Literature-based discovery approaches for evidence-based healthcare: a systematic review.
Literature-Based Discovery (LBD) is a text mining technique used to generate novel hypotheses from vast amounts of literature sources, by identifying links between concepts from disparate sources. One of the main areas where it has been predominantly applied is the healthcare domain, whereby promising results, in the form of novel hypotheses, have been reported. The purpose of this work was to conduct a systematic literature review of recent publications on LBD in the healthcare domain in order to assess the trends in the approaches used and to identify issues and challenges for such systems. The review was conducted following the principles of the Kitchenham method. The selected studies have been scrutinized and the derived findings have been reported following the PRISMA guidelines. The review results reveal useful information regarding the application areas, the data sources considered, the approaches used, the performance in terms of accuracy and reliability and future research challenges. The results of this review will be beneficial to LBD researchers and other stakeholders in the healthcare domain, by providing them with useful insights on the approaches to adopt, data sources to consider, evaluation model to use and challenges to reflect on. The synthesis of the results of this work has shed light on recent issues and challenges that drive new LBD models and provides avenues for their application in other diverse areas in the healthcare domain. To the best of our knowledge, no such recent review has been conducted.


Angiotensin II plays an important role in maintaining blood pressure in postmenopausal women receiving hormone replacement therapy.
We investigated the role of angiotensin (Ang) II in maintaining blood pressure (BP) by administering a small dose of candesartan, an Ang II type 1 receptor antagonist, in postmenopausal women receiving long-term hormone replacement therapy (HRT). A single dose of 2 mg of candesartan was administered orally to 13 normotensive postmenopausal women receiving HRT (continuous combined conjugated estrogen and medroxyprogesterone acetate orally; HRT group) and 13 normotensive postmenopausal women not receiving HRT (control group). Both BP and heart rate (HR) were measured at baseline and at 1, 2, 3, 4, 5, and 6 h after administration. Plasma renin activity (PRA) and Ang I, Ang II, and bradykinin concentrations were measured at baseline and 4 h after the administration of candesartan. Candesartan lowered the BP and raised the HR in both groups. However, the decrease in BP was significantly greater in the HRT group than in the control group (P < .05), whereas no significant difference in the change in HR was observed between the two groups. In the HRT group, significant increases were found in PRA, Ang I, and Ang II (all P < .05) and a significant decrease in bradykinin (P < .01) with candesartan treatment. In the control group, candesartan as associated with an increase in PRA (P < .05) but not in Ang I, Ang II, or bradykinin. Based on our study results, Ang II plays an important role in maintaining BP in normotensive postmenopausal women receiving HRT. Maintenance of BP may be dependent on the balance between the hypertensive effect of Ang II and the hypotensive effect of bradykinin.


A medical evaluation of the use of qat in North Yemen.
The data presented in this paper examine the frequent statements that the regular use of the drug qat by the people of North Yemen is harmful to their health. The research strategy employed performance of blind physical examinations as well as extensive interviews with 335 females and 371 males in and around the cities of Sanaa, Taiz and Hodeida who had been selected using a quota sample. The sample was classified into heavy, light and non-chewers of the qat plant, and systematic comparisons were made. In general, few diseases or conditions occurred with enough frequency to permit detailed analysis and fewer yet were associated with qat-use. Where associations occurred, differences by sex were often strong. Conditions most strongly associated with use by both sexes were histories of gastritis and insomnia, and the general body system groupings of gastrointestinal disorders. In males the strongest associations were with the histories of anorexia, constipation, insomnia and headaches, as well as the general history of respiratory difficulties. In females strong associations were seen between qat-use and the diagnosis of acute gastritis, and histories of jaundice, bronchitis and hepatic diseases. When effects of age and residence were corrected for by Mantel-Haenszel odds ratios on these items, some of the associations were diminished even further. In general, remarkably few of the allegations regarding the direct effects of qat-use on health by Western visitors to Yemen were supported by this study.


Application of the combined use of fused silica capillary columns and NPD for the toxicological determination of codeine and ethylmorphine in a human overdose case.
The applicability of capillary gas chromatography to the toxicological analysis of extracts of human tissue samples was investigated for codeine and ethylmorphine in a case of drug overdose. After column extraction, the samples were injected onto a fused silica capillary column, using a direct injection technique. The nitrogen-phosphorus detector provided excellent stability and sensitivity without the need for extensive clean-up procedures.


Hydrometrocolpos Presenting as a Huge Abdominal Swelling and Obstructive Uropathy in a 4 Day Old Newborn: A Diagnostic Challenge.
Abdominal swelling is an uncommon presentation in newborn babies. A combination of huge abdominal swelling, obstructive uropathy and imperforate hymen in newborns has not been reported in the medical literature. We report a 4 days old newborn with a rare presentation of hydrometrocolpos which posed a diagnostic challenge and consequently resulted in delays in diagnosis and treatment. Hydrometrocolpos should be considered as a differential diagnosis in neonates who present with huge abdominal swelling.


Complete genome sequence of Acinetobacter baumanni J1, a quorum sensing-producing algicidal bacterium, isolated from Eastern Pacific Ocean.
The Acinetobacter baumanni J1 isolated from surface water of the Eastern Pacific Ocean, demonstrated significant algicidal activity on the algae Alexandrium tamarense. Interestingly, this strain showed the ability to produce an acyl-homoserine lactone (AHL) quorum sensing molecule. To better understand its AHL producing mechanism and its ecological functions, the genome of A. baumanni strain J1 was completely sequenced. The genome contained a circular chromosome of 3,948,465 bp with an average GC content of 39.9 mol%. A total of 3707 protein coding genes, 41 tRNA genes and 16 rRNA genes were obtained. In silico genome annotation identified a LuxI putative gene located on contig 4. Subsequent thin-layer chromatography analysis indicated that C8-AHL could be produced by A. baumanni J1, which confirmed the authenticity of the LuxI gene. Taken together, this work describes an algicidal bacterium that is capable of producing an AHL molecule, which may represent a valuable tool for developing microbial methods to control harmful algae.


A histologic study of the growth of the subglottis after endolaryngeal trauma.
In young rabbits the histologic features of the growth of the subglottis were studied after an endolaryngeal trauma. This lesion of the larynx leading to a subglottic stenosis, caused specific pathologic changes of the cricoid cartilage and the subepithelial tissues. Activation of chondrocytes resulted in proliferation and regeneration of destructed cartilage. The normal subepithelial structures were replaced by granulation tissue differentiating into a thick fibrous scar and into cartilage. This ectopic cartilage together with the repaired cricoid formed a composite thickened 'ring'-like cartilaginous structure in the adult stage.


Efficacy and non-toxicity of ciclopirox olamine-loaded liposomes against Cryptococcus neoformans clinical isolates.
The aim of this study was to evaluate the efficacy and non-toxicity of ciclopirox olamine-loaded liposomes against Cryptococcus neoformans clinical isolates. Initially, 24-1 fractional experimental design was carried out to obtain an optimized formulation of liposomes containing CPO (CPO-LipoC), which were then used to prepare stealth liposomes (CPO-LipoS). Liposomal formulations were characterized by their mean size diameter, polydispersity index (PDI), and drug encapsulation efficiency (EE%). Immunosuppressed mice were exposed to CPO-LipoS at 0.5 mg/kg/day for 14 days to verify possible histopathological alterations in the liver and kidneys. Immunosuppressed mice infected with C. neoformans were treated with CPO-LipoS at 0.5 mg/kg/day for 14 days to quantify the fungal burden in spleen, liver, lungs, and brain. CPO-LipoS presented a mean size diameter, PDI, and EE% of 101.4 ± 0.7 nm, 0.307, and 96.4 ± 0.9%, respectively. CPO-LipoS was non-toxic for the liver and kidneys of immunosuppressed mice. At the survival curve, all infected animals submitted to treatment with CPO-LipoS survived until the end of the experiment. Treatment with CPO-LipoS reduced C. neoformans cells in the spleen (59.3 ± 3.4%), liver (75.0 ± 3.6%), lungs (75.7 ± 6.7%), and brain (54.2 ± 3.2%). CPO-LipoS exhibit antifungal activity against C. neoformans, and the encapsulation of CPO into stealth liposomes allows its use as a systemic drug for treating cryptococcosis.


Effects of Carbamazepine and Valproate on Serum Aspartate Aminotransferase, Alanine Aminotransferase and Gamma - Glutamyltransferase in Children.
Epilepsy is one of the most common neurological diseases in childhood and adolescence. Carbamazepine (CBZ) and valproate (VPA) have been widely used as the first generation of antiepileptic drugs (AED). The aim of the study has been to evaluate and compare the effect of CBZ and VPA monotherapy on aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) serum levels in children. The study has included 100 patients (boys 57/girls 43, age range 1 to 18 years), who have been treated with CBZ or VPA, as initial monotherapy, for at least 12 months. Patients with liver lesions or patients who have been treated with other drugs have been excluded from the study. The initial serum enzyme levels (AST, ALT and GGT) and after 12 months of treatment have been compared. 53/100 (53%) patients have been treated with CBZ and 47/100 (47%) patients have been treated with VPA.The initial level of enzymes were within the referece range. After one year-long treatment AST was elevated at 4/53 (7.5%) CBZ patients and 9/47 (19.15%) VPA patients (x2 test =3.965, p<0.05). ALT was elevated at 5/53 (9.4%) CBZ patients and 9/47 (19.15%) VPA patients (x2 test =6.953, p<0.05). GGT was elevated at 18/53 (34%) CBZ patients and 7/47 (14.9%) VPA patients (x2 test =4.831, p<0.05). The levels of enzymes AST and ALT have been elevated statistically significant in VPA group and GGT in CBZ group.


Sublethal Cd-induced cellular damage and metabolic changes in the freshwater crab Sinopotamon henanense.
To explore whether sublethal cadmium (Cd) exposure causes branchial cellular damages and affects the metabolic activity in brachyuran crustaceans, the freshwater crab Sinopotamon henanense was exposed to 0.71, 1.43, and 2.86 mg/L Cd(2+) for 3 weeks. Gill morphology, metabolic activity (activities of isocitrate dehydrogenase (IDH), cytochrome c oxidase (CCO) and lactate dehydrogenase (LDH), mRNA expression of CCO active subunit 1 (cco-1) and ldh, as well as ATP levels) in crab muscle were investigated. The results showed that sublethal Cd exposure caused profound morphological damages in the gills. The branchial epithelial cells were disorganized and vacuolized. Ultrastructurally, a decrease in number of apical microvilli, vacuolized mitochondria, and condensed chromatin were observed in gill epithelial cells. Correspondingly, the Cd exposure also induced downregulations of cco-1 and ldh mRNA expression and reduced activities of IDH, CCO, and LDH, in accordance with the lower ATP level in crab muscle. These results led to the conclusion that gill damage caused by sublethal Cd exposure could lead to an impairment of oxygen uptake of S. henanense, and the inhibition of metabolic activity decreases the oxygen demand of the crab and assists them to survive under the condition of lower oxygen availability. These effects add to our understanding on toxic effects of Cd and survival management of S. henanense subchronically exposed to sublethal Cd.


