cell-specific normalization of data obtained from more complex in vitro models as one example of the analytical limits which lower the full potential of these complex model systems.


Treatment of reverse osmosis (RO) concentrate by the combined Fe/Cu/air and Fenton process (1stFe/Cu/air-Fenton-2ndFe/Cu/air).
To decompose or transform the toxic and refractory reverse osmosis (RO) concentrate and improve the biodegradability, 1stFe/Cu/air-Fenton-2ndFe/Cu/air were developed to treat RO concentrate obtained from an amino acid production plant in northern China. First, their operating conditions were optimized thoroughly. Furthermore, 5 control experiments were setup to confirm the superiority of 1stFe/Cu/air-Fenton-2ndFe/Cu/air and synergistic reaction between Fe/Cu/air and Fenton. The results suggest that the developed method could obtain high COD removal (65.1%) and BOD5/COD ratio (0.26) due to the synergistic reaction between Fe/Cu/air and Fenton. Under the optimal conditions, the influent and effluent of 1stFe/Cu/air-Fenton-2ndFe/Cu/air and 5 control experiments were analyzed by using UV, FTIR, EEM and LC, which confirm the superiority of 1stFe/Cu/air-Fenton-2ndFe/Cu/air. Therefore, the developed method in this study is a promising process for treatment of RO concentrate.


In vivo evaluation of safety and performance of a nitinol venous stent in an ovine iliac venous model.
Obstruction of the iliocaval venous outflow tract is a common cause of acute and chronic venous symptoms. Percutaneous stenting is now frequently performed to alleviate obstruction in the central venous system. However, currently used stents were primarily designed for biliary or arterial indications and may not be optimal for use in the venous system. This study evaluated the safety and performance of a novel venous stent (NVS) designed specifically for venous applications in an in vivo venous animal model. The study evaluated vascular response and safety of the NVS compared with the Wallstent Stent (WS; Boston Scientific, Marlborough, Mass) at baseline, 56, and 180 days in adult sheep. Four sheep received a single NVS in the iliac vein for acute evaluation, and eight underwent bilateral iliac vein stenting using a single NVS on one side and a single WS on the other for longer-term follow-up. Fluoroscopy and intravascular ultrasound imaging were performed at implantation to identify iliac vein diameters at baseline and again at 56 and 180 days. Both iliac veins from all 56-day and 180-day animals (n = 16) underwent histologic examination. Three sections from each vessel were reviewed for intimal strut coverage, luminal thickening, thrombus, and evidence of venous injury. Student t-tests were used to compare mean iliac vein diameters for the WS and the NVS. Stent placement of the NVS and WS was successful to within 5 mm of the preselected location in all animals. During follow-up, no clinical evidence of stent thrombosis or obstruction >50% occurred in any limb. Sections of the stented vein at 56 and 180 days exhibited complete or nearly complete endothelial cell coverage, no or minimal luminal thrombus, and virtually complete neointimal coverage of every strut. The WS and NVS both caused an increase in iliac vein diameters immediately after stenting. At 180 days, there was no difference in iliac vein diameter or the percentage change in diameter compared with diameters immediately after stenting as measured by venography and intravascular ultrasound. In an ovine iliac vein model, a new NVS studied to 180 days was free of thrombotic complications and significant luminal stenosis. These data support clinical evaluation of this NVS in appropriately designed human clinical trials.


Chemical composition and antifungal activity of essential oils and supercritical CO2 extracts of Apium nodiflorum (L.) Lag.
Aerial parts of Apium nodiflorum collected in Portugal and Italy were submitted to hydrodistillation; also a supercritical fluid extract was obtained from Italian plants. The extracts were analyzed by GC and GC/MS. Both essential oils, obtained from Portuguese and Italian plants, posses high content of phenylpropanoids (51.6 vs. 70.8%); in the former, the percentage split in myristicin (29.1%) and dillapiol (22.5%), whereas in the latter, the total percentage is only of dillapiol (70.8%). The co-occurrence of myristicin and dillapiol is frequent because dillapiol results from enzymatic methoxylation of myristicin. Antimicrobial activity of phenylpropanoids has been patented, what suggest the potential of plants with high amounts of these compounds. Minimal inhibitory concentration (MIC) and minimal lethal concentration, determined according to NCCLS, were used to evaluate the antifungal activity of the essential oils against yeasts, Aspergillus species and dermatophytes. Essential oils exhibited higher antifungal activity than other Apiaceae against dermatophytes, with MIC ranging from 0.04 to 0.32 μl/ml. These results support the potential of A. nodiflorum oil in the treatment of dermatophytosis and candidosis.


