Psychological interventions for adolescent psychosis: a pilot controlled trial in routine care.
Evidence for the recommendation to deliver Cognitive Behavioural Therapy (CBT) and Family Interventions (FI) to under-18s with psychosis derives from adult research, and no previous study has focused exclusively on an adolescent population. We evaluated adaptations of these therapies for adolescent inpatients with psychosis (CBTpA and FIpA), delivered as an adjunct to inpatient standard care (SC). Thirty adolescent inpatients with psychotic symptoms on admission were sequentially allocated to receive CBTpA+SC (n=10); FIpA+SC (n=10) or SC alone (n=10). Psychotic symptoms and functioning were measured at admission and discharge. Group comparisons did not reach conventional significance, but effect sizes in this pilot study showed a promising impact of CBTpA compared to SC alone, in reducing symptoms (ES: d=0.6), with smaller effect sizes for functioning (d=0.2) and for FIpA (symptoms, d=0.1 and functioning, d=0.4). There was no advantage of either additional treatment in reducing length of stay, but self-report satisfaction ratings were higher for both psychological therapies. The study is the first to focus on an exclusively adolescent population, using appropriately adapted therapy protocols. Findings suggest that the interventions are feasible, acceptable and helpful for adolescents with psychosis. Larger randomised controlled trials are now needed.


Arrhythmogenic right ventricular dysplasia: clinical results with implantable cardioverter defibrillators.
Arrhythmogenic right ventricular dysplasia is a clinical entity characterized by fatty infiltration of the right ventricle and left bundle morphology ventricular tachycardia occurring in young patients. The most common cause of death is tachyarrhythmic. Pharmacological and nonpharmacological therapies, including implantable cardioverter defibrillators, have been used to treat the arrhythmias. However, right ventricular endocardial leads in this population may be associated with an increased risk of perforation and suboptimal sensing and defibrillation efficacy due to the diseased right ventricle. We report on 12 patients with arrhythmogenic right ventricular dysplasia who were treated with implantable cardioverter defibrillators. The mean age was 31 +/- 9 years (range 15-48). Patients presented with presyncope (5), syncope (4), or cardiac arrest (3). All patients had electrocardiographic abnormalities characteristic of the condition. During programmed electrical stimulation nine patients had sustained ventricular tachycardia, while three patients had no inducible arrhythmia. Transvenous leads were placed in nine patients. In these patients pacing thresholds were significantly higher, R-wave amplitudes were significantly lower and defibrillation thresholds were not significantly different than in a cohort of patients without right ventricular dysplasia. There were no acute or chronic complications of right ventricular lead placement. Follow-up averaged 22 +/- 13 months (range 1-45). There was one sudden death at 1 month of follow-up. Of the 12 patients, 8 have had appropriate therapy delivered by the implantable defibrillator. Six patients are currently on sotalol to reduce the frequency of implantable defibrillator discharges. In conclusion, implantable cardioverter defibrillators with nonthoracotomy leads are feasible and safe in patients with arrhythmogenic right ventricular dysplasia. The frequency of appropriate therapy is high, supporting the use of implantable cardioverter defibrillators in this population.


Skin conductance at baseline and postheel lance reflects sympathetic activation in neonatal opiate withdrawal.
Skin conductance (SC) provides an objective measure of autonomic system regulation through sympathetic-mediated filling of sweat glands. This study aimed to test the utility of SC to detect sympathetic activation in neonatal abstinence syndrome (NAS). Fourteen term (mean, SE: 38.8 ± 0.35 weeks gestational age) neonates with chronic prenatal opiate exposure were enrolled. SC (peaks/seconds and mean of peaks) was measured at baseline, during heel lance/squeeze (HLS) and recovery from HLS at 24-48 (mean 38) hours of life prior to treatment for NAS. Blinded coders with established reliability assessed neonates using the Modified Finnegan Neonatal Scoring System (MFNSS). Nonparametric tests were used to determine group differences, phase differences from baseline to HLS and HLS to recovery, and associations between MFNSS and SC measures. Neonates that would later require morphine treatment for NAS (n = 6) had higher baseline SC mean of peaks than those that did not require treatment (n = 8) (p < 0.05). Moreover, there were unique phase differences between groups and SC positively correlated with MFNSS (p < 0.05). SC provides early identification of NAS severity. However, a larger sample is needed to determine sensitivity and specificity of SC for early identification of NAS and treatment effectiveness.


Effects of follicle-stimulating hormone and human chorionic gonadotropin on gonadal steroidogenesis in two siblings with a follicle-stimulating hormone beta subunit mutation.
To quantify gonadal steroid responses to different gonadotropin regimens. Transversal clinical study. Academic medical center. A 41-year-old woman and her 37-year-old brother with isolated FSH deficiency due to a homozygous Tyr76X FSH beta subunit gene (FSHB) mutation. Initially, serial LH samples were drawn overnight. After 2-day dexamethasone suppression, steroids were measured at baseline and after hCG, recombinant FSH, or hCG + recombinant FSH administration. Pulse number, peak amplitude, and mean overnight LH levels, as well as basal and stimulated FSH, LH, T, E(2), DHEAS, 17alpha-hydroxyprogesterone (17-OHP), and androstenedione (A). The mean +/-SD overnight LH was 49.2 +/- 5.7 mIU/mL and 9.1 +/- 2.9 mIU/mL; there were 8 pulses/8 hours and 9 pulses/9 hours, with mean amplitudes of 53.4 +/- 6.5 mIU/mL and 11.7 +/- 1.9 mIU/mL, for the woman and man, respectively. There was no steroid response to recombinant FSH, hCG, or hCG + recombinant FSH in the woman. In the man, T increased after hCG, recombinant FSH, and hCG + recombinant FSH, whereas E(2), A, and 17-OHP increased only after hCG + recombinant FSH. This report constitutes the first detailed endocrine study of a man with isolated FSH deficiency due to an FSHB mutation and suggests that FSH may have a positive regulatory effect on healthy LH-stimulated Leydig cells, probably mediated by its primary action on Sertoli cells, in a paracrine mechanism.


The MHC gamma block matching: Impact on unrelated hematopoietic stem cell transplantation outcome.
Matching for HLA-A, -B, -C, -DRB1, -DQB1 alleles is the gold standard in hematopoietic stem cell transplantation (HSCT). However, this is often not enough to prevent postransplantational complications. The HLA mismatches (MM) have been associated with higher risk of acute graft versus host disease (GvHD). Gamma block (GB) is located in central HLA region, between HLA-B/C and HLA-DRB/DQB blocks and contains many inflammatory and immune regulatory genes. Single nucleotide polymorphisms (SNPs) within that block can be considered as markers for MHC haplotype matching. Aim of the research was to test whether MM in GB impact the outcome of HSCT in 51 patients transplanted with HLA 10/10 matched unrelated donor. The recipient-donor pairs were typed using PCR SSP kit that detects 25 SNPs within GB. Fifteen out of 51 (29.41%) pairs were GT matched (GT-M) while 36 out of 51 pairs (70.59%) were mismatched (GT-MM). In a univariate analysis, GT-MM was a significant risk factor associated with aGvHD (P = 0.041), although this association was not seen in multivariate analysis. No significant difference in overall survival and relapse occurrence was seen. These results were obtained on a small sample, and it is necessary to further test the possible role of GT matching in unrelated HSCT.


Constructing defective-functionalized g-C3N4 homojunction for efficient photocatalytic detoxification of lemon yellow in an aqueous solution and beverage.
The content of food colorant in food and environment should be limited to a safe range. Thus, cost-effective, and environmental-friendly detoxification technology is urgent for food safety and environmental protection. In this work, defective-functionalized g-C3N4 was successfully fabricated via intermediate engineering strategy. The prepared g-C3N4 possesses large specific surface area with abundant in-plane pores. Carbon vacancy and N-CO unit are introduced into g-C3N4 molecular framework, endowing the different degrees of n-type conductivity in varied domains. And then the n-n homojunction is generated. This homojunction structure is demonstrated to be efficient in separation and transfer of photoinduced charge carriers, and causes enhanced photocatalytic detoxification of lemon yellow under visible light. Furthermore, as-prepared g-C3N4 in lemon tea enable completely removed lemon yellow without obvious effect on its overall acceptability. The findings deepen the understanding on the defect-induced self-functionality of g-C3N4, and prove the application potential of photocatalytic technology in contaminated beverages.


Central venous catheter sepsis in surgical newborns.
We examined central venous catheter (CVC) sepsis in newborn surgical patients, as this group appeared to have a higher incidence of this complication. During a 3-year period 79 patients on the surgical service required a tunneled, cuffed, Broviac CVC. Nineteen patients (24% or 9.9 episodes per 1000 catheter days) had proven sepsis and 8 (10% or 1.9/1000 catheter days) had suspected sepsis. An intestinal stoma was definitely related to CVC sepsis ( p<0.001). Other risk factors included lower gestational age, more operations, and younger age at first stoma. Temperature, white blood cell (WBC) count, and platelet count did not correlate with CVC sepsis. We found no better indicator of CVC sepsis than the presentation of an ill child. Certainly temperature, WBC, and platelet count are not reliable indicators. Surgeons have little control over the factors that were found to be related to CVC sepsis. It would appear reasonable from these results to maintain a high index of suspicion in the high-risk groups, to use peripherally inserted central catheters (PIC lines) as the first line of long-term vascular access, and to bring CVCs out of a nonabdominal site, perhaps the scalp, in patients with stomas.


Beneficial effects of splenectomy on liver regeneration in a rat model of massive hepatectomy.
Small-for-size syndrome is a widely recognized clinical complication after living donor liver transplantation or extended hepatectomy due to inadequate liver mass. The purpose of this study was to investigate the role of splenectomy in rats after massive hepatectomy, a surrogate model of small-for-size graft. Rats were divided into eight groups, each with 20 animals: 50% hepatectomy (50% Hx), 50% hepatectomy+splenectomy (50% Hx+Sp), 60% Hx, 60% Hx+Sp, 70% Hx, 70% Hx+Sp, 90% Hx and 90% Hx+Sp. The following parameters were evaluated: liver function tests (ALT, AST and TBIL), liver regeneration ratio, DNA synthesis, proliferation cell nuclear antigen, hepatic oxygen delivery (HDO2) and hepatic oxygen consumption (HVO2). The liver regeneration ratio was enhanced in the Hx+Sp groups (P<0.05). In addition, compared with the Hx groups, the Hx+Sp groups had better liver functions (P<0.05). DNA synthesis and proliferation cell nuclear antigen were also increased in the Hx+Sp groups compared with the Hx groups (P<0.05). Furthermore, in the Hx+Sp groups, HDO2 and HVO2 were increased over those in the Hx groups (P<0.05), and were positively correlated with the liver regeneration ratio. Splenectomy significantly improved liver function, and enhanced DNA synthesis and proliferation cell nuclear antigen after massive hepatectomy in rats. This operation could be mediated through increased HDO2 and HVO2, which facilitate liver regeneration.


