Role of molecular weight-dependent spectral properties in regulating Cu(II) binding by dissolved organic matter from different sources.
The complexation of metals with dissolved organic matter (DOM) under different compositions and molecular weights (MWs) will result in different environmental fate and toxicity, but the specific role and impact of DOM MWs remain less well understood. This study explored the metal binding characteristics by DOM with different MWs from different sources, including sea, river, and wetland waters. The results of fluorescence characterization showed that the >1 kDa high-molecular-weight (HMW)-DOM were mainly from terrestrial sources while the low-molecular-weight (LMW)-DOM fractions were mostly from microbial sources. Based on UV-Vis spectroscopic characterization, the LMW-DOM contained more unsaturated bonds than its HMW counterpart, and the substituents are generally dominated by polar functional groups. Summer DOM had more unsaturated bonds and a higher metal binding capacity than winter DOM. Furthermore, DOM with different MWs had significantly different Cu binding properties. In addition, Cu binding with microbially derived LMW-DOM mainly caused the change in the peak at 280 nm, while binding with terrigenous HMW-DOM resulted in the change of the 210 nm peak. Compared with the HMW-DOM, most of the LMW-DOM had stronger Cu-binding ability. Correlation analysis indicates that metal binding ability of DOM mainly depends on its concentration, number of unsaturated bonds and benzene rings, and types of substituents during interactions. This work provides an improved understanding of the metal-DOM binding mechanism, the role of composition- and MW-dependent DOM from different sources, and thus the transformation and environmental/ecological role of metals in aquatic systems.


Treating Acute Leukemia During the COVID-19 Pandemic in an Environment With Limited Resources: A Multicenter Experience in Four Latin American Countries.
The COVID-19 pandemic is a colossal challenge for global health; nonetheless, specific subgroups face considerably higher risks for infection and mortality. Among patients with malignant diseases, those with hematologic neoplasms are at a higher risk for poor outcomes. The objective of this study was to register treatment modifications associated with the COVID-19 pandemic and their short-term consequences in Latin America. Multicenter, prospective, observational, cohort study including patients older than 14 years from 14 centers in four countries (Mexico, Peru, Guatemala, and Panama) who had a confirmed diagnosis of acute leukemia, and who were undergoing active treatment since the first COVID-19 case in each country until the cutoff on July 15, 2020. We recruited 635 patients. Treatment modifications because of the COVID-19 pandemic were reported in 40.8% of cases. The main reason for such modifications was logistic issues (55.0%) and the most frequent modification was chemotherapy delay (42.0%). A total of 13.1% patients developed COVID-19 disease, with a mortality of 37.7%. Several factors were identified as independently associated with mortality, including a diagnosis of acute myeloid leukemia (odds ratio 2.38 [95% CI, 1.47 to 3.84]; P < .001), while the use of telemedicine was identified as a protective factor (odds ratio 0.36 [95% CI, 0.18 to 0.82]; P = .014). These results highlight the collateral damage of COVID-19 in oncology patients.


Positive psychological states and coping with severe stress.
Providing care to a spouse or partner who is dying and then losing that person are among the most stressful of human experiences. A longitudinal study of the caregiving partners of men with AIDS showed that in addition to intense negative psychological states, these men also experienced positive psychological state states throughout caregiving and bereavement. The co-occurrence of positive and negative psychological states in the midst of enduring and profoundly stressful circumstances has important implications for our understanding of the coping process. Coping theory had traditionally focused on the management of distress. This article describes coping processes that are associated with positive psychological states in the context of intense distress and discusses the theoretical implications of positive psychological states in the coping process.


The prognostic role of optical coherence tomography in diabetic macular edema patients undergoing early dexamethasone implant shift.
To determine the prognostic characteristics of optical coherence tomography (OCT) parameters by evaluating diabetic macular edema (DME) patients with early dexamethasone (DEX) shift after three doses of intravitreal ranibizumab (RNB) injection. Fifty-four eyes of 34 patients who had DEX implant after three doses of RNB were included in this retrospective study. Early DEX shift includes patients who received direct DEX implant replacement after three doses of RNB load. Baseline OCT values and factors affecting best corrected visual acuity (BCVA) and central macular thickness (CMT) response were analyzed with logistic regression analyses. The presence of subretinal fluid and hyperreflective spot (HRS) >20 were found to be a negative predictive factor for anatomical response. (p = 0.009, p = 0.001, respectively) Low initial BCVA creates a positive effect on visual gain.( p = 0.041) Giant outer nuclear layer cysts, completely disrupted inner segment-outer segment and HRS > 20 have a negative effect on visual gain. (p = 0.025, p = 0.043, p = 0.023, respectively) According to the receiver operating characteristic analysis, the subretinal fluid volume threshold at which >20% reduction in CMT occurs was determined to be 0.85 mm3. (sensitivity 70%, specificity 84% area under the curve 0.817, p = 0.021). The presence of high number of HRS and high subretinal fluid volume at the baseline negatively affect prognosis even in patient groups with early DEX shift.


Anaphylactic shock due to rupture of a hepatic hydatid cyst into a pericystic blood vessel following blunt abdominal trauma.
Partial drainage of a hepatic hydatid cyst into a pericystic blood vessel caused anaphylactic shock following minimal blunt abdominal trauma in a child. A case report including diagnostic procedures and treatment is presented.


The road from ICPD to SDGs: Health returns of reducing the unmet need for family planning in India.
This study attempts to estimate the impact of reducing the unmet need for family planning on the key maternal and child health indicators in India from 1993 to 2016, and projecting this for the period from 2016 to 2030. The data have been compiled from various sources such as the United Nations' World Population prospects, national family health surveys and the sample registration system. The family planning and demographic projection modules of 'Spectrum', a modular computer simulation program, were used to estimate the impact of family planning programmes on reproductive, maternal and child health outcomes in India from 1993 to 2030. Reduction of the unmet need for family planning averted approximately 56 million unintended pregnancies, 7 million unsafe abortions and 167,000 maternal deaths between 1993 and 2016. It is expected that an additional 41 million unintended pregnancies, 5 million unsafe abortions and 124,000 maternal deaths can be avoided by reducing the unmet need for family planning to 5% by 2030. Similarly, the declining unmet need for family planning between 1993 and 2016 led to a reduction in the pregnancy rate, abortion rate, and risk-adjusted infant and under-five mortality rates by 27 per 1000 married women, 1.8 per million married women, 10 per 1000 live births and 15 per 1000 live births, respectively. It is expected that approximately 24 pregnancies per 1000 married women, 1.6 abortions per million married women, 10 risk adjusted infant deaths per 1000 live births, and 14 under-five deaths per 1000 live births can be avoided by reducing the unmet need for family planning to 5% by 2030. The findings of this study advocate that family planning is one of the best return on-investment strategies for India to achieve several targets under the reproductive, maternal and child health-related sustainable development goals.


The gut microbiome in psoriasis and psoriatic arthritis.
This review summarizes existing research on the gut microbiome composition and function in psoriasis and psoriatic arthritis, exploring potential roles in disease pathogenesis, progression, and management. A strong relationship between skin, joint, and gastrointestinal inflammation exists, as demonstrated by an increased prevalence of psoriasis, psoriatic arthritis, and inflammatory bowel disease co-occurring together; however, the link between them has not been fully elucidated. Studies analyzing the gut microbiome in psoriasis and psoriatic arthritis reveal a unique pattern of dysbiosis. With regard to the gut microbiome's role in psoriasis and psoriatic arthritis pathogenesis, we discuss several theories including intestinal permeability, altered immune homeostasis, and imbalance of short- and medium-chain fatty acid-producing bacteria. We also discuss how the gut microbiome affects patient risk of psoriatic arthritis and other serious comorbidities, and how fecal microbes could be used clinically as therapeutic targets or markers of disease.


Laparoscopic adrenalectomy for metastatic disease: Retrospective cohort with long-term, comprehensive follow-up.
Several malignancies metastasize to the adrenal gland, especially non-small cell lung cancer, renal cell carcinoma, and melanoma. Adrenalectomy is associated with prolonged survival, but laparoscopic adrenalectomy for this indication is controversial. Our objective was to characterize and quantify outcomes after laparoscopic adrenalectomy for metastases to the adrenal gland. A prospectively maintained surgical database and institutional cancer registry were queried for patients who underwent adrenalectomy for metastases. From 1995 to 2016, a total of 62 patients underwent adrenalectomy for metastases, with 59 (95.%) having been performed laparoscopically. Primary end points were cumulative probability of 5-year survival and median survival. Patients in the institutional series were compared with Surveillance, Epidemiology, and End Results patients with metastatic non-small cell lung cancer, renal cell carcinoma, and melanoma. There were no deaths within a 30-day period, 6 complications, and 2 conversions to open adrenalectomy. Non-small cell lung cancer (N = 20), renal cell carcinoma (N = 14), and melanoma (N = 8) were the 3 most common adrenal metastases. Overall, cumulative probability of 5-year survival was 37% and median survival was 34 months (95% CI 26-53 months). Median survival for non-small cell lung cancer was 26 months, for renal cell carcinoma was 67 months, and for melanoma was 30 months (P = NS). There was no demonstrable survival benefit for metachronous versus synchronous presentations, no association with size or disease-free interval, nor the presence/history of other metastases. Laparoscopic adrenalectomy for metastases is safe when performed by experienced surgeons. Outcomes are similar or improved compared with series with predominantly open adrenalectomies. Patients selected for laparoscopic adrenalectomy to treat metastatic disease also have prolonged survival compared with Surveillance, Epidemiology, and End Results patients with metastatic non-small cell lung cancer, renal cell carcinoma, or melanoma who do not undergo resection of metastatic disease.


[An unusual case of gunshot wound to the head].
We are going to present a special case of head injury caused by a gunshot. In this case it resulted in a fracture of the skull, but the bullet did not penetrate the skull. It was deflected by the bone, leaving the body at an angle. But bone fragments, acting as secondary bullets, penetrated the brain. In spite of a massive cerebral trauma and brain injury, no retrograde amnesia could be diagnosed. The patient recovered to such an extent, that he could return to his former job. Special characteristics of head injuries caused by bullets will be referred to.