[Repairing large alar defects by using a retro-grade auricular flap].
To evaluate a retro-grade auricular flap for repairing large alar defects. Twenty-nine adult cadavers were anatomically used for vascular investigation of the frontal, nasal and temporal regions by injecting a dye into the main vessels. Based on the anatomical study in these regions, a retro-grade auricular flap was designed for repairing alar defects in 16 patients. The blood supply of the auricle could be nourished by the inner carotid artery system from the supratrachlear artery and supraorbital artery through the frontal arterial anastomotical network into the frontal branch of the superficial temporal artery. It is then passing the main trunk of the superficial temporal artery into the ear area through the auricular branches of the superficial temporal artery. The retro-grade auricular island flap could be formed by basing the supratrachlear artery and the supraorbital artery through the vascular network between the superficial temporal artery and the supratrachlear artery or the supraorbital artery. Sixteen patients with large alar defects and half-sized nasal defects were successfully repaired by this technique. The retro-grade auricular island flap, based on the inner carotid artery system, could be a good and safe flap for repairing a large alar defect or half-sized nasal reconstruction.


Impact of route of delivery on continence and sexual function.
Urinary and fecal incontinence have been linked to pregnancy and childbirth. This article reviews the rates of pelvic floor dysfunction following vaginal delivery and cesarean section as cited in short-term and long-term follow-up studies.


The cassava (Manihot-esculenta Crantz)'s nitrate transporter NPF4.5, expressed in seedling roots, involved in nitrate flux and osmotic stress.
AtNPF4.5/AIT2, which was predicted to be a low-affinity transporter capable for nitrate uptake, was screened by ABA receptor complex in Arabidopsis ten years ago. However, the molecular and biochemical characterizations of AtNPF4.5 in plants remained largely unclear. In this study, the function of a plasma-membrane-localized and root-specifically-expressed gene MeNPF4.5 (Manihot-esculenta NITRATE TRANSPORTER 1 PTR FAMILY4.5), an ortholog of the Arabidopsis thaliana NPF4.5, was investigated in cassava roots as a nitrate efflux transporter on low nitrate medium and an influx transporter following exposure to high concentration of external nitrates. Moreover, RNA interference (RNAi) of MeNPF4.5 reduced the nitrate efflux capacity but the overexpressing cassava seedlings increased the ability of efflux from the elongation to the mature zone of root under low nitrate treatments. Besides, MeNPF4.5-RNAi expression reduced the nitrate influx capacity but enhanced nitrate absorption in parts of overexpressing plants from the meristem, elongation to mature zone of roots under high nitrate conditions. Furthermore, MeNPF4.5-RNAi seedlings survived owing to roots that could grow normally, but the MeNPF4.5-over-expressors showed adverse growth under 7% PEG6000 stress, suggesting that MeNPF4.5 negatively regulated the osmotic stress and was involved in nitrate flux through cassava seedlings.


Fine structure of the cuticle of the desert scorpion, Hadrurus arizonensis.
The structure of the sclerite and intersegmental cuticle of the opithosoma of the desert scorpion, Hadrurus arizonensis, has been examined by transmission electron microscopy. The sclerite cuticle contains a four-layered epicuticle, a hyaline exocuticle, an inner exocuticle and an endocuticle. The outer part of the hyaline exocuticle and the whole of the inner exocuticle are constructed of helicoidally arranged planes of microfibrils. Within the endocuticle, the overall architecture is not helicoidal as previously assumed, but consists of bundles of microfibrils oriented horizontally and vertically. Microbibrils of the inner exocuticle and the endocutile are seen as simple unstained rods, but those of the hyaline exocuticle are electron dense rods with an unstained central core. The intersegmental cuticle contains a four-layered epicuticle and a procuticle. In detail, its fine structure differs in most respects from that of the sclerite cuticle. Electron microscopy reveals that hyaline exocuticle, previously assumed to be continuous from sclerite to intersegmental membrane, is absent in the latter.


Evaluating Burning Mouth Syndrome as a Comorbidity of Atypical Odontalgia: The Impact on Pain Experiences.
This study aimed (1) to investigate the differences in clinical characteristics of patients between 2 groups, those who have atypical odontalgia (AO) only and those who have AO with burning mouth syndrome (BMS), and (2) to assess the influence of psychiatric comorbidity factors on patients' experiences. Medical records and psychiatric referral forms of patients visiting the Psychosomatic Dentistry Clinic of Tokyo Medical and Dental University between 2013 and 2016 were reviewed. The final sample included 2 groups of 355 patients: those who have AO only (n = 272) and those who have AO with BMS (AO-BMS; n = 83). Clinicodemographic variables (gender, age, comorbid psychiatric disorders, and history of headache or sleep disturbances) and pain variables (duration of illness, pain intensity, and severity of accompanying depression) were collected. Initial pain assessment was done using the Short-Form McGill Pain Questionnaire, and depressive state was determined using the Zung Self-Rating Depression Scale. The average age, female ratio, and sleep disturbance prevalence in the AO-only group were significantly lower than those in AO-BMS group. AO-BMS patients rated overall pain score and present pain intensity significantly higher than did the AO-only patients (P = 0.033 and P = 0.034, respectively), emphasizing sharp (P = 0.049), hot-burning (P = 0.000), and splitting (P = 0.003) characteristics of pain. Patients having comorbid psychiatric disorders had a higher proportion of sleep disturbance in both groups and a higher proportion of depressive state in the AO-only group. AO-BMS patients have different epidemiological characteristics, sleep quality, and pain experiences compared to AO-only patients. The presence of psychiatric comorbidities in both groups may exacerbate sleep quality. We suggest that BMS as a comorbid oral disorder in AO patients contributes to a more intensively painful experience.


Subclinical alveolitis in immunologic systemic disorders.
Subclinical alveolitis is a frequent finding in immunologic systemic disorders. However the significance of subclinical alveolar inflammation does not seem to be univocal and varies according to the disease. The fact that pulmonary involvement is rare during the course of extrathoracic granulomatosis like Crohn's disease or primary cirrhosis and that subclinical alveolitis is frequent suggests that alveolar inflammation may be the expression in the lung of a systemic immune disorder. In contrast subclinical alveolitis in collagen-vascular diseases, particularly progressive systemic sclerosis, is frequently associated with abnormalities of lung parenchyma as assessed by CT scan supporting the hypothesis that subclinical alveolitis is associated with development of ILD. Close follow-up of these patients is needed to better determine whether subclinical alveolitis precedes ILD and whether early detection of subclinical alveolitis in immunologic systemic disorders may identify those patients that are at risk for the development of ILD in the future.


NLR-1/CASPR Anchors F-Actin to Promote Gap Junction Formation.
Gap junctions are present in most tissues and play essential roles in various biological processes. However, we know surprisingly little about the molecular mechanisms underlying gap junction formation. Here, we uncover the essential role of a conserved EGF- and laminin-G-domain-containing protein nlr-1/CASPR in the regulation of gap junction formation in multiple tissues across different developmental stages in C. elegans. NLR-1 is located in the gap junction perinexus, a region adjacent to but not overlapping with gap junctions, and forms puncta before the clusters of gap junction channels appear on the membrane. We show that NLR-1 can directly bind to actin to recruit F-actin networks at the gap junction formation plaque, and the formation of F-actin patches plays a critical role in the assembly of gap junction channels. Our findings demonstrate that nlr-1/CASPR acts as an early stage signal for gap junction formation through anchoring of F-actin networks.


A preliminary study on the seasonal body temperature rhythms of the captive mountain hare (Lepus timidus).
The mountain hare (Lepus timidus) is a year-round active herbivore adapted to survive the boreal winter. Captive mountain hares (N=4) were implanted with intraabdominal thermosensitive loggers to record their core body temperature (T(b)) for a year and during food deprivation (8-48h) in summer and winter. The average T(b) was 38.7+/-0.01 degrees C in summer and 38.3+/-0.01 degrees C in winter. The yearly T(b) correlated positively with the ambient temperature. The 24-h T(b) was the highest from late scotophase to early photophase in summer and winter and the lowest during middle-late photophase in summer or during early-middle scotophase in winter. The range of the 24-h oscillations in T(b) increased in three animals in winter. Food deprivation did not induce hypothermia in summer or winter. These preliminary data suggest that the mountain hare can spare a modest amount of energy with the wintertime reduction in T(b).


Patient-reported outcomes in older breast cancer survivors with and without prior chemotherapy treatment.
Little is known about long-term treatment-related symptoms in older breast cancer survivors. We characterized long-term patient-reported symptoms and examined factors associated with the presence and severity of symptoms, and symptom interference with daily activities. Texas Cancer Registry (TCR) Medicare linkage data was used to identify breast cancer patients age 65 and older with local/regional stage disease diagnosed between 2012-2013. Symptom burden was assessed using breast-specific items from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™). Demographic and clinical data also were collected. Logistic regression models were used to assess the association between symptom burden and respondent sociodemographic and clinical characteristics. Of 4448 eligible patients, 1594 (response-rate 35.8%) completed questionnaires. Of these, 1245 eligible respondents were included in the analysis based on self-reported data. Median time from diagnosis to survey completion was 68 months (IQR: 62-73). Most frequently reported symptoms were fatigue/lack of energy (76.8%), aching muscles (72.1%) and aching joints (72.5%). Receipt of chemotherapy was associated with higher symptom burden. Patients treated with adjuvant chemotherapy had higher risk of numbness/tingling (OR: 3.16; 95% CI: 2.36-4.24), hair loss (OR: 2.72; 95% CI: 2.05-3.60), and fatigue/lack of energy (OR: 1.80; 95% CI: 1.29-2.52). Similarly, patients who received chemotherapy were more likely to report the majority of symptoms as moderate to severe and as interfering with daily activities. Receipt of chemotherapy is associated with significant symptom burden more than 5 years after breast cancer treatment. Long-term chemotherapy impact should be discussed with patients in a shared-decision making process and approaches to symptom management during survivorship care are needed.