Clinical features, treatment outcomes and mortality risk of tuberculosis sepsis in HIV-negative patients: a systematic review and meta-analysis of case reports.
Tuberculosis sepsis (TBS) is sepsis due to the Mycobacterium species causing tuberculosis (TB). It seems to be rare in HIV-negative patients and mainly individual case reports have been reported. This systematic review summarizes the epidemiology, clinical features, and treatment outcomes of TBS in HIV-negative patients. An electronic search of PubMed, Embase, Web of Science, and Google Scholar was performed to identify published case reports of TBS between January 1991 and September 2022. Twenty-five articles reported 28 cases of TBS in HIV-negative patients, among which 54% (15/28) were women; with 50% (14/28) of patients not having reported predisposing factors. A total of 64% (18/28) of patients died, and the diagnosis was obtained for many of them only post-mortem. Two of the reports mentioned the BCG vaccination status. A higher proportion of deaths occurred in patients with delayed diagnosis of sepsis. The probability of survival of patients diagnosed with tuberculosis sepsis was 68% on day 10; 41% on day 20; and 33% on day 30 after admission. Our review showed TBS occurred in HIV-negative patients and some of them have no known immunocompromised underlying co-morbidity. TBS might not be rare as clinicians thought but might be prone to be missed. In endemic settings, M. tuberculosis etiology of sepsis should be accounted for early, irrespective of HIV infection status.


Combination of 5 Hz repetitive transcranial magnetic stimulation (rTMS) and tactile coactivation boosts tactile discrimination in humans.
A combination of 5 Hz repetitive transcranial magnetic stimulation (rTMS) over the left primary somatosensory cortex together with tactile coactivation applied to the right index-finger representation (coac + rTMS) boosted tactile discrimination ability tested on the right index-finger. Applying coactivation alone caused a 0.25 mm lowering in tactile discrimination thresholds. In contrast, after coac + rTMS we found a significant further improvement of discrimination thresholds in comparison to the coactivation-induced perceptual changes alone. We demonstrate that the individual further improvement after coac + rTMS depended on the effectiveness of the coactivation protocol when applied alone. Subjects, who showed little gain in tactile performance after coactivation alone, showed the largest improvement after coac + rTMS implying that the combined application was selective for poor learners. The selective effects of coac + rTMS are discussed in respect to N-methyl-D-aspartate receptor activation.


[The alkaline phosphatase activity of the blood serum as a factor reflecting the chronic inflammatory process in the skin in generalized forms of psoriasis, neurodermatitis, eczema and trophic ulcers].
Blood serum alkaline phosphatase (AP) level was found elevated in the patients suffering from eczema, neurodermatitis, eczema with large skin sites involved, and in those with trophic ulcers of various origins, as against normal subjects and reference patients with sarcoidosis and Kaposi's sarcoma. Elevated level of the enzyme activity is directly related to exacerbation stage and size of the skin site involved; this level reduced after therapy and this reduction was associated with clinical improvement. No concomitant visceral abnormalities (calculous cholecystitis, liver cirrhosis, or malignant tumors) were detected in the examinees, that might influence the blood serum AP activity.


Brain functional alterations in patients with anorexia nervosa: A meta-analysis of task-based functional MRI studies.
The goal of this study was to discern the neural activation patterns associated with anorexia nervosa (AN) in response to tasks related to body-, food-, emotional-, cognitive-, and reward- processing. A meta-analysis was performed on task-based fMRI studies, revealing that patients with AN showed increased activity in the left superior temporal gyrus and bilaterally in the ACC during a reward-related task. During cognitive-related tasks, patients with AN also showed increased activity in the left superior parietal gyrus, right middle temporal gyrus, but decreased activity in the MCC. Additionally, patients with AN showed increased activity bilaterally in the cerebellum, MCC, and decreased activity bilaterally in the bilateral precuneus/PCC, right middle temporal gyrus, left ACC when they viewed food images. During emotion-related tasks, patients with AN showed increased activity in the left cerebellum, but decreased activity bilaterally in the striatum, right mPFC, and right superior parietal gyrus. Patients with AN also showed increased activity in the right striatum and decreased activity in the right inferior temporal gyrus and bilaterally in the mPFC during body-related tasks. The present meta-analysis provides a comprehensive overview of the patterns of brain activity evoked by task stimuli, thereby augmenting the current comprehension of the pathophysiology in AN.


A multidisciplinary approach to breast biopsy.
The explosion in technological advances has provided physicians and patients more options in the diagnostic breast biopsy arena. Successful collaborative relationships between nurses, physicians, and all health care workers and detailed patient education are essential to provide optimum patient care. Survival in health care today mandates that perioperative nurses and their colleagues move outside traditional environments to provide quality, cost-effective care to patients and their family members. The aim of this collaborative approach to breast biopsy is to provide patients with the most expedient, accurate, cost-effective diagnoses with the least amount of physical and psychological trauma.


Hidden Markov model segmentation to demarcate trajectories of residual apnoea-hypopnoea index in CPAP-treated sleep apnoea patients to personalize follow-up and prevent treatment failure.
Continuous positive airway pressure (CPAP), the reference treatment for obstructive sleep apnoea (OSA), is used by millions of individuals worldwide with remote telemonitoring providing daily information on CPAP usage and efficacy, a currently underused resource. Here, we aimed to implement data science methods to provide tools for personalizing follow-up and preventing treatment failure. We analysed telemonitoring data from adults prescribed CPAP treatment. Our primary objective was to use Hidden Markov models (HMMs) to identify the underlying state of treatment efficacy and enable early detection of deterioration. Secondary goals were to identify clusters of rAHI trajectories which need distinct therapeutic strategies. From telemonitoring records of 2860 CPAP-treated patients (age: 66.31 ± 12.92 years, 69.9% male), HMM estimated three states differing in variability within a given state and probability of shifting from one state to another. The daily inferred state informs on the need for a personalized action, while the sequence of states is a predictive indicator of treatment failure. Six clusters of rAHI trajectories were identified ranging from well-controlled patients (cluster 0: 669 (23%); mean rAHI 0.58 ± 0.59 events/h) to the most unstable (cluster 5: 470 (16%); mean rAHI 9.62 ± 5.62 events/h). CPAP adherence was 30 min higher in cluster 0 compared to clusters 4 and 5 (P value < 0.01). This new approach based on HMM might constitute the backbone for deployment of patient-centred CPAP management improving the personalized interpretation of telemonitoring data, identifying individuals for targeted therapy and preventing treatment failure or abandonment. The online version contains supplementary material available at 10.1007/s13167-021-00264-z.


[Test tube technique for field diagnosis of hemoglobin S (author's transl)].
Laboratory diagnosis of sickle-cell anemia requires expensive equipment often too sophisticated for rural dispensaries. Therefore haemoglobin precipitation in solutions of neutral salts appears to be a specific and reliable test, as valid as Emmel test, and easily performed during mass campaigns or within the technical and financial limitation of rural medicine.


Screening, cloning and overexpression of Aspergillus niger phytase (phyA) in Pichia pastoris with favourable characteristics.
Using gene cloning and overexpression to obtain a potential industrial phytase as a feed additive to upgrade the nutritional quality of phytate-rich seed-based animal feed. A phyA gene from a high extracellular phytase-producing Aspergillus niger sp. was cloned and overexpressed in Pichia pastoris GS115 using the secretive expression vector pPICZalphaA. After cultivation for 4 days in buffered methanol complex medium (BMMY) containing methanol for induction, catalytically active phytase was secreted as a predominantly extracellular protein. The activity of the expressed phytase in fermented broth was 30 000-fold higher than that of native phytase with a specific activity of 503 U mg(-1). The Lineweaver-Burk plot indicated K(m) values of 0.196 mmol l(-1) for sodium phytate and 18.16 mmol l(-1) for p-nitrophenylphosphate (pNPP). Thermostability studies showed that recombinant phytase retained 70% activity after exposure to 90 degrees C for 5 min and 65% activity after 30 min, much higher than for commercial phytase. The higher activity and high thermostability of recombinant phytase enable it to withstand the temperatures of the feed pelleting process. The characteristics of this recombinant phytase, especially the good thermostability, are likely to render it of potential industrial importance.


Pharmacological studies of proctolin receptors on foregut and hindgut of Blaberus craniifer.
Proctolin (Arg-Tyr-Leu-Pro-Thr) and proctolin analogs modified at position 1, 2, or 5 caused dose dependent contractions of Blaberus fore- and hindgut. The varying contractile effects between both tissues revealed the possible presence of receptor subtypes as identified by [GABA1]-proctolin. A single population of binding sites (Kd approximately 100 nM) was deduced from Scatchard analysis. In addition, nanomolar concentrations of proctolin induced a dose-dependent hydrolysis of phosphoinositides (PIns) augmented by GTPgammaS (1 microM) on foregut membranes but no accumulation of cAMP. Proctolin induced contractions are likely mediated via a phospholipase C linked to a heptahelical receptor bound to heterotrimeric G-proteins.


Cumulative dose response study comparing HFA-134a albuterol sulfate and conventional CFC albuterol in patients with asthma.
As a result of the pending ban on chlorofluorocarbon production, the non-chlorofluorocarbon propellant 1,1,1,2-tetrafluoroethane (HFA-134a) is being evaluated as a replacement for CFCs in metered-dose inhalers. This cumulative dose response study compared the safety and bronchodilator efficacy of 16 cumulative inhalations of albuterol sulfate in an HFA-134a, CFC-free propellant system (108 microg of albuterol sulfate, equivalent to 90 microg of albuterol base) with that of equivalent doses of albuterol in a conventional CFC propellant system. Twenty-two patients with at least a 12-month history of stable asthma, who were currently taken an inhaled beta-adrenergic bronchodilator, and who had a FEV1 between 40% and 80% of predicted, were enrolled in this randomized, modified-blind, two-period crossover study. One, 1, 2, 4, and 8 inhalations of study drug were self-administered at 30-minute intervals, resulting in 16 cumulative inhalations. Pulmonary function and safety measures were assessed after each dosing interval. A significant dose response was found for HFA-134a albuterol sulfate and CFC albuterol with regard to changes in FEV1, serum potassium, heart rate, and blood pressure after 16 cumulative inhalations. No significant differences were demonstrated between HFA-134a albuterol sulfate and CFC albuterol for any FEV1 or safety parameter at any cumulative dose level. No clinically meaningful laboratory or physical examination abnormalities were found with administration of either HFA-134a albuterol sulfate or CFC albuterol. HFA-134a albuterol sulfate provides bronchodilation comparable to CFC albuterol and has a similar safety profile.