Ketamine relaxes airway smooth muscle contracted by endothelin.
Endothelins (ETs) are synthesized not only in vascular endothelial cells but also in airway epithelial cells. Increased ET-1 has been demonstrated in bronchial epithelium of asthmatic patients, and, in severe asthma attacks, ET-1 increases in plasma and bronchoalveolar lavage fluid. In this study, we investigated whether ketamine (KET) relaxes ET-induced tracheal contractions. Female guinea pigs were killed with an overdose of pentobarbital. The trachea was removed and cut spirally into two strips that were mounted in an organ bath filled with Krebs-bicarbonate buffer. The response of each strip to 10(-7) M carbachol was taken as 100% contraction to which the response to ET was referred. The contribution of the epithelium to the relaxant effect of KET was studied in denuded tracheae or in the presence of 5 x 10(-5) M indomethacin. ET-1 (3 x 10(-8) M) induced contractions that were 76 +/- 3% of those induced by carbachol. KET reversed the response to ET-1 in a dose-dependent fashion. Similarly, ET-2 (3 x 10(-8) M) induced contractions that were 74 +/- 5% of those induced by carbachol, and KET also reversed this response in a dose-dependent manner. In epithelium-denuded strips, ET-1 induced contractions that were 104 +/- 3% of those induced by carbachol, and KET still reversed this response. The tonic phase of the response to ET-1 was equal (100 +/- 6%) to the response to carbachol, and KET did not affect it significantly. In the presence of ryanodine, KET reduced the ET-1-induced contraction from 67 +/- 2% to 36 +/- 3.%, P < 0.01. In the presence of nicardipine, KET also inhibited the ET-1-induced contraction. We conclude that KET relaxes the tracheal smooth muscle contracted by ETs via a mechanism that is independent of the tracheal epithelium. The relaxant effect of KET on the ET-induced contraction of the trachealis muscle is not dependent upon blockade of 1) sarcolemma influx of Ca2+ through the dihydropyridine Ca2+ channel or 2) the release of intracellular Ca2+ through the ryanodine-sensitive intracellular Ca2+ channel. It is likely that the action of KET relaxing ET-induced tracheal contractions is at some point of the inositol 1,4,5-trisphosphate signaling pathway.


The relationship between hip, knee and ankle muscle mechanical characteristics and gait transition speed.
The purpose of the present study was to explore the relationship between mechanical characteristics of hip, knee and ankle extensor and flexor muscle groups and gait transition speed. The sample included 29 physically active male adults homogenized regarding their anthropometric dimensions. Isokinetic and isometric leg muscle mechanical characteristics were assessed by an isokinetic dynamometer, while individual walk-to-run (WRT) and run-to-walk transition speeds (RWT) were determined using the standard increment protocol. The relationship between transition speeds and mechanical variables scaled to body size was determined using Pearson correlation and stepwise linear regression. The highest correlations were found for isokinetic power of ankle dorsal flexors and WRT (r=.468, p<.01) and the power of hip extensors and RWT (r=.442, p<.05). These variables were also the best predictors of WRT and RWT revealing approximately 20% of explained variance. Under the isometric conditions, the maximal force and rate of force development of hip flexors and ankle plantar flexors were moderately related with WRT and RWT (ranged from r=.340 to .427). The only knee muscle mechanical variable that correlated with WRT was low velocity knee flexor torque (r=.366, p<.05). The results generally suggest that the muscle mechanical properties, such as the power of ankle dorsal flexors and hip extensors, influence values of WRT and RWT.


Correction to: A De Novo Frameshift Mutation in TNFAIP3 Impairs A20 Deubiquitination Function to Cause Neuropsychiatric Systemic Lupus Erythematosus.
Figure 4a in Manuscript ID#JOCI-D-19-00318 has been revised due to the replacement of immunoblot lane of β-catenin by Zo-1 in NHA group.


Role of biological membranes in slow-wave sleep.
Two involvements of cellular membranes in slow-wave sleep (SWS) are discussed. In the first the endoplasmic reticulum (ER) is focussed upon, and in the second, the plasmalemma, where specific binding sites (receptors?) for promoters of slow-wave sleep are believed to be located. The study concerning the ER focuses on an enzyme in the brain, glucose-6-phosphatase, which, although present at low levels, manifests greatly increased activity during SWS compared to the waking state. The work on the plasmalemma has to do with the specific binding of muramyl peptides, inducers of slow-wave sleep, to various cells, and membrane preparations of various sorts, including those from brain tissue. Such cells as macrophages from mice, B-lymphocytes from human blood, and cells from a cell line (C-6 glioma) have been examined in this context.


Fetal biometry at 14-40 weeks' gestation.
Normal ranges for a wide variety of biometrical parameters were established from cross-sectional data on 1040 normal singleton pregnancies resulting in livebirth at term of normal, and appropriately grown infants. Patients were selected so that the birth weight distribution was similar to that reported by Yudkin and colleagues' and the ranges can, therefore, be used for any population that has a similar birth weight distribution.


Cyto- and genotoxicity of a vanadyl(IV) complex with oxodiacetate in human colon adenocarcinoma (Caco-2) cells: potential use in cancer therapy.
The complex of vanadyl(IV) cation with oxodiacetate, VO(oda) caused an inhibitory effect on the proliferation of the human colon adenocarcinoma cell line Caco-2 in the range of 25-100 μM (P < 0.001). This inhibition was partially reversed by scavengers of free radicals. The difference in cell proliferation in the presence and the absence of scavengers was statistically significant in the range of 50-100 μM (P < 0.05). VO(oda) altered lysosomal and mitochondria metabolisms (neutral red and MTT bioassays) in a dose-response manner from 10 μM (P < 0.001). Morphological studies showed important transformations that correlated with the disassembly of actin filaments and a decrease in the number of cells in a dose response manner. Moreover, VO(oda) caused statistically significant genotoxic effects on Caco-2 cells in the low range of concentration (5-25 μM) (Comet assay). Increment in the oxidative stress and a decrease in the GSH level are the main cytotoxic mechanisms of VO(oda). These effects were partially reversed by scavengers of free radicals in the range of 50-100 μM (P < 0.05). Besides, VO(oda) interacted with plasmidic DNA causing single and double strand cleavage, probably through the action of free radical species. Altogether, these results suggest that VO(oda) is a good candidate to be evaluated for alternative therapeutics in cancer treatment.


Magnetic compression anastomosis (magnamosis) in a porcine esophagus: Proof of concept for potential application in esophageal atresia.
Magnetic compression anastomosis (magnamosis) is the process of forming a sutureless anastomosis of the gastrointestinal tract using two magnetic Harrison rings. It has been shown to be effective in stomach, small bowel and colon, but has not been implemented in the esophagus. A pure esophageal atresia porcine model was developed to test the concept. Five pigs weighing between 35 and 65 kg were used. In all pigs, a percutaneous endoscopic gastrostomy (PEG) tube was placed, and a right thoracotomy was performed. Esophageal atresia was simulated by transecting the esophagus with a cutting stapler, and magnets were placed endoscopically to approximate the two ends of the esophagus. In the first pig, the tissue within the magnetic ring was excised endoscopically to achieve immediate patency. In the second pig, approximation of the blind esophageal ends was reinforced with 3-4 externally-placed sutures but immediate patency was not performed. In the last three pigs, both external suture reinforcement and immediate patency were performed. The pigs survived for 10-14 days and received nutrition through PEG tube. At necropsy, an esophagram was performed, the specimen was explanted and a leak test was performed. The first pig died in the early postoperative period from a leak owing to separation of the magnets. The second pig died from aspiration before the anastomosis formed. The last three pigs survived until the study endpoint. The third pig had a contained leak owing to the staple line being placed between the magnets; this was not clinically significant. The last two pigs had well-formed anastomoses. Burst tests showed no leak when injecting saline up to 30 mmHg. Magnamosis is technically feasible for esophagoesophageal anastomoses. A survival model for pure esophageal atresia was developed and refined in pigs. Further work in this area may lead to clinical use in humans.


Heart surgery and quality of life: a prospective study on ischemic patients.
Recently, an interest has developed in the use of quality of life instruments to provide a more comprehensive assessment of the impact of disease and treatments on patients' everyday lives over time, particularly in the cardiovascular field. To evaluate changes in quality of life of patients with a coronary heart disease and undergoing heart surgery and to identify patients on which to concentrate stronger rehabilitative intervention, an observational prospective study with repeated measurements has been designed. A total of 259 consecutive coronary heart disease patients (211 males, 48 females, aged 63 (S.D., 9 years) are included into the study. Quality of life has been assessed by means of Karnofsky Performance Status Scale and Nottingham Health Profile (6 dimensions of quality of life) preoperatively, at 2 and 6 months. Changes in quality of life scores at short and mid term and the influence of possible predictors have been investigated. Separate scores have been considered for each dimension of quality of life as well as a global statistics accounting for the multidimensionality of quality of life. Quality of life increased by 57, 64, 72, 52, 23, 44 and 56% for Karnofsky Performance Status Scale, energy, pain, emotion, sleep, social and mobility respectively at 2 months; at 6 months a further increase of 18% in sleep only occurred. Global scores appeared to be significantly influenced by sex, age class, preoperative NYHA, type of angina, associated procedure and complication at surgery. The increase of quality of life concentrates mainly at an early stage of post-operative period. The preoperative factors tested, allow to stratify patients based on quality of life and to identify those on which to concentrate stronger rehabilitative intervention.


Lung deposition and toxicological responses evoked by multi-walled carbon nanotubes dispersed in a synthetic lung surfactant in the mouse.
In the present work, we elaborated a synthetic lung surfactant composed of dipalmitoyl phosphatidylcholine (DPPC), phosphatidylglycerol, cholesterol and bovine serum albumin (BSA), as a vehicle to study the lung toxicity of pristine multi-walled carbon nanotubes (MWCNT). MWCNT were dispersed in surfactant, saline or saline containing DPPC, BSA, Pluronic(®) F68 or sodium dodecyl sulfate, for comparison. Dispersions were characterized visually, and by light microscopy, dynamic light scattering and transmission electronic microscopy (TEM). Deposition of surfactant-dispersed MWCNT in the lung of BALB/c mice upon single or repeated administrations was analyzed by histology and TEM. Inflammation and airway remodeling were assessed in bronchoalveolar lavage fluid (BALF) or lung tissue of mice by counting cells and quantifying cytokines, tumor growth factor (TGF)-β1 and collagen, and by histology. We found that the elaborated surfactant is more effective in dispersing MWCNT when compared to the other agents, while being biocompatible. Surfactant-dispersed MWCNT distributed all throughout the mouse airways upon single and repeated administrations and were observed in alveolar macrophages and epithelial cells, and in infiltrated neutrophils. Mice that received a single administration of MWCNT showed neutrophil infiltrate and greater concentrations of tumor necrosis factor (TNF)-α, keratinocyte-derived chemokine (KC) and interleukin (IL)-17 in BALF when compared to controls. After repeated MWCNT administrations, increases in macrophage number, KC and TGF-β1 levels in BALF, and collagen deposition and mucus hyperplasia in lung tissue were observed. Altogether, the elaborated lung surfactant could be a valuable tool to further study the toxicological impact of pristine MWCNT in laboratory animals.


