Examining Truth and State-Sponsored Media Campaigns as a Means of Decreasing Youth Smoking and Related Disparities in the United States.
To analyze the impact of Truth and state-sponsored anti-tobacco media campaigns on youth smoking in the United States, and their potential to reduce tobacco-related health disparities. Our study included data from the 2000-2015 Monitoring the Future study, an annual nationally representative survey of youth in 8th (n = 201 913), 10th (n = 194 468), and 12th grades (n = 178 379). Our primary exposure was Gross Rating Points (GRPs) of Truth or state-sponsored anti-tobacco advertisements, from Nielsen Media Research. Modified Poisson regression was used to assess the impact of a respondent's GRPs on smoking intentions, past 30-day smoking participation, and first and daily smoking initiation. Additive interactions with sex, parental education, college plans, and race/ethnicity were used to test for differential effects of campaign exposure on each outcome. Greater campaign exposure (80th vs. 20th GRP percentile) was associated with lower probabilities of smoking intentions among 8th graders, smoking participation among 8th and 12th graders, and initiation among 8th graders. Greater exposure was associated with a greater reduction in the likelihood of smoking participation among 10th and 12th grade males than females; 10th and 12th graders with parents of lower education versus those with a college degree; and 12th graders who did not definitely plan to go to college relative to those who did. Media campaign exposure was associated with a lower likelihood of youth smoking behaviors. Associations were more pronounced for groups disproportionately affected by smoking, including youth of lower socioeconomic status. Media campaigns may be useful in reducing smoking disparities and improving health equity. Few recent studies have investigated the impact of anti-tobacco media campaigns on youth smoking and their potential to reduce tobacco-related health disparities in the United States. We found media campaigns-specifically state-sponsored media campaigns-reduced the likelihood of several smoking outcomes among youth, with some evidence that they mitigate disparities for disproportionately affected groups.


Limited proteolysis of a trypanosomal hypoxanthine phosphoribosyltransferase yields crystals that diffract X-rays to near atomic resolution.
Two crystal forms of the hypoxanthine phosphoribosyltransferase from Trypanosoma cruzi were grown and characterized. Proteolytic modification at the C-terminus of the recombinant enzyme yielded monoclinic crystals that diffract X-rays to higher resolution than the original, trigonal crystal form. Data from the monoclinic crystal form enabled determination of the crystal structure for the trypanosomal HPRT to 1.4 A resolution.


Using a Six-Domain Framework to Include Biopsychosocial Information in the Standard Medical History.
The traditional approach to physicians' history taking is designed to facilitate diagnosis and treatment of biomedical conditions. However, in the 21st century, health is critically influenced by the interaction of biomedical conditions and nonbiomedical factors such as patient's ability to manage chronic disease and the social determinants of health. Interventions to expand routine history taking to include nonbiomedical factors have not been widely adopted, possibly due to the difficultly of incorporating long checklists into routine care and the inability to achieve consensus on the relevant behavioral or social determinants of health content applicable to all patients. In 2015-2016, we introduced medical students to a 6-domain (biomedical and psychiatric conditions, behavioral health, living environment/resources, social support, and functional status) approach to history taking and instructed them to elicit information from each domain alongside the traditional approach. Students were required to obtain information from each domain in one admitting history or one daily progress note, discuss their findings with the attending physician, and involve members of the medical team in addressing concerns and barriers in the care of that patient. Students' history notes were reviewed for completeness and compared to those from a student control group. Students also completed a 10-question evaluation of the model. The intervention was conducted during a 1-month rotation on a hospitalist general medicine service from May 2015 through August 2016. Patient history and daily progress notes were collected from 38 fourth-year intervention students and compared to 24 control students on the same service from the previous year. Compared to control students, intervention students provided more patient information (p ≤ .001) in all nonbiomedical domains except behavioral health. Intervention students reported that the 6-domain model helped them identify clinical information that could be addressed with existing resources and prompted involvement of social workers, pharmacists, and nurses in care planning. They also indicated the framework added clinically valuable information and enhanced team-based care. A domain-based framework can be used by medical students to identify clinically relevant behavioral conditions and social determinants of health tailored to individual patients while avoiding long standardized checklists. Arguably, routine collection of behavioral and social determinants of health is a necessary first step in enhancing physicians' awareness and skills in working with health care teams to address nonbiomedical determinants of patients' health.


A 2-methyleneoxetane analog of orlistat demonstrating inhibition of porcine pancreatic lipase.
The 2-methyleneoxetane analog 2 of orlistat (OLS, 1) has been synthesized and tested against porcine pancreatic lipase (PPL). Despite the loss of the carbonyl group, a potential site for hydrogen bonding interaction with the enzyme and the key element in the acylation by OLS, 2 has activity comparable to 1.


Inhalation toxicity of (1-->3)-beta-D glucan: recent advances.
To investigate the effects of (1-->3)-beta-D-glucan after inhalation, animals were exposed to different forms of glucan and the number of lung lavage cells was determined 24 h after exposure. None of the different forms assayed caused any increase in cell numbers. In animals exposed to endotoxin, all types of cells were increased after 24 h. A simultaneous exposure to curdlan reduced this increase in a dose-related fashion. The results suggest that (1-->3)-beta-D-glucan-related acute injury to the lung is induced by mechanisms other than those induced by inflammagenic agents such as endotoxin.


In the cystoscopic follow-up of non-muscle-invasive transitional cell carcinoma, NMP-22 works for high grades, but unreliable in low grades and upper urinary tract tumors.
Two percent of the bladder non-muscle-invasive (NMI) transitional cell carcinomas (TCC) are associated with upper urinary tract (UUT) TCC. We evaluated the role of nuclear matrix protein-22 (NMP-22) (BladderChek) test in the diagnosis of lower urinary tract and UUT-TCC. From March 2009 to June 2011, 122 patients with bladder NMI-TCC underwent 205 control cystoscopy. A total of 95 (78 men and 17 women, mean age 60.7 years, range, 27-88) patients who were followed regularly with NMP-22 test and with follow-up cystoscopies (145 episodes; min. 1-max. 5) were included in this study. For routine monitoring of the UUT, IVU or CT urography was used once a year for high grades (HG), and once in every other year for low grades (LG). The sensitivity and specificity of NMP-22 were evaluated by ROC curves, and sensitivity, specificity, and positive and negative predictive values were calculated. Chi-square test was used for the differences between the subgroups. Cystoscopy and NMP-22 results of the patients included in the study revealed the sensitivity (44.4%) of the test was very low and the specificity (98.4%) was quite high (p < 0.001). Among the 10 cystoscopies where NMP-22 was negative, but cystoscopy was positive for tumor, 8 had LG and 2 had HG TCC. NMP-22 was never positive in low-grade tumors, in other words, all of the NMP-22-positive 8 tumors were high grade. On the other hand, in 20% (2/10) of the cases, NMP-22 can be negative although the tumor was high grade. Two (2.1%) HG UUT-TCC were detected in 95 patients. These 2 patients were within the 125 cystoscopies (75 patients) where both NMP-22 and cystoscopy were negative for tumor. Nuclear matrix protein-22 cannot detect LG TCC. However, it detects overwhelming majority of HG TCC. For this reason, positive NMP-22 test largely indicates HG TCC. NMP-22 is also not reliable in UUT-TCC, even in HG tumors.


PD-L1 expressed from tumor cells promotes tumor growth and invasion in lung cancer via modulating TGF-β1/SMAD4 expression.
Programmed death ligand-1 (PD-L1) has a known association with the prognosis of human cancers because of its ability to alter tumor immune surveillance via its interaction with PD-1. We questioned whether expression of PD-L1 in tumor cells could directly promote tumor growth and invasiveness in non-small cell lung cancer (NSCLC). Real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate PD-L1 messenger RNA (mRNA) expression in lung tumors. The prognostic value of PD-L1 mRNA was assessed by Cox regression model. Transcriptional regulation of PD-L1 by human papillomavirus (HPV) 16/18 E6 oncoprotein or by epidermal growth factor receptor (EGFR) mutation in lung cancer cells was examined by Western blot and luciferase reporter assay. The cell growth and invasion were evaluated by colony formation, soft agar growth, and Boyden chamber assay. The PD-L1 mRNA levels showed a positive association with HPV 16/18 E6 oncoprotein and with EGFR mutation in 223 surgically resected NSCLC patients. The prognostic significance of PD-L1 was more commonly observed in patients with high PD-L1/E6 positive and high PD-L1/EGFR mutant tumors. Mechanistically, upregulation of PD-L1 transcription by E6 or mutant EGFR occurred largely through the ERK-C/EBPβ-TLR4-NF-κB cascade. PD-L1 promotes the efficacy of colony formation, soft agar growth, and cell invasion. PD-L1 upregulates BAG-1 to reduce transforming growth factor (TGF)-β1 expression, and the decrease in SMAD4 because of TGF-β1 occurs through the p53/microRNA (miR)-224 axis. The decreases in TGF-β1 and SMAD4 are responsible for PD-L1-mediated cell invasiveness. Induction of PD-L1 by E6 oncoprotein or mutant EGFR through the ERK-C/EBPβ-TLR4-NF-κB cascade may promote tumor growth and invasiveness in NSCLC because of decreasing TGF-β1 and SMAD4 expression.


Fatty acids inhibit insulin-mediated glucose transport associated with actin remodeling in rat L6 muscle cells.
In skeletal muscle cells, insulin stimulates cytoskeleton actin remodeling to facilitate the translocation of glucose transporter GLUT4 to plasma membrane. Defect of insulin-induced GLUT4 translocation and actin remodeling may cause insulin resistance. Free fatty acids cause insulin resistance in skeletal muscle. The aim of this study was to investigate the effects of fatty acids on glucose transport and actin remodeling. Differentiated L6 muscle cells expressing c-myc epitope-tagged GLUT4 were treated with palmitic acid, linoleic acid and oleic acid. Surface GLUT4 and 2-deoxyglucose uptake were measured in parallel with the morphological imaging of actin remodeling and GLUT4 immunoreactivity with fluorescence, confocal and transmission electron microscopy. Differentiated L6 cells showed concentration responses of insulin-induced actin remodeling and glucose uptake. The ultrastructure of insulin-induced actin remodeling was cell projections clustered with actin and GLUT4. Acute and chronic treatment with the 3 fatty acids had no effect on insulin-induced actin remodeling and GLUT4 immunoreactivity. However, insulin-mediated glucose uptake significantly decreased by palmitic acid (25, 50, 75, 100 μmol/L), oleic acid (180, 300 μmol/L) and linoleic acid (120, 180, 300 μmol/L). Oleic acid (120, 300 μmol/L) and linoleic acid (300 μmol/L), but not palmitic acid, significantly decreased insulin-mediated GLUT4 translocation. These data suggest that fatty acids inhibit insulin-induced glucose transport associated with actin remodeling in L6 muscle cells.