The Uterine Environment and Childhood Obesity Risk: Mechanisms and Predictions.
Childhood obesity is a growing health problem in many populations, hence the urgent need to unravel the underlying mechanisms. Some evidence suggests that exposure to suboptimal intrauterine environments can program foetal metabolic health, with adverse consequences in later life, including susceptibility to childhood obesity. Factors such as high and low foetal birth weight, excessive gestational-weight-gain, maternal stress and smoking are all associated with increased risk of childhood obesity in observational studies. Animal models, where both genetic background and the postnatal environment can be carefully controlled, suggest that several different mechanisms, including epigenetic changes, dysregulation of adipose tissue development and programming of appetite, may be key drivers of developmental programming of childhood obesity. However, the influence of genetics and the post-natal environment are much more difficult to disentangle as independent effects in human studies, which are also complicated by low follow-up rates. Suboptimal intrauterine environments interact with maternal and foetal genetics and with the postnatal environment to contribute to the risk of childhood obesity. Maternal metabolic challenges, for example obesity and insulin resistance, contribute to the risk of foetal overgrowth and subsequent adiposity in childhood. To protect the long-term health of populations, research focusing on effective means of identifying and intervening in the transgenerational cycle of childhood obesity is required.


Protective roles of mitochondrial manganese-containing superoxide dismutase against various stresses in Candida albicans.
Candida albicans contains copper- and zinc-containing superoxide dismutase but also two manganese-containing superoxide dismutases (MnSODs), one in the cytosol and the other in the mitochondria. Among these, the SOD2 gene encoding mitochondrial MnSOD was disrupted and overexpressed to investigate its roles in C. albicans. The null mutant lacking mitochondrial MnSOD was more sensitive than wild-type cells to various stresses, such as redox-cycling agents, heating, ethanol, high concentration of sodium or potassium and 99.9% O2. Interestingly, the sod2/sod2 mutant was rather more resistant to lithium and diamide than the wild-type, whereas overexpression of SOD2 increased susceptibility of C. albicans to these compounds. The inverse effect of mitochondrial MnSOD on lithium toxicity was relieved when the sod2/sod2 and SOD2-overexpressing cells were grown on the synthetic dextrose medium containing sulphur compounds such as methionine, cysteine, glutathione or sulphite, indicating that mitochondrial MnSOD may affect lithium toxicity through sulphur metabolism. Moreover, disruption or overexpression of SOD2 increased or decreased glutathione reductase activity and cyanide-resistant respiration by alternative oxidase, respectively. Taken together, these findings suggest that mitochondrial MnSOD is important for stress responses, lithium toxicity and cyanide-resistant respiration of C. albicans.


Microbial changes in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients.
The aim of this prospective, two center study was to investigate the dynamics of the microbial changes in relation to the development of ulcerative oral mucositis in autologous SCT (autoSCT) recipients. Fifty-one patients were diagnosed with multiple myeloma and treated with high-dose melphalan followed by autoSCT. They were evaluated before, three times weekly during hospitalization, and three months after autoSCT. At each time point an oral rinse was collected and the presence or absence of ulcerative oral mucositis (UOM) was scored (WHO scale). Oral microbiome was determined by using 16S rRNA amplicon sequencing and fungal load by qPCR. Twenty patients (39%) developed UOM. The oral microbiome changed significantly after autoSCT and returned to pre-autoSCT composition after three months. However, changes in microbial diversity and similarity were more pronounced and rapid in patients who developed UOM compared to patients who did not. Already before autoSCT, different taxa discriminated between the 2 groups, suggesting microbially-driven risk factors. Samples with high fungal load (>0.1%) had a significantly different microbial profile from samples without fungi. In conclusion, autoSCT induced significant and reversible changes in the oral microbiome, while patients who did not develop ulcerative oral mucositis had a more resilient microbial ecosystem.


Anti-inflammatory ligustilides from Ligusticum chuanxiong Hort.
Four new ligustilides chuanxiongnolide R1 (1), chuanxiongnolide R2 (2), chuanxiongdiolide R1 (3) and chuanxiongdiolide R2 (4) together with eight known derivatives (5-12) were isolated from the root of Ligusticum chuanxiong Hort. Their structures were elucidated by HR-ESI-MS, UV, IR, 1D and 2D NMR (HSQC, HMBC, (1)H-(1)H COSY, NOESY) methods. The absolute configurations were confirmed via the circular dichroism (CD) spectrum. The anti-inflammatory assay in LPS-triggered RAW 264.7 macrophages was carried out on the twelve compounds. 1, 3, 5 and 6 showed significant inhibitory effects against LPS-induced NO production.


ACT001 Ameliorates ionizing radiation-induced lung injury by inhibiting NLRP3 inflammasome pathway.
Radiotherapy is a prevalent treatment modality for thoracic tumors; however, it can lead to radiation-induced lung injury (RILI), which currently lacks effective interventions. ACT001, a prodrug of micheliolide, has demonstrated promising clinical application potential, yet its impact on RILI requires further validation. This study aims to investigate the radioprotective effects of ACT001 on RILI and elucidate its underlying mechanism. Sprague-Dawley rats were utilized to induce RILI following 20 Gy X-ray chest irradiation, and lung tissue inflammation and fibrosis were assessed using hematoxylin and eosin (H&E) and Masson staining. Lung injury, inflammation, and oxidative stress markers were evaluated employing commercial kits. Pyroptosis-related differentially expressed genes (DEGs) were analyzed using a microarray dataset from the Gene Expression Omnibus (GEO) database, and their functions and hub genes were identified through protein-protein interaction networks. Pyroptosis-related genes were detected via RT-qPCR, western blotting, immunofluorescence, and immunohistochemistry. The results demonstrated that ACT001 ameliorated RILI, diminished pro-inflammatory cytokine release and fibrosis, and mitigated the activation of the NLRP3 inflammasome while inhibiting pyroptosis in lung tissue. In conclusion, our study reveals that ACT001 can suppress NLRP3 inflammasome-mediated pyroptosis and improve RILI, suggesting its potential as a novel protective agent for RILI.


Common mutations in Cuban cystic fibrosis patients.
So far, more than 1500 mutations have been reported in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Mutational spectrum varies in accordance with geographic and/or ethnic origin. In this study, we have analyzed seven common CF mutations (p.F508del, p.G542X, p.R1162X, p.N1303K, p.R334W, p.R553X and c.3120+1G>A) taking into account the ethnic origin of the Cuban population which is mainly influenced by Spanish and sub-Sahara African contribution. All but p.N1303K have been detected in our patients, the p.F508del being the most prevalent (37.9%). Overall, six mutations showed frequencies above 1% accounting for 55.5% of the Cuban CF alleles.


Evaluation of liver lesions.
The differential diagnosis of a liver mass is large and requires understanding of the clinical and imaging features of liver lesions. A detailed history, physical examination, hepatic biochemical tests, and imaging studies are all essential in making the diagnosis. Decisions regarding specific imaging modalities for diagnoses, the use of liver biopsy, therapeutic options, and appropriate follow-up are all determined by the presentation of the lesion and associated patient characteristics.


Developmental capacity of in vitro-matured human oocytes retrieved from polycystic ovary syndrome ovaries containing no follicles larger than 6 mm.
To test the developmental competence of oocytes in a nonhCG-triggered in vitro maturation (IVM) system when oocyte-cumulus complexes (OCC) are retrieved from antral follicles with a diameter of <6 mm. Prospective cohort study. Tertiary university-based referral center. From January 2010 to September 2011, 121 patients with polycystic ovaries/polycystic ovary syndrome underwent 239 IVM cycles in total. In 58 of these cycles (44 patients), all antral follicles had a diameter of <6 mm on the day of oocyte retrieval. NonhCG-triggered IVM of oocytes, fresh or vitrified/warmed embryo transfer (ET). Oocyte diameter, maturation rate, fertilization rate, embryo development and morphology, implantation rate, clinical pregnancy rate, ongoing pregnancy rate. Oocyte retrieval yielded 16.7 OCC/cycle, and 50.8% of oocytes completed IVM. The mean oocyte diameter increased from 108.8 ± 4.3 μm to 111.9 ± 4.1 μm after IVM. Mean fertilization rate was 63.7%, and 45.4% of 2-pronuclei oocytes developed into a morphologically good-quality embryo on day 3 after intracytoplasmic sperm injection. Fresh ET resulted in two ongoing pregnancies (2/37; 5.4%). Deferred vitrified-warmed ET led to an ongoing pregnancy rate of 34.6% (9/24). Three healthy babies were born and eight pregnancies were still ongoing. Oocytes retrieved from follicles with a diameter of <6 mm grow during a 40-hour IVM culture can acquire full competence in vitro, as illustrated by their development into healthy offspring. Endometrial quality appears to be a crucial determinant of pregnancy after nonhCG-triggered IVM.


Identification and quantification of tamoxifen and four metabolites in serum by liquid chromatography-tandem mass spectrometry.
We have developed a method for the determination of tamoxifen (tam) and its metabolites 4-hydroxytamoxifen (4OHtam), N-demethyltamoxifen (NDtam), N-dedimethyltamoxifen (NDDtam), tamoxifen-N-oxide (tamNox), and 4-hydroxy-N-demethyltamoxifen (4OHNDtam) in 50 microl human serum. Serum proteins were precipitated with acetonitrile. Deuterated-tamoxifen (D5 tam) was added as internal standard. Sample supernatant was injected into an on-line reversed-phase extraction column coupled with a C18 analytical column and analytes were detected by tandem mass spectrometry. The lower limits of quantification were 0.25 ng/mL for 4OHtam, NDtam and tam, 1.0 ng/mL for NDDtam and tamNox. Ranges of within- and between-day variation were 2.9-15.4% and 4.4-12.9%, respectively.