Survey of the Endophytic Bacteria Inhabiting Wild Daucus Seed Using 16S rRNA Gene Amplicon Sequencing.
We report a preliminary survey of the endophytic bacterial microbiota of seed from wild carrot (Daucus carota) using 16S rRNA gene amplicon sequencing. Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria were the most abundant phyla detected, while Bacillus, Massilia, Paenibacillus, Pantoea, Pseudomonas, Rhizobium, Sphingomonas, and Xanthomonas were the most abundant genera.


Lower extremity edema from bladder compression of the iliac veins.
Two elderly men were referred to our vascular clinic for the management of bilateral lower extremity edema of 2 to 3 months' duration. Their evaluation included phlebograms, which demonstrated external compression of their iliac veins. CT scans of the pelvis suggested that large bladders caused the compression. Each patient had mild symptoms of prostatism. Transurethral resection of the prostate was recommended to and accepted by each patient. Decompression of the bladder was accompanied by complete relief of the lower extremity venostasis in both patients. Review of the literature yielded only eight similar cases of this unusual cause of lower extremity edema.


Placebo effects in adult and adolescent patients with schizophrenia: combined analysis of nine RCTs.
To examine characteristics of placebo responders and seek optimal criteria of early improvement with placebo for predicting subsequent placebo response in patients with schizophrenia. Data of 672 patients with schizophrenia randomized to placebo in nine double-blind antipsychotic trials were analyzed. Multiple logistic regression analyses were conducted to examine associations between placebo response at week 6 (i.e., a ≥ 25% reduction in the Positive and Negative Syndrome Scale [PANSS] score) and gender, age, study locations, baseline PANSS total or Marder 5-Factor scores, and per cent PANSS score reduction at week 1. Predictive power of improvement at week 1 for subsequent response was investigated; sensitivity and specificity of incremental 5% cutoff points between 5% and 25% reduction in the PANSS total score at week 1 were calculated. Per cent PANSS total score reduction at week 1 and lower PANSS Marder disorganized thought scores at baseline were significantly associated with subsequent placebo response. A 10% reduction in a per-protocol analysis or a 15% reduction in last-observation-carried-forward analysis in the PANSS total score at week 1 showed the highest predictive power. These findings are informative to identify potential placebo responders at the earliest opportunity for optimal trial design for schizophrenia.


Long non-coding RNA NEAT1 promotes bladder progression through regulating miR-410 mediated HMGB1.
LncRNA NEAT1 is reported as a crucial oncogene in multiple cancers. But, its biological role in bladder cancer is barely understood. Therefore, we concentrated on the function and role of NEAT1 in bladder cancer. Firstly, NEAT1 expression in bladder cancer cells was determined and it was displayed NEAT1 was significant elevated. NEAT1 was knockdown and overexpressed in T24 and J82 cells. Then it was indicated that NEAT1 silence greatly inhibited bladder cancer cell proliferation with an increased ratio of apoptotic cells and severe cell cycle arrest. Overexpression of NEAT1 exhibited a reversed process in bladder cancer cells. Additionally, in vivo experiments were employed using establishment of nude mice models. NEAT1 knockdown inhibited bladder cancer growth while increase of NEAT1 promoted bladder cancer development in vivo. By employing the bioinformatics analysis, we speculated that miR-410 was as a downstream target of NEAT1. Then, the targeting association between them was proved in our research and we implicated miR-410 was dramatically restrained in bladder cancer cells. Meanwhile, it was exhibited that miR-410 was negatively regulated by NEAT1. Apart from these, HMGB1 was speculated as a downstream target of miR-410. Dual-luciferase reporter assay was used to prove the correlation between miR-410 and HMGB1. Up-regulation of miR-410 restrained HMGB1 levels and NEAT1 can regulate HMGB1 level via sponging miR-410. To sum up, we implied NEAT1/miR-410/HMGB1 axis participated in bladder cancer.