Comparison of antimicrobial resistance patterns in dogs with bacterial keratitis presented to a veterinary teaching hospital over two multi-year time periods (1993-2003 and 2013-2019) in the Southeastern United States.
To report clinical characteristics of dogs with bacterial keratitis, identify the most common bacterial isolates within this population, characterize the bacterial isolates' antimicrobial resistance patterns, and compare those resistance patterns to previously reported resistance patterns. Dogs diagnosed with bacterial keratitis between 2013 and 2019. Data pertaining to breed; Schirmer tear test I results; use of cyclosporine, tacrolimus, or corticosteroids at time of ulcer diagnosis; bacterial genus or species isolated; and resistance to selected antimicrobials as measured by Kirby-Bauer disk diffusion were collected. Resistance patterns were compared to those reported by Tolar et al. (2006). One hundred seventy bacterial isolates were cultured from 138 eyes from 130 dogs. Of these dogs, 45% were brachycephalic, 62% had STT <15 mm/min, and 28% were receiving a corticosteroid at the time of examination. The most common isolates were Staphylococcus pseudintermedius (31%), β-hemolytic Streptococcus spp. (28%), and Pseudomonas aeruginosa (18%). Compared to the 1993-2003 study period, there were significant increases in resistance to cephalothin and polymyxin B among S. pseudintermedius isolates. β-hemolytic Streptococcus spp. and P. aeruginosa isolates had no significant changes in resistance to the tested antimicrobials. Isolates of S. pseudintermedius, β-hemolytic Streptococcus spp., and P. aeruginosa had minimal changes in resistance between the two study periods. In this population, monotherapy with ciprofloxacin or combination therapy of tobramycin and a first-generation cephalosporin continue to be appropriate for use in cases of suspected bacterial keratitis while awaiting results of susceptibility testing.


Investigation of equid paleodiet from Schöningen 13 II-4 through dental wear and isotopic analyses: Archaeological implications.
The paleodietary traits of the equid population from Schöningen 13 II-4 were investigated through tooth mesowear and microwear analyses, as well as stable isotopic analyses. The mesowear pattern observed on the upper teeth indicates a low abrasion diet with a significant amount of browse in the diet of the horses. The tooth microwear analysis and the isotopic data confirm that the horses from Schöningen 13 II-4 were mixed feeders, like many populations from other Pleistocene localities in Northern and Eastern Europe. Microwear also provides information on seasonal changes in the diet of the horses and offers the possibility to test hypotheses about the presence of one or several horse populations. Our analysis determined that the assemblage of horse remains from Schöningen 13 II-4 resulted from multiple accumulation events, which took place at different periods of time.


Health Technology Assessment of Drugs in Ireland: An Analysis of Timelines.
The National Centre for Pharmacoeconomics (NCPE) is commissioned by the Corporate Pharmaceutical Unit of the Health Service Executive (HSE-CPU) to assess the evidence for the comparative effectiveness and cost effectiveness of drugs for use by patients in Ireland. All new drugs are required to undergo rapid review (RR) appraisal by the NCPE. Following this, high-cost drugs or those predicted to have a significant budget impact then undergo a full health technology assessment (HTA) appraisal by the NCPE. The objective of this paper was to quantify each stage of the timeline from marketing authorisation (MA) to completion of HTA appraisal and explore the association between submission features and the time to appraise RRs and HTAs. All RRs and HTAs submitted to the NCPE (2015-2017 inclusive) were included in the dataset. Several dates and features of each submission were also listed for the purpose of analysis. A total of 158 RR and 49 HTA appraisals were completed by the NCPE between 2015 and 2017. The median time from MA to submission of RR was 59 days; the median time to appraise RR was 31.5 days. Only 49% of RRs appraised (2015-2017 inclusive) were recommended for HTA. The median time from RR decision to submission of HTA was 115 days, and the median time taken by the NCPE to appraise an HTA was 131 days. This paper identifies which stages of the process make a substantial contribution to the HTA timeline. Time to submission of RR varied widely between submissions, with only a few companies choosing to submit prior to an MA being granted. The average RR appraisal time was in line with the 4-week timeframe set out in a 2016 agreement. The time to appraise an HTA was longer than the 90-day timeframe.


Emphysematous cholecystitis during the treatment of heat stroke.
During a heat stroke, microvascular injury may occur as a result of thermal damage and systemic hypoperfusion. We present a case of an older woman who experienced emphysematous cholecystitis during a treatment of heat stroke. A 91-year-old woman presented unconscious with a blood pressure, pulse, and core temperature of 73/48 mmHg, 135 bpm, and 39.8°C, respectively. The patient was diagnosed with heat stroke. Twenty-two hours after arrival, the patient fell into septic shock. We diagnosed emphysematous cholecystitis and performed an emergency cholecystectomy. As the bile culture was positive for Clostridium perfringens, meropenem was administered. The patient was transferred for rehabilitation 32 days after admission. Emphysematous cholecystitis can present during a treatment of heat stroke. An abdominal X-ray examination should be performed during treatment of heat stroke in the acute phase regardless of the physical assessment.


Borderline tuberculoid leprosy misdiagnosed as Cheilitis Granulomatosa Miescher: A case report.
Macrocheilia, as an initial manifestation of leprosy, is uncommon. We present a case of a 50-year-old female, with lower lip swelling, initially diagnosed as Cheilitis Granulomatosa Miescher. Unresponsiveness to local intralesional corticosteroids necessitated further evaluation. Repeat tissue sampling yielded a confirmatory diagnosis of borderline tuberculoid leprosy, which was managed successfully.


Guided self-help for functional (psychogenic) symptoms: a randomized controlled efficacy trial.
Functional (psychogenic or somatoform) symptoms are common in neurology clinics. Cognitive-behavioral therapy (CBT) can be an effective treatment, but there are major obstacles to its provision in practice. We tested the hypothesis that adding CBT-based guided self-help (GSH) to the usual care (UC) received by patients improves outcomes. We conducted a randomized trial in 2 neurology services in the United Kingdom. Outpatients with functional symptoms (rated by the neurologist as "not at all" or only "somewhat" explained by organic disease) were randomly allocated to UC or UC plus GSH. GSH comprised a self-help manual and 4 half-hour guidance sessions. The primary outcome was self-rated health on a 5-point clinical global improvement scale (CGI) at 3 months. Secondary outcomes were measured at 3 and 6 months. In this trial, 127 participants were enrolled, and primary outcome data were collected for 125. Participants allocated to GSH reported greater improvement on the primary outcome (adjusted common odds ratio on the CGI 2.36 [95% confidence interval 1.17-4.74; p = 0.016]). The absolute difference in proportion "better" or "much better" was 13% (number needed to treat was 8). At 6 months the treatment effect was no longer statistically significant on the CGI but was apparent in symptom improvement and in physical functioning. CBT-based GSH is feasible to implement and efficacious. Further evaluation is indicated. This study provides Class III evidence that CBT-based GSH therapy improves self-reported general health, as measured by the CGI, in patients with functional neurologic symptoms.


COVID-19 pandemic-related changes in wellness behavior among older Americans.
COVID-19 has taken its toll on citizens in all 50 states of the United States. The United States (U.S.) leads the world with 30,291,863 confirmed reported cases and 549,664 deaths as of March 29, 2021 compared to globally confirmed cases at 127,442,926 and 2,787,915 deaths as of March 29, 2021. The U.S. federal government primarily left the response to the virus to individual states, and each implemented varying measures designed to protect health of citizens and the state's economic well-being. Unintended consequences of the virus and measures to stop its spread may include decreased physical activity and exercise, shifting access and consumption of food, and lower quality-of-life. Therefore, our primary goal was to quantify the impact of COVID-19 on health and well-being by measuring changes in physical activity, mental health-quality of life, food security and nutrition in adults ages 40 and older. We believed shifts in health behaviors would be more prevalent in minorities, less educated, lower socio-economic status, older adults, and those with underlying health conditions, so a secondary goal was to determine the impact of COVID-19 on these sub-populations. We conducted an online survey with 9969 adults 40 years and older between 9 August and 15 September 2020 in urban areas across the four U.S. census regions. The survey included questions about demographic variables, pre-existing health conditions, physical activity, access to food, quality-of-life, and nutritional food status and asked participants to respond with information from pre-pandemic and pandemic conditions. We used paired-sample t-tests to detect changes in variables after the start of the pandemic and Cohen's d to determine effect sizes. Our main findings showed a decrease in physical activity since the onset of COVID-19 for minorities and non-minorities. Food security also slightly increased for minorities during the pandemic, but we found no other changes in food security, quality-of-life indicators, or nutritional status of those who responded to this survey. It is concerning that physical activity declined. Such activity helps maintain physical and mental health, and it is also an important time to socialize for many older adults. In many ways, our data indicate that the older adult population in U.S. cities may be more resilient than expected during the pandemic. However, the pandemic could have negative impacts that we did not detect, either due to the survey instrument or the timing of our survey, so the health and well-being of older adults should continue to be monitored in order to mitigate potential negative impacts.


Vets at the cutting edge.
Vets Now's Cutting Edge induction programme is a launch pad for vets seeking a career in emergency and critical care medicine. The course leader is Aoife O'Sullivan.


The beneficial effects of Qigong on elderly depression.
Health Qigong, especially the Eight-Section Brocades (or Baduanjin), has been well established as an effective adjunct intervention to alleviate depressive symptoms of older adults. The easy to learn and safe format of health Qigong allows the promotion and employment by health care professionals to improve the physical and psychosocial wellness of older adults. The cultural relevance of Qigong practice enhances its popularity as a health maintenance practice in Chinese community. In general, the antidepressive effects of Qigong are put forward through psychosocial, physiological, and neurobiological mechanisms. More specific, the beneficial effects of Qigong can be further substantiated by findings of several research studies.


A systematic review of the incidence and clinical significance of postoperative meniscus transplant extrusion.
To determine the incidence and clinical significance of postoperative meniscus transplant extrusion. A systematic search was performed using PubMed and Cochrane online databases. Inclusionary criteria were English language, clinical trials of meniscus transplantation published from 1984 to 2014, and meniscus extrusion measured on magnetic resonance imaging (MRI). Twenty-three studies were included, in which 814 menisci were implanted into 803 patients. MRIs were obtained from 2 days to 10 years postoperatively. Eighteen studies used fresh-frozen meniscus transplants implanted with bone (n = 612) or suture fixation (n = 116); four studies, cryopreserved transplants; and one, irradiated transplants. Three measurements assessed extrusion: absolute millimeters of extrusion (0-8.8 mm), relative percentage of extrusion (0-100%), and the percent of transplants that were extruded (0-100 %). Relationships between transplant extrusion and clinical rating scales, joint space narrowing on standing radiographs, and arthrosis progression were inconclusive. Non-anatomic placement of lateral meniscus transplants and suture fixation of medial and lateral transplants were associated with greater extrusion in two studies. Inconsistencies among studies prevent conclusions regarding the incidence and clinical significance of meniscus transplant extrusion. Even so, the short- to mid-term results were encouraging for knee function with daily activities and low rates of failure requiring transplant removal. A postoperative MRI showing more than 3-mm extrusion occurring in some studies suggested technique and/or implant sizing problems that required correction. Future studies should report absolute transplant extrusion, relative percent of extrusion, percent of transplant within the tibiofemoral compartment, and the percent of transplants that are extruded. IV.