Identification of key genes associated with overwintering in Anoplophora glabripennis larva using gene co-expression network analysis.
Anoplophora glabripennis (Coleoptera: Cerambycidae) is a major quarantine pest in forestry. It is widely distributed throughout many regions such as Asia, Europe, and North America, and has enormous destructive potential for forests. The larvae of A. glabripennis overwinter in a dormant state with strong cold tolerance, and whether the larvae survive winter determines the population density in the following year. However, the molecular mechanisms of this process are not clear. RNA sequencing (RNA-Seq) analysis of A. glabripennis larvae at five overwintering stages identified 6876 differentially expressed genes (DEGs). Among these, 46 functional genes that might respond to low temperature were identified. Weighted gene co-expression network analysis revealed that the MEturquoise module was correlated with the overwintering process. The STPK, PP2A, DGAT, and HSF genes were identified as hub genes using visualization of gene network. In addition, four genes related to sugar transport, gluconeogenesis and glycosylation were screened, which may be involved in the metabolic regulation of overwintering larvae. The protein-protein interaction network indicated that ribosomal protein and ATP synthase may play an important role in connecting with other proteins. The expression levels of fifteen hub genes were further validated by quantitative RT-PCR, and the results were consistent with RNA-Seq. This study demonstrates key genes that may reveal the molecular mechanism of overwintering in A. glabripennis larvae. The genes may be the potential targets to prevent larvae from surviving the cold winter by developing new biological agents using genetic engineering.


Sf9 Cells Metabolism and Viability When Coinfected with Two Monocistronic Baculoviruses to Produce Rabies Virus-like Particles.
This work aimed to describe the dynamics of the Sf9 insect cells death and primary metabolism when this host is infected simultaneously by two recombinant baculoviruses (BV) expressing rabies glycoprotein (BVG) and matrix protein (BVM) genes to produce rabies virus-like particles (VLP) at different multiplicities of infection (MOI). Schott flasks essays covering a wide range of MOI for both BV were performed. Viable cell density, cell viability, glucose, glutamine, glutamate, lactate, ammonium, and rabies proteins concentrations were monitored over the infection phase. The expression of both recombinant proteins was not limited by glucose, glutamine, and glutamate in a broad MOI (pfu/cell) range of BVG (0.15-12.5) and BVM (0.1-5.0) using SF900 III serum free culture medium. Death phase initiation and the specific death rate depend on BV MOI. The wave pattern of nutrient/metabolite profiles throughout the viral infection phase is related to the baculovirus lytic cycle. The optimal MOIs ratio between BVG (2.5-4.5) and BVM (1.0-3.0) for maximum protein expression was defined. The produced rabies VLP sizes are close to 78 nm. In general, these work outputs bring a better understanding of the metabolic performance of Sf9 cells when infected by BV for producing VLP, and specifically, for progressing in a rabies VLP vaccine development.


Decreased emotion recognition and reduced focus on facial hallmarks in behavioral variant frontotemporal dementia compared to primary psychiatric disorders and controls.
Early diagnosis of behavioral variant frontotemporal dementia (bvFTD) is challenging due to symptomatic overlap with primary psychiatric disorders (PPD). As emotion recognition deficits are early and key features of bvFTD, the aim was to explore processes driving social cognition deficits that may aid in the differentiation between bvFTD and PPD. The total sample (N = 51) included 18 patients with bvFTD, 11 patients with PPD (mood, autism spectrum and psychotic disorders) and 22 controls from the Alzheimer Center Amsterdam of the Amsterdam UMC. Emotion recognition was assessed with the Ekman 60 Faces test, during which eye tracking metrics were collected in the first 5 s a face was presented. Group differences in dwell time on the total image as well as the circumscribed eyes area and mouth area were analysed using ANOVA, with post hoc comparisons. Patients with bvFTD scored lowest, patients with PPD scored intermediate and controls scored highest on emotion recognition. During facial processing, patients with bvFTD spent less dwell time on the total image than controls (mean difference 11.3%, F(2, 48) = 6.095, p = 0.004; bvFTD-controls p = 0.001, 95% confidence interval [CI] -892.64, -239.70). Dwell time on the eyes area did not differ between diagnostic groups, whilst patients with bvFTD spent less dwell time on the mouth area than PPD patients (mean difference 10.7%; F(2, 48) = 3.423, p = 0.041; bvFTD-PPD p = 0.022, 95% CI -986.38, -79.47) and controls (mean difference 7.8%; bvFTD-controls p = 0.043, 95% CI -765.91, -12.76). In bvFTD, decreased emotion recognition may be related to reduced focus on facial hallmarks. These findings suggest a valuable role for biometrics in social cognition assessment and the differentiation between bvFTD and PPD.


The hph-1 mouse: a model for dominantly inherited GTP-cyclohydrolase deficiency.
Dominantly inherited guanosine triphosphate (GTP)-cyclohydrolase deficiency, otherwise known as Segawa's disease or dopa-responsive dystonia, has a wide spectrum of phenotypic expression ranging from asymptomatic to very severe. Penetrance is more frequent in women as compared with men, and there is a variable occurrence of diurnal variation in symptom intensity. Biochemical characterization of the disease has demonstrated lower cerebrospinal fluid levels of tetrahydrobiopterin (BH4), neopterin, and homovanillic acid and low levels of tyrosine hydroxylase protein in the striatum. To investigate the pathophysiology, we have begun to characterize biogenic amine and BH4 metabolism in the GTP cyclohydrolase deficient hph-1 mouse. The data show low brain levels of BH4, catecholamines, serotonin, and their metabolites together with low levels of tyrosine hydroxylase protein within the striatum. The hph-1 mouse therefore provides a good model system in which to study the human disease.


Transcription start site and induction kinetics of the araC regulatory gene in Escherichia coli K-12.
The in vivo transcription start site of the araC message was determined by S1 nuclease mapping of hybrids formed between labeled DNA, and RNA extracted from cells grown under a variety of physiological conditions, including the interval of transient derepression following arabinose addition. Under all conditions tested, transcription initiated from the same nucleotide position at -148.


Autologous peripheral blood stem cell transplantation in acute myeloblastic leukaemia and myelodysplastic syndrome patients: evaluation of tumour cell contamination of leukaphereses by cytogenetic and molecular methods.
We evaluated 18 acute myeloblastic leukaemia (AML) and myelodysplastic syndrome (MDS) patients with abnormal karyotype at diagnosis who underwent peripheral blood stem cell (PBSC) transplantation. To evaluate the presence of residual tumour cells, bone marrow (BM) samples and PBSC collections were analysed by cytogenetics and in selected cases also by fluorescence in situ hybridisation (FISH) and molecular studies. All patients were considered to be in morphologic and cytogenetic complete remission (CR) at the time of mobilisation. Seven patients showed neoplastic cells in PBSC harvest and/or BM specimen before reinfusion. Cytogenetic studies revealed contamination in apheretic collections in one patient only, while three patients had BM but not PBSC contamination. Three more patients had leukaemic cells both in the BM and PBSC. All but one (with only BM contamination) of these patients relapsed within 9 months. However, five more patients relapsed after transplantation: in four cases there was no cytogenetic sign of contamination either in PBSC or BM cells and in one case no molecular evidence was revealed either. This study suggests that, whereas the presence of leukaemic cells in autologous grafts correlates with a poor prognosis, the lack of detection of tumour cells is not always predictive of long-term disease-free survival. More importantly, PBSC collections from AML patients are not contaminated by leukaemic cells if the BM is disease-free.


A murine sarcoma virus-associated protein kinase: interaction with actin and microtubular protein.
A low molecular weight (LMW) protein phosphokinase enzyme that binds to actin has been isolated from murine sarcoma virions; this kinase activity is not present in nontransforming murine leukemia viruses. Sephadex G-75 gel filtration and affinity chromatography on actin-Sepharose conjugates allow a significant level of purification of this enzyme. The enzyme associates with microtubular proteins and inhibits the in vitro polymerization of microtubules. This study represents the first isolation of a sarcoma virus-associated protein that possesses the ability to interact directly with two major components of the cytoskeletal system.


Effect of early rehabilitation on activities of daily living in patients with aspiration pneumonia.
To assess the effect of early rehabilitation on improving activities of daily living (ADL) in elderly patients with aspiration pneumonia. Using the Japanese Diagnosis Procedure Combination inpatient database, we retrospectively analyzed consecutive patients with aspiration pneumonia at admission who received early rehabilitation (n = 48 201) or did not receive any rehabilitation (n = 64 357) from July 2010 to March 2013. Early rehabilitation was defined as any type of physical rehabilitation initiated within 7 days after admission. The proportions of improved ADL scores from admission to discharge were compared between the early rehabilitation group and the non-rehabilitation group using a multivariable logistic regression analysis and instrumental variable analysis. The proportion of improved ADL scores was higher in the early rehabilitation group than in the non-rehabilitation group (25.4% vs 33.9%; P < 0.001). The multivariable logistic regression analysis showed that the early rehabilitation group exhibited significant improvement in ADL (odds ratio 1.57; 95% confidence interval 1.50-1.64; P < 0.001). The instrumental variable analysis showed that early rehabilitation was associated with increased proportion of improved ADL (risk difference 8.2%; 95% confidence interval 6.9-9.5%; P < 0.001). The present results suggest that early rehabilitation might improve ADL during hospitalization in patients with aspiration pneumonia. Geriatr Gerontol Int 2016; 16: 1181-1187.


From the ranks of mammary progesterone mediators, RANKL takes the spotlight.
Whether during the diestrus phase of the estrous cycle or with pregnancy onset, the mitogenic effects of progesterone are well-established in the murine mammary epithelium. Importantly, progesterone-induced mitogenicity is critical for mammary tumor promotion, providing one explanation for the increase in breast cancer-risk observed with prolonged progestin-based hormone therapy. At the cellular level, progesterone projects its mitogenic influence through an evolutionary conserved paracrine mechanism of action. In this regard, recent studies provide compelling support for receptor activator of NF-kB ligand (RANKL) as a key paracrine mediator of the progesterone mitogenic signal. Induction of RANKL is sufficient to elicit mammary ductal side-branching and alveologenesis, the very morphogenetic responses elicited by progesterone during pregnancy and at diestrus. Significantly, the proliferative and pro-survival signals triggered by RANKL are also required for progestin-promotion of mammary tumorigenesis, underscoring a dual role for RANKL in progesterone-dependent mammary morphogenesis and tumorigenesis. Recently, RANKL has been shown to be critical for progesterone-induced expansion of the mammary stem cell population (and its lineal descendents), thereby advancing our conceptual understanding not only of RANKL's involvement in normal mammary morphogenesis but also in breast cancer risk associated with sustained hormone exposure. Finally, these studies together suggest that chemotherapeutic intervention of RANKL signaling represents a feasible approach for the effective prevention and/or treatment of hormone-responsive breast cancers.