Management of Reproductive Diseases in Male Small Ruminants.
Reproductive tract diseases can be a significant cause of subfertility or infertility in male small ruminants. Affected males can usually be identified early by performing routine serologic screening and yearly breeding soundness examinations. Early diagnosis will either maximize treatment success or expedite culling decisions. Once clinical signs of diseases develop, prognosis for breeding ability declines. Veterinary practitioners should used ancillary diagnostic techniques, such as ultrasound examination and laboratory testing to acquire a diagnosis and determine prognosis of reproductive lesions. Some diseases (eg, brucellosis) should be ruled out immediately to cull affected animals and minimize transmission within the herd.


The relationship of benign prostatic hyperplasia's symptoms severity with the risk of developing atrial fibrillation.
Attention is drawn to the increased incidence of atrial fibrillation (AF) in benign prostatic hyperplasia (BPH) patients recently. Early predicting of AF in these patients can help in decreasing its clinical consequences. The aim of our study is to determine the association between BPH symptoms and AF predictors atrial electromechanical delay (AEMD) and the P-wave dispersion (PWD). 218 healthy individuals recently diagnosed with BPH were assigned into three groups according to symptoms severity using the International prostate symptom score (IPSS) questionnaire. The first group with mild symptoms (IPSS score between 0 and 7, n = 78), the second group with moderate symptoms (IPSS score between 8 and 19, n = 86), and the third group with severe symptoms (IPSS score between 20 and 35, n = 54). PWD and AEMD calculations were performed for all participants. There were statistically significant differences between the three groups in terms of AEMD and PWD (p < .01 and p < .01, respectively). In all three study groups, a significant positive correlation was observed between IPSS questionnaire scores and both AEMD and PWD (for AEMD r = .29, p = .013 and for PWD r = .27, p = .017). On the other hand, there were significant differences between the three groups in terms of the inflammatory markers C-reactive protein (CRP) and fibrinogen (p < .01 and p < .01, respectively) and in terms of serum testosterone levels (p < .01). We concluded that periodic evaluation of patients with BPH in terms of symptoms severity can be helpful not only from urological aspect, but also in the early prediction of possible serious cardiovascular morbidity and mortality.


Genetic approaches to ciliate pattern formation: from self-assembly to morphogenesis.
In the cortex of ciliates, thousands of basal bodies, with their associated cytoskeletal appendages and networks, are arranged in an elaborate pattern whose reproduction at division involves complex morphogenetic movements. Genetic analysis demonstrates that pattern formation relies both on local constraints imposed by the pre-existing organization, and on the differential interpretation of inductive signals by different cell territories whose individual developmental properties are reset at each division.


An innovation in curriculum content and delivery of cancer education within undergraduate nurse training in the UK. What impact does this have on the knowledge, attitudes and confidence in delivering cancer care?
This was an evaluation of an innovation in curriculum content and delivery within undergraduate nursing education in the UK. Its purpose was to investigate the effect on knowledge, attitudes and confidence in delivering cancer care. The study design was a pre-test post-test survey design with a comparison group. Participants were two cohorts of undergraduate nursing students (n(intervention) = 84, n(comparison) = 91). The intervention cohort were exposed to a new 3.5 day programme of cancer education, coproduced with patients, carers and health professionals, which focused on cancer as a life changing long-term condition. The comparison cohort had been exposed to a 2 day programme produced by a lecturer. Following exposure to the new model for the delivery of undergraduate nurse cancer education, the intervention cohort demonstrated good overall knowledge of the impact of cancer, more positive attitudes towards cancer treatment and more confidence in their ability to deliver cancer care. Attitudes were more positive and confidence in ability to support cancer patients at all stages of the cancer journey were greater than in the comparison group. Insights gained into the cancer patient and carer perspectives were highly valued. This study has found that a new model for the delivery of cancer education focusing on survivorship and delivered in partnership with patients, carers and clinicians, may improve knowledge, attitudes and confidence in the delivery of cancer care. Further work is now needed, using a more robust experimental design, to investigate the generalisability of the results to other education programs.