Some unanswered questions in Duchenne muscular dystrophy.
Though the molecular and biochemical bases of Duchenne muscular dystrophy are known, many questions still remain unanswered. They range from the nature and cause of gene deletions to the relationship between dystrophin defects and the clinical phenotype, both in affected males and female carriers. These questions are discussed in the light of recent developments.


Assessment of the healing process after percutaneous implantation of a cardiovascular device: a systematic review.
The healing process, occurring after intra-cardiac and intra-vascular device implantation, starts with fibrin condensation and attraction of inflammatory cells, followed by the formation of fibrous tissue that slowly covers the device. The duration of this process is variable and may be incomplete, which can lead to thrombus formation, dislodgement of the device or stenosis. To better understand this process and the neotissue formation, animal models were developed: small (rats and rabbits) and large (sheep, pigs, dogs and baboons) animal models for intra-vascular device implantation; sheep and pigs for intra-cardiac device implantation. After intra-vascular and intra-cardiac device implantation in these animal models, in vitro techniques, i.e. histology, which is the gold standard and scanning electron microscopy, were used to assess the device coverage, characterize the cell constitution and detect complications such as thrombosis. In humans, optical coherence tomography and intra-vascular ultrasounds are both invasive modalities used after stent implantation to assess the structure of the vessels, atheroma plaque and complications. Non-invasive techniques (computed tomography and magnetic resonance imaging) are in development in humans and animal models for tissue characterization (fibrosis), device remodeling evaluation and device implantation complications (thrombosis and stenosis). This review aims to (1) present the experimental models used to study this process on cardiac devices; (2) focus on the in vitro techniques and invasive modalities used currently in humans for intra-vascular and intra-cardiac devices and (3) assess the future developments of non-invasive techniques in animal models and humans for intra-cardiac devices.


Bronchopulmonary dysplasia is associated with polyhydramnios in a scan for novel perinatal risk factors.
The pathogenesis of bronchopulmonary dysplasia (BPD) is multifactorial, and there are limited data about prenatal exposures and risk of BPD. Our study performed parallel analyses using a logistic regression model in a cohort of 4527 infants with data from a curated registry and using a phenome wide association study (PheWAS) based on ICD9/10-based phecodes. We examined 20 prenatal exposures from a neonatal intensive care unit (NICU) curated registry database related to pregnancy and maternal health as well as 94 maternal diagnosis phecodes with a PheWAS analysis. In both the curated registry and PheWAS analyses, polyhydramnios was associated with an increased risk of BPD (OR 5.70, 95% CI 2.78-11.44, p = 1.37 × 10-6). Our data suggest that polyhydramnios may be a clinical indicator of premature infants at increased risk for bronchopulmonary dysplasia. Combining curated registry data with PheWAS analysis creates a valuable tool to generate hypotheses. Polyhydramnios was significantly associated with bronchopulmonary dysplasia in both a curated registry and by ICD coding analysis with a phenome wide association study (PheWAS). Preterm polyhydramnios may be a clinical indicator of infants at increased risk for developing bronchopulmonary dysplasia after preterm birth. Combining curated registry with PheWAS analysis creates a valuable tool to generate hypotheses about perinatal risk factors and morbidities associated with preterm birth.


Weighted score ratios (WRS) give transparent weighting in multicriteria sustainability assessments - A case study on removal of pharmaceutical residues from wastewater.
Sustainability assessment using multicriteria analysis (MCA) is a structured way of including criteria from the three sustainability dimensions (environmental, economic, and social) when comparing different alternatives. A problem with the conventional MCA methods is that the consequences of the weights given to different criteria are not transparent. Here, we amend the simple additive weighting MCA method with weighted score ratios (WSRs), which are used during the sustainability assessment to show how the weights affect the valuation of the criteria (e.g., cost per kg CO2e). This enables comparisons to other sustainability assessments and reference values from society, which increases the transparency and can make weighting more objective. We applied the method to a comparison of technologies for removal of pharmaceutical residues from wastewater. Due to growing concern about the effects that pharmaceutical residues can have on our environment, implementations of advanced technologies are increasing. However, they entail high requirements of energy and resources. Therefore, many aspects must be considered to make a sustainable choice of technology. In this study, a sustainability assessment was performed of ozonation, powdered activated carbon and granular activated carbon for removal of pharmaceutical residues at a large wastewater treatment plant (WWTP) in Sweden. The outcome showed that powdered activated carbon is the least sustainable choice for the studied WWTP. Whether ozonation or granular activated carbon is most sustainable depends on how climate impact and energy use are valued. The total sustainability of ozonation is affected by how the electricity is assumed to be produced, whereas for granular activated carbon it depends on whether the carbon source is of renewable or fossil origin. Using WSRs allowed the participants in the assessment to make conscious choices on how they weighted different criteria in relation to how these criteria are valued in society at large.


Kinetic and microbiological characterization of aerobic granules performing partial nitritation of a low-strength wastewater at 10 °C.
A granular airlift reactor enriched in ammonia oxidizing bacteria (AOB) was operated at 10 °C performing stable partial nitritation in the long-term. The reactor treated a synthetic low-strength influent during 250 days with an average nitrogen loading rate of 0.63 ± 0.06 g N L(-1) d(-1). Nitrate production was barely detected, being the average concentration in the effluent of 0.6 ± 0.3 mg N-NO3 L(-1). Furthermore, a suitable effluent for a subsequent reactor performing the anammox process was achieved. A maximum specific growth rate as high as 0.63 ± 0.05 d(-1) was determined by performing kinetic experiments with the granular sludge in a chemostat and fitting the results to the Monod model. Pyrosequencing analysis showed a high enrichment in AOB (41 and 65% of the population were identified as Nitrosomonas genus on day 98 and 233, respectively) and an effective repression of nitrite oxidizing bacteria in the long-term. Pyrosequencing analysis also identified the coexistence of nitrifying bacteria and heterotrophic psychrotolerant microorganisms in the granular sludge. Some psychrotolerant microorganisms are producers of cryoprotective extracellular polymeric substances that could explain the better survival of the whole consortia at cold temperatures.


Intragenic loss of function mutations demonstrate the primary role of FMR1 in fragile X syndrome.
Nearly all cases of fragile X syndrome result from expansion of a CGG trinucleotide repeat found in the 5' untranslated portion of the FMR1 gene. Methylation of the expanded repeats correlates with down-regulation of transcription of FMR1; thus fragile X syndrome is postulated to be due to a loss of function of the FMR1 gene product, and this has been demonstrated at the protein level. However, the nature of the mutation offers the possibility of methylation spreading to adjacent genes with consequent loss of expression and contribution to the phenotype. Deletions of FMR1 and flanking sequence (some of substantial size) have been reported in patients with phenotypes consistent with a diagnosis of fragile X-syndrome, however, none is strictly intragenic. We report here the identification of two different intragenic loss of function mutations in FMR1: a single de novo nucleotide deletion in a young male patient (IJ) and an inherited two basepair change in an Adult male (SD), each with classical features of fragile X syndrome.


Clinical, biopsy, and mass spectrometry characteristics of renal apolipoprotein A-IV amyloidosis.
Apolipoprotein A-IV associated amyloidosis (AApoAIV amyloidosis) is a rare cause of amyloidosis with only a single reported case. Here we describe the clinical, biopsy, and mass spectrometry characteristics of 11 cases of renal AApoAIV amyloidosis encompassing 9 men and 2 women with a mean age at diagnosis of 63.5 years. Progressive chronic kidney disease (mean serum creatinine 2.9 mg/dl) was the most common cause for biopsy with proteinuria absent or minimal in all except one. Hematological and serological evaluation was negative in 9 patients, while 2 had a monoclonal gammopathy. The renal biopsy findings were striking and showed large amounts of eosinophilic Congo-red positive amyloid deposits restricted to the renal medulla with sparing of the renal cortex. In 6 cases, peritubular amyloid was noted in addition to the interstitial involvement. Immunofluorescence studies were negative for immunoglobulins. Electron microscopy showed nonbranching fibrils measuring 7 to 10 nm in diameter. Laser microdissection of the amyloid deposits followed by mass spectrometry showed large spectra number (a semiquantitative measure of abundance) for AApoAIV protein ranging from 49 to 169 (average 85), serum amyloid protein (average 19), and apolipoprotein E (average 48). Importantly, no peptides were detected for any other forms of known amyloidogenic precursor proteins. Thus, renal AApoAIV amyloidosis typically presents with progressive chronic kidney disease and histologically exhibits extensive medullary involvement with sparing of the cortex. The diagnosis is best established by mass spectrometry. Hence, a high degree of suspicion and examination of the renal medulla is required to make the diagnosis.


Awareness of the specialty of oral and maxillofacial surgery among health care professionals in Pondicherry, India.
The aim of this study is to establish the level of knowledge among dental, medical, and paramedical professionals of the hospital, regarding the role of oral and maxillofacial surgery in health care. This study also aims to highlight the perception of the medical professionals and what they think an oral and maxillofacial surgeon does. A survey was done at Jawaharlal Institute of Postgraduate Medical and Research Institute, Pondicherry, India, in 2006. The result showed that out of 100, only 41% of the medical students, 76% of the medical practitioners, and 58% of the paramedical workers have heard of the name of the specialty. While the dental professionals realize the scope of the specialty to a larger extent, medical professionals are not fully aware of the expertise the specialty has to offer.


Facile synthesis of Fe-modified lignin-based biochar for ultra-fast adsorption of methylene blue: Selective adsorption and mechanism studies.
A novel Fe-modified lignin-based biochar (Fe-LB) was fabricated via a facile one-step carbonization method for methylene blue (MB) removal from wastewater. Fe-LB exhibited a high specific surface area (885.97 m2/g) and micropore volume (0.3203 m3/g), and demonstrated high affinity for MB with the maximum adsorption capacity of 2.7-fold by Fe-LB than LB. It was found that quick adsorption could be achieved in 15 min with the MB removal efficiency of 100% and adsorption capacity reached 200 mg/g. Selective adsorption studies indicated that Fe-LB preferentially adsorbed MB in high salt and multiple dye systems (binary, ternary, and quaternary) over a wide pH range from 2 to 12. The removal efficiency of CR was greatly improved due to the synergistic effect between MB and CR in the binary system. This work demonstrated that Fe-LB can effectively remove dye contaminants and possessed great potential in the treatment of MB polluted dye wastewater.


Weight concerns, postexperimental smoking, and perceived difficulty in quitting in Argentinean adolescents.
To assess the relationship among weight concerns, smoking, and perceived difficulty in quitting among Argentinean adolescents. Logistic regression and profile analyses, stratified by sex, were used to estimate the associations among 8th and 11th grade students (n=2524). Weight concerns were associated with current smoking status and also with perceived quitting difficulty among female, but not male, Argentinean high school students. Profile analyses determined parallel profiles of weight concerns between female smokers and nonsmokers and between male smokers and nonsmokers. The presence of weight concerns among adolescent females may require special consideration in smoking prevention and cessation programs.