A longitudinal study of cognition change during early menopausal transition in a rural community.
To characterize changes in cognition that occur during the hormonal transitions of menopause. We conducted a longitudinal population-based study in Kinmen, Taiwan, recruiting all women age 40-54 years who were premenopausal and without a history of hormone replacement therapy (HRT) or hysterectomy. The cognitive measures used to assess function included the Auditory-Verbal Learning Test, visual memory, verbal fluency, Trail Making Test and digit span. A total of 694 eligible women participated in the baseline study, and 573 women (83%) completed follow-up 18 months later. After excluding 78 women who received hysterectomy or HRT, the final sample was composed of 495 subjects, of whom 114 (23%) progressed to perimenopause during follow-up. Women who remained premenopausal were younger than those who became perimenopausal (44.7 +/- 2.3 years versus 47.1 +/- 3.0 years, p < 0.01). All follow-up cognitive scores in women who entered perimenopause were slightly better than baseline measures except for Rey Auditory-Verbal Learning Test, which decreased by 0.23 (S.D. = 2.9, p = 0.3). At follow-up, cognitive function except for verbal fluency did not differ significantly between women who stayed premenopausal and those became perimenopausal after controlling for age, education, and baseline cognitive scores. Women who entered perimenopause have an average of 1.3 items (S.D. = 0.4) less in verbal fluency measures as compared with their premenopausal peers at the follow-up period. The menopausal transition might not accompany significant cognitive decline except for verbal fluency.


Transforming growth factor-beta1 protects against pulmonary artery endothelial cell apoptosis via ALK5.
Transforming growth factor (TGF)-beta1 has been reported to cause endothelial cell apoptosis. However, conflicting data have also demonstrated that TGF-beta1 promotes endothelial cell survival. In this study, the effect of TGF-beta1 on apoptosis of cultured bovine pulmonary artery endothelial cells (PAEC) induced by multiple stimuli was investigated. TGF-beta1 protected against apoptosis of bovine PAEC induced by serum deprivation or the VEGF receptor inhibitor SU-5416, but not by UV light exposure or TNFalpha. Neither caspase-8 nor caspase-12 was activated by serum deprivation or the VEGF receptor blocker. However, blockade of VEGF receptors activated caspase-9, an effect that was abolished by TGF-beta1. Furthermore, serum deprivation and inhibition of VEGF receptors significantly decreased the protein level of Bcl-2, an effect that was also abrogated by TGF-beta1. In addition, the baseline level of Bcl-2 was enhanced by TGF-beta1 and reduced by inhibition of activin receptor-like kinase 5 (ALK5), a TGF-beta1 type I receptor. Furthermore, inhibition of ALK5 caused apoptosis of bovine PAEC. These results suggest that TGF-beta1 signaling is critical for maintenance of bovine PAEC survival. Finally, the protective effects of TGF-beta1 on bovine PAEC apoptosis and Bcl-2 reduction were abolished by ALK5 inhibition, but not by inhibition of non-SMAD signaling pathways. Also, TGF-beta1 activated SMAD2 and SMAD1/5, an effect that was abolished by ALK5 inhibition. The results of this study suggest that TGF-beta1 protects against bovine PAEC apoptosis, possibly through ALK5-mediated Bcl-2 induction and subsequent inhibition of the mitochondria-mediated intrinsic pathway of apoptosis. Understanding the mechanism by which TGF-beta1 promotes endothelial cell survival may provide a better treatment for apoptosis-dependent vascular diseases, such as emphysema.


Correlation between the expression of the histone H4 mRNA variant H4-v.1 and the levels of histone H4-(86-100) and H4-(89-102) (OGP) in various rat tissues and alveolar macrophages.
We studied the expression of the osteogenic and antinociceptive C-terminal histone H4-related peptide fragments, H4-(89-102) (OGP) and H4-(86-100), respectively, within various rat tissues and isolated alveolar macrophages (AM) by radioimmunoassay (RIA). OGP was located mainly within the bone marrow, spleen, thymus, and lungs whereas H4-(86-100) was more concentrated within the bone marrow, lymph nodes, spinal cord, pituitaries and thymus. The expression pattern of the two peptides showed similarities with the tissue expression pattern of the histone H4 mRNA variant H4-v.1. In rat AM, OGP and H4-(86-100) levels were significantly stimulated (2.6- and 1.9-fold, respectively) by LPS (1 microg/ml), along with H4-v.1 mRNA (4.1-fold), but not whole histone H4 (1.1-fold) nor total histone H4 mRNA (1.1-fold). The results suggest that H4-v.1 mRNA may play a role in the synthesis of the naturally occurring peptides H4-(86-100) and OGP via the alternative translation product H4-(84-102), but not whole histone H4.


The Effect of Virtual Reality Glasses and Stress Balls on Pain and Vital Findings During Transrectal Prostate Biopsy: A Randomized Controlled Trial.
This study aimed to determine effect of virtual reality (VR) glasses and stress balls (SB) on patients' pain and vital signs during transrectal prostate biopsy. This experimental research was conducted using a pre or post-procedure randomized controlled model. The study population consisted of 96 male patients who were admitted to the TRUS Unit of the Urology Department of a state hospital in southeastern Turkey for prostate biopsy. The patients were divided into three groups by block randomization as 32 for VR, 32 for SB, and 32 for the control group. A Patient Information Form and the Visual Analogue Scale were used to collect data. In data analysis, number, percentage, mean, standard deviation, chi-square, dependent group t-test, and ANOVA tests were used. Comparing mean values of pain and vital signs between the groups, there was no statistically significant difference in terms of pre-test mean scores (P > .05). After Tukey advanced analysis, we found that VR and SB significantly decreased pain, diastolic blood pressure, pulse, and respiratory rate and significantly increased oxygen saturation (P < .05). We found that VR glasses and squeezing SBs during the transrectal prostate biopsy procedure reduced pain and positively affected vital signs.


Potential for interactions between dietary supplements and prescription medications.
The objective of this study was to assess the frequency of clinically significant interactions caused by concurrent use of dietary supplements and prescription medication. We conducted a cross-sectional, point-of-care survey and combined the findings with a review of patient medical records. Patients treated at Mayo Clinic (Rochester, Minn) in 6 different specialty clinics were surveyed for their use of dietary supplements. Concurrent use of prescription medications was obtained from patients' medical records. We used the Lexi-Interact online medication and dietary supplement interaction analysis program to assess the potential clinical significance of each interaction. We surveyed 1818 patients; 1795 responded (overall response rate of 98.7%) and 710 (39.6%) reported use of dietary supplements. In total, 107 interactions with potential clinical significance were identified. The 5 most common natural products with a potential for interaction (garlic, valerian, kava, ginkgo, and St John's wort) accounted for 68% of the potential clinically significant interactions. The 4 most common classes of prescription medications with a potential for interaction (antithrombotic medications, sedatives, antidepressant agents, and antidiabetic agents) accounted for 94% of the potential clinically significant interactions. No patient was harmed seriously from any interaction. A small number of prescription medications and dietary supplements accounted for most of the interactions. The actual potential for harm was low.


Effect of different pH conditions on the in vitro digestibility and physicochemical properties of citric acid-treated potato starch.
The objective of this study was to investigate the influence of citric acid (CA) treatment (10, 20, and 30% of dry starch weight) under different pH conditions (3.5, 4.5, and 5.5) on the physicochemical properties, in vitro digestibility and prebiotic effects of potato starch. With the CA content increased, the degree of substitution of CA-starch treated at pH 3.5 and 4.5 wad significantly increased i.e. from 0.125 to 0.418 and from 0.078 to 0.167, respectively (p<0.05), except for starch treated at pH 5.5 (from 0.023 to 0.030). The resistant starch (RS) content of CA-starch was effectively increased compared to pH control made by changing pH from 3.5 to 5.5 with hydrochloric acid alone. The results of X-ray diffraction and swelling power were affected by pH condition, whereas they were less affected by the percentage of CA. Swelling power of treated starch also significantly decreased as the pH level decreased (p<0.05). Probiotic bacteria B. bifidum and L. acidophilus grown in medium with citrate starch showed substantial viability. These results suggest that pH conditions of CA modification substantially affect the degree of CA substitution, physicochemical properties, and nutritional value.


Chiral recognition of binaphthyl derivatives using electrokinetic chromatography and steady-state fluorescence anisotropy: effect of temperature.
The effect of temperature on the chiral recognition of binaphthyl derivatives in the presence of poly sodium N-undecanoyl-LL-leucyl-leucinate (poly LL-SULL) is examined using electrokinetic chromatography (EKC) and steady-state fluorescence anisotropy. An examination of the effect of temperature suggests that the chiral recognition of 1,1'-binaphthyl-2,2'-diol enantiomers improves with increasing temperature, whereas lower temperatures resulted in better enantiosolectivity in the case of 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate enantiomers. In addition, steady-state fluorescence anisotropy results show that the anisotropy of the two enantiomers are different when complexed to poly-(LL) SULL. As would be expected, the enantiomer that binds stronger to the chiral pseudostationary phase, as evidenced by EKC experiments, had higher anisotropy values. The results of this study suggest that steady-state fluorescence anisotropy can be used to gain further insight into chiral recognition.


Fasting and L-364,718 prevent cholecystokinin-induced elevations of plasma insulin levels.
Sulfated CCK-8 but not non-sulfated CCK-8 induced a dose-dependent increase in plasma insulin levels in fed mice. In fasted mice, however, the CCK peptides caused a non-significant to minimal elevation of plasma insulin. Refeeding fasted mice for 1 h prior to CCK-8-S administration was sufficient to cause a significant elevation of plasma insulin levels. The peripheral CCK antagonist, L-364,718, prevented the CCK-8-S-induced elevation of plasma insulin observed in fed mice. In conclusion, CCK produces a nutrition-dependent increase in plasma insulin levels in vivo via an action upon peripheral CCK receptors.