The analgesic defect of C57BL/6J-bgJ/bgJ (beige-J: Chediak-Higashi syndrome) mice transmitted by adoptive transfer of spleen cells to normal littermates.
We recently discovered and reported that C57BL/6J-bgJ/bgJ (beige-J) mice have a deficiency in their analgesic response to intracerebroventricularly-administered morphine in the tail-flick test. Postulating a link between these findings and the known immunological defect of beige-J mice (Chediak-Higashi syndrome), we examined the effect of splenectomy on beige-J mice and the adoptive transfer of their mononuclear spleen cells to normal littermate controls (2 x 10(7) cells via tail vein). Eight days after these interventions, the splenectomized beige-J mice responded nearly as well as normal mice to centrally administered morphine in the tail-flick test. The adoptive transfer recipients, in contrast, nearly completely lost their response to the analgesic action of morphine in this test. From the combined results, the spleen appears to be a significant factor in the analgesic defect of beige-J mice and, furthermore, mononuclear splenocytes appear to be the source of a substance that can transfer this defect to otherwise normal animals.


Ultrathin, elastic, and self-adhesive nanofiber bio-tape: An intraoperative drug-loading module for ureteral stents with localized and controlled drug delivery properties for customized therapy.
During the postoperative management of urinary diseases, oral or intravenous administration of drugs and implanting ureteral stents are usually required, making localized drug delivery by ureteral stent a precise and effective medication strategy. In the traditional drug loading method, the drug was premixed in the implants in production lines and the versatility of drugs was restricted. However, the complex situation in the urinary system fails the possibility of finding a "one fits all" medication plan, and the intraoperative drug-loading of implants is highly desired to support customized therapy. Here, we designed an ultrathin (8 μm), elastic, and self-adhesive nanofiber bio-tape (NFBT) that can easily encapsulate drugs on the stent surface for controllable localized drug delivery. The NFBT exhibited high binding strength to a ureteral stent, a sustained release over 7 d in PBS for hydrophilic drug, and a zero-order release curve over 28 days for the hydrophobic drug nitrofurantoin (NFT). Further in vivo experiments using a porcine ureteral tract infection model demonstrated that NFBT loaded with NFT could significantly reduce the bacterial concentration in urine. The total amount of NFT delivered by the NFBT was about 2.68 wt% of the recommended dose for the systemic administration.


Free D- and L-amino acids in ventricular cerebrospinal fluid from Alzheimer and normal subjects.
Free D-Ser, D-Asp and total D-amino acids were significantly higher (p < 0.05) in Alzheimer (AD) ventricular CSF than in normal CSF. There was no significant difference in the total L-amino acids between AD and normal CSF, but L-Gln and L-His were significantly higher (p < 0.05) in AD-CSF. The higher concentrations of these D- and L-amino acids in AD ventricular CSF could reflect the degenerative process that occurs in Alzheimer's brain since ventricular CSF is the repository of amino acids from the brain.


Bio-reduction of N-nitrosodimethylamine (NDMA) using a hydrogen-based membrane biofilm reactor.
N-Nitrosodimethylamine (NDMA) is a disinfection by-product shown to be carcinogenic, mutagenic, and teratogenic. A feasible detoxification pathway for NDMA is a three-step bio-reduction that leads to ammonia and dimethylamine. This study examines the bio-reduction of NDMA in a H2-based membrane biofilm reactor (MBfR) that also is active in nitrate and sulfate reductions. In particular, the study investigates the effects of H2 availability and the relative loadings of NDMA, nitrate, and sulfate, which potentially are competing electron acceptors. The results demonstrate that NDMA was bio-reduced to a major extent (i.e., at least 96%) in a H2-based MBfR in which the electron-equivalent fluxes from H2 oxidation were dominated by nitrate and sulfate reductions. NDMA reduction kinetics responded to NDMA concentration, H2 pressure, and the presence of competing acceptors. The most important factor controlling NDMA-reduction kinetics was the H2 availability, controlled primarily by the H2 pressure, and secondarily by competition from nitrate reduction.