Treatment of unusual Kock pouch urinary calculi with extracorporeal shock wave lithotripsy.
Since the establishment of extracorporeal shock wave lithotripsy for the treatment of upper urinary tract calculi, further potential applications have been explored. We report the successful use of extracorporeal shock wave lithotripsy for the treatment of obstructive calculi on staples within the afferent nipple of a Kock pouch ureteroileal urinary diversion.


Characteristics of primary cutaneous lymphoma according to WHO-EORTC classification in Korea.
Primary cutaneous lymphoma (PCL) is an extranodal non-Hodgkin lymphoma with primary involvement of the skin. Epidemiological data on PCLs according to the World Health Organization/European Organization for Research and Treatment of Cancer classification (WHO-EORTC) has not been investigated in Korea to date. To evaluate the demographic characteristics, clinical and histological features, and survival data of patients with PCL according to the WHO-EORTC classification. In total, 93 patients with PCL were retrospectively identified from an extensive review of medical records over a 16-year period. The tumours found included primary cutaneous CD30+ lymphoproliferative disorders, extranodal natural killer/T-cell lymphoma and primary cutaneous diffuse large B-cell lymphoma. We found that 81.6% of the patients had primary cutaneous T-cell and natural killer-cell lymphoma, and 16.2% had primary cutaneous B-cell lymphoma, with 2.2% having precursor haematological neoplasms. The median age was 52 years (range 3-95) and the male : female ratio was 1: 1.16. The 5-year survival rate was 92.5%. The incidence rates of many PCL subtypes in Koreans differ from those of other countries.


Autologous red blood cell transfusion does not result in a more profound increase in pulmonary capillary wedge pressure compared to saline in critically ill patients: A randomized crossover trial.
Transfusion-associated circulatory overload (TACO) is a major cause of severe transfusion-related morbidity. Transfusion of red blood cells (RBCs) has been shown to induce hydrostatic pressure overload. It is unclear which product-specific factors contribute. We set out to determine the effect of autologous RBC transfusion versus saline on pulmonary capillary wedge pressure (PCWP) change. In a randomized crossover trial, patients who had undergone coronary bypass surgery were allocated to treatment post-operatively in the intensive care unit with either an initial 300 ml autologous RBC transfusion (salvaged during surgery) or 300 ml saline infusion first, followed by the other. Primary outcome was the difference in PCWP change. Secondary outcome measures were the difference in extra-vascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI). Change in PCWP was not higher after autologous RBC transfusion compared to saline (ΔPCWP 0.3 ± 0.4 vs. 0.1 ± 0.4 mmHg). ΔEVLWI and ΔPVPI were significantly decreased after autologous RBC transfusion compared to saline (ΔEVLWI -1.6 ± 0.6 vs. 0.2 ± 0.4, p = 0.02; ΔPVPI -0.3 ± 0.1 vs. 0.0 ± 0.1, p = 0.01). Haemodynamic variables and colloid osmotic pressure were not different for autologous RBC transfusion versus saline. Transfusion of autologous RBCs did not result in a more profound increase in PCWP compared to saline. RBC transfusion resulted in a decrease of EVLWI and PVPI compared to saline. Our data suggest that transfusing autologous RBCs may lead to less pulmonary oedema compared to saline. Future studies with allogeneic RBCs are needed to investigate other factors that may mediate the increase of PCWP, resulting in TACO.


The hydrodynamic basis of the vacuum cleaner effect in continuous-flow PCNL instruments: an empiric approach and mathematical model.
Passive removal of stone fragments in the irrigation stream is one of the characteristics in continuous-flow PCNL instruments. So far the physical principle of this so-called vacuum cleaner effect has not been fully understood yet. The aim of the study was to empirically prove the existence of the vacuum cleaner effect and to develop a physical hypothesis and generate a mathematical model for this phenomenon. In an empiric approach, common low-pressure PCNL instruments and conventional PCNL sheaths were tested using an in vitro model. Flow characteristics were visualized by coloring of irrigation fluid. Influence of irrigation pressure, sheath diameter, sheath design, nephroscope design and position of the nephroscope was assessed. Experiments were digitally recorded for further slow-motion analysis to deduce a physical model. In each tested nephroscope design, we could observe the vacuum cleaner effect. Increase in irrigation pressure and reduction in cross section of sheath sustained the effect. Slow-motion analysis of colored flow revealed a synergism of two effects causing suction and transportation of the stone. For the first time, our model showed a flow reversal in the sheath as an integral part of the origin of the stone transportation during vacuum cleaner effect. The application of Bernoulli's equation provided the explanation of these effects and confirmed our experimental results. We widen the understanding of PCNL with a conclusive physical model, which explains fluid mechanics of the vacuum cleaner effect.


Net-cost model for workplace interventions.
Few methods exist for comprehensively examining the costs and benefits of ergonomic interventions applicable to a variety of economic sectors and settings. An instrument for data collection and data analysis at the facility level is presented. In this net-cost model intervention costs are defined by equipment and labor costs for the interventions as well as the avoided costs of lost work time, medical care, and productivity improvements. Net-cost estimates for three case studies show that ergonomic interventions applied appropriately can result in substantial cost savings for the companies. It would be prudent to incorporate a protocol for collecting cost and effectiveness data in the standard operating procedures of companies introducing ergonomic interventions. Validation of the net-cost model through prospective studies is necessary. This model may be used to determine the net-cost of implemented or proposed ergonomic interventions in industrial facilities.


Domestic ducks play a major role in the maintenance and spread of H5N8 highly pathogenic avian influenza viruses in South Korea.
The H5N8 highly pathogenic avian influenza viruses (HPAIVs) belonging to clade 184.108.40.206 spread from Eastern China to Korea in 2014 and caused outbreaks in domestic poultry until 2016. To understand how H5N8 HPAIVs spread at host species level in Korea during 2014-2016, a Bayesian phylogenetic analysis was used for ancestral state reconstruction and estimation of the host transition dynamics between wild waterfowl, domestic ducks and chickens. Our data support that H5N8 HPAIV most likely transmitted from wild waterfowl to domestic ducks, and then maintained in domestic ducks followed by dispersal of HPAIV from domestic ducks to chickens, suggesting domestic duck population plays a central role in the maintenance, amplification and spread of wild HPAIV to terrestrial poultry in Korea.


[Initial results of investigations into the proliferation kinetics of enterocytes (author's transl)].
The changes of absorption appearing in man and caused by aging are probably due to disturbances of the proliferation and exfoliation kinetics of the enterocytes of the small intestine mucosa. The relevant experimental examinations available are insufficient because the results were obtained from a few animals only. Our own systematic autoradiographic examinations of rats are designed to contribute to a clarification of this problem which is important for practice.


Comparison of the effects of velocity-based vs. traditional resistance training methods on adaptations in strength, power, and sprint speed: A systematic review, meta-analysis, and quality of evidence appraisal.
We estimated the effectiveness of using velocity feedback to regulate resistance training load on changes in muscle strength, power, and linear sprint speed in apparently healthy participants. Academic and grey literature databases were systematically searched to identify randomised trials that compared a velocity-based training intervention to a 'traditional' resistance training intervention that did not use velocity feedback. Standardised mean differences (SMDs) were pooled using a random effects model. Risk of bias was assessed with the Risk of Bias 2 tool and the quality of evidence was evaluated using the GRADE approach. Four trials met the eligibility criteria, comprising 27 effect estimates and 88 participants. The main analyses showed trivial differences and imprecise interval estimates for effects on muscle strength (SMD 0.06, 95% CI -0.51-0.63; I2 = 42.9%; 10 effects from 4 studies; low-quality evidence), power (SMD 0.11, 95% CI -0.28-0.49; I2 = 13.5%; 10 effects from 3 studies; low-quality evidence), and sprint speed (SMD -0.10, 95% CI -0.72-0.53; I2 = 30.0%; 7 effects from 2 studies; very low-quality evidence). The results were robust to various sensitivity analyses. In conclusion, there is currently no evidence that VBT and traditional resistance training methods lead to different alterations in muscle strength, power, or linear sprint speed.


Peptide dissociation patterns in secondary ion mass spectrometry under large argon cluster ion bombardment.
The analysis of organic and biological substances by secondary ion mass spectrometry (SIMS) has greatly benefited from the use of cluster ions as primary bombarding species. Thereby, depth profiling and three-dimensional (3D) imaging of such systems became feasible. Large Ar(n)(+) cluster ions may constitute a further improvement in this direction. To explore this option, large Ar(n)(+) cluster ions (with n ~1500 Ar atoms per cluster) were used to investigate the emission of positive secondary ions from two peptide specimens (angiotensin I and bradykinin) by orthogonal time-of-flight SIMS using bombarding energies 6, 10 and 14 keV. For both peptides, the protonated molecular ion is observed in the mass spectra. In addition, distinct fragmentation patterns were observed; these indicate that fragment ions under Ar cluster irradiation form primarily via cleavage of bonds along the peptide backbone whereas the rapture of side chains occurs much less frequently. These features appear to be similar to low-energy collision-induced dissociation pathways. Tentatively, these findings can then be ascribed to the concerted action of the large number of Ar atoms in the impact zone of cluster at the surface: these low-energy Ar species (with an average energy of few eV) may effect the cleavage of the peptide bonds and lead, eventually, to the emission of the fragment ions.


From manganese oxidation to water oxidation: assembly and evolution of the water-splitting complex in photosystem II.
The manganese cluster of photosystem II has been the focus of intense research aiming to understand the mechanism of H2O-oxidation. Great effort has also been applied to investigating its oxidative photoassembly process, termed photoactivation that involves the light-driven incorporation of metal ions into the active Mn4CaO5 cluster. The knowledge gained on these topics has fundamental scientific significance, but may also provide the blueprints for the development of biomimetic devices capable of splitting water for solar energy applications. Accordingly, synthetic chemical approaches inspired by the native Mn cluster are actively being explored, for which the native catalyst is a useful benchmark. For both the natural and artificial catalysts, the assembly process of incorporating Mn ions into catalytically active Mn oxide complexes is an oxidative process. In both cases this process appears to share certain chemical features, such as producing an optimal fraction of open coordination sites on the metals to facilitate the binding of substrate water, as well as the involvement of alkali metals (e.g., Ca2+) to facilitate assembly and activate water-splitting catalysis. This review discusses the structure and formation of the metal cluster of the PSII H2O-oxidizing complex in the context of what is known about the formation and chemical properties of different Mn oxides. Additionally, the evolutionary origin of the Mn4CaO5 is considered in light of hypotheses that soluble Mn2+ was an ancient source of reductant for some early photosynthetic reaction centers ('photomanganotrophy'), and recent evidence that PSII can form Mn oxides with structural resemblance to the geologically abundant birnessite class of minerals. A new functional role for Ca2+ to facilitate sustained Mn2+ oxidation during photomanganotrophy is proposed, which may explain proposed physiological intermediates during the likely evolutionary transition from anoxygenic to oxygenic photosynthesis.