Inclusion bodies.
All viruses in the family Potyviridae which have been studied cytologically (currently 111) induce cylindrical inclusions in host cytoplasm. These inclusions are controlled by portions of the virus genome, therefore, viruses which induce them are related. Viruses in other groups do not induce this type of inclusion. Cylindrical inclusions have come to be recognized as one of the main characteristics of the family Potyviridae. They are used in diagnosis of diseases induced by these viruses. For diagnostic purposes the family can be separated into four subdivisions on the basis of differences in cylindrical inclusion morphologies. Assigning viruses to subdivisions assists in virus identification at the specific and in some instances at the strain level.


Ultrasound biomicroscopy in uveitis-glaucoma-hyphema syndrome.
To assess anterior segment anatomy in uveitis-glaucoma- hyphema syndrome. Retrospective case series. Nine pseudophakic eyes (nine patients) with complete or incomplete uveitis-glaucoma-hyphema syndrome underwent ultrasound biomicroscopy. Ultrasound biomicroscopy revealed intraocular lens malposition in each case. Of the eight eyes with posterior chamber intraocular lenses, haptics were in contact with the iris pigment epithelium (four eyes) or the pars plicata (three eyes) or prolapsed into the angle recess near a filtration bleb internal ostium (one eye). All other posterior chamber intraocular lens haptics were located in the ciliary sulcus with the exception of two in the capsular bag. Both haptics in the eye with the anterior chamber intraocular lens had eroded into the ciliary body. By its ability to detect haptic position, ultrasound biomicroscopy can assist in elucidating the cause of uveitis-glaucoma-hyphema syndrome and in deciding on the course of treatment.


Suppression of mouse complement activity by contaminants of technical grade pentachlorophenol.
Pentachlorophenol (PCP) is an antimicrobial agent used chiefly for the preservation of wood. Subchronic oral exposure (14 days) to Technical Grade PCP significantly inhibited the functional activity of female B6C3F1 mouse complement when measured in a microtiter hemolytic assay. When evaluated one day following the final exposure the highest administered dose (100 mg/kg) significantly suppressed the Classical complement pathway, the Spontaneous C1 autoactivation pathway, the Alternate pathway and the level of complement component, C3. Reconstitution studies using C5-deficient serum also demonstrated deleterious effects on this complement component. The Classical pathway was the most sensitive to Technical Grade PCP effects. Animals treated with 100 mg/kg Technical Grade PCP had CH 50 levels 30% of vehicle controls. Animals treated for 14 days and allowed a 15 day recovery period had CH 50 values 36% of control and animals which recovered for 30 days had only 52% of the complement activity of control animals. C3 recovery studies also demonstrated continued suppression on days 15 and 30 post-final exposure. Doses of 10 and 30 mg/kg did not produce the marked effects observed with the highest dose; however, a dose-dependent trend was observed for all responses. Animals treated with 100 mg/kg of EC-7, a PCP preparation with reduced amounts of contaminating dioxins and dibenzofurans, did not demonstrate detrimental effects on the complement system.


[Correction of autoimmune mechanisms underlying the development of type I diabetes mellitus by methods of cell therapy].
The modern concept of development of autoimmune diabetes mellitus is considered. The authors discuss possibilities to correct immune disturbances and support?--cells regeneration by therapy with the use of donor pancreatic cells, bone marrow cells (hemopoietic and stromal) and umbilical cord blood cells.


Dynamics of carbon monoxide binding by heme proteins.
Rebinding of carbon monoxide to myoglobin and to cytochrome P-450 after removal by a light flash occurs down to 50 degrees K for myoglobin and 25 degrees K for cytochrome P-450 in glycerol-water solution. Above 240 degrees K the reaction is second order; between 240 degrees and 200 degrees K the rebinding becomes exponential and independent of the carbon monoxide concentration. Below 150 degrees K the reaction follows a power law and is approximately 10(3) times faster for cytochrome P-450 than for myoglobin.


[The Impact of Asymptomatic Left Ventricular Dilatation on the Course of Anterior Myocardial Infarction.]
to elucidate effect of asymptomatic left ventricular (LV) dilatation on the course of myocardial infarction (MI). LV remodeling and diastolic function, as well as inter- and intraventricular asynchrony were studied in 58 patients with primary anterior MI without signs of heart failure and ejection fraction >40% on month 12 of the disease. Patients were divided into 2 groups: with normal-sized left ventricle (LV end diastolic size [EDS] <5.5 cm) (n=28), and with mild LV dilatation (LV EDS 5.6-5.9 cm) (n=30). At month 12 of MI patients with asymptomatic LV dilatation were characterized by more pronounced signs of pathological remodeling, diastolic LV dysfunction, inter- and intraventricular asynchrony.


Intensive Care Unit Environment and Sleep.
Patients undergoing treatment in intensive care unit are in an extremely vulnerable state and require a complex multidisciplinary approach. Adequate sleep is required to maintain physiologic functions of the human body. Good sleep quality plays a vital role in the process of recovery. Sleep disruption in intensive care settings is a well-known fact. The consequences of sleep deprivation can cause numerous complications including delayed mechanical ventilation wean, neurocognitive dysfunction, decreased immune function and increased mortality rates. This review describes how the intensive care unit environment impacts sleep architecture.


Unearthing a provincial medical school and its students - A history of the 1834 'School of Practical Medicine and Surgery' at the Sussex County Hospital, Brighton, England.
The 19th century was a period of rapid change in English medical education. Little is known about the important contribution of smaller, hospital-based, provincial medical schools which sprang up to provide important practical training opportunities for students, typically as a foundation for further training and examination in London. One such example is the 1834 Brighton 'School of Practical Medicine and Surgery', which was based at the Sussex County Hospital and recognised by the Royal College of Surgeons and Worshipful Society of Apothecaries. Unlike many other 19th century medical schools, the history of the Brighton school is largely undocumented. Although it remained dependent upon London through the 'College and Hall' examination system, this article shows that the school's pragmatic and adaptive educational approach allowed it to play an important role in educating future doctors in Brighton from 1834 into at least the early 20th century.


Androgen receptor coregulators NOCR1, TIF2, and ARA70 may account for the hydroxyflutamide insensitivity of prostate cancer cells.
Prostate cancer cells can switch from an androgen-dependent state to an androgen-independent state after a continuous androgen ablation therapy. However, the molecular mechanisms underlying this switch are still unclear. Therefore, we explored the change in androgen receptor (AR)-related gene expression during this transition in a novel cell model. Prostate cancer cells were continuously treated with competitive androgen receptor inhibitor hydroxyflutamide for 1.5 years, which yielded an flutamide-insensitive LNCaP subline, LNCaP-flu, as confirmed by MTT assays, flow cytometry, and electron microscopy. We analyzed the differences in gene expression in LNCaP-flu cells and LNCaP cells using gene chips and follow-up RT-PCR. Over 2,428 genes were differentially expressed between these cell lines: 1,194 were down-regulated and 1,234 were up-regulated. Three genes in particular were considered related to the androgen-dependent transition: NCOR1, TIF2 (NCOA2), and ARA70 (NCOA4). There were no apparent changes in expression of the androgen receptor or prostate-specific antigen. ARs and associated coregulators play a central role in the flutamide-insensitive transition of prostate cancer cells. Although AR expression does not change during this transition, the change in AR coregulators may be a critical factor in the development of antiandrogen insensitivity.


Psychosocial correlates of regular syphilis and HIV screening practices among female sex workers in Uganda: a cross-sectional survey.
Limited data are available regarding correlates of regular sexually transmitted infections (STIs) and HIV screening among female sex workers (FSW) in Sub-Saharan Africa. In this study, we aimed to assess the frequency of regular syphilis and HIV screening and the psychosocial correlates associated with screening among FSW in Uganda. This cross-sectional correlational study was conducted among 441 FSW, aged 17-49 years. We enrolled FSW through peer referrals and ascertained self-reported data on number of serological tests for HIV, syphilis and other STIs in the prior 12 months using an interviewer-administered questionnaire. In addition, we assessed attitudes, norms, social influences and self-efficacy towards 3-monthly Syphilis and 6-monthly HIV testing. We estimated the correlates of regular STI and HIV testing using negative binomial regression. Of the respondents 420 (95.2%) reported to have ever taken an HIV test with 297 (67.4%) testing two or more times in the prior 12 months. Over half of the respondents (59%) reported ever taking a syphilis test with only 62 (14.1%) reporting testing three or more times in the prior 12 months. After adjusting for socio-demographics, attitude and norms, high perceived self-efficacy was associated with a 33% increase in the likelihood of repeated HIV testing [prevalence ratio (PR), 1.33, 95% confidence interval (CI) 1.15-1.53] while low perceived confidence was associated with a 25% decrease in the likelihood of repeated HIV testing (PR, 0.75, 95% CI 0.63-0.89). Similarly low attitudes and norms were associated with a decrease of 52.6% (PR, 0.47, 95% CI 0.37-0.61) and 47% (PR, 0.53, 95% CI 0.41-0.69) in the likelihood of repeated syphilis testing respectively. Compared to HIV, uptake of repeated syphilis testing was very low. Correlates of HIV testing include; perceived self-efficacy amidst barriers and perceived confidence for HIV and low attitudes and accepting norms for syphilis. Health campaigns should emphasize overcoming barriers to HIV testing while promoting attitudes and norms including integration of serological syphilis testing and other STIs into HIV services.


Evaluation and comparison of commercially available Aloe vera L. products using size exclusion chromatography with refractive index and multi-angle laser light scattering detection.
Raw materials supplied as Aloe vera L. (sometimes referred to as Aloe barbadensis) samples often contain different composition of low and high molecular weight components when analyzed by size exclusion chromatography. One major reason for variable compositions of commercial A. vera L. materials is that they are produced by different manufacturing techniques. Consistent composition of matter based upon a given standard has been difficult to define. In addition, the method of quantifying and characterization of these commercially available materials has not been agreed upon within the industry. The end user, whether a researcher, a manufacturer, a marketing arm of industry or the consumer, should know that they are receiving a consistent product. A blind study of 32 various A. vera L. samples from different manufacturers, and a prepared sample of fresh A. vera L. gel with the commercial, biologic drug Acemannan Immunostimulanttrade mark, were analyzed for content of high molecular weight (polysaccharides) material by size exclusion chromatography with refractive index detection (SEC/RI) and SEC/RI coupled with multi-angle laser light scattering (MALLS) detection. Results from the SEC/RI analysis showed significant variation in the high molecular weight content, and the MALLS analysis also showed significant variation versus SEC/RI. In addition, HPLC analysis of the anthraquinone content showed that all samples contained significantly less than that of the raw, unwashed aloe gel. The variation of results from all analysis is attributed to differing methods in which the samples were processed by the different manufacturers.