Trends in incidence and detection of advanced breast cancer at biennial screening mammography in The Netherlands: a population based study.
The aims of this study were to determine trends in the incidence of advanced breast cancer at screening mammography and the potential of screening to reduce it. We included a consecutive series of 351,009 screening mammograms of 85,274 women aged 50-75 years, who underwent biennial screening at a Dutch breast screening region in the period 1997-2008. Two screening radiologists reviewed the screening mammograms of all advanced screen detected and advanced interval cancers and determined whether the advanced cancer (tumor > 20 mm and/or lymph node positive tumor) had been visible at a previous screen. Interval cancers were breast cancers diagnosed in women after a negative screening examination (defined as no recommendation for referral) and before any subsequent screen. Patient and tumor characteristics were compared between women with advanced cancer and women with non-advanced cancer, including ductal carcinoma in situ. A total of 1,771 screen detected cancers and 669 interval cancers were diagnosed in 2,440 women. Rates of advanced cancer remained stable over the 12-year period; the incidence of advanced screen-detected cancers fluctuated between 1.5 - 1.9 per 1,000 screened women (mean 1.6 per 1,000) and of advanced interval cancers between 0.8 - 1.6 per 1,000 screened women (mean 1.2 per 1,000). Of the 570 advanced screen-detected cancers, 106 (18.6%) were detected at initial screening; 265 (46.5%) cancers detected at subsequent screening had been radiologically occult at the previous screening mammogram, 88 (15.4%) had shown a minimal sign, and 111 (19.5%) had been missed. Corresponding figures for advanced interval cancers were 50.9% (216/424), 24.3% (103/424) and 25.1% (105/424), respectively. At multivariate analysis, women with a ≥ 30 months interval between the latest two screens had an increased risk of screen-detected advanced breast cancer (OR 1.63, 95%CI: 1.07-2.48) and hormone replacement therapy increased the risk of advanced disease among interval cancers (OR 3.04, 95%CI: 1.22-7.53). We observed no decline in the risk of advanced breast cancer during 12 years of biennial screening mammography. The majority of these cancers could not have been prevented through earlier detection at screening.


A sample extraction method for faster, more sensitive PCR-based detection of pathogens in blood culture.
Three mechanistically different sample extraction methodologies, namely, silica spin columns, phenol-chloroform, and an automated magnetic capture of polymer-complexed DNA (via an Automate Express instrument), were compared for their abilities to purify nucleic acids from blood culture fluids for use in TaqMan assays for detection of Staphylococcus aureus. The extracts from silica columns required 100- to 1000-fold dilutions to sufficiently reduce the powerful PCR inhibitory effects of the anticoagulant sodium polyanetholsulfonate, a common additive in blood culture media. In contrast, samples extracted by either phenol-chloroform or the Automate Express instrument required little or no dilution, respectively, allowing for an approximate 100-fold improvement in assay sensitivity. Analysis of 60 blood culture bottles indicated that these latter two methodologies could be used to detect lower numbers of pathogens and that a growing S. aureus culture could be detected 2 hours earlier than when using silica columns. Of the three tested methodologies, the Automate Express instrument had the shortest time to result, requiring only approximately 80 minutes to process 12 samples. These findings highlight the importance of considering the mechanism when selecting a DNA extraction methodology, given that certain PCR inhibitors act in a similar fashion to DNA in certain chemical environments, resulting in copurification, whereas other methodologies use different chemistries that have advantages during the DNA purification of certain types of samples.


Hemorrhagic morbidity in placenta accreta spectrum with and without placenta previa.
The incidence of placenta accreta spectrum (PAS; pathologic diagnosis of placenta accreta, increta or percreta) continues to rise in the USA. The purpose of this study is to compare the hemorrhagic morbidity associated with PAS with and without a placenta previa. This was a retrospective cohort study of 105 deliveries from 1997 to 2017 with histologically confirmed PAS comparing outcomes in women with and without a coexisting placenta previa. We used the Wilcoxon rank sum test to compare continuous data and Chi-square or Fisher's exact test for categorical data. We also performed log-binomial regression to calculate risk ratios adjusted for depth of invasion (aRR) and 95% confidence intervals (CI). We identified 105 pregnancies with PAS. Antenatal diagnosis of PAS was higher in women with coexisting placenta previa (72.3%) than those without (6.9%, p < 0.001). Women with coexisting placenta previa had greater median estimated blood loss and more units of packed red blood cells transfused (both p ≤ 0.03). Women with placenta previa were more likely to undergo a hysterectomy (RR 2.7; 95% CI 1.8-3.8) and be admitted to the intensive care unit (aRR 3.3; 95% CI 1.1-9.6). Among women with PAS, those with a coexisting placenta previa experienced greater hemorrhagic morbidity compared to those without. In addition, PAS without placenta previa typically was not diagnosed prior to delivery. This study further supports the recommendation for multi-disciplinary planning and assurance of resources for pregnancies complicated by PAS. In addition, our results highlight the need for mobilization of resources for those pregnancies where PAS is not diagnosed until delivery.


Prostate-specific antigen testing in hypogonadism: implications for the safety of testosterone-replacement therapy.
Hypogonadal men have lower prostate volumes and serum prostate-specific antigen (PSA) levels than age-matched controls. When present, prostate cancer in hypogonadal men is more aggressive than in eugonadal men, and given the lack of specificity of PSA for diagnosing prostate cancer, a more accurate test would be desirable in hypogonadal men. Once testosterone-replacement therapy is started in hypogonadal men, PSA levels should be measured regularly; however, there is often an initial rise 3-6 months after starting treatment. A rise of >0.5 ng/mL within this time requires further investigation.


On the classification of penis carcinoma and its 10-year survival.
With respect to the primary tumor there is no difference between the proposal of the UICC and the Heidelberg version for TNM classification of the penis carcinoma. Clinically the Heidelberg scheme seems more practical, but there were no statistical differences between them. With respect to the prognosis for the patient, the size and localization of the primary tumor are of secondary importance. What is important is the degree of tumor spreading in the lymph system. From this point of view, one needs only to differentiate between T1 (tumor restricted to the penis) and T2 (tumor extending the bounds of the penis). On the other hand, size, localization, and degree of infiltration of penis carcinoma do have different therapeutic consequences, so from this point of view the differentiation of the primary tumor from T1 up to T4 should be retained. With respect to the classification of the state of the corresponding lymph system it is our opinion that the UICC proposal is too differentiated and has little meaning. In its stead, the Heidelberg scheme is clear and simple. Any examiner can complete it. With the help of life tables extending beyond 10 years after diagnosis we were able to determine that 5 years is not a sufficiently long time to clsoe a case of penis cancer. Even with proper treatment, the patient may suffer up to 10 years or more from the disease. In patients aged between 50 and 59 years of age the cancer seems to grow faster; in spite of proper and intensive treatment those patients had a clearly limited life expectancy. In patients aged 60-69 and more so in those between 70 and 79 years of age the tumor seemed to grow slowly and often had no effect on the survival rate.


Androgen increases the number of cells in fetal mouse spinal cord cultures: implications for motoneuron survival.
Androgen effects were studied in organotypic cultures of the E12 fetal mouse lumbosacral spinal cord labeled in utero with [3H]thymidine on E10. Following continuous exposure to androgens for one month in vitro, the number of labeled cells was significantly increased in whole explants, and in hemisected segments in the presence or absence of co-cultured fetal thigh muscle. Because lumbosacral motoneurons undergo their final mitosis predominantly on E10 and thus remain permanently labeled, the results suggest that androgens increase neuronal numbers by directly modulating motoneuron survival rather than stimulating mitosis. These findings demonstrate for the first time that in addition to the well documented role of the muscle target in motoneuron survival, the direct neuronotrophic effects of androgen at the level of the spinal cord must also be considered.


Biventricular pacing: impact on exercise-induced increases in mitral insufficiency in patients with chronic heart failure.
Mitral regurgitation (MR) in chronic heart failure (CHF) patients frequently worsens with exercise. Cardiac resynchronization therapy (CRT) reduces MR at rest, but its effects on exercise-induced worsening of MR are incompletely explored. The present study examined the influence of CRT on MR during submaximal exercise in CHF patients. Eleven patients with CHF who were treated with CRT underwent echocardiography while performing steady-state exercise during four conduction modes (intrinsic rhythm, right ventricular [RV], biventricular [BiV] and left ventricular [LV] pacing). Measurements of MR were jet area planimetry, effective regurgitant orifice area, peak MR flow rate and regurgitant volume. At rest and during exercise, there were no differences in dyssynchrony between intrinsic rhythm and RV pacing. BiV and LV pacing reduced dyssynchrony at rest and during exercise compared with intrinsic conduction and RV pacing, and there were no differences in the magnitude of these effects between these two pacing modes. At rest, RV pacing increased MR compared with intrinsic conduction (MR regurgitant volume; P<0.05), whereas BiV and LV pacing reduced MR (reductions in effective regurgitant orifice area and jet area; P<0.02, and MR flow rate; P<0.05 with BiV pacing from intrinsic conduction). MR significantly increased on exercise with intrinsic rhythm and RV pacing, whereas with LV and BiV pacing, there were no significant exercise-induced increases in any MR variable. There were relationships between changes in measures of dyssynchrony and reductions in MR at rest and during exercise. CRT reduces MR at rest and during exercise, and prevents exercise-induced MR. Reductions in MR during exercise correlate with improvements in dyssynchrony.


Women's views and experiences of augmentation of labour with synthetic oxytocin infusion: A qualitative evidence synthesis.
To explore and synthesise women's views and experiences of augmentation of labour with synthetic oxytocin infusion. A qualitative evidence synthesis was conducted. The SPIDER acronym was used to develop the search terms and determine the inclusion criteria. Six bibliographic databases: MEDLINE, CINAHL, EMBASE, PsycINFO, Maternity and Infant Care and Web of Science Core Collection were searched in October 2021. Grey literature sources, EThOS, DART-Europe, and the World Health Organization's Clinical Trials Registry were searched, and reference lists of included studies were reviewed. Methodological quality of included studies was assessed using the Evidence for Policy and Practice Information and Co-ordinating (EPPI) Centre assessment tool. Data were synthesised thematically. The confidence of each review finding was assessed using the Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual). Research ethical approval was not required. Women of any age, parity, and cultural background who underwent augmentation of labour with synthetic oxytocin infusion were included. A total of 9306 citations were retrieved. Twenty-five studies conducted across 14 countries met the inclusion criteria and contributed data. Three principal analytical themes emerged: feeling stuck; past and present shaping the future; and cause and effect of augmentation of labour. The decision to augment women's labour was often performed without their informed consent. Women's views and experiences of augmentation of labour were shaped according to their knowledge, beliefs and support received during labour. Irrespective of the context, women consistently associated augmentation of labour with pain. Clinical guidelines on augmentation of labour need to be informed by research that includes women's views and experiences as a main outcome. Future research exploring the experience of augmentation of labour rather than the experience of labour dystocia would be beneficial. Increasing women's awareness and knowledge of augmentation of labour may help to ensure that their informed consent is obtained. Healthcare providers should discuss the effects, side effects and implications of augmentation of labour with women, ideally before labour.