BMP9 maintains the phenotype of HTR-8/Svneo trophoblast cells by activating the SDF1/CXCR4 pathway.
Bone morphogenetic protein 9 (BMP9) has been shown to regulate processes such as angiogenesis, endothelial dysfunction, and tumorigenesis. However, the role of BMP9 in preeclampsia (PE) is unclear. The purpose of this study was to investigate the role and mechanism of BMP9 in PE. The effects of BMP9 on the viability, migration and invasion of HTR-8/Svneo cells were investigated by CCK-8 assay, wound healing assay and Transwell invasion assay. The effect of BMP9 on apoptosis of HTR-8/Svneo cells was detected by flow cytometry. Plasma levels of BMP9, SDF1 and CXCR4 were detected by ELISA kit. qRT-PCR and Western blot were used to detect the expression levels of each gene in the cells. Overexpression of BMP9 promoted the proliferation and migration of trophoblast cells and inhibited apoptosis. Knockdown of BMP9 had the opposite effect. The levels of BMP9, SDF1 and CXCR4 in the plasma of PE patients were down-regulated, and BMP9 was positively correlated with the levels of SDF1 and CXCR4. BMP9 also significantly upregulated the mRNA and protein levels of SDF1 and CXCR4 in HTR-8/SVneo cells. Further mechanistic studies found that BMP9 promoted the migration and invasion of HTR-8/SVneo cells and inhibited apoptosis by activating the SDF1/CXCR4 pathway. We demonstrate for the first time that BMP9 promoted the migration and invasion of HTR-8/SVneo cells and inhibits apoptosis by activating the SDF1/CXCR4 pathway. This suggests that BMP9 may be a biomarker molecule for PE.


Degradation products of mangiferin by gamma irradiation with inhibitory effects on NO production.
The xanthone glucoside mangiferin (1) was converted by γ-irradiation into three new compounds, mangiferdiol (2), mangiferinol (3), and isomangiferinol (4). The new compound 2 containing two hydroxymethyl groups instead of a ketone moiety exhibited significantly improved inhibitory activity against nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with IC50 value 47.1 ± 1.7 μM, compared to the mother mangiferin.


The effect of rosemary Extract and cold plasma treatments on bacterial community diversity in poultry ground meats.
To provide safer food, many technologies have been used to preserve food. One such technology is cold plasma, which can reduce viable bacterial counts in various food matrices. However, bacterial communities in food matrices before and after cold plasma treatment have not been investigated. In this communication, the EcoPlates™ were used to physiologically profile bacterial communities from poultry ground meat treated with rosemary, cold plasma or both. The cultures in the plates were incubated at 25 °C for seven days in an OmniLog® system. Responses of the bacterial communities to 31 chemicals were measured on formazan production. The results show that the three parameters of the Gompertz growth curves were observed in all samples, 2-hydroxybenzoic acid could not be used, while pyruvic acid methyl ester was used for a carbon source by the bacterial communities from all meat samples, each bacterial community metabolized different numbers of chemical compounds at different rates, and reduction of bacterial functional diversity was observed in the poultry meat samples treated with cold plasma and rosemary. In the future, investigations on whether the physiological profiling in bacterial communities be used as an indicator for effectiveness of cold plasma treatment of meat samples.


The Impact of Outpatient Laboratory Alerting Mechanisms in Patients with AKI.
AKI is an abrupt decrease in kidney function associated with significant morbidity and mortality. Electronic notifications of AKI have been utilized in patients who are hospitalized, but their efficacy in the outpatient setting is unclear. We evaluated the effect of two outpatient interventions: an automated comment on increasing creatinine results (intervention I; 6 months; n=159) along with an email to the provider (intervention II; 3 months; n=105), compared with a control (baseline; 6 months; n=176). A comment was generated if a patient's creatinine increased by >0.5 mg/dl (previous creatinine ≤2.0 mg/dl) or by 50% (previous creatinine >2.0 mg/dl) within 180 days. Process measures included documentation of AKI and clinical actions. Clinical outcomes were defined as recovery from AKI within 7 days, prolonged AKI from 8 to 89 days, and progression to CKD with in 120 days. Providers were more likely to document AKI in interventions I (P=0.004; OR, 2.80; 95% CI, 1.38 to 5.67) and II (P=0.01; OR, 2.66; 95% CI, 1.21 to 5.81). Providers were also more likely to discontinue nephrotoxins in intervention II (P<0.001; OR, 4.88; 95% CI, 2.27 to 10.50). The median time to follow-up creatinine trended shorter among patients with AKI documented (21 versus 42 days; P=0.11). There were no significant differences in clinical outcomes. An automated comment was associated with improved documented recognition of AKI and the additive intervention of an email alert was associated with increased discontinuation of nephrotoxins, but neither improved clinical outcomes. Translation of these findings into improved outcomes may require corresponding standardization of clinical practice protocols for managing AKI.


Gut microbiome differences between metformin- and liraglutide-treated T2DM subjects.
Metformin and glucagon-like peptide-1 (GLP-1) agonists are widely used for treating type two diabetes mellitus (T2DM). While recent studies suggest these drugs might modify the gastrointestinal tract (GIT) microbiome, further confirmation is required from human clinical trials. Here, we compare, in patients with T2DM, the effects of metformin (n = 18 subjects) and liraglutide (n = 19), a GLP-1 agonist, on their GIT microbiomes over a 42 day period (n = 74 samples) using 16S ribosomal RNA (rRNA) sequencing. We found that these drugs had markedly different effects on the microbiome composition. At both baseline and Day 42, subjects taking metformin had a significant increase (Baseline adj. P = .038, Day 42 adj. P = .041) in the relative abundance of the bacterial genus Sutterella, whereas liraglutide dosing is associated with a significant increase (Baseline adj. P = .048, Day 42 adj. P = .003) in the genus Akkermansia, a GIT bacteria positively associated with gut barrier homoeostasis. Bacteroides and Akkermansia relative abundances were also significantly associated with duration of subject diabetes (adj P < .05). Specifically, there was a significantly higher abundance of Akkermansia in subjects with short and medium durations than those with long duration of diabetes. To our knowledge, this is the first report of GLP-1 agonist-associated changes in the human microbiome and its differentiating effects to metformin. Our study suggests that modulation of the GIT microbiome is a potentially important component in the mechanism of action of these drugs.


Can we improve pollen season definitions by using the symptom load index in addition to pollen counts?
Airborne pollen measurements are the foundation of aerobiological research and provide essential raw data for various disciplines. Pollen itself should be considered a relevant factor in air quality. Symptom data shed light on the relationship of pollen allergy and pollination. The aim of this study is to assess the spatial variation of local, regional and national symptom datasets. Ten pollen season definitions are used to calculate the symptom load index for the birch and grass pollen seasons (2013-2014) in Austria. (1) Local, (2) regional and (3) national symptom datasets are used to examine spatial variations and a consistent pattern was found. In conclusion, national datasets are suitable for first insights where no sufficient local or regional dataset is available and season definitions based on percentages provide a practical solution, as they can be applied in regions with different pollen loads and produce more constant results.


Is the Autorefractor reading closest to manifest refraction? A comparison of the patient's previous spectacles and the 6600 Autorefractor reading.
In a study of 56 patients, the old glasses of a previously refracted individual were as close to the final subjective refraction as the reading obtained with a 6600 Autorefractor. Therefore, the previous spectacle correction might logically be used for the starting point of a subjective refraction, with retinoscopy or automatic refractor results being used for this purpose in patients whose previous spectacle refraction is unknown or in the first refraction of an aphakic patients.


Clues from planarians about interleukin-17A and stress that result from light avoidance: IL-17A antagonists reduce defensive responding in flatworms.
Emerging evidence links interleukin-17A (IL-17A) to anxiety and stress. Circulating levels of IL-17A are elevated in patients with anxiety disorders, and pharmacological blockade of IL-17 signaling or genetic deletion of IL-17 reduces anxiety-like behaviors in mice. Given that IL-17 is one of the most conserved cytokines among animal phyla, we tested the hypothesis that anti-IL-17 treatments reduce defensive responding in planarians, the simplest animal with bilateral symmetry and a CNS with cephalization. The endpoint selected was light avoidance, which is a common phenotype of planarians and rodents and an index of defensive responding that is reduced by anxiolytic compounds in both species. Planarians were placed at the midline of a Petri dish containing water or test solution that was equally split into light and dark halves. Planarians exposed to a selective IL-17A antibody (0.1, 1, 10 pM) over a 5-min interval spent more time in the light than water-exposed planarians. Cyanidin (0.01, 0.1 1, 10 µM), an anti-inflammatory flavonoid and non-selective IL-17A inhibitor, also increased time spent in the light. Motility was not affected by IL-17A antibody or cyanidin at concentrations that reduced light avoidance, although higher concentrations reduced motility (>10 µM). Our results show that IL-17A antagonists reduce defensive responding in planarians and suggest conservation of IL-17A effects on aspects of anxiety-related behaviors.


Incidence, characteristics and risk factors of marked hyperbilirubinemia after allogeneic hematopoietic cell transplantation with reduced-intensity conditioning.
To analyze the incidence, characteristics and risk factors of hyperbilirubinemia after allogeneic hematopoietic cell transplantation with reduced-intensity conditioning (allo-RIC), we conducted a retrospective study in three Spanish centers. We analyzed 452 consecutive patients receiving allo-RIC. Of these, 92 patients (20%) developed marked hyperbilirubinemia (>4 mg/day or >68.4 μM) after allo-RIC. The main causes of marked hyperbilirubinemia after transplant were cholestasis due to GVHD or sepsis (n=57, 62%) and drug-induced cholestasis (n=13, 14%). A total of 22 patients with marked hyperbilirubinemia (24%) underwent liver biopsy. The most frequent histological finding was iron overload alone (n=6) or in combination with other features (n=6). In multivariate analysis, the risk factors for marked hyperbilirubinemia after allo-RIC were non-HLA-identical sibling donors (hazard ratio (HR) 2.2 (95% confidence interval (CI) 1.4-3.6) P=0.001), female donors to male recipients (HR 2.1 (95% CI 1.3-3.3) P=0.003) and high levels of bilirubin and γ-glutamyl transpeptidase before transplant (HR 4.5 (95% CI 2.5-8.4) P<0.001 and HR 4.6 (95% CI 2.6-8.1) P<0.001, respectively). Patients with marked hyperbilirubinemia showed higher 4-year nonrelapse mortality (HR 1.3 (95% CI 1-1.7), P=0.02) and lower 4-year OS (HR 1.4 (95%CI 1.3-1.7), P<0.001) than patients without. In conclusion, we confirm that marked hyperbilirubinemia is frequent and diverse after allo-RIC. Development of marked hyperbilirubinemia after allo-RIC is associated with worse outcome of the procedure.