Estimation of the subunit stoichiometry of the membrane-associated daptomycin oligomer by FRET.
Daptomycin is a lipopeptide antibiotic that kills Gram-positive bacteria by depolarizing their cell membranes. This antibacterial action of daptomycin is correlated with the formation of membrane-associated oligomers. We here examine the number of subunits contained in one oligomer using fluorescence resonance energy transfer (FRET). The results suggest that the oligomer contains approximately 6 to 7 subunits, or possibly twice this number if it spans both membrane monolayers.


Spatial and temporal features of ambient air-quality over Taiwan.
This study analyzed a time series data of daily subPSI values to determine the temporal and spatial characteristics of ambient air-quality in Taiwan by employing the Varimax rotational method. The first and second rotational principal components nearly accounted for 54 and 19% for the variation of subPSI values over Taiwan. The factor loadings between rotational principal components and subPSI values of air pollutants identified the first and second components as combustion and photochemical sources, respectively. Time series analysis of rotational component scores associated with regions showed the relationships between rotational components and subPSI values and also revealed the optimum simulation period for combustion and photochemical sources.


Discrimination of type I from insulin-treated type II diabetic patients by C-peptide measurement.
Residual B-cell function was assessed in 61 type I and 17 type II insulin-treated diabetics by measuring plasma C-peptide concentration before and after i.v. injection of 1 mg glucagon to evaluate a possible difference in response to the test in the two groups. Fasting and post-stimulatory C-peptide levels were significantly higher in type II diabetics than in type I (0.45 +/- 0.25 vs 0.12 +/- 0.10 nmol/l for basal IRCP, 0.39 +/- 0.19 vs 0.06 +/- 0.11 nmol/l for delta IRCP, p less than 0.0001), but there was some overlap in individual values. Twenty-one percent of type I and 29% of type II diabetics had values in the overlap area. These percentages were reduced to 6% and 12%, respectively when only long-term (duration of diabetes more than five years) type I diabetics were considered. These data indicate that a glucagon test is useful to discriminate most type I diabetics from insulin-treated type II diabetics.


Critical factors in the successful expansion of Pneumococcal Conjugate Vaccine in India during the COVID-19 pandemic.
India had decided to roll out PCV in India in 2015, but successful implementation of any new vaccine introduction mandates an enormous effort. PCV was scaled up during the COVID-19 pandemic, which posed new, unprecedented challenges in the vaccine rollout. However, India successfully expanded PCV in the country in record time across all states and Union Territories. During the pandemic, supply-side restrictions, delayed vaccine shipments, staff shortages, and restrictions in conducting training negatively affected the roll-out of PCV across the country. However, despite the ongoing pandemic, India successfully rolled out PCV across the country in 7 months. In this review, the authors have conducted a narrative review to delineate the crucial factors that helped in the successful expansion of PCV.


Acute pyelonephritis revealing an exceptional form of horseshoe kidney: A case report.
The horseshoe kidney is a malformation of the upper urinary tract where the kidney is U-shaped. This condition results the fusion of the lower poles of the right and left kidneys on the midline. We report a case of pyelonephritis revealing a rare form of horseshoe kidney with fusion of the lower pole of the right kidney with the upper pole of the left kidney, initially treated with urine drainage. Multiple etiological conditions may contribute to the development of a horseshoe kidney, in particular: the genetic/chromosomal predisposition, intrauterine environment and structural factors affecting kidney development and migration. Horseshoe kidneys reveal a veritable range of anatomical and embryological peculiarities, always suspect pyelonephritis on a horseshoe kidney in the presence of febrile abdominal pain in a patient with malformations.


A flexible Ag/AgCl micro reference electrode based on a parylene tube structure.
In the effort of developing micro-electrochemical sensors, the miniaturization of reference electrodes has been a challenging task. In this paper, a flexible micro reference electrode with an internal electrolyte reservoir is reported. This new device is based on a unique microfabricated parylene tube structure, which is filled with Cl- rich electrolyte, into which a 50 μm diameter silver (Ag) wire covered with a 7.4 μm thick silver chloride (AgCl) layer is inserted. The distal end of the tube is filled with potassium chloride (KCl) saturated agarose gel. The Ag wire, thick AgCl layer, and internal electrolyte reservoir lead to a long operation time and a stable reference voltage. The drift over a 10-hour period has been found to be less than 2 mV. The total operation time of the device has exceeded 100 hours. Furthermore, the compatibility with microfabrication allows the integration of other components, leading to truly miniaturized electrochemical sensors or sensing systems. To prove this, we demonstrated a pH sensor by combining the reference electrode and an iridium oxide electrode monolithically integrated on the surface of the parylene tube.


Systemic administration of Shikonin ameliorates cognitive impairment and neuron damage in NPSLE mice.
Shikonin is an anti-inflammatory natural herbal drug extracted from Lithospermum erythrorhizon and its therapeutic effect on neuropsychiatric systemic lupus erythematosus (NPSLE) is yet unknown. In our study, Shikonin significantly reversed the cognitive impairment and alleviated the brain tissue damage in NPSLE mice. The permeability of blood-brain barrier was also verified to be repaired in Shikonin-treated NPSLE mice. In particular, we found that Shikonin alleviated neuroinflammation through inhibiting β-catenin signaling pathway, thereby depressing the activation of microglia and the loss of neuronal synapses. Overall, Shikonin may be a promising candidate drug for NPSLE through diminishing neuroinflammation and repairing neuron damage.


Risk Factors for Low-Flow Related Ischemic Complications and Neurologic Worsening in Patients with Complex Internal Carotid Artery Aneurysm Treated by Extracranial to Intracranial High-Flow Bypass.
The revascularization technique has remained indispensable for complex aneurysms. However, risk factors for low-flow related ischemic complications (LRICs) and neurologic worsening (NW) have been less well documented. We evaluated the risk factors for LRICs and NW in 67 patients treated with extracranial to intracranial bypass graft using radial artery or saphenous vein graft for complex internal carotid artery (ICA) aneurysm with ICA occlusion. Intraoperative middle cerebral artery pressure (MCAP) by backup superficial temporal artery to middle cerebral artery bypass was measured. The MCAP ratio was the ratio of the MCAP after release of the graft bypass to the initial MCAP. LRICs were defined as new neurologic deficits and ipsilateral cerebral blood flow reduction in single-photon emission computed tomography. Early and late NW were defined as an increase in 1 or more modified Rankin Scale at discharge and at the 12-month follow-up examination. During a median follow-up period of 13.3 months, LRICs were observed in 7 patients (10%). The Cox proportional hazards model showed that an MCAP ratio ≤0.80 was significantly related to LRICs. Multivariate logistic regression analysis revealed that perforating artery ischemia was significantly associated with early NW (n = 13, 19%) and late NW (n = 7, 13%). It also showed that LRICs were also significantly related to late NW. The present study showed that regardless of the graft type, the MCAP ratio was associated with LRICs, which were related to late NW in patients with complex ICA aneurysms treated by extracranial to intracranial high-flow bypass graft.


Clinical and pathological aspects of first report of Tunga penetrans infestation on southern brown howler monkey (Alouatta guariba clamitans) in Rio Grande do Sul, Brazil.
Tungiasis is a neglected neotropical disease caused by penetration of Tunga spp. into the skin of the host. Two primates were rescued from nearby different indigenous villages, and the clinical, pathological, and parasitological features of tungiasis were described. Flea identification occurred through their morphometry and was confirmed with the use of a dichotomous key. Monkey 1 was parasitized by 23 sand fleas and, after treatment, was assigned to the animal rehabilitation center. Monkey 2 was in poor body condition and died shortly after clinical examination. At necropsy, this primate was parasitized by 26 specimens of sand fleas. Both animals altered their tree behavior by staying on the ground for long periods. This parasitic relationship implies the possibility of enlargement of the sand flea dispersion. Thus, this is the first record of Tunga penetrans occurrence in wild Alouatta guariba clamitans.


[Hormonal treatment of undescended testes].
Undescended testes are a very common congenital problem of the urogenital tract. Altered spermatogenesis and fertility as well as an elevated risk for oncologic degeneration are known facts associated with testicular malposition. There is broad international consensus among the various disciplines that the treatment of undescended testes should be completed by the age of 12 months. Following the guideline of the German Working Group of Scientific Medical Societies (AWMF), hormonal treatment should be offered to patients with bilateral undescended testicles. This article reviews the literature and disputes the reasoning of the recommendation to treat undescended testes hormonally.


Pulmonary development in the fetal one-humped camel: morphometry.
The structural development of the fetal camel lung is described and quantified morphometrically in this report. During fetal development the lung weight and volume increased polynomially with body length. The correlation coefficient between lung weight and body length is +0.991, and between lung volume and body length is +0.995. Volume density of the future bronchial tree showed a progressive increment with gestational age and is relatively higher in male than female fetuses, and the differences are statistically significant at 340-420 mm CRL. The proportion of lung tissue occupied by saccular airspaces increased enormously during the canalicular and alveolar stage, and the differences between both sexes are statistically significant at the former stage. The number of alveoli per unit area correlates closely with body length (r = +0.928) and the correlation coefficient between alveolar diameter and body length is +0.991. On the other hand, the correlation coefficient between the number of alveolar ducts per unit area and body length is -0.993, and is about +0.977 between the diameter of alveolar ducts and body length.


OUTCOME OF CLIVAL CHORDOMAS AFTER SKULL BASE SURGERIES WITH MEAN FOLLOW-UP OF 10 YEARS.
Skull base chordomas are clinically malignant because of the difficulty of total removal, high recurrence rate, and occasional drop metastasis. Although aggressive surgical resection and postoperative radiation have been recommended, the long-term outcome remains unsatisfactory. From 1992 to 2011, we treated 24 patients with skull base chordoma using aggressive surgical removal as a principal strategy. Skull base approaches were selected according to tumor extension to remove the tumor and surrounding bone as completely as possible. After surgery, all patients were closely observed with MRI to find small and localized recurrent tumors, which were treated with gamma-knife radiosurgery or surgical resection. The mean postoperative follow-up duration was 10.2 years (range, 1-17.2 years). The 5-, 10-, and 15-year overall survival rates were 86%, 72%, and 72%, respectively. The 5- and 10-year progression-free survival rates were 47% and 35%, respectively. Tumor extension to the brainstem and partial tumor removal were the factors related to poor survival. Our results suggest that aggressive surgical removal improves the long-term outcome of patients with skull base chordoma. We would like to emphasize that skull base chordomas should be aggressively removed using various skull base approaches.