Hydrochemical characteristics and microbial community evolution of Pinglu River affected by regional abandoned coal mine drainage, Guizhou Province, China.
Pinglu River in southwestern China was continuously polluted by acid mine drainage (AMD) from abandoned coal mines, and AMD has become a major source of recharge to the river (43.26% of total flow), resulting in structural changes in the physicochemical properties and microbial communities of river water and sediments. In this study, we collected abandoned coal mine drainage, river water, and river sediment samples for comprehensive analysis. Results indicated that the hydrochemical types of AMD from abandoned coal mines were mainly SO4-Ca·Mg. The pH of river water in Pinglu River decreased from upstream to downstream due to AMD, with the hydrochemical type gradually changing from SO4·HCO3-Ca·Mg to SO4-Ca·Mg. The variation of pH along the river sediments was less than that of water samples, which remained weakly alkaline. However, high-throughput sequencing revealed a gradual decrease in microbial diversity in river sediments from upstream to downstream. The core bacteria groups in the upstream sediments were mainly attributed to the phylum Proteobacteria and Actinobacteriota, mainly including Geobacter, Anaeromyxobacter, Marmoricola, and Phycicoccus. The relative abundance of Gaiella, MND1, and Pseudolabrys in sediment samples gradually increased with the confluence of AMD, and the differences in microbial communities may be attributed to pH, TOC, and TP. Results of phenotype prediction demonstrated that the relative abundance of anaerobic microorganisms in river sediment gradually decreased from upstream to downstream (from 24.77 to 12.46%), presumably due to the large amount of oligotrophic AMD converge.


Childhood trauma, IL-6 and weaker suppression of the default mode network (DMN) during theory of mind (ToM) performance in schizophrenia.
Both low-grade systemic inflammation and functional connectivity of the default mode network (DMN) during rest have recently been observed to mediate the association between childhood trauma (CT) and behavioural performance on an emotion recognition task. Whether inflammation also mediates the association between CT and functional connectivity of the DMN during social cognitive task performance is unknown. 51 patients with schizophrenia (SZ) or schizoaffective disorder (SZA) and 176 healthy participants completed a theory of mind (ToM) task during fMRI. IL-6 was measured in plasma using ELISA. DMN connectivity was measured during performance of the fMRI ToM task. To examine DMN connectivity, we selected 4 a priori seeds of the DMN, i.e., the medial prefrontal cortex (PFC), right lateral parietal (LP), left LP, and posterior cingulate cortex (PCC) according to the Harvard-Oxford Cortical and Subcortical Atlas (http://www.cma.mgh.harvard.edu/fsl_atlas.html) as implemented in CONN. Patients showed significantly increased DMN connectivity compared to healthy participants between each of the four seeds of the DMN and with other clusters in the brain. Across the entire sample, higher levels of IL-6 predicted increased connectivity between the mPFC and regions encompassing the cerebellum (<0.001 FWE). IL-6 mediated the association between physical neglect and weaker suppression of the posterior cingulate cortex (PCC) DMN seed -left precentral and postcentral gyrus (βINDIRECT = .0170, CI: 0.0008 to.0506) connectivity during ToM performance. This is the first study to our knowledge that provides evidence that higher plasma IL-6 mediates the association between higher childhood neglect and increased DMN connectivity during ToM task performance. Consistent with our previous study that IL-6 mediated the association between early life stress exposure and reduced connectivity of the DMN during rest, here IL-6 mediated the association between early life stress and increased connectivity of the DMN during ToM based cognitive processing. These findings suggest a biological mechanism for how chronic stress impacts social cognitive processing.


Effect of corticosteroid binding globulin on the pharmacokinetics of prednisolone in rats.
The effect of exogenous corticosteroid binding globulin (CBG) on the pharmacokinetics of intravenous prednisolone was determined in rats to test the "free hormone hypothesis." A dose of CBG to yield 95% binding with 1000 ng/ml of prednisolone in vitro in rat plasma or saline was administered before dosing 2 mg/kg of prednisolone hemisuccinate or methylprednisolone intravenously. Drug concentrations in plasma samples were assayed by HPLC. Single administration of CBG decreased apparent prednisolone clearance by 56% (155 to 66 ml/min/kg) and reduced apparent VSS by 35% (4.1 to 2.7 L/kg) (p < 0.001). Methylprednisolone pharmacokinetics, studied as a negative control because the drug does not bind to CBG, did not change. The corticosteroid bound to CBG does not appear to be available for removal by clearance organs.


Effect of OS-0689, a novel SERM, on periarterial nerve function in tail arteries of ovariectomized rats.
We have previously shown that OS-0689 attenuates the rise in tail skin temperature of ovariectomized rats, which is believed to be relevant to human symptoms of hot flush. In this study, we elucidate the mechanism underlying the ameliorating effects of OS-0689 on elevated tail skin temperature. Female Sprague-Dawley rats were ovariectomized and orally treated with OS-0544 (1 mg/kg), OS-0689 (3 mg/kg; (+)-enantiomer of OS-0544) or 17beta-estradiol (3 mg/kg; E2) for 1 week. At 1, 3 or 6 weeks after ovariectomy, the vasoconstrictions and vasorelaxations induced by periarterial nerve stimulation (PNS), l-noradrenaline (NA), and rat calcitonin gene-related peptide (CGRP) in isolated tail arteries were compared between OVX and sham-operated rats. Three weeks after ovariectomy, vasoconstrictions in response to PNS and NA in the arteries of OVX rats were markedly less than those in the arteries of sham-operated rats. However, at 1 and 6 weeks after ovariectomy the stimuli-induced vasoconstrictions in the arteries of OVX rats were greater than those of sham-operated rats. Moreover, NA reactivity was not attenuated in the mesenteric arteries at 3 weeks after ovariectomy. OS-0544, OS-0689 and E2 prevented the decrease in vasoconstrictions in the tail arteries. Vasorelaxations in response to PNS and rat CGRP were significantly greater in the arteries of OVX rats than in those of the sham-operated rats. OS-0689 inhibited the increase in vasorelaxation induced by both stimuli, whereas E2 had no effects. Ovariectomy not only decreases adrenergic function but also enhances CGRPergic function in rats' tail arteries. OS-0689 improves both impairments and thereby improves on rat hot flush.


The relative frequencies and distribution of immunoglobulin-bearing cells in the intestinal mucosa of neonatal and weaned pigs and their significance in the development of secretory immunity.
A comparative immunohistochemical study has been made of cells containing immunoglobulins IgM; IgA and IgG in the intestines of pigs varying in age from 2 days to 12 weeks. Cells with cytoplasmic IgM appeared in the lamina propria earlier than those containing either IgA or IgG. The duodenum appeared to be the preferred site of infiltration, the numbers of cells occurring in duodenal mucosa were consistently higher than at other levels of intestine irrespective of immunoglobulin class. Igm cells formed the majority of immunoglobulin contained cells in the lamina propria of the small bowel in suckling pigs upto 4 weeks of age. But in the weaned animal the proportion of IgM cells gradually declined with maturity until by the time the pigs were 12 weeks old nearly 90 per cent of the cells contained IgA.


Optimal foraging by deposit-feeding invertebrates: Roles of particle size and organic coating.
Feeding experiments were conducted on marine, deposit-feeding benthic invertebrates to test the predictions of an optimal foraging model. Food item selection based on sediment particle size and presence or absence of an organic coating on particles was investigated. Animals displaying a wide range of feeding mechanisms were studied in particle size-selection experiments using artificial sediment of closely controlled size composition. Nine of 10 species from 4 phyla ingested smaller particles in greater proportions than the particles were present in the sediment. In experiments where animals fed on a mixture of two particle types, one with and one without a surface protein coating, 6 of 7 species from 3 phyla ingested preferentially the protein-coated beads. While these trends of selection of smaller particles and protein-coated particles follow qualitatively the predictions of the optimal foraging model, the animals did not ingest exclusively the preferred particle types. Mechanics of particle handling rather than behavioral responses to particle characteristics appear to offer the better explanation for the observed selection patterns. In particular, the results support strongly the recently proposed role of mucous adhesion in particle selection by deposit feeders.These and other results from studies of deposit feeders suggest that factors in addition to food item selection must be considered when testing the assumptions and predictions of optimal foraging theory. Specifically, feeding energetics are also affected by postfood-selection processes such as variation of ingestion rate. Furthermore, the effects of abiotic environmental factors on foraging behavior cannot be overlooked in evaluating the optimality of foraging behavior; variable water velocity affected differently the particle size selectivity of 3 sympatric polychaete species in these studies.


Visual alertness and brain diffusion tensor imaging at term age predict neurocognitive development at preschool age in extremely preterm-born children.
Cognitive development is characterized by the structural and functional maturation of the brain. Diffusion-weighted magnetic resonance imaging (dMRI) provides methods of investigating the brain structure and connectivity and their correlations with the neurocognitive outcome. Our aim was to examine the relationship between early visual abilities, brain white matter structures, and the later neurocognitive outcome. This study included 20 infants who were born before 28 gestational weeks and followed until the age of 6.5 years. At term age, visual alertness was evaluated and dMRI was used to investigate the brain white matter structure using fractional anisotropy (FA) in tract-based spatial statistics analysis. The JHU DTI white matter atlas was used to locate the findings. The neuropsychological assessment was used to assess neurocognitive performance at 6.5 years. Optimal visual alertness at term age was significantly associated with better visuospatial processing (p < .05), sensorimotor functioning (p < .05), and social perception (p < .05) at 6.5 years of age. Optimal visual alertness related to higher FA values, and further, the FA values positively correlated with the neurocognitive outcome. The tract-based spatial differences in FA values were detected between children with optimal and nonoptimal visual alertness according to performance at 6.5 years. We provide neurobiological evidence for the global and tract-based spatial differences in the white matter maturation between extremely preterm children with optimal and nonoptimal visual alertness at term age and a link between white matter maturation, visual alertness and the neurocognitive outcome at 6.5 years proposing that early visual function is a building block for the later neurocognitive development.