Integration of CuS/ZnIn2S4 flower-like heterojunctions and (MnCo)Fe2O4 nanozyme for signal amplification and their application to ultrasensitive PEC aptasensing of cancer biomarker.
Vascular endothelial growth factor 165 (VEGF165) is a crucial regulator of angiogenesis and works as a major protein biomarker of cancer metastasis. Therefore, its quantitative detection is pivotal in clinic. In this work, CuS/ZnIn2S4 flower-like heterojunctions had strong and stable photocurrents, which behaved as photoactive material to construct a photoelectrochemical (PEC) aptasensor for detecting VEGF165, combined by home-prepared (MnCo)Fe2O4 nanozyme-mediated signal amplification. The interfacial photo-induced electron transfer mechanism was chiefly discussed by UV-vis diffuse reflectance spectroscopy in details. Specifically, the (MnCo)Fe2O4 modified VEGF165 aptamer was released from the PEC aptasensing platform for its highly specific affinity to target VEGF165, which terminated the color precipitation reaction, ultimately recovering the PEC signals. The developed sensor displayed a wider linear range from 1 × 10-2 to 1 × 104 pg mL-1 with a smaller limit of detection (LOD) of 0.1 fg mL-1. This study provides some valuable insights for building other ultrasensitive aptasensors for clinical assays of cancer biomarkers in practice.


Interactions of the antibiotics neomycin B and chlortetracycline with the hammerhead ribozyme as studied by Zn2+-dependent RNA cleavage.
We have investigated the interactions of two antibiotics, neomycin B and chlortetracycline (CTC), with the hammerhead ribozyme using two Zn(2+) cleavage sites at U4 and A9 in its catalytic core. CTC-dependent inhibition of Zn(2+) cleavage was observed in all cases. In contrast, we unexpectedly observed acceleration of A9 cleavage by neomycin under low ionic strength conditions similar to those used to study inhibition of hammerhead substrate cleavage by this antibiotic. This result provides evidence that the inhibitory mechanism of neomycin does not include competition with the metal ion bound to the A9/G10.1 metal-ion binding site, as previously proposed. Under high ionic strength conditions, optimized for Zn(2+)-dependent cleavage, we observed neomycin-dependent inhibition of cleavage at both A9 and U4. The ability of neomycin to both inhibit and accelerate Zn(2+) cleavage suggests that there is either more than one neomycin binding site or multiple binding modes at a single site in the hammerhead ribozyme. Furthermore, the accessibilities and/or affinities of disparate neomycin binding sites or binding modes are dependent on the ionic strength and the pH of the medium.


INTERIM ANALYSIS OF PRIMARY HEALTHCARE SPECIALISTS TRAINING IN THE UNIVERSALLY PROGRESSIVE MODEL OF HOME-BASED SERVICES: ANTICIPATED PROSPECTS IN THE SOCIAL AREA.
This is an overview of the Interim analysis of primary healthcare specialists training in a universally progressive model of home-based services in the city of Astana, Akmola, and North Kazakhstan regions. A total of 482 persons were trained. Questionnaires filled in by trainees were analyzed.


Botulinum toxin.
The National Institutes of Health Consensus Development Conference on Clinical Use of Botulinum Toxin brought together neurologists, ophthalmologists, otolaryngologists, speech pathologists, and other health care professionals as well as the public to address: the mechanisms of action of botulinum toxin, the indications and contraindications for botulinum toxin treatment, the general principles of technique of injection and handling for its safe and effective use, and the short-term and long-term side effects and complications of therapy. Following 2 days of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared their consensus statement. Among their findings, the panel recommended that (1) botulinum toxin therapy is safe and effective for treating strabismus, blepharospasm, hemifacial spasm, adductor spasmodic dysphonia, jaw-closing oromandibular dystonia, and cervical dystonia; (2) botulinum toxin is not curative in chronic neurological disorders; (3) the safety of botulinum toxin therapy during pregnancy, breast feeding, and chronic use during childhood is unknown; (4) the long-term effects of chronic treatment with botulinum toxin remain unknown; and (5) botulinum toxin should be administered by committed interdisciplinary teams of physicians and related health care professionals with appropriate instrumentation. The full text of the consensus panel's statement follows.


Perinatal and maternal outcomes according to timing of induction of labour: A systematic review and meta-analysis.
The risk of adverse perinatal and maternal outcomes increases with gestational age, and although induction of labour may reduce these risks, the optimal timing of induction remains unknown. We carried out a systematic review and meta-analysis, to determine the gestational age at which induction should be offered. We searched Cochrane Central Register of Controlled Trials, Medline, and Embase databases from inception to July 2022, to identify randomised trials comparing induction of labour at or beyond 37' weeks gestation with expectant management or delayed induction, and according to the gestational age at planned induction. We undertook random effects meta-analysis and pooled estimates as odds ratios with 95% confidence intervals. We assessed risk of bias of studies using the Cochrane Risk of Bias tool 2.0. We included 44 trials (23,960 women and 22,191 offspring) from 1,839 citations in our meta-analysis. The odds of perinatal death (odds ratio 0.42, 95% confidence interval 0.22 to 0.81; 26 studies, 20,154 offspring), stillbirth (0.40, 0.16 to 0.98; 25 studies, 19,412 offspring), admission to neonatal intensive care unit (0.86, 0.78 to 0.96; 23 studies, 18,846 offspring), and caesarean section (0.90, 0.83 to 0.98; 40 studies, 23,616 women) were reduced in the induction of labour group compared to expectant management or delayed induction. The odds of admission to neonatal intensive care unit (0.82, 0.70 to 0.96; 6 studies, 9,316 offspring) were lower with induction of labour at 41 weeks compared to induction at or after 42 weeks' gestation, and the odds of caesarean section were reduced with labour induction at 39 weeks' compared to induction at or after 40 weeks' (0.83, 0.74 to 0.93; 8 studies, 7,677 women). There were no significant differences in pregnancy outcomes by method of induction of labour. Induction of labour compared to expectant management or delayed induction reduces the risk of adverse pregnancy outcomes, and the optimal timing may depend on the specific outcome of interest.


Compound inheritance of a low-frequency regulatory SNP and a rare null mutation in exon-junction complex subunit RBM8A causes TAR syndrome.
The exon-junction complex (EJC) performs essential RNA processing tasks. Here, we describe the first human disorder, thrombocytopenia with absent radii (TAR), caused by deficiency in one of the four EJC subunits. Compound inheritance of a rare null allele and one of two low-frequency SNPs in the regulatory regions of RBM8A, encoding the Y14 subunit of EJC, causes TAR. We found that this inheritance mechanism explained 53 of 55 cases (P < 5 × 10(-228)) of the rare congenital malformation syndrome. Of the 53 cases with this inheritance pattern, 51 carried a submicroscopic deletion of 1q21.1 that has previously been associated with TAR, and two carried a truncation or frameshift null mutation in RBM8A. We show that the two regulatory SNPs result in diminished RBM8A transcription in vitro and that Y14 expression is reduced in platelets from individuals with TAR. Our data implicate Y14 insufficiency and, presumably, an EJC defect as the cause of TAR syndrome.


MUC-1 gene is associated with prostate cancer death: a 20-year follow-up of a population-based study in Sweden.
Anti-adhesion mucins have proven to play an important part in the biology of several types of cancer. Therefore, we test the hypothesis that altered expression of MUC-1 is associated with prostate cancer progression. We retrieved archival tumour tissue from a population-based cohort of 195 men with localised prostate cancer (T1a-b, Nx, M0) that has been followed for up to 20 years with watchful waiting. Semi-automated, quantitative immunohistochemistry was undertaken to evaluate MUC-1 expression. We modelled prostate cancer-specific death as a function of MUC-1 levels accounting for age, Gleason grade and tumour extent, and calculated age-adjusted and multivariate adjusted hazard ratios (HR). Men that had tumours with an MUC-intensity lower or higher than normal tissue had a higher risk of dying in prostate cancer, independent of tumour extent and Gleason score (HR 5.1 and 4.5, respectively). Adjustment for Gleason grade and tumour stage did not alter the results. Men with a Gleason score > or =7 and MUC-1 deviating from the normal had a 17 (RR=17.1 95% confidence interval=2.3-128) times higher risk to die in prostate cancer compared with men with Gleason score <7 and normal MUC-1 intensity. In summary, our data show that MUC-1 is an independent prognostic marker for prostate cancer death.


Long-term results of silicone tube in filtering surgery for eyes with neovascular glaucoma.
We operated on 59 eyes with advanced neovascular glaucoma (37 eyes in diabetic patients and 22 eyes in patients with central retinal vein occlusion) using a trabeculectomy technique that includes a simple silicone tube as the draining element. Mean (+/- 1 S.D.) intraocular pressure preoperatively was 57 +/- 8.7 mm Hg. During follow-up periods ranging from one to five years, the mean intraocular pressure decreased to 27 +/- 16.5 mm Hg. Adequate control of intraocular pressure (24 mm Hg or less) was achieved in 37 eyes (63%). Only four eyes required enucleation. Nine silicone tubes had to be removed because of necrosis of the scleral flap and conjunctival perforation or because they were expulsed. Surgery relieved the severe ocular pain even when intraocular pressure was not satisfactorily controlled.


A multicentre observational study of the prevalence, management, and outcomes of subsegmental pulmonary embolism.
The incidence of subsegmental pulmonary embolism (SSPE) has increased with improvements in imaging technology. There is clinical equipoise for SSPE treatment, with conflicting evidence of improved mortality or reduced venous thromboembolism recurrence with anticoagulation. SSPE studies have significant heterogeneity and often lack adequately matched disease comparator groups. To determine the prevalence, management, and outcomes of SSPE and compare them to patients with main, lobar, segmental, and no pulmonary embolism (PE). All adult patients undergoing CT pulmonary angiography (CTPA) between 2013 and 2019, at 3 UK hospitals were included in the study. CTPA reports were text mined for language relating to PE, and then further manually screened for the presence and anatomical location of PE. Patient groups were propensity matched by age, sex, and year of CTPA prior to analysis. 3-month outcomes of major bleeding, VTE recurrence, and death were recorded. 79 (3.8%) SSPEs were identified from 2,055 diagnoses of PE, and 14,300 CTPA reports. 44 (56%) of SSPEs were single artery emboli, 25 (32%) were multiple unilateral emboli, and 10 (13%) were multiple bilateral emboli. Mortality, VTE recurrence and major bleeding were similar at 3 months across all groups. 87.3% of SSPE imaging reports had an additional radiological diagnosis, with pleural effusion (30%), consolidation (19%), and cardiomegaly (19%) being the most common. The prevalence of SSPE was 3.8% of all PEs and there were a substantial number of additional radiological findings in the SSPE group that may have accounted for their symptoms.