Myeloid Sarcoma of the Uterine Cervix as Presentation of Acute Myeloid Leukaemia after Treatment with Low-Dose Radioiodine for Thyroid Cancer: A Case Report and Review of the Literature.
The development of acute myeloid leukaemia after low-dose radioiodine therapy and its presentation as a myeloid sarcoma of the uterine cervix are both rare events. We report a case of acute myeloid leukaemia revealed by a myeloid sarcoma of the uterine cervix in a 48-year-old woman, 17 months after receiving a total dose of 100 mCi (131)I for papillary thyroid cancer. A strict hematological follow-up of patients treated with any dose of (131)I is recommended to accurately detect any hematological complications which might have been underestimated. Unusual presentations, such as chloroma of the uterine cervix, may reveal myeloid malignancy and should be kept in mind.


Liver resection with thrombectomy as a treatment of hepatocellular carcinoma with major vascular invasion: results from a retrospective multicentric study.
The role of liver resection (LR) of hepatocellular carcinoma with macroscopic vascular thrombosis (MVT) remains controversial. The aim of this study is to evaluate whether the presence of MVT should still be considered a contraindication for LR. Retrospective study was carried out on 62 patients who underwent LR and thrombectomy for hepatocellular carcinoma complicated by MVT. Of the 62 patients, 15 (36.5%) had tumor thrombus (TT) in the peripheral portal vein (Vp1), 5 (12.2%) in second branch (Vp2), and 21 (51.3%) in the first branch/portal vein trunk (Vp3), while on the hepatic/cava vein side, 8 (12.9%) had TT in the main trunk of the hepatic veins (Vv2) and 3 (4.8%) had TT reaching the vena cava/right atrium (Vv3). Perioperative major morbidity was 14.5%, while in-hospital mortality was 4.8%. Overall, 1, 3, and 5-year survival rates were 53.3%, 30.1%, and 20%, and disease-free survival rates were 31.7%, 20.8%, and 15.6%, respectively. There were no differences in survival about the MVT localized in Vp1, Vp2, or Vp3 (P = .77), while we found a statistical trend between patients with Vv2 and Vv3 (P = .06). Surgical resection seems to be justified in these patients, and the presence of MVT should no longer be considered an absolute contraindication for LR.


Carbon-11-Labeled Methionine PET/CT in Patients With FDG-Occult Multiple Myeloma: A Prospective Pilot Study.
In a pilot study (ClinicalTrials.gov NCT02646085), seven patients with treated multiple myeloma and negative FDG PET/CT underwent amino acid imaging with 11C-methionine PET/CT. In five participants, 11C-methionine PET/CT showed focal uptake corresponding with lytic lesions; two to 18 lesions were found (SUVmax, 2.8-6.4). Findings indicated a potential role for 11C-methionine PET/CT in detecting residual disease after negative FDG PET/CT, thereby guiding further treatment.


Effects of litter size on behavioral development in mice.
The effect of litter size on behavioral development was investigated in 1384 offspring from 114 litters of CD-1 control mice. Litters were classified in four groups of size: 5 to 7 (I), 8 to 10 (II), 11 to 13 (III), and 14 to 17 (IV). Group III was regarded as the control group. The offspring were examined for behavioral development including surface righting at Postnatal Days (PND) 4 and 7, negative geotaxis at PNDs 4 and 7, cliff avoidance at PND 7, swimming behavior at PNDs 4 and 14, and olfactory orientation at PND 14. In behavioral development, surface righting at PND 7 was significantly affected in group I. Swimming direction at PND 4 was significantly affected in group IV, and those effects showed significant tendencies to be retarded as litter size increased. Other measured parameters showed no significant effect of litter size.


Specific patient-related prognostic factors for rotator cuff repair: a systematic review.
Many studies that describe factors affecting outcome in primary rotator cuff repair (RCR) have been published, but so far there is no review that summarizes them. This systematic review was conducted to identify prognostic factors influencing functional (clinical) outcome and radiologically proven cuff integrity after RCR. A literature search was conducted up to July 2013 for prospective studies that describe prognostic factors affecting outcome in primary RCR. Inclusion criteria were open or arthroscopic repair of a full-thickness supraspinatus or infraspinatus tear. Included outcome measures were shoulder function and cuff integrity. Studies describing revision surgery, muscle transpositions, and subscapular or partial-thickness tears and those with retrospectively collected data were excluded, as were studies without linear or multivariate regression. The literature search resulted in 662 hits, and 12 of those studies were included in this review. Moderate evidence was found for increasing age, larger tear size, and additional biceps or acromioclavicular procedures to have a negative influence on cuff integrity at follow-up as well as for Workers' Compensation Board status to have a negative influence on functional outcome after RCR. There is limited evidence that performance of an additional acromioclavicular procedure has a negative influence on functional outcome. There was insufficient evidence for other described prognostic factors. Several patient-specific factors influencing functional and radiologic outcome after RCR have been identified. These factors can guide orthopedic surgeons in their decision-making process as to whether to operate on their patients.


Double burden: Exploring the digital divide in the Burmese educational system following the 2021 coup d' etat and the COVID-19 pandemic.
The 2021 military coup d'état in Myanmar and the Coronavirus (COVID-19) pandemic commencing at the end of 2019 have had major impacts on the already existing digital divide in this Southeast Asian country. This paper aims to explore the effects of these two events on the digital divide and their consequences on the learning practices of students in Myanmar. Following a broad review of relevant literature, primary data were collected from students in Myanmar about their use of IT for online learning and the outcomes. The raw data resulting from this field research has been shared with stakeholders who analyzed, evaluated, and commented on it during expert interviews. The main findings are: IT usage for online education among students in Myanmar is a matter of major concern. A majority of students nationwide have no access to computers. The IT skill level in the country corresponds to this finding and is only on an average level. Smartphones are more accessible but are often old or of lower quality. Internet connections are available but are vulnerable to disruptions initiated by the military regime. Therefore, it can be concluded that students in Myanmar in many cases did not have the technical equipment or skills necessary to learn effectively through the usage of IT during the national crises. Nevertheless, it can be stated that IT helped and was also supportive in sustaining and improving the well-being of students in Myanmar.


Survival promotion of rat cerebellar granule neurons by co-culture with pontine explant.
Cultured cerebellar granule neuron (CGN) of the rat is the most frequently used model system for analysis of activity-dependent neuronal survival. CGNs do not survive longer than 2 weeks in a standard culture medium unless KCl (or other excitants such as glutamate) is added. It is assumed that KCl represents synaptic activity, but no tests have been made on whether the survival of CGNs really depends on the synaptic input. Here we co-cultured CGNs with an explant of the pons including the basilar pontine nucleus (BPN), which is one of the input sources of CGNs in vivo, to confirm if synaptic input is really a determinant for the survival of these cells. In this co-culture system, the viability of CGNs was significantly increased without the addition of KCl. The survival promotion was confined to the population of CGNs having contact with neurites of BPN and was cancelled by an application of tetrodotoxin or antagonists of glutamate receptors, indicating that the survival depended on synaptic activity. Explants of other glutamatergic tissues including the hippocampus failed to promote the survival, although neurites grew out from these explants as vigorously as from the BPN explants. Calcium and FM1-43 imaging examinations revealed that the CGNs had formed functional synapses with the BPN explant but not with the hippocampal explant. These results, confirming the assumption that synaptic activity determines neuronal survival, provide evidence for presynaptic contribution to the survival.


[Lichen sclerosus et atrophicus and lichen ruber planus].
We describe a 67 year old woman who suffers from lichen sclerosus et atrophicus. The clinical and histologic findings are mixed with those of lichen planus or respectively the alterations of both diseases.


Polarizability and aromaticity index govern AhR-mediated potencies of PAHs: A QSAR with consideration of freely dissolved concentrations.
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants associated with adverse human effects including cancer, and the aryl hydrocarbon receptor (AhR) is a key ligand-activated transcription factor mediating their toxicity. However, there is presently a lack of data on AhR potencies of PAHs. Simple, transparent, interpretable and predictive quantitative structure-activity relationship (QSAR) models are helpful, especially with the consideration of freely dissolved concentrations linked to bioavailability. Here, QSAR models on AhR-mediated luciferase activity of PAHs were developed with nominal median effect concentrations (EC50, nom) and freely dissolved concentration (EC50, free) as endpoints, and quantum chemical and Dragon descriptors as predictor variables. Results indicated that only the EC50, free model met the acceptable criteria of QSAR model (determination coefficient (R2) > 0.600, leave-one-out cross validation (QLOO2) > 0.500, and external validation coefficient (QEXT2) > 0.500), implying that it has good goodness-of-fit, robustness and external predictive power. Molecular polarizability and aromaticity index reflecting the partition behavior and intermolecular interactions can effectively predict AhR-mediated potencies of PAHs. The results highlight the necessity of adoption of the freely dissolved concentration in the QSAR modeling and more in silico models need to be further developed for different animal models (in vivo or in vitro).


Novel Therapeutics for Management of Lupus Nephritis: What Is Next?
Lupus nephritis is a severe, organ-threatening manifestation of systemic lupus erythematosus. The current standard of care in the treatment of lupus nephritis is limited to broad-spectrum immunosuppressants, which have significant concerns of short- and long-term toxicity. With traditional approaches, kidney survival and patient outcomes have remained suboptimal. Robust research in the therapeutics of lupus nephritis has resulted in development of many novel drugs targeting specific inflammatory response pathways. Some newer agents have shown a definitive signal of benefit when added to standard of care. With the advent of precision medicine in nephrology, lupus nephritis treatment may undergo a shift toward incorporating approaches using these newer drugs and individualizing care of our patients. This review highlights major advances in management of lupus nephritis over the last 25 years and explores the ongoing trials of emerging therapies in lupus nephritis.


Can prognostic factors be used to direct therapy in chronic lymphocytic leukemia?
Chronic lymphocytic leukemia (CLL) shows a heterogeneous clinical course, which can be explained in part by prognostic factors. Most patients do not need treatment at the time of first diagnosis. The identification of prognostic factors is of major interest if strategies can be devised to treat patients according to their individual risk profile or biological subgroup. Currently, in spite of a wealth of prognostic factors, individualized treatment approaches in different genetic or risk groups are the exemption in CLL. This review summarizes the most important prognostic and predictive factors in CLL, with particular emphasis on factors affecting treatment decisions in clinical trials and routine practice.