Evaluation of 18F-FDG uptake for detecting lymph node metastasis of gastric cancer: a prospective pilot study for one-to-one comparison of radiation dose and pathological findings.
Gastric cancer exhibits various degrees of fluorine F-18 fluorodeoxyglucose ((18)F-FDG) uptake on positron emission tomography/computed tomography (PET/CT). We evaluated the relationship between (18)F-FDG uptake and the presence/absence of metastasis in individual lymph nodes (LN) on a one-to-one basis. We analyzed 21 patients with gastric cancer. We injected (18)F-FDG intravenously in the morning, and gastrectomy with LN dissection was performed in the afternoon of the same day. Radiation doses were measured at each LN using a well-type counter, and we then compared (18)F-FDG uptake, the shortest diameter, and pathological examination results for each LN. In our study, 906 LNs were analyzed, including 115 metastatic LNs. Metastatic LNs showed significantly higher (18)F-FDG uptake (P < 0.0001), and were significantly enlarged (P < 0.0001). The receiver operating characteristics (ROC) curve had a larger area under the curve (0.71) for (18)F-FDG uptake than for the shortest LN diameter (0.60). Considering histology, the ROC curve for intestinal type adenocarcinoma had a larger area under the curve than that for diffuse type (0.75 vs 0.61). F-FDG uptake is potentially a more useful variable than LN diameter for discriminating between LN with and without metastasis, especially in intestinal type gastric cancer cases.


Prevention of atrial fibrillation following cardiac surgery: basis for a novel therapeutic strategy based on non-hypoxic myocardial preconditioning.
Atrial fibrillation is the most common complication of cardiac surgical procedures performed with cardiopulmonary bypass. It contributes to increased hospital length of stay and treatment costs. At present, preventive strategies offer only suboptimal benefits, despite improvements in anesthesia, surgical technique, and medical therapy. The pathogenesis of postoperative atrial fibrillation is considered to be multifactorial. However oxidative stress is a major contributory factor representing the unavoidable consequences of ischemia/reperfusion cycle occurring in this setting. Considerable evidence suggests the involvement of reactive oxygen species (ROS) in the pathogenic mechanism of this arrhythmia. Interestingly, the deleterious consequences of high ROS exposure, such as inflammation, cell death (apoptosis/necrosis) or fibrosis, may be abrogated by a myocardial preconditioning process caused by previous exposure to moderate ROS concentration known to trigger survival response mechanisms. The latter condition may be created by n-3 PUFA supplementation that could give rise to an adaptive response characterized by increased expression of myocardial antioxidant enzymes and/or anti-apoptotic pathways. In addition, a further reinforcement of myocardial antioxidant defenses could be obtained through vitamins C and E supplementation, an intervention also known to diminish enzymatic ROS production. Based on this paradigm, this review presents clinical and experimental evidence supporting the pathophysiological and molecular basis for a novel therapeutic approach aimed to diminish the incidence of postoperative atrial fibrillation through a non-hypoxic preconditioning plus a reinforcement of the antioxidant defense system in the myocardial tissue.


Optimum pH for nuclear sex identification using quinacrine.
Preparations of quinacrine stained interphase nuclei from buccal smears and hair root sheaths were mounted in MacIlvaine's buffer at various pH's in an attempt to obtain optimum differentiation of X- and Y-chromatin. Relatively high pH (5-8) was associated with intense nuclear fluorescence. Background nuclear fluorescence decreased with lower pH's (2-4), revealing distinct granules. X-chromatin is best differentiated against this decreased background, while positive identification of Y-chromatin is more certain in the absence of confusing granules. Hence optimum pH for X-chromatin screening in quinacrine stained preparations is approximately 3.0, that for Y-chromatin screening 5.5.