New liquid chromatography assays for simultaneous quantification of antihypertensives atenolol and valsartan in their dosage forms.
Nowadays, various single-pill combinations are used as the best choice in hypertension management. However, these pills made a high challenge to analysts in terms of quality control assays. We have developed three sensitive, selective, fast, simple, green, accurate, precise, and robust isocratic high-performance liquid chromatography methods for simultaneous determination of valsartan and atenolol in dosage forms. To find the appropriate high-performance liquid chromatography conditions for the separation of the examined drugs, various columns, isocratic mobile phase systems were tried, and successful attempts were performed. The used columns proved to be indispensably applicable and gave a shorter analysis time and peak symmetries. This reduction in total run time leads to low solvent consumption and makes all methods more economical. The linearity, accuracy, and precision remained within the acceptable limits. Therefore, all developed methods are suitable for the routine quality control analysis of any pharmaceutical preparation containing the two tested drugs with the proposed chromatographic methods advantages for checking quality during stability studies of their pharmaceutical preparations.


Multiple gastrointestinal stromal tumors with a germline c-kit mutation.
Familial gastrointestinal stromal tumor (GIST) is a rare autosomal dominant genetic disorder; thus far, only seven families have been reported with c-kit germline mutations. Presented herein is a case of multiple intestinal GIST in a 38-year-old man with a germline mutation of the c-kit gene. Operative specimens of the jejunal segment and multiple wedge resection specimens included approximately 30 masses, ranging in size from 1.0 to 6.0 cm. Microscopically, the tumors were composed of CD117-positive spindle/epitheloid cells with variable numbers of mitotic counts, a characteristic of GIST. The mitotic rate increased to more than 5/50 high-power fields. Interestingly, marked hypertrophy of the myenteric plexus with CD117-positive cells was identified in the intestinal segment. By polymerase chain reaction-single-strand conformation polymorphism analysis and direct DNA sequencing, a heterozygous c-kit missense mutation at nucleotide 1676 of codon 559 (T --> C, Val --> Ala), part of the juxtamembrane domain, was detected in the normal tissue. The same mutation was homozygous in the tumor samples. The present case is the first proven case of multiple GIST with a c-kit germline mutation in Korea and is distinguishable from other reported germ-line c-kit mutations because the same 1676 T --> C missense mutation occurs in the normal allele as well as the affected allele, although the significance of the identical mutations remains to be investigated.


Short-term impact of the COVID-19 pandemic on a population-based screening program for colorectal cancer in Catalonia (Spain).
The COVID-19 pandemic caused the suspension at all levels of the Catalan FIT-based CRC screening program on March 12, 2020. Screening invitations to FIT were resumed on September 1, 2020. We aimed to assess the short-term impact of the pandemic and describe strategies implemented to minimize harm by the disruption of the FIT-based CRC screening in the Metropolitan Area of Barcelona. We analyzed participation rate, colonoscopy adherence, time intervals to colonoscopy, detection rates, and advanced-stage cancers in 2019 and 2020. To identify perceived distress levels during the suspension of the screening we conducted a phone interview. As a result of the suspension, 43% of the individuals due for screening did not receive their invitation by December 31, 2020. A percent decrease of 5.1% in participation and of 8.9% in colonoscopy adherence among invitees between January-March was observed, with a recovery to 2019 levels when the screening activities were restarted. The time interval between a positive test to colonoscopy was longer in 2020 than in 2019. A decrease in advanced neoplasia rate and an increase in later stages of CRC were also observed. Individuals with a positive test did not report higher levels of perceived distress compared to those with a negative test. Although the disruption of screening had a temporary impact on participation and colonoscopy adherence, timing delay continues and a large backlog in the invitation of the target population remains. Thus, it is critical to implement strategies to minimize the long-term effects.


Gut health benefit and application of postbiotics in animal production.
Gut homeostasis is of importance to host health and imbalance of the gut usually leads to disorders or diseases for both human and animal. Postbiotics have been applied in manipulating of gut health, and utilization of postbiotics threads new lights into the host health. Compared with the application of probiotics, the characteristics such as stability and safety of postbiotics make it a potential alternative to probiotics. Studies have reported the beneficial effects of components derived from postbiotics, mainly through the mechanisms including inhibition of pathogens, strengthen gut barrier, and/or regulation of immunity of the host. In this review, we summarized the characteristics of postbiotics, main compounds of postbiotics, potential mechanisms in gut health, and their application in animal production.


Diabetic myelopathy.
Diabetic myelopathy occurred in 41% of 75 consecutive, unselected diabetic patients in an autopsy study; clinical peripheral neuropathy occurred in 13%, and histologic radiculopathy in 21%. Infection represented 2.7% of the cord lesions. Posterior column demyelination, seen in 27%, apparently has the same metabolic-toxic origin as diabetic neuropathy and radiculopathy; it is an independent lesion, not a secondary manifestation of peripheral demyelination. It occurs slightly more frequently in those with juvenile-onset diabetes. Spinal cord infarcts, seen in 19%, are related to anteriolar sclerosis of the intrinsic vessels of the spinal cord. They have a higher incidence in diabetics than in a nondiabetic aging population, show a predilection for the white matter, and are usually small. The myelopathy is not related to patient age or duration of diabetes. It is often clinically occult.


Disturbance of neural respiratory control in neonatal mice lacking GABA synthesizing enzyme 67-kDa isoform of glutamic acid decarboxylase.
To examine the role of GABA in the respiratory rhythm and pattern generation in neonatal mice, we analyzed the function of the respiratory control system of 67-kDa isoform of glutamic acid decarboxylase (GAD67)-deficient neonatal mice. In these mutant (GAD67-/-) mice, GABA levels in the brainstem were reduced to about 30% of those in wild-type (GAD67+/+) mice. In in vivo preparations, ventilatory parameters were analyzed by whole body plethysmography and electromyography of intercostal muscles. GAD67-/- mice exhibited abnormal respiratory patterns, i.e. irregular respiratory rhythm, and periodic gasp-like respiration followed by shallow breathing with short inspiratory duration and apnea. In in vitro GAD67-/- brainstem-spinal cord preparations, inspiratory C4 burst duration was shorter than that in GAD67+/+ preparations. Whole cell recordings revealed that activities of inspiratory neurons in the ventral medulla of GAD67-/- mice were characterized by a short depolarization period and a paucity of firing during the inspiratory phase. Superfusion of the in vitro GAD67-/- preparation with 10 microM GABA prolonged C4 burst duration and partly restored a normal pattern of inspiration, although the restoration was limited. These results indicate that reduced GABA levels during the perinatal period induce malfunction in the respiratory control system. We suggest that GABAergic transmission is not essential for basic respiratory rhythm generation but plays an important role in the maintenance of regular respiratory rhythm and normal inspiratory pattern in neonatal mice.


Hip axis length as an independent risk factor for hip fracture independently of femural bone mineral density in Caucasian elderly Brazilian women.
Studies carried out in several countries and in different ethnic groups have suggested that the hip axis length (HAL) may be a risk factor for hip fractures. To evaluate if the HAL is an independent risk factor for hip fractures in elderly Caucasian Brazilian women, this study includes 112 participants sustaining proximal femur osteoporosis. Through HAL and bone mineral density (BMD) measurements, a statistical analysis using a multivaried regression curve was done. HAL was significantly longer in women sustaining a hip fracture than in the control group (99.24 +/- 5.9 mm vs. 96.95 +/- 5.6 mm, P < 0.05). After adjusting the standard HAL deviation for neck and trochanter BMD, OR was 1.43 (IC 95% 0.29 - 1.07; P < 0.08). When HAL was categorized for 97.8 mm (average HAL in all women), OR was 2.24 (IC 95% 1.04 - 4.84; P < 0.05). In conclusion, HAL may be associated with risk of hip fracture regardless of age, weight or BMD of elderly Brazilian Caucasian women.


Usefulness of chromoendoscopy and magnifying narrow band imaging endoscopy for diagnosis of demarcation of adenocarcinoma in Barrett's esophagus.
It is often difficult to accurately delineate the borders and extent of early-stage esophageal adenocarcinoma in patients with Barrett's esophagus using conventional white light endoscopy. Chromoendoscopy enhances the characteristics of the mucosa and improves detection and delineation of small or flat lesions difficult to identify by conventional endoscopy. Magnifying endoscopy with narrow-band imaging (NBI) is a novel endoscopic imaging technology that contrasts the vascular architecture and surface structure of the superficial mucosa. As magnifying NBI can view only a narrow area of the mucosa, this method cannot determine the circumference of the lesion and evaluate its complete extent. Indigocarmine chromoendoscopy is useful for delineating the extent of Barrett's adenocarcinoma. Chromoendoscopy and magnifying NBI are complementary methods, with both being required for the accurate diagnosis of tumor extent in patients with superficial Barrett's esophageal adenocarcinoma.


Receptive-field structure of direction-selective ganglion cells projecting to the goldfish tectum.
The receptive field of a direction-selective unit of any type consists of an excitatory center 3 degrees -5 degrees in size, a near inhibitory surround and a far surround upon which illumination exerts an influence for both spontaneous activity and specific cell response.


Advanced musculoskeletal physiotherapy practice: The patient journey and experience.
As many patients referred to orthopaedic and rheumatology services do not require medical or surgical interventions, advanced practice physiotherapists (APPs) have been introduced into hospital services to triage the care of these patients. Patient perspectives are critical to review the acceptance of this model of care and potential for expansion into primary care. This study aimed to explore the clinical journeys, and the experiences and perceptions of patients attending APP services. Semi-structured interviews (n = 10) were conducted with patients across two hospital sites, with narrative data subjected to a thematic analysis. MSK journeys were mapped via medical chart and interview data, with surveys collecting demographics. Patient journeys involved multiple contact points and some duplication in MSK health services. Overall, experiences of the APP service were positive, with faster access into the hospital system and patients valued the interpersonal and professional skills of the APP. Having already attended a physiotherapist, some patients did have a preconception of what the APP could offer them. However, initial concerns were mitigated following the APP appointment, as the APP had extensive MSK knowledge. Hospitals remained the preferred location for MSK appointments due to availability of diagnostics and 'specialists', and close proximity of the doctor. Patients were positive about the new MSK APP service and benefits related to shorter wait times and seeing a specialist who listened and involved them in their management. However, a cultural shift regarding patient perceptions of the 'specialists' in hospitals and the role of a physiotherapist is required.