Using health administrative data to model associations and predict hospital admissions and length of stay for people with eating disorders.
Eating disorders are serious mental illnesses requiring a whole of health approach. Routinely collected health administrative data has clinical utility in describing associations and predicting health outcome measures. This study aims to develop models to assess the clinical utility of health administrative data in adult eating disorder emergency presentations and length of stay. Retrospective cohort study on health administrative data in adults with eating disorders from 2014 to 2020 in Sydney Local Health District. Emergency and admitted patient data were collected with all clinically important variables available. Multivariable regression models were analysed to explore associations and to predict admissions and length of stay. Emergency department modelling describes some clinically important associations such as decreased odds of admission for patients with Bulimia Nervosa compared to Anorexia Nervosa (Odds Ratio [OR] 0.31, 95% Confidence Interval [95%CI] 0.10 to 0.95; p = 0.04). Admitted data included more predictors and therefore further significant associations including an average of 0.96 days increase in length of stay for each additional count of diagnosis/comorbidities (95% Confidence Interval [95% CI] 0.37 to 1.55; p = 0.001) with a valid prediction model (R2 = 0.56). Health administrative data has clinical utility in adult eating disorders with valid exploratory and predictive models describing associations and predicting admissions and length of stay. Utilising health administrative data this way is an efficient process for assessing impacts of multiple factors on patient care and predicting health care outcomes.


Predictors of the trajectory of cognitive functioning in the first 6 months after allogeneic hematopoietic stem cell transplantation.
Certain subgroups of patients may be particularly vulnerable to cognitive decline after treatment with allogeneic hematopoietic stem cell transplant (HCT). The objective of this study was to identify predictors of cognitive functioning changes within the first 6 months after HCT. Fifty-eight adults treated with allogeneic HCT (53% male, mean 48 years of age) completed neuropsychological tests of learning/memory, psychomotor efficiency/processing speed, and executive functioning/working memory at three time points: pre-HCT and day 100 and 6 months post transplant. On average, there was significant improvement in learning/memory (p = 0.002), psychomotor efficiency/processing speed (p < 0.0001), and executive functioning/working memory (p < 0.0001), at 6 months. Multilevel modeling identified predictors of divergence from this trajectory; Karnofsky performance status <80 was associated with worsening learning/memory over time; peak severity of acute graft-versus-host disease >=Grade 2 was associated with worsening psychomotor efficiency/processing speed; and greater years of education predicted a faster improvement in psychomotor efficiency/processing speed. Other factors were associated with cognitive functioning over time: higher intelligence quotient (IQ) was associated with better cognitive functioning, and older age, being male, and greater pretransplant comorbidities were associated with worse cognitive functioning. Overall, cognitive performance appears to improve over the first 6 months after transplant. However, pretransplant and posttransplant factors may influence this trajectory.


Association of weight change with progression of meniscal intrasubstance degeneration over 48 months: Data from the Osteoarthritis Initiative.
To investigate the association of weight change over 48 months with progression of meniscal intrasubstance degeneration (MID). We studied 487 subjects with MID at baseline and after 48 months using 3-T MRI with the same protocol (FSE sequences with and without fat suppression). These participants lost weight (≥3%, n = 141), had moderate weight gain (3-10%, n = 77), substantial weight gain (>10%, n = 15) or maintained stable weight (n = 254). Progression of MID to a meniscal tear was assessed using the WORMS grading system and compared among weight change groups using logistic regression. ANOVA and chi-square tests were used to study the differences in subjects' characteristics. Progression of MID increased from weight loss to substantial weight gain (p < 0.001) and was significantly more likely with both moderate weight gain (odds ratio [OR], 4.9; 95% confidence interval [CI] 2.4-8.9) and substantial weight gain (OR, 9.5; 95% CI 3.2-28.5) compared to stable weight. Results were similar in both menisci for moderate weight gain (medial: OR, 6.8; 95% CI 3.5-11.3; lateral: OR, 2.6; 95% CI 1.1-6.6) and substantial weight gain (medial: OR, 21.0; 95% CI 5.1-80.7; lateral: OR, 9.7; 95% CI 0.95-100.2). Weight gain is associated with an increased likelihood that meniscal intrasubstance degeneration will progress with the risk increasing with greater weight gain. • Subjects who gained weight were more likely to develop meniscal tears. • Greater amount of weight gain was associated with an increasing likelihood of progression. • Prevention of weight gain has health benefits for the meniscus.


Cloning and characterisation of a glucoamylase gene (GlaM) from the dimorphic zygomycete Mucor circinelloides.
This article reports a novel strategy for the cloning of glucoamylase genes using conserved sequences and semi-nested PCR and its application in cloning the GlaM glucoamylase gene and cDNA from the dimorphic zygomycete Mucor circinelloides. The deduced 609-amino-acid enzyme (including signal peptide) is 63% identical to the Rhizopus oryzae raw starch-degrading glucoamylase and is the third glucoamylase reported to have the putative starch-binding domain placed N-terminally. The C-terminal catalytic domain is separated from the starch-binding domain by a serine/threonine-rich linker. An alignment of the cloned gene and cDNA sequences showed that the gene contains three introns. The transcriptional start site and the site of polyadenylation were defined by primer extension and 3'RACE, respectively. The atypical Kozak sequence is identical to the one used in R. oryzae in positions -1 to -4. Northern slot blots revealed that glucoamylase transcription is induced during growth on starch and repressed by glucose. In silico analysis of the 1.9-kb promoter sequence cloned by inverse PCR revealed the presence of several putative regulatory elements, most notably a 19-bp sequence containing six overlapping copies of the Saccharomyces cerevisiae Nrg1p binding sequence.


Oliguria as an early indicator of mortality risk in patients with multiple myeloma and renal impairment.
A change in urine output has been recently recognized as a valuable biomarker of acute kidney injury that is associated with mortality in critically ill patients. We investigated the prognostic impact of oliguria for survival outcomes in multiple myeloma (MM) patients presenting with renal impairment (RI). Retrospective data on 98 patients with MM and RI, who received initial treatment with novel therapies, were analyzed. Oliguria was defined as a urine output of <0.5 mL/kg/h. The baseline median eGFR was 39.7 mL/min (range, 5.1-59.8). Achievement of renal complete response (CR) was observed in 39.8% of patients. Nine patients (9.2%) presented with oliguria at initial diagnosis, and 4 initially required dialysis. Over a median follow-up period of 17.1 months (range, 1.7-100.0), the median overall survival (OS) was 38.7 months (95% CI 25.0-52.5). Multivariate analyses indicated that oliguria at diagnosis [hazard ratio (HR) 3.628, 95% CI 1.366-9.849, P=0.011], and thrombocytopenia <100×10(9)/L at diagnosis (HR 2.534, 95% CI 1.068-6.015, P=0.035), were significantly associated with overall survival. Oliguria was significantly associated with higher mortality in MM patients with RI. Therefore, close monitoring of urine output could be important for these patients.


Renal localization, expression, and developmental regulation of P450 4F cytochromes in three substrains of spontaneously hypertensive rats.
Cytochrome P450 4F isoforms have been shown to metabolize arachidonic acid to generate 20-hydroxyeicosatetraenoic acid (20-HETE), a potent eicosanoid that modulates vascular tone and renal tubular function. 20-HETE production in the kidney is implicated in the development of essential hypertension in the spontaneously hypertensive rat (SHR). In this study, we determined CYP4F mRNA localization and distribution in rat liver and kidney by in situ hybridization and real time quantitative PCR. CYP4Fs are regionally distributed in the kidney with CYP4F1, 4F4, and 4F5 being expressed more in the renal cortex than medulla while CYP4F6 shows higher medullary expression. We investigated developmental CYP4F gene expression in three different substrains of SHR. Distinct age-dependent patterns of expression were seen for individual CYP4F isoforms in Wistar-Kyoto (WKY) and three SHR substrains (B2, C, and A3). A steady increase in CYP4F1 expression with age was seen in each of the three substrains which correlate well with increased 20-HETE levels and elevated blood pressure seen in these animals. CYP4F4 expression increased significantly at 8 weeks followed by a precipitous fall in WKY and A3 strains at 12 weeks of age. In strains B2 and C, CYP4F4 levels started declining as early as 8 weeks of age. CYP4F5 and 4F6 levels fluctuated with age in a biphasic manner with a different profile for each sub-strain. Based on the expression profile and catalytic activity, CYP4F1 seems to be the most critical 4F isoform involved in the production of 20-HETE in the SHR kidney.


Prevalence of gastrointestinal parasites and molecular identification of beta-tubulin mutations associated with benzimidazole resistance in Haemonchus contortus in goats from selected districts of Uganda.
Gastrointestinal parasites are among the most economically important pathogens of small ruminants causing serious economic losses and animal welfare problems for the livestock industry worldwide. The emergence of anthelmintic resistant H. contortus in small ruminants is a serious problem because it undermines effective helminth control and results in reduced productivity. Little is known about resistance to benzimidazoles (BZ) in Haemonchus in goats and sheep in Uganda. The objective of this study was to determine the prevalence of gastrointestinal parasites and to identify the presence of benzimidazole resistance associated mutations in the β-tubulin isotype 1 gene of Haemonchus contortus in goats from selected districts of Uganda. A total of 200 goats from 10 districts of Uganda slaughtered at Kalerwe abattoir in Kampala were sampled for H. contortus adult worms. Faecal samples were also collected to detect other intestinal parasites. Faecal microscopy and analysis were performed using flotation and sedimentation techniques. DNA was extracted from adult worms and PCR and sequencing of the ITS- 2 region and β-tubulin isotype 1 gene performed to identify H. contortus species and to determine the presence of mutations associated with anthelmintic resistance respectively. Faecal microscopy showed that the most prevalent intestinal parasites were coccidia (98%), strongyles (97.5%), Strongyloides (82%), Paramphistomum (74.5%), Moniezia (46%), Fasciola (1.5%) and Trichuris (1%). Most goats had a high intestinal burden of coccidia (≥ 5000 oocyst per gram) and strongyles (≥ 1000 egg per gram), 65% and 67.5%, respectively. The prevalence of H. contortus adult worms was 63% (126/200). Sequencing of the partial β-tubulin isotype 1 gene of 54 Haemonchus contortus adult male isolates revealed the presence of mutations associated with anthelmintic resistance. The F200Y mutation was the most common mutation (13% of samples with good beta-tubulin sequences) followed by the E198A and E198K mutations, both found in 9% of sequenced samples. Mutation F167Y was not identified in any of the samples and there were no heterozygous individuals for any of the SNPS associated with BZ resistance that were identified in this study. These findings highlight the need for controlled use of anthelmintics especially benzimidazoles, to enable sustainable control of H. contortus in Uganda, and a need for further investigation to understand the resistance of other parasites identified in this study.