Conversion of substance P to C-terminal fragments in human plasma.
Substance P is rapidly converted by enzyme(s) in human plasma to des-[Arg1Pro2]-substance P (fragment 3-11) and to des-[Arg1Pro2Lys3Pro4]-substance P (fragment 5-11). These metabolites were isolated by HPLC and partially sequenced. No evidence was obtained for deamidation of substance P in plasma or for the formation of the N-terminal tetrapeptide [Arg-Pro-Lys-Pro]. The data suggest that substance P is metabolized in human plasma by an enzyme with the specificity of dipeptidyl-aminopeptidase IV. Consistent with this hypothesis, the rate of degradation of substance P measured with an antibody directed against the N-terminal region is 2-3-fold greater than measured with a C-terminally directed antibody. The degrading activity of plasma was purified 522-fold and was eluted from a gel filtration column in the molecular weight zone 150 000-170 000 and from a chromatofocusing column in the pH range 4.5 to 5.5.


An Environmental Scan of Consumer-Initiated Germline Genetic Testing for Health Risks.
As patient access to laboratory testing outside the clinic grows, health care providers can expect to confront increasing questions about the utility and interpretation of consumer-initiated genetic testing for health risks. We sought to characterize the marketplace diversity of consumer-initiated germline genetic testing options. An environmental scan was conducted to identify germline genetic testing companies that offer testing for at least one diagnosable health condition and are available for purchase by consumers in the US market without a visit to one's health care provider. We limited our scope to tests available between October 1, 2019, and September 30, 2021. We characterized variability in the content and processes used by 21 companies offering 74 distinct test products that met our inclusion and exclusion criteria. A minority (8 of 21 companies) offered tests that assessed the presence of at least 1 US Centers for Disease Control and Prevention Tier 1 condition for which detection can impact an individual's clinical care and for which evidence-based guidelines for detection and management exist.


Comparison of biometry and intraocular lens power calculation performed by a new optical biometry device and a reference biometer.
To compare biometry measurements and intraocular lens (IOL) power calculations obtained by a new optical A-scan interferometer biometer (Galilei G6) (new biometer) and a partial coherence interferometer biometer (IOLMaster 500) (reference biometer). Private practice, Recife, Brazil. Retrospective comparative study. Cataract patients who had biometric measurements with the new biometer and the reference biometer were included in the study. Comparisons were performed for axial length (AL), keratometry (K), anterior chamber depth (ACD), and IOL power calculation to reach emmetropia with an Acrysof SN60WF IOL using the Haigis formula. The Pearson correlation coefficient and the 95% limits of agreement (LoA) were calculated. The paired Student t test and the Wilcoxon test were used to assess differences between devices. Eighty-eight eyes (88 patients) were studied. Both biometers provided statistically similar mean IOL power to reach emmetropia, AL, keratometry, and ACD measurements (P > .05). The differences in these variables did not vary as their mean values increased, and there was a strong positive correlation between the values obtained by both devices for each variable. The 95% LoA values for AL, mean keratometry, ACD, and IOL power were 0.27 mm, 1.08 diopters (D), 0.66 mm, and 1.56 D, respectively. The 2 devices were comparable with regard to mean IOL power, mean AL, K, and ACD measurements. However, the wide range of differences between the devices suggests they should not be used interchangeably.


Impact of personality psychopathology on outcome in short-term cognitive-behavioral therapy for Axis I disorders.
Cognitive behavioral therapy (CBT) is efficacious for many Axis I disorders, though its effectiveness in the real world, for patients with Axis II comorbidity is less well known. This study examines the effectiveness of CBT for Axis I disorders in three groups of patients: those with personality disorders, those with personality disorder traits and those with no Axis II pathology. Consecutive referrals of patients with non-psychotic Axis I disorders were assessed for short-term CBT in a University Teaching Unit. While the acceptance rate was lower for individuals with personality disorders, there were no group differences in dropout rates. Of those who completed therapy (mean number of sessions=17.8, SD=11.2), those in the Personality Disorders group (n=45) had 4 sessions more on average than the Personality Disorder Traits group (n=42) or the No Axis II Group (n=266). All 3 groups were equally successful, whether the outcome was therapist opinion of success, the clinical global impression, or the reliable change index based on patient-reported symptom change. Intent to treat analysis results paralleled those of the completer analysis. Our findings indicate that the presence of a personality disorder does not negatively impact therapy adherence or success in short-term CBT for an Axis I disorder.