Nanowire membrane-based nanothermite: towards processable and tunable interfacial diffusion for solid state reactions.
Interfacial diffusion is of great importance in determining the performance of solid-state reactions. For nanometer sized particles, some solid-state reactions can be triggered accidently by mechanical stress owing to their large surface-to-volume ratio compared with the bulk ones. Therefore, a great challenge is the control of interfacial diffusion for solid state reactions, especially for energetic materials. Here we demonstrate, through the example of nanowire-based thermite membrane, that the thermite solid-state reaction can be easily tuned via the introduction of low-surface-energy coating layer. Moreover, this silicon-coated thermite membrane exhibit controlled wetting behavior ranging from superhydrophilic to superhydrophobic and, simultaneously, to significantly reduce the friction sensitivity of thermite membrane. This effect enables to increase interfacial resistance by increasing the amount of coating material. Indeed, our results described here make it possible to tune the solid-state reactions through the manipulation of interfacial diffusion between the reactants.


Effects of enzymes on organic matter conversion in anaerobic fermentation of sludge to produce volatile fatty acids.
Sludge hydrolysis is a vital step in anaerobic digestion of sludge. This study compared the efficacy of free versus immobilized enzymes at different concentrations in promoting sludge disintegration. Pretreatment with 1,000 mg/L immobilized enzymes was more efficient in promoting sludge disintegration than free enzymes at the same concentration. Under the optimized conditions, volatile fatty acids (VFAs) were produced at 10.6 g/L, accounting for 85 % of total soluble chemical oxygen demand. Improved VFA production was attributed to the release of large amounts of polysaccharides and proteins from the enzymatically pretreated sludge. Released organic matter are the substrates for VFAs generated by the determined microbial community of Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, and Chloroflexi. In this study, anaerobic fermentation was used to successfully convert organic matter in sludge into high-value-added VFAs. Therefore, this process can be selected as a strategy to reduce carbon emissions from wastewater treatment plants (WWTPs).


Development of a genomic site for gene integration and expression in Enterococcus faecalis.
Enterococcus faecalis, a gram-positive opportunistic pathogen, has become one of the leading causes of nosocomial infections. Normally a resident of the gastrointestinal tract, extensive use of antibiotics has resulted in the rise of E. faecalis strains that are resistant to multiple antibiotics. This, compounded with the ability to easily exchange antibiotic determinants with other bacteria, has made certain E. faecalis infections difficult to treat medically. The genetic toolbox for the study of E. faecalis has expanded greatly in recent years, but has lacked methodology to stably introduce a gene in single copy in a non-disruptive manner for complementation or expression of non-native genes. In this study, we identified a specific site in the genome of E. faecalis OG1RF that can serve as an expression site for a gene of interest. This site is well conserved in most of the sequenced E. faecalis genomes. A vector has also been developed to integrate genes into this site by allelic exchange. Using this system, we complemented an in-frame deletion in eutV, demonstrating that the mutation does not cause polar effects. We also generated an E. faecalis OG1RF strain that stably expresses the green fluorescent protein and is comparable to the parent strain in terms of in vitro growth and pathogenicity in C. elegans and mice. Another major advantage of this new methodology is the ability to express integrated genes without the need for maintaining antibiotic selection, making this an ideal tool for functional studies of genes in infection models and co-culture systems.


Immunotoxicity of the pyrrolizidine alkaloid monocrotaline following subchronic administration to C57Bl/6 mice.
Monocrotaline (MCT) is a member of a class of compounds known as pyrrolizidine alkaloids (PAs). PAs are found in the leaves and seeds of a variety of plant species. The potential intoxication of livestock and man through the ingestion of contaminated grains and other foods makes PAs a significant toxicological concern. MCT exposure in rats results in lesions to hepatic and cardiopulmonary tissues as well as alterations in lymphoid organ cellularity. However, no previous studies have investigated MCT-induced functional alterations in the immune system. In the present study, MCT was administered by gavage for 14 days at 0, 10, 25, 50, 75, and 150 mg/kg to female C57Bl/6 mice. The antibody-mediated immune response to sheep red blood cells (SRBC) was assessed using the plaque-forming cell (PFC) assay and the hemolytic antibody isotope release assay (HAIR). Additionally, the cytotoxic T-lymphocyte (CTL) response to allogeneic P815 tumor cells was determined after MCT exposure. Although hepatic and pulmonary lesions are common sequelae to MCT exposure in rats, the C57Bl/6 mouse appeared to be more resistant to these effects on the basis of histopathological examination. Furthermore, the overt toxicity of MCT was minimal with respect to organ weight changes in liver, kidney, and lung. In contrast, a dose-dependent suppression in the antibody response to SRBC was observed with a minimum significant dose of 25 mg/kg. At this dose the number of anti-SRBC PFC per 10(6) spleen cells and the amount of anti-SRBC antibody measured in the HAIR assay were 57 and 59% of control, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Stress level across stages of in vitro fertilization in subsequently pregnant and nonpregnant women.
To examine the relationship between stress and IVF outcome in women and to compare prospective ratings of IVF stress to retrospective ratings. Women completed daily stress ratings for one complete IVF cycle. Three days after the pregnancy test women completed a questionnaire that asked them to recall the stress of IVF. Based on the results of treatment, women were assigned to the nonpregnant (n = 23) or pregnant (n = 17) group and their daily stress ratings were compared. In addition, prospective and retrospective ratings were compared. The nonpregnant group reported more stress during specific stages of IVF and had a poorer biologic response to treatment than the pregnant group. It also was found that women recalled the stress of the waiting period as greater than their ongoing experience of it as measured by their daily ratings. The pattern of differences between the nonpregnant and pregnant group on stress and biologic factors indicates that stress is related to IVF outcome. Certain data suggest that negative feedback about the progress of treatment communicated to patients responding poorly to IVF (nonpregnant group) may have increased their stress level. However, the direction of causality between stress and IVF outcome remains speculative. Differences between prospective and retrospective stress ratings may reflect women's attempt to cope with the strain of the waiting period.


MicroRNAs in the development and neoplasia of the mammary gland.
Study on the role of microRNAs (miRs) as regulators of gene expression through posttranscriptional gene silencing is currently gaining much interest,due to their wide involvement in different physiological processes. Understanding mammary gland development, lactation, and neoplasia in relation to miRs is essential. miR expression profiling of the mammary gland from different species in various developmental stages shows their role as critical regulators of development. miRs such as miR-126, miR-150, and miR-145 have been shown to be involved in lipid metabolism during lactation. In addition, lactogenic hormones influence miR expression as evidenced by overexpression of miR-148a in cow mammary epithelial cells, leading to enhanced lactation. Similarly, the miR-29 family modulates lactation-related gene expression by regulating DNA methylation of their promoters. Besides their role in development, lactation and involution, miRs are responsible for breast cancer development. Perturbed estrogen (E2) signaling is one of the major causes of breast cancer. Increased E2 levels cause altered expression of ERα, and ERα-miR cross-talk promotes tumour progression. miRs, such as miR-206, miR-34a, miR-17-5p, and miR-125 a/b are found to be tumour suppressors; whereas miR-21, miR-10B, and miR-155 are oncogenes.Studies using an ACI rat model showed similar findings of miR dysregulation due to excess E2, and a natural phenol antioxidant ellagic acid showed therapeutic properties by reversing the miR dysregulation. This review focuses on the recent findings concerning the role of miRs in developmental stages of the mammary gland (mainly lactation and involution stages) and their involvement in breast cancer progression. Further studies in this area will help us understand the molecular details of mammary gland biology,as well as miRs that could be therapeutic targets of breast cancer.


[Electron beam tomography in coronary disease. Prevalence and distribution of coronary calcifications and their relationship with coronary risk factors in 650 patients].
The extent of coronary calcification demonstrated by electron beam tomography was correlated with the individual cardiac risk profile. The possible presence of coronary calcifications was studied by electron beam tomography (EBT) in 650 patients (526 men, 124 women; mean age 54 +/- 10 [28-81] years) with known or suspected coronary heart disease. Depending on the degree of density and the size of the lesion a score was calculated according to an international standard. No calcification was shown to be present in 202 patients (score of 0). A score of more than 0 was calculated in 73.8% of men and 48.4% of women. The average score was 227.8 +/- 24.8 in men, compared with 65.3 +/- 26.5 in women (P < 0.001). There were significantly more calcifications in older patients: Men aged 71-75 years had the highest score, 859.4, while the lowest, 9.6, was in those aged 36 to 40 years. The most important variables for the presence of calcification were age (relative risk per age group: 1.6), male sex (relative risk: 4.3), hypertension (relative risk: 2.4) and nicotine consumption (relative risk: 1.8). The median point score in patients without known risk factors was 1.3, with one known factor it was 7.2, and with three it was 48.0. The vessel segment most affected with calcification was the anterior interventricular branch with an average score of 84. Together with an evaluation of the risk profile EBT provided a better assessment of individual risk than conventional examination.


In Patients Treated by Selective Internal Radiotherapy, Cellular In Vitro Immune Function Is Predictive of Survival.
In patients with liver malignancies, the cellular immune function was impaired in vitro after selective internal radiotherapy (SIRT). Because immunosuppression varied substantially, in the current study, we investigated in 25 SIRT patients followed up for ten years whether the lymphocyte function was correlated with survival. Peripheral blood mononuclear cells were stimulated with four microbial antigens (tuberculin, tetanus toxoid, Candida albicans and CMV) before therapy and at four time points thereafter, and lymphocyte proliferation was determined by H3-thymidine uptake. The median sum of the responses to these four antigens decreased from 39,464 counts per minute (CPM) increment (range 1080-204,512) before therapy to a minimum of 700 CPM increment on day 7 after therapy (0-93,187, p < 0.0001). At all five time points, the median survival in patients with weaker responses was 2- to 3.5-fold shorter (p < 0.05). On day 7, the median survival in patients with responses below and above the cutoff of a 2 CPM increment was 185 and 523 days, respectively (χ2 = 9.4, p = 0.002). In conclusion, lymphocyte function could be a new predictor of treatment outcome after SIRT.