[Alkaline encrusted cystitis secondary to Proteus mirabilis infection in a HIV infected patient].
We described for the first time an alkaline encrusting cystitis in a patient with the acquired immune deficiency. This is an entity characterized by severe dysuria and long standing urinary frequency, alkaline urine and radiographically visible calcification of the urinary bladder. It has been observed in patients with permanent Foley catheter, persistent infections due to microorganisms with urolytic activity, urinary bilharziosis or tuberculosis, or malignant bladder tumors. None of these entities were described and the patient had all conditions for this syndrome.


Binocular summation of chromatic changes as measured by visual reaction time.
We determined visual reaction times to monocular and binocular changes in the luminance of isochromatic stimuli and to monocular and binocular changes in the color of isoluminant stimuli. Two isoluminant color changes were tested: chromatic variations along the red-green axis of Boynton's (1986) two-stage color vision model and chromatic variations along the yellow-blue axis of the same model. The results indicate a greater degree of binocular summation for luminance change than for color change. This result was largely independent of the motor component of reaction time.


Pharmacogenetics of the cytochromes P450: Selected pharmacological and toxicological aspects.
With the availability of detailed genomic data on all 57 human cytochrome P450 genes, it is clear that there is substantial variability in gene product activity with functionally significant polymorphisms reported across almost all isoforms. This article is concerned mainly with 13 P450 isoforms of particular relevance to xenobiotic metabolism. After brief review of the extent of polymorphism in each, the relevance of selected P450 isoforms to both adverse drug reaction and disease susceptibility is considered in detail. Bleeding due to warfarin and other coumarin anticoagulants is considered as an example of a type A reaction with idiosyncratic adverse drug reactions affecting the liver and skin as type B. It is clear that CYP2C9 variants contribute significantly to warfarin dose requirement and also risk of bleeding, with a minor contribution from CYP4F2. In the case of idiosyncratic adverse drug reactions, CYP2B6 variants appear relevant to both liver and skin reactions to several drugs with CYP2C9 variants also relevant to phenytoin-related skin rash. The relevance of P450 genotype to disease susceptibility is also considered but detailed genetic studies now suggest that CYP2A6 is the only P450 relevant to risk of lung cancer with alleles associated with low or absent activity clearly protective against disease. Other cytochrome P450 genotypes are generally not predictors for risk of cancer or other complex disease development.


Bone marrow transplantation for Niemann-Pick mice.
The Niemann-Pick mice which received bone marrow transplants showed a decreased accumulation of sphingomyelin and cholesterol quantitatively in their spleen. The sphingomyelin deposit in the bone marrow was also reduced histochemically. However, the neurological manifestations were not improved by the bone marrow graft.


Rationally designed protein cross-linked hydrogel for bone regeneration via synergistic release of magnesium and zinc ions.
The development of recombinant protein cross-linked injectable hydrogels with good mechanical strength and effective drug loading capacity for bone regeneration is extremely attractive and rarely reported. Here, we report the fabrication of a smart hydrogel delivery system by incorporating a rationally designed T4 lysozyme mutant (T4M) to mediate the localized delivery and synergistic release of Mg2+ and Zn2+ for bone repair. Apart from its intrinsic antibacterial properties, T4M bears abundant free amine groups on its surface to function as effective covalent crosslinkers to strengthen the hydrogel network as well as exhibits specific binding affinity to multivalent cations such as Zn2+. Moreover, the integrin receptor-binding Arg-Gly-Asp (RGD) sequence was introduced onto the C-terminus of T4 lysozyme to improve its cellular affinity and further facilitate rapid tissue regeneration. The final composite hydrogel displays excellent injectability, improved mechanical properties, antibacterial activity, and unique bioactivities. The effective loading of Mg2+/Zn2+ in the hydrogels could mediate the sequential and sustained release of Mg2+ and Zn2+, thereby resulting in synergistic enhancement on bone regeneration through modulation of the MAPK signaling pathway. We believe that the strategy proposed in this paper opens up a new route for developing protein cross-linked smart delivery systems for tissue regeneration.


Effects of daily oral subtoxic doses of a wet lead-based paint on cattle.
Cattle were dosed daily with a wet lead-based paint at a rate of about 6 mg of lead per kg per day for 60 weeks. The cattle did not exhibit overt symptoms of lead toxicosis. Blood and fecal samples collected during the study, and tissue samples obtained at slaughter of the animals were analyzed for lead by atomic absorption spectrophotometer equipped with a graphite furnace. Levels of lead in whole blood generally did not exceed 0.5 ppm. The residues of lead in feces reached as high as 1000 ppm. Highest residues in tissues were in calcified bone, the kidney cortex, kidney medulla, and then in liver. Residues of lead in muscle, brain, spleen, and bone marrow were similar to residues of lead in the control animal. Calves born to 2 test animals had elevated levels of lead in bone, kidney and liver.


Silyl resveratrol derivatives as potential therapeutic agents for neurodegenerative and neurological diseases.
Natural phenolic compounds found in food have demonstrated interesting preventive and therapeutic effects on a large variety of pathologies. Indeed, some of them, such as resveratrol (RES), have been examined in clinical trials. Nevertheless, their success has been scarce mainly due to their low bioavailability. In this study, we found serendipitously that O-silyl RES derivatives exerted a better neuroprotective activity than resveratrol itself and decided to explore them as potential drugs for neurodegenerative and neurological diseases. We have also designed and prepared a series of O-silyl RES prodrugs to improve their bioavailability. We found that di-triethylsilyl and di-triisopropylsilyl RES derivatives were better in vitro neuroprotective and anti-inflammatory agents than RES. Among these derivatives and their corresponding acyl-, glycosyl- and carbamoyl-prodrugs, 3,5-triethylsilyl-4'-(6″-octanoylglucopyranosyl) resveratrol 26 showed the best profile on toxicity and neuroprotective activity in zebra fish embryo. Compound 26 was also capable of reducing the loss of motor coordination in a 3-nitropropionic acid mice model of Huntington's disease, in a similar way to RES. However, 26 diminished pro-inflammatory cytokine IL-6 to a higher extent than RES and improved the latency to fall in the rotarod test by 10% with respect to RES. Finally, we investigated 26 and RES as potential treatments on an experimental autoimmune encephalomyelitis (EAE) multiple sclerosis mice model. We observed that, in a therapeutic regimen, 26 significantly diminished the progression of EAE severity and reduced the percentage of animals with moderate to severe clinical score, whereas RES showed no improvement.


Processing visual ambiguity in fractal patterns: Pareidolia as a sign of creativity.
Creativity is a highly valued and beneficial skill that empirical research typically probes using "divergent thinking" (DT) tasks such as problem solving and novel idea generation. Here, in contrast, we examine the perceptual aspect of creativity by asking whether creative individuals are more likely to perceive recognizable forms in ambiguous stimuli -a phenomenon known as pareidolia. To this end, we designed a visual task in which participants were asked to identify as many recognizable forms as possible in cloud-like fractal images. We found that pareidolic perceptions arise more often and more rapidly in highly creative individuals. Furthermore, high-creatives report pareidolia across a broader range of image contrasts and fractal dimensions than do low creatives. These results extend the established body of work on DT by introducing divergent perception as a complementary manifestation of the creative mind, thus clarifying the perception-creation link while opening new paths for studying creative behavior in humans.


catena-Poly[[bis-(nitrato-κO)cobalt(II)]-bis-[μ-1,4-bis-(pyridin-3-ylmeth-oxy)benzene-κN:N']].
In the title compound, [Co(NO(3))(2)(C(18)H(16)N(2)O(2))(2)](n), the Co(II) ion is located on an inversion center and is six-coordinated in an octa-hedral environment defined by four N atoms of the pyridine rings and two O atoms of the nitrate anions. The ligands link the Co(II) ions into a linear chain running along [201]. One O atom of the nitrate ligand is disordered over two positions with site-occupancy factors of 0.59 (4) and 0.41 (4).


Induction of LTP-like changes in human auditory cortex by rapid auditory stimulation: an FMRI study.
Previously we have shown that rapid sensory stimulation, in this case, auditory tone pips, can induce long-lasting plastic changes akin to Long Term Potentiation (LTP) within adult human sensory cortex. In a previous study, auditory LTP was reflected as an increase in the amplitude of the N1 component of the auditory event-related potential as measured by EEG. The goal of the present study was to investigate potential effects of LTP-like changes on the hemodynamic response of the human auditory cortex. Silent sparse-sampled fMRI recordings were obtained while subjects passively listened to tone-pips both before and after a short block of rapidly presented auditory tone-pips (auditory tetanus) was delivered. The BOLD response within the primary auditory cortex was significantly enhanced after the auditory tetanus. This is the first study demonstrating LTP-like changes of the hemodynamic response in the auditory system, and thus supports the growing literature demonstrating LTP can be induced in adult human cortex. These results have implications in the fields of perceptual learning and rehabilitation.


Short amplicon STR multiplex for stain typing.
We developed a short tandem repeat (STR) typing kit based on DNA database systems that are included in, for example, the Interpol Standard Set of Loci recommendations (i.e., TH01, VWA, D3S1358, FGA) and the gender typing system Amelogenin. Two different multiplex sets were tested using the fluorescent dyes FAM, JOE, and VIC. The PCR results were compared to the commercially available AmpFISTR Blue kit, which contains the STRs D3S1358, VWA, and FGA. The advantage of our multiplex compared with the Blue kit was the generation of shorter amplicons (<200 bp) and the higher combined power of discrimination.


Melatonin induced increase in gamma-interferon production by murine splenocytes.
Previously, we demonstrated that production of gamma-interferon (gamma-IFN) by the mouse splenocytes isolated at night was higher than from those isolated in the morning. In this paper we show that melatonin increased gamma-IFN production by murine splenocytes. Moreover, this stimulating effect was significantly higher (10 times) in the cells isolated at night than in those isolated in the morning (2 times).