Familial gingival fibromatosis: a report of two patients.
This report describes two patients with familial gingival fibromatosis. Treatment for both patients involved gingivectomies to provide acceptable gingival function and appearance. The first patient has been monitored for only a short period, the second patient for 11 years. Neither patient has shown any recurrence of the condition.


Comparison of a new Light Diagnostics and the CMV Brite to an in-house developed human cytomegalovirus antigenemia assay.
Antigenemia, i.e. detection and quantification of human cytomegalovirus (HCMV) peripheral blood pp65-positive leukocytes, is still one of the two major assays available for diagnosis and monitoring of HCMV infections. To evaluate the performance of a new commercial assay under development (Light Diagnostics). To compare the performance of the new assay with a commercial assay (CMV Brite) already available on 300 blood samples from immunocompromised patients using as a reference the original in-house developed assay. Although 30 blood samples gave discrepant results among the 3 antigenemia assays, the Light Diagnostics detected an overall number of antigenemia-positive blood samples (sensitivity 84%) identical to that detected by CMV Brite (sensitivity 88%) and in-house assay (91/300, 30.3%). Problems of non-specific cytoplasmic staining were encountered with the CMV Brite assay in 219/300 (73%) blood samples. The Light Diagnostics assay provides results comparable to those of the reference assay both in terms of specificity and sensitivity (number of pp65-positive leukocytes).


Adenosine 3':5'-monophosphate-dependent in vitro phosphorylation of synaptosomal membrane proteins from rat corpus striatum following systemic administration of L-DOPA and bromocriptine.
In vitro phosphorylation of synaptosomal membrane preparation from rat striata was stimulated by addition of 5 microM cAMP, Administration of L-DOPA to rats treated previously with an L-amino acid decarboxylase inhibitor, or administration of bromocriptine resulted in a marked decrease in the in vitro phosphorylation presumably by increasing endogenous cAMP levels and thereby stimulating endogenous protein phosphorylation.


The prevalence of neurosensorial hearing loss among cystic fibrosis patients from Hospital de Clínicas de Porto Alegre.
Cystic fibrosis (CF) is considered one of the most prevalent lethal genetic disorders. The life expectancy of those patients has been rising. Besides the well-known prevalence of chronic rhinosinusitis, neurosensory hearing loss (NSHL) due to the large use of ototoxic antibiotics may be another problem that should receive special attention in otolaryngology (ENT). Define retrospectively the prevalence of NSHL among patients with CF from the Hospital de Clínicas de Porto Alegre (HCPA) and based on this data discuss the need for a specific out patient ENT-CF clinic. Files from CF HCPA patients were reviewed for age at diagnosis, the current age, types of antibiotics used, number of treatments, percentage with audiologic evaluation and its respective results. One hundred and seven files were reviewed. The mean age at diagnosis was 1.33 years old (SD 1.97, range 0-12). The mean age of the sample was 7.87 (SD 4.49, range 1-22). Audiologic evaluation was performed in 39.3% (42) of the patients. 28.56% (12) had some degree of NSHL, while 36.3% did not present acoustic reflex. From 667 treatments with antibiotics, 49.5% were with tobramycin, 43.4% with amycacin and 7% with gentamicin. The prevalence of NSHL among CF patients supports the need for a specific ENT-CF outpatient clinic. This clinic would help on the prevention and treatment of NSHL due to the use of ototoxic antibiotics and on the better understanding/control of rhinosinusal disorders.


Ecological transition and sustainable development: integrated statistical indicators to support public policies.
The evolution of the concept of sustainability and the availability of new statistical information requires constant checks on the set of indicators so that they accurately perform the task of representing well-being in our society. The Sustainable Development Goals refer to various development domains relating to environmental, social, economic, and institutional issues that have been placed at the basis of the Missions envisaged by the National Recovery and Resilience Plan (NRRP). Specifically, the subject of ecological transition and the related statistical indicators and the evaluations of the effectiveness of the programming implemented by the NRRP to pursue it in practice are of significant interest. The numerous data available were analyzed at a regional level through multivariate statistical methodologies (Totally Fuzzy and Relative method) capable of synthesizing the various information to evaluate the territorial adequacy of the economic planning of its various components. Through the representation on a GIS basis of the geographical distribution of the synthesis values of the fuzzy indices, the paper highlights the different starting point existing between Italian regions. So, these integrated statistical indicators can help public policies to be oriented in a more coherent way with their environmental declared objectives. Starting from the availability of multiple data, it is developed an integrated approach to the evaluation of the local government policies in place and to monitor the progress of subsequent interventions by the Italian government.


Urine collection in infants and children.
June Rogers and Caroline Saunders review current evidence and best practice regarding obtaining a urine specimen from children.


Growth factors modify the epidermal growth factor receptor through multiple pathways.
Previous results have shown that tumor promoters modify the properties of the epidermal growth factor (EGF) receptor through the activation of protein kinase C. Diacylglycerol-generating factors such as platelet-derived growth factor (PDGF) and p28sis should activate protein kinase C and alter EGF receptor properties in a similar manner. To test directly the involvement of protein kinase C in the action of media from v-sis-transformed cells on the EGF receptor, Swiss 3T3 cells were first extensively treated with various concentrations of the tumor-promoter phorbol dibutyrate (PDBu) This treatment reduced levels of active protein kinase C in the cells, making them less responsive to subsequent rechallenge with the tumor promoter. The results demonstrate that there are at least two components to the action of media from v-sis transformed cells on EGF binding: a labile factor that confers protein kinase C independence and a stable factor that appears to be dependent on protein kinase C. The action of the first factor cannot be mimicked by transforming growth factor-beta or EGF in either the presence or absence of PDGF. The action of the second factor is similar to that of PDGF. These findings indicate that heterologous regulation of the EGF receptor can occur through both protein kinase C-dependent and -independent pathways.


Widespread somatic L1 retrotransposition in normal colorectal epithelium.
Throughout an individual's lifetime, genomic alterations accumulate in somatic cells1-11. However, the mutational landscape induced by retrotransposition of long interspersed nuclear element-1 (L1), a widespread mobile element in the human genome12-14, is poorly understood in normal cells. Here we explored the whole-genome sequences of 899 single-cell clones established from three different cell types collected from 28 individuals. We identified 1,708 somatic L1 retrotransposition events that were enriched in colorectal epithelium and showed a positive relationship with age. Fingerprinting of source elements showed 34 retrotransposition-competent L1s. Multidimensional analysis demonstrated that (1) somatic L1 retrotranspositions occur from early embryogenesis at a substantial rate, (2) epigenetic on/off of a source element is preferentially determined in the early organogenesis stage, (3) retrotransposition-competent L1s with a lower population allele frequency have higher retrotransposition activity and (4) only a small fraction of L1 transcripts in the cytoplasm are finally retrotransposed in somatic cells. Analysis of matched cancers further suggested that somatic L1 retrotransposition rate is substantially increased during colorectal tumourigenesis. In summary, this study illustrates L1 retrotransposition-induced somatic mosaicism in normal cells and provides insights into the genomic and epigenomic regulation of transposable elements over the human lifetime.


Prevalence and molecular characterization of bovine Cryptosporidium isolates in India.
A survey based on PCR assay of 18S SSU rRNA gene revealed a 30.2% infection with Cryptosporidium spp., out of 457 faecal samples collected from neonatal bovine calves across three different regions of India. The PCR-RFLP pattern of the gene in all the positive cases established the species as Cryptosporidium parvum. Highest prevalence was recorded in the monsoon months (37.3%) and in the calves showing acute diarrhoea (32.3%). The calves below 15 days of age were mostly affected (45.1%). The infection was more prevalent in the northern parts (35.4%) of the country than in the eastern or southern parts. Results indicated that C. parvum was the only species of Cryptosporidium prevalent in bovine calves in three different geographical regions of India.


Does changing the predicted dynamics of a phospholipase C alter activity and membrane binding?
The enzymatic activity of secreted phosphatidylinositol-specific phospholipase C (PI-PLC) enzymes is associated with bacterial virulence. Although the PI-PLC active site has no obvious lid, molecular-dynamics simulations suggest that correlated loop motions may limit access to the active site, and two Pro residues, Pro(245) and Pro(254), are associated with these correlated motions. Whereas the region containing both Pro residues is quite variable among PI-PLCs, it shows high conservation in virulence-associated, secreted PI-PLCs that bind to the surface of cells. These regions of the protein are also associated with phosphatidylcholine binding, which enhances PI-PLC activity. In silico mutagenesis of Pro(245) disrupts correlated motions between the two halves of Bacillus thuringiensis PI-PLC, and Pro(245) variants show significantly reduced enzymatic activity in all assay systems. PC still enhanced activity, but not to the level of wild-type enzyme. Mutagenesis of Pro(254) appears to stiffen the PI-PLC structure, but experimental mutations had minor effects on activity and membrane binding. With the exception of P245Y, reduced activity was not associated with reduced membrane affinity. This combination of simulations and experiments suggests that correlated motions between the two halves of PI-PLC may be more important for enzymatic activity than for vesicle binding.


Is the inverted surface landing more suitable in evaluating ankle braces and ankle inversion perturbation?
To investigate biomechanical (kinematic) differences between 2 ankle brace testing protocols: landing on an inverted surface (IS) and inversion drop on an inversion platform. Five trials in each of 4 dynamic movement conditions were performed: inversion drop and drop landing from 0.45 m onto an IS without and with an ankle brace. A 7-camera motion analysis system was used to obtain the 3-dimensional kinematics. A 2 × 2 (brace × movement) repeated measures analysis of variance was used to evaluate selected variables for inversion drop and IS landing. Research laboratory. Eleven healthy subjects participated in the study. None. Maximum ankle frontal plane and sagittal plane joint angles, range of motion, and maximum angular velocity. The IS landing resulted in significantly earlier maximum inversion, inversion velocities, dorsiflexion range of motion (ROM), contact dorsiflexion velocity, and maximum dorsiflexion velocity compared with the inversion drop. The ankle brace application during the IS landing reduced the contact plantarflexion angle, dorsiflexion ROM and maximum dorsiflexion velocity, and maximum inversion. The results from this study showed that the IS landing protocol produced significantly earlier maximum inversion angle and velocity and inversion velocities compared with the inversion drop protocol. These results showed that the IS landing is more demanding and should be considered in future investigations of ankle braces and lateral ankle performance/injury mechanisms.