A 17-year experience on bilaterality of ovarian germ cell tumors in pediatric population and its clinical implications: A single-center study.
Since the incidence of ovarian germ cell tumor (GCT) in pediatric population is low, there is little information regarding this tumor. A synchronous and metachronous bilateral mass is not infrequently observed in GCT patients. It is important to prevent early ovarian failure and preserve fertility. We retrospectively reviewed the medical records of 112 patients less than 18 years surgically treated for ovarian GCT between 2008 and 2021 at the Department of Pediatric surgery of the Seoul National University Hospital (SNUH). Among these, 13 patients (11.6%) had bilateral masses. In metachronous masses, the recurrence period and therapeutic approach were evaluated. When ovarian failure was a concern, fertility preservation was attempted. Mean age was 8.1 ± 4.0 years. Patients with a bilateral mass were older (p = 0.004). Follow-up was 39.6 ± 40.6 months. Five patients had a synchronous mass, and 8 patients experienced metachronous recurrence. Two patients with a synchronous mass had a metachronous neoplasm (n = 1) and recurrence (n = 1). Patients with metachronous recurrence started menstruation except for two patients who had not reached puberty. The mean recurrence interval was 45.9 ± 38.6 months. Ovum banking was requested for 6 patients and performed in 2. During our 17 years of experience, bilaterality was observed in 11.6% of GCT patients. Metachronous mass occurs after 5 years. A longer follow-up plan is needed for early detection. Our multidisciplinary approach to preserve fertility seemed to be successful with close cooperation with gynecologists.


Safety and immunogenicity of two recombinant DNA COVID-19 vaccines containing the coding regions of the spike or spike and nucleocapsid proteins: an interim analysis of two open-label, non-randomised, phase 1 trials in healthy adults.
We assessed the safety and immunogenicity of two recombinant DNA vaccines for COVID-19: GX-19 containing plasmid DNA encoding the SARS-CoV-2 spike protein, and GX-19N containing plasmid DNA encoding the SARS-CoV-2 receptor-binding domain (RBD) foldon, nucleocapsid protein, and plasmid DNA encoding the spike protein. Two open-label non-randomised phase 1 trials, one of GX-19 and the other of GX-19N were done at two hospitals in South Korea. We enrolled healthy adults aged 19-49 years for the GX-19 trial and healthy adults aged 19-54 years for the GX-19N trial. Participants who tested positive by serological testing for SARS-CoV-2 were excluded. At 4-week intervals, the GX-19 trial participants received two vaccine doses (either 1·5 mg or 3·0 mg), and the GX-19N trial participants received two 3·0 mg doses. The vaccines were delivered intramuscularly using an electroporator. The participants were followed up for 52 weeks after first vaccination. Data collected up to day 57 after first vaccination were analysed in this interim analysis. The primary outcome was safety within 28 days after each vaccination measured in the intention-to-treat population. The secondary outcome was vaccine immunogenicity using blood samples collected on day 43 or 57 after first vaccination measured in the intention-to-treat population. The GX-19 (NCT044445389) and GX-19N (NCT04715997) trials are registered with ClinicalTrials.gov. Between June 17 and July 30, 2020, we screened 97 individuals, of whom 40 (41%) participants were enrolled in the GX-19 trial (20 [50%] in the 1·5 mg group and 20 [50%] in the 3·0 mg group). Between Dec 28 and 31, 2020, we screened 23 participants, of whom 21 (91%) participants were enrolled on the GX-19N trial. 32 (52%) of 61 participants reported 80 treatment-emergent adverse events after vaccination. All solicited adverse events were mild except one (2%) case of moderate fatigue in the 1·5 mg GX-19 group; no serious vaccine-related adverse events were detected. Binding antibody responses increased after second dose of vaccination in all groups (p=0·0002 in the 1·5 mg GX-19 group; p<0·0001 in the 3·0 mg GX-19; and p=0·0004 for the spike protein and p=0·0001 for the RBD in the 3·0 mg GX-19N group). GX-19 and GX-19N are safe and well tolerated. GX-19N induces humoral and broad SARS-CoV-2-specific T-cell responses. GX-19N shows lower neutralising antibody responses and needs improvement to enhance immunogenicity. The Korea Drug Development Fund, funded by the Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare.


Hypertension and triglyceride catabolism: implications for the hemodynamic model of the metabolic syndrome.
We sought to determine if hypertensive adults have a blunted triglyceride catabolic rate (TG K(2)) and if related hemodynamic and vascular alterations are determinants of TG K(2). Fasting levels of insulin, glucose, lipoproteins and plasma catecholamines were measured in 10 normotensive and 10 hypertensive adults. TG K(2) was determined by an intravenous fat tolerance test. Forearm blood flow, maximum forearm blood flow and minimal forearm vascular resistance were determined by strain gauge plethysmography. Vascular compliance and systemic hemodynamics were measured by computerized arterial pulse waveform analysis. Compared to normotensives, hypertensives had a significantly elevated blood pressure (145 +/- 8/94 +/- 11 versus 111 +/- 15/74 +/- 14 mm Hg, p < 0.001), systemic vascular resistance (1695 +/- 441 versus 1172 +/- 430 dynes x sec x cm(-5), p = 0.02) and reduced large vessel compliance (11.7 +/- 3.6 versus 15.1 +/- 3.1 ml/mm Hg x 100, p = 0.04). There were no significant group differences in TG K(2) (3.07 +/- 2.01 versus 2.88 +/- 2.12 mg/dL/min, p = 0.85) or other metabolic and anthropometric variables. TG K(2) was not predicted by the forearm vascular measures or the hemodynamic variables, but was correlated to waist/hip ratio (r = -0.71, p = 0.001), fasting triglycerides (r = -0.64, p = 0.003), and male gender (r = 0.56, p = 0.012). An enhanced TG K(2) was independently predicted by a reduced small vessel compliance (r = -0.61, p = 0.006). Elevated blood pressure per se and hypertension-related hemodynamic and vascular alterations are not associated with reduced TG K(2) or other metabolic abnormalities. Rather, aspects of the insulin resistance syndrome are closely related to abdominal adiposity. The independent association between small vessel compliance and TG K(2) deserves further investigation.


Radiofrequency Ablation and Augmentation in the Management of Spinal Metastases: Clinical Experience in 41 Patients.
To evaluate functional outcome after combined radiofrequency ablation and vertebral augmentation in patients with metastatic spinal tumors using visual analog scale and Oswestry Disability Index scores. This retrospective study included 41 patients with metastatic spinal tumors. There were 19 women and 22 men with a mean age of 67 years (range, 45-87 years). Visual analog scale and Oswestry Disability Index were used to assess the intensity of pain and quality of life. The assessments were performed before the procedure and at 1 week and 1, 2, 3, and 6 months after the procedure. No serious complications were seen in the periprocedural period. Two patients (4.8%) had transient neurological motor deficits without cement leakage, and 1 patient had a pulmonary embolism with transient mild symptoms. The comparison of preprocedural visual analog scale and Oswestry Disability Index scores with postprocedural scores up to 6 months after treatment revealed significant pain control and good functional state. Spinal metastasis is a frequent entity in the growing population of patients with cancer. A multidisciplinary approach using several nonsurgical and minimally invasive methods (e.g., radiofrequency ablation, vertebroplasty, balloon kyphoplasty) is key to successful management, and combining these procedures is effective against spinal metastatic pain.


Neonatal mortality and morbidity associated with preterm breech presentation.
A retrospective study was performed on 88 live-born preterm infants with breech presentation. The neonatal mortality (NNM) was 18.2%, and 13.3% after correction for congenital malformations incompatible with life. 62.5% were delivered vaginally, and 37.5% by cesarean section (CS). In spite of the fact that most CSs were done for indications associated with increased fetal and neonatal morbidity and mortality, overall morbidity was comparable in the two groups. Mortality was higher in the vaginal group. Entrapment of the fetal head (7.3% of vaginal deliveries) and prolapse of the cord (4.5%) were major complications of preterm breech delivery. They resulted in two cases of neonatal death (NND) and three cases of neonatal asphyxia. Prolapse of the cord was in all cases associated with footling presentation. The authors consider these results in favor of routine CS in preterm breech presentation.


The investigation of cellular and humoral immune reactivity in patients with tumours of the bladder.
The authors investigated the cellular immune reactivity by measuring the lymphocyte blast transformation, immune globulins and some glycoproteins in the sera of patients with papilloma and carcinoma of the bladder. They found a change in the cellular immune reactivity, but none in immune globulin concentration. Among the glycoproteins the acute phase reactant proteins changed significantly.


Cesium-mediated electron redistribution and electron-electron interaction in high-pressure metallic CsPbI3.
Electron-phonon coupling was believed to govern the carrier transport in halide perovskites and related phases. Here we demonstrate that electron-electron interaction enhanced by Cs-involved electron redistribution plays a direct and prominent role in the low-temperature electrical transport of compressed CsPbI3 and renders Fermi liquid (FL)-like behavior. By compressing δ-CsPbI3 to 80 GPa, an insulator-semimetal-metal transition occurs, concomitant with the completion of a slow structural transition from the one-dimensional Pnma (δ) phase to a three-dimensional Pmn21 (ε) phase. Deviation from FL behavior is observed upon CsPbI3 entering the metallic ε phase, which progressively evolves into a FL-like state at 186 GPa. First-principles density functional theory calculations reveal that the enhanced electron-electron coupling results from the sudden increase of the 5d state occupation in Cs and I atoms. Our study presents a promising strategy of cationic manipulation for tuning the electronic structure and carrier scattering of halide perovskites at high pressure.


Alkaloids from single skins of the Argentinian toad Melanophryniscus rubriventris (ANURA, BUFONIDAE): An unexpected variability in alkaloid profiles and a profusion of new structures.
GC-MS analysis of single-skins of ten Melanophryniscus rubriventris toads (five collections of two toads each) captured during their breeding season in NW Argentina has revealed a total of 127 alkaloids of which 56 had not been previously detected in any frog or toad. Included among these new alkaloids are 23 new diastereomers of previously reported alkaloids. What is particularly distinguishing about the alkaloid profiles of these ten collections is the occurrence of many of the alkaloids, whether known or new to us, in only one of the ten skins sampled, despite two skins being obtained from each breeding site of the five populations. Many of the alkaloids are of classes known to have structures with branched-chains (e.g. pumiliotoxins and tricyclic structures) that are considered to derive from dietary mites. A large number of previously reported and new alkaloids are also of unclassified structures. Only a very few 3,5-disubstituted-indolizidine or -pyrrolizidine alkaloids are observed that have a straight-chain carbon skeleton and are likely derived from ant prey. The possible relationship of these collections made during the toad's brief breeding episodes to sequestration of dietary arthropods and individual alkaloid profiles is discussed.