[Effect of serum osmolarity, arterial blood pressure and volume loss on IOP during hemodialysis, hemofiltration and simultaneous hemofiltration/hemodialysis (author's transl)].
In 29 patients suffering from chronic renal failure intraocular pressure was measured during different therapeutic regimens. Conventional hemodialysis (principle of transport diffusion, n = 15) led to an increase in IOP after one hours treatment. In individuals complaining of headaches during dialysis a marked increase in IOP was observed indicating a disequilibrium syndrome. Hemofiltration is characterized by mass transfer and exchange of plasma water. When this treatment was applied to 6 patients IOP was elevated during the second hour. Simultaneous hemofiltration/hemodialysis (n = 8) had no influence on IOP behaviour. Statistically there was no correlation between the behaviour of serum osmolarity, arterial blood pressure, loss of body weight and IOP.


Surface study of apoB1694-1880, a sequence that can anchor apoB to lipoproteins and make it nonexchangeable.
Apolipoprotein B (apoB) is a nonexchangeable apolipoprotein. During lipoprotein assembly, it recruits phospholipids and triacylglycerols (TAG) into TAG-rich lipoprotein particles. It remains bound to secreted lipoproteins during lipid metabolism in plasma. The beta1 region (residues 827-1880) of apoB has a high amphipathic beta strand (AbetaS) content and is proposed to be one region anchoring apoB to lipoproteins. The AbetaS-rich region between apoB37 and apoB41 (residues 1694-1880) was cloned, expressed, and purified. The interfacial properties were studied at the triolein/water (TO/W) and air/water (A/W) interfaces. ApoB[37-41] is surface-active and adsorbs to the TO/W interface. After adsorption the unbound apoB[37-41] was removed from the aqueous phase. Adsorbed apoB[37-41] did not desorb and could not be forced off by increasing the surface pressure up to 23 mN/m. ApoB[37-41] adsorbed on the TO/W interface was completely elastic when compressed and expanded by +/-13% of its area. On an A/W interface, the apoB[37-41] monolayer became solid when compressed to 4 mN/m pressure indicating extended beta-sheet formation. It could be reversibly compressed and expanded between low pressure and its collapse pressure (35 mN/m). Our studies confirm that the AbetaS structure of apoB[37-41] is a lipid-binding motif that can irreversibly anchor apoB to lipoproteins.


Impact of Postharvest Putrescine Treatments on Phenolic Compounds, Antioxidant Capacity, Organic Acid Contents and Some Quality Characteristics of Fresh Fig Fruits during Cold Storage.
The storage and shelf life of the fig, which has a sensitive fruit structure, is short, and this results in excessive economic losses. In a study carried out to contribute to the solution of this problem, the effect of postharvest putrescine application at different doses (0, 0.5, 1.0, 2.0, and 4.0 mM) on fruit quality characteristics and biochemical content during cold storage in figs was determined. At the end of the cold storage, the decay rate and weight loss in the fruit were in the ranges of 1.0-1.6% and 1.0-5.0 %, respectively. The decay rate and weight loss were lower in putrescine-applied fruit during cold storage. Putrescine application had a positive effect on the changes in fruit flesh firmness values. The SSC rate of fruit varied between 14 and 20%, while significant differences in the SSC rate occurred depending on storage time and putrescine application dose. With putrescine application, the decrease in the acidity rate of the fig fruit during cold storage was smaller. At the end of the cold storage, the acidity rate was between 1.5-2.5% and 1.0-5.0. Putrescine treatments affected total antioxidant activity values and changes occurred in total antioxidant activity depending on the application dose. In the study, it was observed that the amount of phenolic acid in fig fruit decreased during storage and putrescine doses prevented this decrease. Putrescine treatment affected the changes in the quantity of organic acids during cold storage, and this effect varied depending on the type of organic acid and the length of the cold storage period. As a result, it was revealed that putrescine treatments can be used as an effective method to maintain postharvest fruit quality in figs.


Subclinical Peripheral Arterial Disease in Patients with Acute Ischemic Stroke: A Study with Ultrasonography.
Peripheral arterial disease (PAD) is an advanced form of atherosclerosis defined by an abnormal ankle-brachial index (ABI). However, the ABI provides no information about the location of atherosclerosis. We investigated the clinical implication of PAD confirmed using lower-extremity ultrasonography (LEUS), with consideration of the atherosclerosis location. Patients with acute ischemic stroke who underwent LEUS were enrolled. Patients with PAD were further divided into those with PAD at the proximal (above-popliteal artery, PADP) and distal (below-tibialis artery, PADD) segments. The clinical outcome was compared between patients with and without PAD, and between PADP and PADD. The atherosclerosis location in the cerebral artery was also compared between groups. Among 289 patients, PAD was observed in 108 (37.4%) patients (43 had PADP and 65 had PADD). Patients with PAD were slightly older (P < .001) and had more significant carotid artery stenosis (30.6% versus 12.7%, P < .001) than those without. Patients with PAD had poor 3-month functional outcome than those without (modified-Rankin Scale score: 3 [interquartile range, 1-4] versus 2 [1-3], respectively, P = .003). Diabetes, high-stroke severity, and the presence of PADP (odds ratio, 3.893; 95% confidence interval, 1.454-10.425; P = .007) were independently associated with poor functional outcome at 3 months. Patients with PADP showed higher prevalence of extracranial stenosis than those with PADD (41.9% versus 23.1%; P = .038). Our study suggests that subclinical PAD, especially PADP, is associated with poor functional outcome at 3 months after stroke onset. Interestingly, the location of cerebral atherosclerosis differed according to the location of PAD.


Design, synthesis and biological evaluation of curcumin analogues as novel LSD1 inhibitors.
Histone lysine-specific demethylase 1 (LSD1) was the first discovered histone demethylase. Inactivating LSD1 or downregulating its expression inhibits cancer-cell development, and thus, it is an attractive molecular target for the development of novel cancer therapeutics. In this study, we worked on the structural optimization of natural products and identified 30 novel LSD1 inhibitors. Utilizing a structure-based drug design strategy, we designed and synthesized a series of curcumin analogues that were shown to be potent LSD1 inhibitors in the enzyme assay. Compound WB07 displayed the most potent LSD1 inhibitory activity, with an IC50 value of 0.8 μM. Moreover, WA20 showed an anticlonogenic effect on A549 cells with an IC50 value of 4.4 μM. Molecular docking simulations were also carried out, and the results indicated that the inhibitors bound to the protein active site located around the key residues of Asp555 and Asp556. These findings suggested that compounds WA20 and WB07 are the first curcumin analogue-based LSD1 inhibitors with remarkable A549 suppressive activity, providing a novel scaffold for the development of LSD1 inhibitors.


Sclerosing mesenteritis, a rare cause of a retroperitoneal tumor.
Sclerosing mesenteritis is a chronic and extremely rare inflammatory process that predominantly affects the small bowel mesentery. However, the peripancreatic region, the omentum and the retroperitoneum can also be involved. The etiology and pathogenesis of the disease are as yet unknown, but autoimmune disorders, previous abdominal surgery, trauma, ischemia and drugs could play a role. The clinical picture is nonspecific and varies from asymptomatic to diffuse abdominal complaints. Radiologic work-up and histologic evaluation of a biopsy specimen usually do not reveal typical findings and therefore establishment of the correct diagnosis is challenging. Owing to the rarity of the disease, there is no consensus on optimal pharmaceutical treatment and most patients are treated empirically. Surgical therapy is limited to biopsies for histologic confirmation of the tumor and management of complications. We report a case of a 51-year-old man with a large retroperitoneal mass. Magnetic resonance angiography showed a 9.7 x 7.7 x 5.9 cm tumor above the aortic bifurcation with encasement of the aorta and the vena cava. CT-guided biopsy was inconclusive but surgical biopsy provided a histologic diagnosis of sclerosing mesenteritis. The operative and postoperative course was uneventful and therapy with prednisolone and azathioprine was started. At 6 months' follow-up, the patient was in good condition and asymptomatic. Sclerosing mesenteritis, though a rare entity, should be included in the differential diagnosis when a patient presents with a mesenterial or retroperitoneal tumor.


Fluorescent Carbon Dots: Fantastic Electroluminescent Materials for Light-Emitting Diodes.
Fluorescent carbon dots (CDs) have emerged as fantastic luminescent nanomaterials with significant potentials on account of their unique photoluminescence properties, high stability, and low toxicity. The application of CDs in electroluminescent light-emitting diodes (LEDs) have aroused much interest in recent years. Herein, the state-of-the-art advances of CD-based electroluminescent LEDs are summarized, in which CDs act as active emission layer and interface transport layer materials is discussed and highlighted. Besides, the device structure of CD-based LEDs and preparation methods of CDs are also introduced. Furthermore, the opportunities and challenges for achieving high performance CD-based electroluminescent LED devices are presented. This review article is expected to stimulate more unprecedented achievements derived from CDs and CD-based electroluminescent LEDs, thus further promoting their practical applications in future solid-state lighting and flat-panel displays.


Cutaneous T-cell lymphoproliferative disorders: approach for the surgical pathologist: recent advances and clarification of confused issues.
Cutaneous T-cell lymphoproliferative disorders (CTCLs) remain a subject of confusion and controversy. In this review, the authors discuss diagnostic criteria and classification, including the role of immunohistochemistry and gene rearrangement studies. In addition, cutaneous T-cell pseudolymphomas, the current status of parapsoriasis and other premalignant syndromes, and the clinicopathological variants of mycosis fungoides are discussed. CD30-positive lymphoproliferative disorders and a number of rare variants of CTCL including granulamatous slack skin, subcutaneous (panniculitic) T-cell lymphoma, gamma-delta cutaneous lymphoma, NK/NK-like T-cell lymphoma, and primary cutaneous CD8-positive epidermotropic cytotoxic T-cell lymphoma are also considered.


Influence of maturation and aging on mechanical and biochemical properties of connective tissue in rats.
The influence of maturation and age on the physical and chemical properties of various organs of connective tissue has been studied in rats at ages of 4 weeks, 8 weeks, 4 monhs, 1 year and 2 years. The changes between young (4 weeks old) and adult (4 months to 1 year old) animals were considered as the effects of maturation, whereas the changes between adult and senescent (2 years old) rats were regarded as the effects of aging. Ultimate values, such as ultimate load, tensile strength and breaking strength, or ultimate modulus of elasticity, showed a sharp rise during maturation and a smaller but significant decrease during aging in all organs, such as skin strips, tail tendons, shaft bones, epiphyseal cartilage and aorta rings. Ultimate strain showed a similar pattern, but the maximum occurred earlier. These changes were parallel with the content of insoluble collagen. Other chemical parameters such as soluble collagen or glycosaminoglycans, showed a continuous decrease during the life span, whereas elastin rose continuously. More detailed analysis of mechanical properties in rat skin gave insight into the viscoelastic behaviour of skin. In creep experiments time until break under constant load rose continuously during the life span, whereas ultimate extension rate showed a sharp fall during maturation and a slow decrease during senescence. Stress at low extension degree and moduli of elasticity at low extension degree were decreased by maturation and increased by senescence, exactly the opposite of the changes at high extension degrees. The so-called step phenomenon was increased due to maturation and decreased due to aging. Relaxation and mechanical recovery were changed in the same direction by maturation and aging. Relative viscoelastic parameters, such as the hysteresis phenomenon and relative decrease of stress under cyclic strain, were barely influenced by the aging process. Changes of most of the mechanical parameters at high extension degrees during maturation may be explained by an increase of cross-linking of collagen. Other phenomena such as changes at low extension degrees or parameters of plasticity cannot be explained on this basis. Further studies are needed for a better understanding of the true aging process in connective tissue.