Comparison of dual solvent-stir bars microextraction and U-shaped hollow fiber-liquid phase microextraction for the analysis of Sudan dyes in food samples by high-performance liquid chromatography-ultraviolet/mass spectrometry.
Two sample preparation methods, dual solvent-stir bars microextraction (DSSBME) and U-shaped hollow fiber-liquid phase microextraction (U-shaped HF-LPME), are proposed and critically compared for high-performance liquid chromatography (HPLC)-ultraviolet (UV)/mass spectrometry (MS) analysis of Sudan dyes in this paper. In DSSBME, the organic solvent was confined to a pair of hollow fiber membrane fixed on a stir bar, which can stir by itself, while the hollow fiber in U-shaped HF-LPME was fixed by two microsyringes. The significant factors affecting the microextraction of Sudan dyes in both microextraction techniques have been examined and no obvious difference in the effect of extraction solvent, pH and salt concentration on the extraction efficiency of Sudan dyes was observed except extraction time and stirring speed. Both microextraction techniques were similar in terms of analytical performance from aqueous solutions (LODs ranged from 0.09 to 0.95 microgL(-1) by HPLC-UV and 2.5-6.2 microgL(-1) by HPLC-MS; the absolute LODs ranged from 0.9 to 11.25 pg by HPLC-UV and 5-21.2 pg by HPLC-MS), however, DSSBME was more stable (lower stirring speed required), less sample consuming and much shorter time required to reach extraction equilibrium; while U-shaped HF-LPME was easier to operate and no more special device required. The two microextraction techniques combined with HPLC-UV/MS were successfully applied to the analysis of real samples including strawberry sauce, capsicum oil, salted egg, and two kinds of chilli sauce. Although the LODs of HPLC-UV are lower than that of HPLC-MS by a factor of 10 in this work, the absolute LODs for both HPLC-UV and HPLC-MS are comparable. HPLC-UV cannot identify the suspicious peaks at the same retention time as that of Sudan II and III in salted egg, while HPLC-MS can give exact information of Sudan I-IV in real sample analysis and is more reliable. The sensitivity of HPLC-MS is enough for real sample analysis.


Cell division and turgor-driven stem elongation in juvenile plants: a synthesis.
The growth of hypocotyls and epicotyls has been attributed to the turgor-driven enlargement of cells, a process that is under the control of phytohormones such as auxin. However, the experiments presented here and elsewhere using developing sunflower (Helianthus annuus L.) seedlings raised either in darkness (skotomorphogenesis) or in white light (WL) (photomorphogenesis) indicate that auxin-mediated segment elongation ceases after 1 day, whereas hypocotyl growth continues in the intact system. Based on these results and data from the literature, we propose that hypocotyl growth consists of three inter-related processes: (1) cell division in the apical meristematic regions; (2) turgor-driven cell elongation along the stem; and (3) cell maturation in the basal region of the organ. We document that the closed apical hook (or the corresponding region after opening in WL) is the location where cell division occurs, and suggest that the epidermis and the outer cortex plays an important role in a "pacemaker system" for cell division. Results from the literature support the hypothesis that pectin metabolism in the expansion-limiting epidermal cell wall(s) is involved in wall-loosening and -stiffening. During hypocotyl growth in darkness and WL, turgor pressure is largely maintained, i.e., in H. annuus no hydrostatic pressure-regulated growth occurs. These data do not support the "loss of stability theory" of cell expansion. Finally, we document that turgor maintenance during organ elongation is caused by sucrose catabolism via vacuolar acid invertases, resulting in the generation of hexoses (osmoregulation). Based on these data, we present an integrative model of axial elongation in developing seedlings of dicotyledonous plants and discuss open questions.


One-step selective separation and efficient recovery of valuable metals from mixed spent lithium batteries in the phosphoric acid system.
The recovery of valuable elements in spent lithium-ion batteries (LIBs) has attracted more and more attention. Efficient recovery of valuable elements from spent LIBs with lower consumption and shorter process is the target that people have been pursuing. In this study, the valuable metals (Ni, Co, Mn and Li) and FePO4 products are simultaneously recovered from mixed spent LiNixCoyMnzO2 and LiFePO4 in one step under the optimized condition of 0.88 M H3PO4, a mass ratio of LFP/NCM of 2:1, a L/S ratio of 33:1 and 80 ℃ for 120 min without additional auxiliary reagents. Over 60 % of acid consumption is reduced and the process of adjusting pH is avoidable. The leaching efficiencies of the valuable elements reach up to 99.1 % for Ni, 98.9 % for Co, 99.6 % for Li and 97.3 % for Mn. Almost all of Fe is precipitated as FePO4·2H2O. By means of the empirical model, the research on leaching kinetics demonstrates that the leaching reaction is internal diffusion-controlled with the apparent activation energy of valuable metals less than 30 kJ/mol. Furthermore, the redox reaction mechanism between spent LiBs has been explored. And the intrinsic driving force in the phosphoric acid system is found out. This finding may provide an innovative and selective recycling method for valuable elements from mixed spent LIBs with high economic benefit and fewer environmental footprints.


Headaches in Domestic Medicine by William Buchan.
In this paper, we consider the chapter on headaches contained in William Buchan's Domestic Medicine, a book that enjoyed great success during the second half of the eighteenth and the beginning of the nineteenth centuries, and belongs to the series of public education treatises that began with the publication of Avis au Peuple sur la Sante by Simon Andrè Tissot. In line with the ideals of the Enlightenment, Buchan's aim was to satisfy the needs of people who had no opportunity of consulting a physician by providing them with information about the symptoms and treatment of the most common diseases. One of the distinguishing characteristics of the book is the space dedicated to preventive medicine. In the chapter on headaches, as well as dealing extensively with their etiology, pathogenesis, clinical characteristics and treatment within the conceptual context of humoral medicine, the author also proposed a number of preventive measures that can still be considered fully acceptable today.


Trifunctional of Phosphorus-Doped NiCo2O4 Nanowire Materials for Asymmetric Supercapacitor, Oxygen Evolution Reaction, and Hydrogen Evolution Reaction.
Nowadays, transition-metal oxides are regarded as the most potential materials for the supercapacitor and electrocatalyst. However, the poor electrical conductivity and insufficient active sites limited their development in various fields. Herein, we report the method of phosphorous-doped NiCo2O4 (named as P-NCO) prepared by the two-step strategy: the NiCo2O4 nanostructure is grown on the nickel foams by hydrothermal treatment and subsequently phosphatized in a tube furnace. Successfully, the rich oxygen vacancies and the P element introduced into the NiCo2O4 structure obviously improve the electrical conductivity, and the resulting P-NCO NWs/NF material shows an ultrahigh specific capacitance of 2747.8 F g-1 at 1 A g-1 and a prominent rate performance (maintain 50% at 100 A g-1). Furthermore, the assembled P-NCO NWs/NF//RGO asymmetric supercapacitor has an energy density of 28.2 W h kg-1 even at a high power density of 7750.35 W kg-1. After 10,000 cycles, the capacitance still also has an 88.48% retention rate. As an electrocatalyst, P-NCO NWs/NF has an excellent hydrogen evolution reaction (55 mV at 10 mA cm-2) and oxygen evolution reaction (300 mV at 10 mA cm-2) activities in 1 M KOH solution. This study provides an effective strategy to prepare multifunctional materials.


Drug interactions and multiple drug administration.
Effects of multiple drug administration on adverse drug reactions were studied in 10,518 patients hospitalized on a general medical service during a five-year period. Nine index drug groups, including analgesic, antacid, antiarrhythmic, antimicrobic, anticoagulant, antihypertensive, anti-inflammatory, diuretic, and sedative-tranquilizer drugs, were selected for study. The average number of adverse drug reactions for the anticoagulant and antihypertensive drug groups was higher (p less than 0.05) than for all other drug groups when classified by the number of drugs being taken concurrently (i.e., 0 to 5, 6 to 10, etc.). The rate of reaction for anticoagulant and antihypertensive drug groups was higher (p less than 0.001) than the rate for other drug groups studied. These data suggest a higher risk of adverse drug reactions for patients receiving multiple drugs. The increased risk may result from drug interactions.


Synergistic effect of moxibustion and rehabilitation training in functional recovery of post-stroke spastic hemiplegia.
To evaluate the therapeutic benefit of combining moxibustion and rehabilitation training for functional recovery in post-stroke spastic hemiplegic patients. We randomly divided 84 cases subjecting to inclusion criteria into moxibustion plus rehabilitation training group (MRT group, n=44) and rehabilitation training group (RT group, n=40). Evaluation of therapeutic effect was observed before treatment, 2 weeks during treatment and 6 months after treatment. Spasticity was evaluated using modified Ashworth scale (MAS) and Clinical Spasticity Index (CSI), recovery of motor function was assessed by Brunnstrom recovery stages and Simplified Fugl-Meyer Motor Scale, and performance of activities of daily living (ADL) was measured, and the quality of life was assessed by Patient Reported Outcomes (PRO). Evaluation of upper limbs, hands and lower limbs based on CSI and MAS revealed significant improvements in patients treated with MRT, compared to RT alone, both during and after therapy. CSI and MAS also showed significant improvement in patients at each time point in the MRT group, compared to RT group. Marked improvement in Fugl-Meyer Motor Scale was also observed in MRT group at each time point. Based on Brunnstrom grades of upper limbs, hands and lower limbs, significant differences between the two groups were recorded at all time points during and after therapy. Barthel index (BI) and PRO also confirmed the dramatic differences between the two therapy groups. Our results demonstrate that combination therapy with moxibustion and rehabilitation training offers greater clinical benefits in relieving spasticity, promoting function recovery of motion, improving the performance of ADL, and increasing quality of life in post-stroke spastic hemiplegic patients, compared to RT alone.