A comparison of Texan and Hawaiian strains of the avian eyefluke, philophthalmus gralli, with a cautionary note on the importation of exotic animals.
Philophthalmus gralli (Mathis and Leger, 1910) was introduced into the San Antonio, Texas area within the last 25-30 years from an unknown foreign source. Strains of P. gralli originally from Texas and Hawaii were compared for differences in morphology, growth patterns, mating compatibility, and isozyme mobilities. Metacercarial cysts of the 2 strains were compared for viability after storage at room temperature. Adult stages of the 2 strains were indistinguishable based on sucker ratios, vitellaria, and egg sizes. In single- and multiple-worm infections, both strains exhibited similar growth patterns when reared in chickens. Adults of the 2 strains, when transplanted in concurrent infections, readily cross-inseminated. Isozyme mobilities of 5 enzymes were identical in all adult worms examined from both strains. After 3 days, metacercarial cysts from both strains rapidly lost their ability to excyst. The cysts of the Texan strain remained viable for 4 days longer than the Hawaiian strain, although excystment rates were low during that period. The evolutionary implications of this imported species are discussed.


Psychooncological distress in low-grade glioma patients-a monocentric study.
Patients diagnosed with low-grade glioma (LGG) must live with constant knowledge of an upcoming malignant tumor transformation which may lead to increased anxiety and reduced quality of life. Here, we (1) analyzed the prevalence and risk factors for distress in LGG patients using (2) different screening tools to subsequently (3) evaluate their need for psychological support. Patients with LGG-suspicious findings in MRI studies as well as patients with histopathological confirmed LGG were screened using three established self-assessment instruments (Hospital Anxiety and Depression Scale, Distress Thermometer, EORTC-QLQ-C30-BN20). Screening results were correlated with sociodemographic factors. One hundred forty-nine patients (74 men and 75 women) were prospectively included. Patients were further divided into different subgroups regarding the time of screening and diagnosis. An increased level of distress was observed in 20.8% (mean score 1.21, 95% CI 1.15-1.28) of all patients screened by HADS. Significant associated factors were pre-existing psychiatric disorders (p = 0.003) and psychotropic medication (p = 0.029). HRQoL (p = 0.022) and global health item (p = 0.015), as well as future uncertainty (p = 0.047), assessed by the EORTC-QLQ-C30-BN20 were significantly higher in those patients without histopathological diagnosis. Increased distress was significantly correlated with results in chosen sub-items of the HRQoL questionnaire (p < 0.001). Our results demonstrate the need for frequent distress screening. If specific tools are not available, HRQoL questionnaires can also be used. Patients with pre-existing psychological stress should be offered additional psychooncological support, irrespectively of the time of screening or tumor diagnosis. 4087.


Management and outcomes of hemorrhage after distal pancreatectomy: a multicenter study at high volume centers.
Data on clinically relevant post-pancreatectomy hemorrhage (CR-PPH) are derived from series mostly focused on pancreatoduodenectomy, and data after distal pancreatectomy (DP) are scarce. All non-extended DP performed from 2014 to 2018 were included. CR-PPH encompassed grade B and C PPH. Risk factors, management, and outcomes of CR-PPH were evaluated. Overall, 1188 patients were included, of which 561 (47.2 %) were operated on minimally invasively. Spleen-preserving DP was performed in 574 patients (48.4 %). Ninety-day mortality, severe morbidity and CR-POPF rates were 1.1 % (n = 13), 17.4 % (n = 196) and 15.5 % (n = 115), respectively. After a median interval of 8 days (range, 0-37), 65 patients (5.5 %) developed CR-PPH, including 28 grade B and 37 grade C. Reintervention was required in 57 patients (87.7 %). CR-PPH was associated with a significant increase of 90-day mortality, morbidity and hospital stay (p < 0.001). Upon multivariable analysis, prolonged operative time and co-existing POPF were independently associated with CR-PPH (p < 0.005) while a chronic use of antithrombotic agent trended towards an increase of CR-PPH (p = 0.081). As compared to CR-POPF, the failure-to-rescue rate in patients who developed CR-PPH was significantly higher (13.8 % vs. 1.3 %, p < 0.001). CR-PPH after DP remains rare but significantly associated with an increased risk of 90-day mortality and failure-to-rescue.


31P-NMR spectroscopy of phosphate compartmentation during ischaemia in hearts protected by cardioplegic treatment.
Four tissue compartments, differing in proton and inorganic phosphate concentration, were resolved by 31P-NMR spectroscopy in samples from dog hearts after cardioplegic treatment with HTK solution. Inversion of the physiological cytoplasmic-mitochondrial pH gradient was observed. The considerable ensuing acidosis of the matrix is discussed with regard to a possible delocalization of ferrous ions.


Histologic scoring of gastritis and gastric cancer in mouse models.
Histopathology is a defining endpoint in mouse models of experimental gastritis and gastric adenocarcinoma. Presented here is an overview of the histology of gastritis and gastric cancer in mice experimentally infected with Helicobacter pylori or H. felis. A modular histopathologic scoring scheme is provided that incorporates relevant disease-associated changes. Whereas the guide uses Helicobacter infection as the prototype challenge, features may be applied to chemical and genetically engineered mouse models of stomach cancer as well. Specific criteria included in the combined gastric histologic activity index (HAI) include inflammation, epithelial defects, oxyntic atrophy, hyperplasia, pseudopyloric metaplasia, and dysplasia or neoplasia. Representative photomicrographs accompany descriptions for each lesion grade. Differentiation of genuine tumor invasion from pseudoinvasion is highlighted. A brief comparison of normal rodent versus human stomach anatomy and physiology is accompanied by an introduction to mouse-specific lesions including mucous metaplasia and eosinophilic droplets (hyalinosis). In conjunction with qualified pathology support, this guide is intended to assist research scientists, postdoctoral fellows, graduate students, and medical professionals from affiliated disciplines in the interpretation and histologic grading of chronic gastritis and gastric carcinoma in mouse models.


Physical activity recommendations and cardiovascular disease risk factors in young Hispanic women.
Despite the benefits associated with regular physical activity, there is little epidemiological evidence to support positive health outcomes when meeting physical activity guidelines in high-risk ethnic groups, such as Hispanic women. We compared cardiovascular disease risk factors between young Hispanic women who meet and those who do not meet current physical activity guidelines. Height, weight, waist circumference, and blood pressure were measured in 60 Hispanic women aged 20-39 years. Lipids, C-reactive protein, insulin, and glucose were assessed. Body composition and cardiovascular fitness were assessed by BodPod and maximal oxygen uptake (VO₂(max)) respectively. Participants wore an accelerometer and average minutes (assessed in 10-min bouts) spent in light, moderate, and hard daily activity for weekdays and weekends was determined. Seventy percent of participants did not meet the recommended physical activity guidelines, whereas 30% did so. Following current physical activity guidelines was associated with significantly lower mean cholesterol (mean ± s: 4.2 ± 0.8 vs. 4.7 ± 0.9 mmol · l⁻¹) and triglycerides (0.7 ± 0.3 vs. 1.1 ± 0.6 mmol · l⁻¹), and higher fat-free mass (43.3 ± 3.8 vs. 40.2 ± 5.1 kg) and relative (40.4 ± 7.6 vs. 35.6 ± 7.0 ml · kg⁻¹ · min⁻¹) and absolute (2.5 ± 0.3 vs. 2.1 ± 0.4 litres · min⁻¹) VO₂(max) (P < 0.05). These findings suggest an improved health status in women who meet versus those who did not meet current physical activity guidelines.


CT of pancreatic neoplasms. Part II: The unusual tumors.
The pancreas gives rise to a remarkable variety of neoplasms other than ductal adenocarcinoma. Although no individual type of tumor in this category is prevalent enough to qualify as common, most types are currently encountered with a frequency far greater than that in decades of the recent past. This change is largely the result of the expanded use of contemporary abdominal imaging. The unusual tumors of the pancreas vary greatly in their biologic behavior and, accordingly, in their clinical consequences and therapeutic requirements. Accurate diagnosis, therefore, can be of considerable clinical relevance. Not only is it worthwhile to distinguish one type of unusual pancreatic tumors from another, it is perhaps of even greater consequence to distinguish the unusual tumors from ordinary pancreatic adenocarcinomas. The goals of this discussion are to expand radiologic awareness of these uncommon but interesting pancreatic neoplasms and to increase familiarity with their diagnostically salient features.


Salmonella enterotoxin (stn) gene is prevalent among strains of Salmonella enterica, but not among Salmonella bongori and other Enterobacteriaceae.
All strains and serovars of Salmonella enterica such as serovar Typhimurium, Enteritidis, Dublin, Typhi, etc. were found to carry the Salmonella enterotoxin determinant stn as far as examined in PCR and hybridization studies. However, using MDCK cells for testing the toxicity of the strains under investigation, only a limited number of stn positive strains revealed phenotypically the Salmonella enterotoxin Stn. In contrast to S. enterica, other Enterobacteriaceae including Salmonella bongori were found neither genotypically nor phenotypically Stn toxin positive.


Cytofluorometric purification of diploid and tetraploid cancer cells.
During malignant transformation, cells can increase their ploidy and hence become polyploid (mostly tetraploid). Frequently, however, tetraploid cells undergo asymmetric divisions, in turn entailing a reduction in ploidy and the acquisition of a pseudo-diploid, aneuploid state. To investigate such a stepwise aneuploidization process, we developed a cytofluorometric method (based on the heterogeneity in cell size and/or chromatin content) that allows for the cloning and subsequent functional analysis of cells with distinct ploidies. Here, we detail this methodology, which has been instrumental for investigating the functional link between ploidy status and oncogenesis.


Immunohistochemical demonstration of serotonin-containing CSF-contacting neurons in the submammalian paraventricular organ.
The distribution and morphological aspects of the serotonin-containing neurons in the paraventricular organ of the carp, frog, turtle and chicken were studied by means of an immunoperoxidase technique using serotonin antiserum. In all species the serotonin-containing neurons were seen to have the appearance of the CSF-contacting neurons and to be distributed in the pars ependymalis and the pars hypendymalis of the organ. Particularly, in the frog, the serotonin-containing CSF-contacting neurons, mostly bipolar in shape, were also observed in the pars distalis. Their proximal processes protruded into the ventricular lumen through the ependymal layer with a globular- and triangular-shape. The distal processes projected ependymofugally to the pars distalis and formed a fine plexus in the neuropil of this part. The density of the serotonin fibers in the pars distalis was greater in the carp than in the other species.


Antimicrobial resistance in fecal Escherichia coli isolates from healthy urban children of two age groups in relation to their antibiotic therapy.
The study was performed in the Czech Republic during 2007 to 2009. Of Escherichia coli isolates from 275 children aged 6 weeks, 36% (n = 177) were resistant to 1 to 7 antibiotics. Of isolates from 253 children aged 6 to 17 years, 24% (n = 205) were resistant to 1 to 5 antibiotics. There was no significant difference in the prevalences of antibiotic-resistant E. coli isolates between these groups of children, even though the consumptions of antibiotics were quite different.


The value of saline-aided ultrasound in diagnosing congenital duodenal obstruction.
The aim of the study is to assess the value of saline-aided ultrasound (US) in diagnosing congenital duodenal obstruction (CDO). The neonates with CDO were enrolled in this study, including the neonates confirmed with annular pancreas (AP) by operation, the neonates confirmed with duodenal atresia, the neonates confirmed with duodenum web, and the neonates confirmed with malrotation. Pertinent data were recorded, including the US features, intraoperative findings, and surgical procedures. The methodology of this study is a diagnostic test study which means the US feature is the test and the intraoperative finding is the gold standard. A total of 95 neonates were enrolled, including 33 neonates with AP, 6 neonates with duodenal atresia, 29 neonates with duodenum web, and 27 neonates with malrotation. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the hyperechogenic band for the detection of AP were 78.8% (26/33), 90.3% (56/62), 81.2% (26/32), 88.8% (56/63), and 86.3% (82/95), respectively. The sensitivity, specificity, NPV, and accuracy for the detection of duodenal atresia were 0% (0/6), 100% (89/89), 93.6% (89/95), and 93.6% (89/95), respectively. The sensitivity, specificity, PPV, NPV, and accuracy for the detection of duodenum web were 100% (29/29), 100% (66/66), 100% (29/29), 100% (66/66), and 100% (95/95), respectively. The sensitivity, specificity, PPV, NPV, and accuracy for the detection of malrotation were 100% (27/27), 100% (68/68), 100% (27/27), 100% (68/68), and 100% (95/95), respectively. Saline-aided US is a feasible tool to diagnose CDO.


The predictors of perforated appendicitis in the pediatric emergency department: A retrospective observational cohort study.
Appendiceal perforation has significant effects on perioperative morbidity and postoperative outcome. The present study aimed to identify possible predictive factors associated with perforated appendicitis (PA) in children at admission in the emergency department (ED). In this retrospective observational cohort study, consecutive medical records of children <18 years old with surgically and histopathologically confirmed acute appendicitis (AA) over three years (2013-2015) were analyzed. Patients were divided into two groups: PA and non-perforated appendicitis (NPA). The differences between the two groups and potential predictors of PA were explored using univariate and multivariate analyses. During the study period, 295 patients underwent an appendectomy and had confirmatory AA diagnoses. Ninety-two patients had a PA (31.2%). In the univariate analysis, male gender, vomiting, diarrhea, fever, elevated white blood cell count (WBC) levels, and high C-reactive protein (CRP) were identified as predictors of PA. In the multivariate analysis, male gender (odds ratio [OR]: 3.133; 95% confidence interval [CI]: 1.610-6.096); vomiting (OR: 2.346; 95% CI: 1.141-4.822); diarrhea (OR: 4.549; 95% CI: 1.850-11.181); fever (OR: 3.429; 95% CI: 1.765-6.663); elevated WBC (OR: 2.962; 95% CI: 1.491-5.884) and elevated CRP (OR: 3.061; 95% CI: 1.267-7.396) were variables that predicted the PA in children. Our data indicate that several clinical and biochemical parameters can reliably distinguish between pediatric PA and NPA at admission in the emergency department.


Coronary atherosclerotic burden assessed by SYNTAX scores and outcomes in surgical, percutaneous or medical strategies: a retrospective cohort study.
Coronary atherosclerotic burden and SYNTAX Score (SS) are predictors of cardiovascular events. To investigate the value of SYNTAX scores (SS, SYNTAX Score II (SSII) and residual SYNTAX Score (rSS)) for predicting cardiovascular events in patients with coronary artery disease (CAD). Retrospective cohort study. Single tertiary centre. Medicine, Angioplasty or Surgery Study database patients with stable multivessel CAD and preserved ejection fraction. Patients with CAD undergoing coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI) or medical treatment (MT) alone from January 2002 to December 2015. Primary: 5-year all-cause mortality. Secondary: composite of all-cause death, myocardial infarction, stroke and subsequent coronary revascularisation at 5 years. A total of 1719 patients underwent PCI (n=573), CABG (n=572) or MT (n=574) alone. The SS was not considered an independent predictor of 5-year mortality in the PCI (low, intermediate and high SS at 6.5%, 6.8% and 4.3%, respectively, p=0.745), CABG (low, intermediate and high SS at 5.7%, 8.0% and 12.1%, respectively, p=0.194) and MT (low, intermediate and high SS at 6.8%, 6.9% and 6.5%, respectively, p=0.993) cohorts. The SSII (low, intermediate and high SSII at 3.6% vs 7.9% vs 10.5%, respectively, p<0.001) was associated with a higher mortality risk in the overall population. Within each treatment strategy, SSII was associated with a significant 5-year mortality rate, especially in CABG patients with higher SSII (low, intermediate and high SSII at 1.8%, 9.7% and 10.0%, respectively, p=0.004) and in MT patients with high SSII (low, intermediate and high SSII at 5.0%, 4.7% and 10.8%, respectively, p=0.031). SSII demonstrated a better predictive accuracy for mortality compared with SS and rSS (c-index=0.62). Coronary atherosclerotic burden alone was not associated with significantly increased risk of all-cause mortality. The SSII better discriminates the risk of death. ISRCTN66068876.


TSH reference values for adult Brazilian population.
To establish limits of normal serum TSH for the adult (18 to 60 years) Brazilian population according to recommendations of the National Academy of Clinical Biochemistry. Healthy volunteers were evaluated and those fulfilling the following clinical criteria were selected: absence of known thyroid disease; no use of any interfering medications; no history of head and neck external radiotherapy, type 1 diabetes or autoimmune disease; no family history of thyroid disease, and absence of goiter or palpable nodules. Subjects with anti-thyroperoxidase antibodies and/or altered free T4 were excluded. The sample consisted of 960 subjects (480 males and 480 females). TSH values corresponding to the 2.5th and 97.5th percentiles of the sample were 0.43 and 3.24 mIU/L, respectively. TSH values > 2.5 mIU/L were observed in 9.15% of the volunteers and levels > 3 mIU/L in 3.11%. The present study suggests an upper limit of normal TSH of approximately 3.5 mIU/L.


Antiplasmodial and antitrypanosomal activity of new esters and ethers of 4-dialkylaminobicyclo[2.2.2]octan-2-ols.
Only three drugs are available for the treatment of East African trypanosomiasis. Patients suffer from painful application, severe side effects and increasing resistance against these drugs. Malaria tropica kills more than 2 million people every year mainly due to growing drug resistance. 4-Dialkylaminobicyclo[2.2.2]octan-2-ols and some of their esters have shown activity against both the causative organisms, Trypanosoma brucei rhodesiense and Plasmodium falciparum. Ethers and new esters with markedly higher lipophilicity were prepared in three-step procedures from acyclic synthons. The new compounds were screened for their antiprotozoal activities against T. b. rhodesiense (STIB 900) and P. falciparum K1 (resistant to chloroquine and pyrimethamine), and for their cytotoxicity with L-6 cells by means of in vitro microplate assays. The results were compared to those of the parent compounds indicating that higher lipophilicity increases the antiprotozoal activities. The pivalate 10a showed the highest antitrypanosomal activity. The 4-chlorobenzoate 9b exhibited good antiplasmodial activity and low cytotoxicity. The most active antiplasmodial agent was the benzhydryl ether 13c which was nearly as active as chloroquine against sensitive strains.


Degradation of the four monoiodoinsulin isomers by the insulin protease of rat liver.
The cleavage of insulin by the partially purified insulin protease was studied using the four [125I]tyrosine-monoiodoinsulins (tyrosine A-14 and A-19 of the A-chain; tyrosine B-16 and B-26 of the B-chain). The rates of conversion of the four isomers to trichloroacetic acid-soluble form was in the order B-26 greater than A-14 greater than A-19 greater than B-16. The following was observed in experiments which gave 19/14/5/3 percent conversion to trichloroacetic acid-soluble products: the loss of ability to bind to IM-9 lymphocytes was approx. 55% for all four isomers. About 70% of the radioactivity was in the 'insulin' peak, and about 30% was in peptides smaller than insulin as judged by gel filtration on Sephadex G-50. The descending limb of the 'insulin' peak contained significant amounts of radioactive material not binding to IM-9 lymphocytes. This material showed multiple peaks when applied to high performance liquid chromatography. Other experiments were designed to cause an almost complete degradation of the isomers. Under these conditions, the radioactivity eluted on Sephadex G-50 largely as iodotyrosine (and some small peptides) using the A-14, B-16 and B-26 isomers, whereas iodotyrosine was absent using the A-19 isomer. Thus, the insulin protease appears to first degrade insulin to multiple products with molecular sizes slightly smaller than insulin and subsequently to small peptides (e.g containing tyrosine A-19) and amino acids (e.g. tyrosine A-14, B-16 and B-26).


No SARS-CoV-2 reinfection among staff health-care workers: Prospective hospital-wide screening during the first and second waves in Paris.
Risk of reinfection with SARS-CoV-2 among health-care workers (HCWs) is unknown. We assessed the incidence rate of SARS-CoV-2 reinfection in the real-life setting of a longitudinal observational cohort of HCWs from the Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, France, during the first and second waves of COVID-19 epidemic. From March to December 2020, HCWs were subjected to molecular and serology testing of SARS-CoV-2. Reinfection was defined as a positive test result during the first wave, either by serology or PCR, followed by a positive PCR during the second wave. Evolution of COVID-19 status of HWCs was assessed by a Sankey diagram. A total of 7765 tests (4579 PCR and 3186 serology) were carried out and 4168 HCWs had at least one test result during the follow-up period with a positivity rate of 15.9%. No case of reinfection during the second wave could be observed among 102 positive HCWs of the first wave, nor among 175 HCWs found positive by PCR during the second wave who were negative during the first wave. SARS-CoV-2 reinfection was not observed among HCWs, suggesting a protective immunity against reinfection that lasts at least 8 months post infection.