Effects of resistance training on sarcopenia in patients with intestinal failure: A randomized controlled trial.
The potential effects of resistance training on sarcopenia in patients with intestinal failure (IF) are not fully elucidated. This study aimed to explore the efficacy of a resistance training program on appendicular skeletal muscle index (ASMI), physical performance, body composition, biochemical parameters, and health-related quality of life (HRQOL) in patients with IF exhibiting sarcopenia. A single-center randomized controlled trial was conducted in a Chinese tertiary teaching hospital. Patients with IF exhibiting sarcopenia were randomly assigned to the exercise group or control group. Participants in the exercise group incorporated four sets of resistance training involving the limbs and abdominal and lower back muscles, six times weekly for 4 weeks. The control group received no specific intervention. The primary outcome was the between-group difference in ASMI 4 weeks after intervention. Secondary outcomes included handgrip strength, 6-m gait speed, body composition, biochemical parameters, and HRQOL. A total of 60 participants (control group 30, age 51.2 ± 12.9 years, women 43.3%; exercise group 30, age 53.9 ± 14.5 years, women 56.7%) completed the 4-week intervention trial. For the primary outcome, significant intervention effects were found in ASMI between the exercise group and the control group (mean difference 0.72, 95% CI, 0.56-0.89, P < 0.001). There were notable differences in handgrip strength (mean difference 2.7, 95% CI, 1.7-3.6, P < 0.001), 6-m gait speed (mean difference 0.08, 95% CI, 0.01-0.35, P = 0.034), body composition (including total cell mass, bone mineral content, skeletal muscle mass, lean mass, visceral fat area, total body water, intracellular water, extracellular water, and segmental water-legs), and biochemical parameters (including IGF-1, prealbumin, and hemoglobin) between the two groups (P < 0.05). No significant intervention benefits were observed for other secondary outcomes, including biochemical parameters (including albumin, total bilirubin, etc.) and HRQOL (P > 0.05). In this randomized clinical trial, we observed that 4 weeks of resistance training was associated with improved ASMI, physical performance, biochemical parameters (including IGF-1, prealbumin, and hemoglobin), and body composition in IF patients with sarcopenia. Resistance training can be recommended as a simple and effective method to improve sarcopenia in patients with IF. www.chictr.org.cn, identifier: ChiCTR2100051727.


CA-125 can be part of the tumour evaluation criteria in ovarian cancer trials: experience of the GCIG CALYPSO trial.
CA-125 as a tumour progression criterion in relapsing ovarian cancer (ROC) trials remains controversial. CALYPSO is a large randomised trial incorporating CA-125 (GCIG criteria) and symptomatic deterioration in addition to Response Evaluation Criteria in Solid Tumours (RECIST) criteria (radiological) to determine progression. In all, 976 patients with platinum-sensitive ROC were randomised to carboplatin-paclitaxel (C-P) or carboplatin-pegylated liposomal doxorubicin (C-PLD). CT-scan and CA-125 were performed every 3 months until progression. In all, 832 patients (85%) progressed, with 60% experiencing a first radiological progression, 10% symptomatic progression, and 28% CA-125 progression without evidence of radiological or symptomatic progression. The benefit of C-PLD vs C-P in progression-free survival was not influenced by type of first progression (hazard ratio 0.85 (95% confidence interval (CI): 0.66-1.10) and 0.84 (95% CI: 0.72-0.98) for CA-125 and RECIST, respectively). In patients with CA-125 first progression who subsequently progressed radiologically, a delay of 2.3 months was observed between the two progression types. After CA-125 first progression, median time to new treatment was 2.0 months. In all, 81%of the patients with CA-125 or radiological first progression and 60% with symptomatic first progression received subsequent treatment. CA-125 and radiological tests performed similarly in determining progression with C-PLD or C-P. Additional follow-up with CA-125 measurements was not associated with overtreatment.


Integrative analysis of mRNA and miRNA expression profiles reveals seven potential diagnostic biomarkers for non‑small cell lung cancer.
The present study aimed to explore specific molecular targets for the diagnosis and treatment of non‑small cell lung cancer (NSCLC). The expression profiles of microRNAs (miRNAs) and mRNAs were downloaded from the GEO (GSE102286 and GSE101929) and TCGA databases. After data preprocessing, differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) in cancer and normal tissues were selected and used to construct a DEM‑DEG regulatory network and a protein‑protein interaction (PPI) network. The genes and miRNAs in these networks were subjected to functional enrichment and survival analyses. Several key DEMs and DEGs were verified using RT‑qPCR, and the results were statistically interpreted using a multivariate logistic regression analysis. In this study, 25 DEMs and 789 DEGs common to all datasets were identified, which were then used for the construction of a DEM‑DEG regulatory network and a PPI network module. Survival analyses of 19 DEMs in the DEM‑DEG regulatory network and 36 DEGs in the PPI network module revealed that 34 DEGs (including TOP2A, CCNB1, BIRC5, and TTK) and two miRNAs (miR‑21‑5p and miR‑31‑5p) were significantly associated with NSCLC prognosis. Moreover, RT‑qPCR analysis identified three DEGs and five DEMs that had changes in expression consistent with those observed in the bioinformatic analysis. Finally, a multivariate logistic regression analysis of the data showed that TOP2A, CCNB1, BIRC5, miR‑21‑5p, miR‑193b‑3p, miR‑210‑3p and miR‑31‑5p could be combined for the diagnosis of NSCLC. In conclusion, TOP2A, CCNB1, BIRC5, miR‑21‑5p, miR‑193b‑3p, miR‑210‑3p and miR‑31‑5p may therefore serve as important biomarkers and diagnostic targets for NSCLC.


Nitric oxide reactivity accounts for N-nitroso-ciprofloxacin formation under nitrate-reducing conditions.
The formation of N-nitroso-ciprofloxacin (CIP) was investigated both in wastewater treatment plants including nitrification/denitrification stages and in sludge slurry experiments under denitrifying conditions. The analysis of biological wastewater treatment plant effluents by Kendrick mass defect analysis and liquid chromatography - high resolution - mass spectrometry (LCHRMS) revealed the occurrence of N-nitroso-CIP and N-nitroso-hydrochlorothiazide at concentration levels of 34 ± 3 ng/L and 71 ± 6 ng/L, respectively. In laboratory experiments and dark conditions, produced N-nitroso-CIP concentrations reached a plateau during the course of biodegradation experiments. A mass balance was achieved after identification and quantification of several transformation products by LCHRMS. N-nitroso-CIP accounted for 14.3% of the initial CIP concentration (20 µg/L) and accumulated against time. The use of 4,5-diaminofluorescein diacetate and superoxide dismutase as scavengers for in situ production of nitric oxide and superoxide radical anion respectively, revealed that the mechanisms of formation of N-nitroso-CIP likely involved a nitrosation pathway through the formation of peroxynitrite and another one through codenitrification processes, even though the former one appeared to be prevalent. This work extended the possible sources of N-nitrosamines by including a formation pathway relying on nitric oxide reactivity with secondary amines under activated sludge treatment.


Energy retention, energy expenditure, and growth in healthy immature infants.
Energy balance studies were done during 10-29 days on 15 immature infants of mean birth weight 1581 g. Mean gross energy intake was 757 kJ/kg (181 kcal) and 79% of this was retained, so that metabolizable energy was 602 kJ/kg (143 kcal). Mean resting metabolic rate was 244 kJ/kg (58.1 kcal), and it increased with advancing maturity. Minimum resting metabolism averaged 199 kJ/kg (47.5 kcal). Energy expended in activity increased with maturity, but amounted to less than 17% of the total energy turnover. Postprandial metabolism caused the mean VO2 to rise by 17% in the hour after a feed, and during 24 hr resulted in consumption of energy equivalent to about 10% of the resting metabolism. Stored energy amounted to 230 kJ/kg (55 kcal) and was linearly related to weight gain (r = 0.92). Energy cost of weight gain was 24 kJ/g (5.7 kcal) and energy stored in new tissue was 16.8 kJ/g (4.0 kcal). Maintenance energy requirement at zero growth rate was about 270 kJ/kg (64 kcal).


Application of various cytotoxic endpoints for the toxicity prioritization of fine dust (PM2.5) sources using a multi-criteria decision-making approach.
Fine dust (PM2.5) is generated from various sources, and many studies have reported on the sources of PM2.5. However, the current research on PM2.5 toxicity based on its sources is insufficient. In this study, we developed a framework for the prioritization of fine dust (PM2.5) sources on the basis of the multi-endpoint toxicities using the multi-criteria decision-making method (MCDM). To obtain the multi-endpoint toxicities of PM2.5 sources, cell mortality, reactive oxygen species (ROS), inflammation and mutagenicity were measured for diesel exhaust particles (DEP), gasoline exhaust particles (GEP), rice straw burning particles (RBP), coal combustion particles (CCP) and tunnel dust particles (TDP). The integrative toxicity score (ITS) of the PM2.5 source was calculated using MCDM, which consist of four steps: (1) defining the decision-making matrix, (2) normalization and weighting, (3) calculating the ITS (linear aggregation) and (4) a global sensitivity analysis. The indicator of cell mortality had the highest weight (0.3780) followed by inflammation (0.2471), ROS (0.2178) and mutagenicity (0.1571). Additionally, the ITS based on the sources contributing to PM2.5 resulted in the following order: DEP (0.89), GEP (0.44), RBP (0.40), CCP (0.23) and TDP (0.06). The relative toxicity index (RTI), which represents the ratio of toxicity due to the difference in sources, increases as the contribution of the highly toxic sources increases. The RTI over 1 is closely associated with an increased contribution from highly toxic sources, such as diesel exhaust, gasoline exhaust and biomass burning. It is necessary to investigate the toxicity of various PM2.5 sources and PM2.5 risk based on the sources.


Time ratio disparities among ED patients undergoing head CT.
To assess if patients who underwent head computed tomography (CT) experienced disparities in the emergency department (ED) and if the indication for head CT affected disparities. This study employed a retrospective, IRB-approved cohort design encompassing four hospitals. All ED patients between January 2016 and September 2020 who underwent non-contrast head CTs were included. Furthermore, key time intervals including ED length of stay (LOS), ED assessment time, image acquisition time, and image interpretation time were calculated. Time ratio (TR) was used to compare these time intervals between the groups. A total of 45,177 ED visits comprising 4730 trauma cases, 5475 altered mental status cases, 11,925 cases with head pain, and 23,047 cases with other indications were included. Females had significantly longer ED LOS, ED assessment time, and image acquisition time (TR = 1.012, 1.051, 1.018, respectively, P-value < 0.05). This disparity was more pronounced in female patients with head pain complaints compared to their male counterparts (TR = 1.036, 1.059, and 1.047, respectively, P-value < 0.05). Black patients experienced significantly longer ED LOS, image acquisition time, and image assessment time (TR = 1.226, 1.349, and 1.190, respectively, P-value < 0.05). These disparities persisted regardless of head CT indications. Furthermore, patients with Medicare/Medicaid insurance also faced longer wait times in all the time intervals (TR > 1, P-value < 0.001). Wait times for ED head CT completion were longer for Black patients and Medicaid/Medicare insurance holders. Additionally, females experienced extended wait times, particularly when presented with head pain complaints. Our findings underscore the importance of exploring and addressing the contributing factors to ensure equitable and timely access to imaging services in the ED.