Three-dimensional structure of the presynaptic nerve ending in the ciliary ganglion of the chick embryo: a scanning electron microscopic study.
Presynaptic nerve endings in the ciliary ganglia of chick embryos are 3-dimensionally examined by scanning electron microscopy. Underdeveloped nerve endings attached to the lateral side of the ciliary cells are spoon-like, and show an irregular surface texture and marginal outline with many slender processes and pores. Well-developed nerve endings embracing more than half of the surface of the ciliary cell are cup-like, and show a smooth surface texture and a linear marginal outline with few slender processes and pores. The slender processes come into intimate contact with each other at the margin of the spoon-like nerve endings or cross the pores, seemingly expanding and smoothing the nerve endings. Cytoplasmic processes of the ciliary cells are also described.


A modified semi-nested multiplex malaria PCR (SnM-PCR) for the identification of the five human Plasmodium species occurring in Southeast Asia.
We have modified an existing semi-nested multiplex polymerase chain reaction (PCR) by adding one Plasmodium knowlesi-specific nested PCR, and validated the latter against laboratory and clinical samples. This new method has the advantage of being relatively affordable in low resource settings while identifying the five human Plasmodium species with a three-step PCR.


A comparative study of the physical properties and enzymatic reactions of slow reacting substance of anaphylaxis and some leukotriene D4 isomers.
Eight synthetic isomers of 5-hydroxy-6-S-cysteinylglycine -7,9,11,14-eicosatetraenoic acid were compared with authentic guinea pig SRS-A using UV spectroscopy, high performance liquid chromatography and soybean lipoxygenase. It was found that only the 5S, 6R 7,9trans 11,14cis isomer was similar to SRS-A in all respects. The 5S,6R 7trans, 9,11,14 cis isomer shows similar UV and HPLC characteristics but differs in that it spontaneously undergoes a 1,7 hydride shift reaction and unexpectedly does not react with soybean lipoxygenase.


Utility of Patient-Reported Risk Factors for Identifying Advanced Chronic Kidney Disease Before Outpatient CT: Comparison With Recent ACR/NKF Consensus Criteria.
BACKGROUND. Practices vary for screening patients for risk of renal dysfunction before administration of iodinated contrast medium. A 2020 American College of Radiology/National Kidney Foundation (ACR/NKF) consensus statement provided streamlined screening criteria. OBJECTIVE. The purpose of this study was to assess the yield of patient-reported risk factors for identifying estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m2 before outpatient CT. METHODS. This retrospective study was performed at a health system that implemented an electronic screening form for patients to complete before outpatient CT encounters to report undergoing dialysis, taking cancer-treating medications, having kidney disease, undergoing prior kidney surgery, having diabetes mellitus treated with medication, having hypertension treated with medication, or having multiple myeloma. Patients with any risk factor were required to undergo eGFR testing before CT. Of 44,708 patients completing the form from June 1, 2020, through February 28, 2021, 10,256 patients (5315 men, 4941 women; mean age, 66.8 ± 11.9 [SD] years; range, 21-98 years) underwent eGFR testing on the day of CT. Multivariable regression analysis for predicting reduced eGFR was performed. Findings were compared with those from theoretic use of the ACR/NKF criteria. RESULTS. Same-day testing yielded eGFR less than 30 mL/min/1.73 m2 in 1.4% (144/10,256) of patients. The only significant independent predictors of low eGFR were dialysis (odds ratio [OR], 203.30], kidney disease (OR, 12.55), and diabetes mellitus treated with medication (OR, 2.44). If the ACR/NKF criteria (only kidney disease, defined as dialysis, kidney disease, or prior kidney surgery) had been followed as a trigger for eGFR testing, the number of patients needing testing would have decreased 89.7%, from 10,256 to 1059; yield would have increased to 7.2% (76/1059); and 47.2% (68/144) of patients with low eGFR would have been missed. If the ACR/NKF criteria had been followed but diabetes mellitus been considered a required rather than an optional criterion, the number of patients needing testing would have decreased 77.1%, to 2353; yield would have increased to 4.0% (95/2353); and 34.0% (49/144) of patients with low eGFR would have been missed. CONCLUSION. Using patient-reported risk factors resulted in frequent eGFR testing but low yield of low eGFR. Commonly applied risk factors were not independently associated with low eGFR. CLINICAL IMPACT. Application of ACR/NKF criteria would substantially reduce eGFR testing, but patients with renal dysfunction would be missed. The statement should consider omitting kidney surgery as a trigger for eGFR testing and including diabetes mellitus as a required trigger.


Pollution mechanisms and photochemical effects of atmospheric HCHO in a coastal city of southeast China.
Formaldehyde (HCHO) is a vital reactive carbonyl compound, which plays an important role in the photochemical process and atmospheric oxidation capacity. However, the current studies on the quantification of HCHO impacts on atmospheric photochemistry in southeast coastal areas of China with an obvious upward trend of ozone remain scarce and unclear, thus limiting the full understanding of formation mechanism and control strategy of photochemical pollution. Here, systematic field campaigns were conducted at a typical coastal urban site with good air quality to reveal HCHO mechanism and effects on O3 pollution mechanism during spring and autumn, when photochemical pollution events still frequently appeared. Positive Matrix Factorization model results showed that secondary photochemical formation made the largest contributions to HCHO (69 %) in this study. Based on the photochemical model, the HCHO loss rates in autumn were significantly higher than those in spring (P < 0.05), indicating that strong photochemical conditions constrain high HCHO levels in certain situations. HCHO mechanism increased the ROx concentrations by 36 %, and increased net O3 production rates by 31 %, manifesting that the reduction of HCHO and its precursors' emissions would effectively mitigate O3 pollution. Therefore, the pollution characteristics and photochemical effects of HCHO provided significant guidance for future photochemical pollution control in relatively clean areas.


Unusual silica granulomas of the skin with massive involvement of axillary lymph nodes.
Silica granulomas are rare in the skin. Involvement of the regional lymph nodes seems to be unusual. The case of a 35-year-old man with massive diffuse fibrosis of the axilla with multiple foreign body granulomas and involvement of axillary lymph nodes is presented. The lymph nodes exhibit multiple epithelioid cell granulomas and silicotic nodules which are indistinguishable from similar nodules in mediastinal lymph nodes in pulmonary silicosis. It is assumed that the numerous silica particles which were identified by X-ray microanalysis under the scanning electron microscope and recovered from the mineral ash after incineration were accidentally implanted into the skin at the time of an injury 26 years previously. The long delay between silica exposure and granuloma development is a typical feature of these lesions. The possible mechanisms operative in this process are discussed.


Hepatitis after alendronate.
A 77 year-old woman developed severe hepatitis. No cause was found apart from alendronate medication. The hepatitis resolved after alendronate was stopped.


Tailoring and imaging the plasmonic local density of states in crystalline nanoprisms.
Surface plasmon (SP) technologies exploit the spectral and spatial properties of collective electronic oscillations in noble metals placed in an incident optical field. Yet the SP local density of states (LDOS), which rule the energy transducing phenomena between the SP and the electromagnetic field, is much less exploited. Here, we use two-photon luminescence (TPL) microscopy to reveal the SP-LDOS in thin single-crystalline triangular gold nanoprisms produced by a quantitative one-pot synthesis at room temperature. Variations of the polarization and the wavelength of the incident light redistribute the TPL intensity into two-dimensional plasmonic resonator patterns that are faithfully reproduced by theoretical simulations. We demonstrate that experimental TPL maps can be considered as the convolution of the SP-LDOS with the diffraction-limited Gaussian light beam. Finally, the SP modal distribution is tuned by the spatial coupling of nanoprisms, thus allowing a new modal design of plasmonic information processing devices.


Lectin panning method: the prospective isolation of mouse neural progenitor cells by the attachment of cell surface N-glycans to Phaseolus vulgaris erythroagglutinating lectin-coated dishes.
Retrospective isolation of neural progenitor cells (NPCs) may cause deterioration of the phenotype during the long-term cultivation. Therefore, prospective isolation is essential for understanding the exact characteristics of intact NPCs in the brain. However, few suitable specific cell surface antigens on NPCs that could be used for their prospective isolation are available. The present study demonstrated that within 60 min after initial plating, embryonic day 12 (E12) brain cells firmly attach to several types of lectin-coated culture wells, including Phaseolus vulgaris erythroagglutinating lectin (E-PHA), concanavalin A (Con A) and wheat germ agglutinin (WGA). Approximately 80% of the cells isolated from E-PHA-coated wells expressed the nestin antigen, which is a specific intracellular marker for NPCs and the ratio of 5-bromo-2'-deoxyuridine (BrdU)-positive/nestin-positive cells to the cells attached on the E-PHA-coated wells was significantly higher than that of the cells attached on the wells coated with other adhesive substrates. The cells that were isolated from the E-PHA-coated wells continued to attach to the well for 1 week, while those isolated from Con A- and WGA-coated wells lost their attachment after 6 days and 1 day, respectively. Furthermore, the cells isolated from the E-PHA-coated wells grew quite satisfactorily and formed numerous attached neurospheres. Their growth rate was almost equal to that observed in suspension cultures. These results indicate that the lectin panning method enables the prospective, quick and easy isolation of mouse NPCs without requiring a fluorescence-activated cell sorter (FACS) system.


A study of the interaction between bromocresol green dye and bovine, ovine and equine serum globulins.
In human medicine it has been shown that the bromocresol green (BCG) dye-binding method for the determination of serum albumin is not entirely specific, the dye reacting also with certain human serum globulins. This causes over-estimation of albumin when reaction times are prolonged beyond 30 seconds. In the present study, serum albumin values obtained from three animal species by the "immediate", i.e. less than 30 seconds, BCG reaction were compared with those by the 10-minute BCG reaction. Albumin-depleted sera were prepared using an affinity chromatography technique and their reactions and those of purified gamma globulin preparations with the dye were studied. In cattle, sheep and horses, serum albumin values obtained by the 10-minute reaction were higher than those obtained by the "immediate" BCG reaction, the differences being statistically significant. Purified gamma globulin did not react with the BCG dye after 10 minutes, but other globulins did. There were differences between the species in the magnitude of the reaction of their globulins with BCG dye.


Seasonal variation and controlling factors of anaerobic ammonium oxidation in freshwater river sediments in the Taihu Lake region of China.
Anaerobic ammonium oxidation (anammox) has been recently recognized as an important pathway for the removal of fixed nitrogen (N) from aquatic systems. However, the functions of anammox in freshwater river systems remain uncertain. In this study, we evaluated the occurrence of anammox activity in two rivers in the Taihu Lake region in China during a seasonal survey. Homogenized sediments were incubated with (15)N-labeled NO3(-) and NH4(+) amendments to determine the potential importance of the anammox process relative to canonical denitrification. Production of (29)N2 and (30)N2 in slurries was determined using membrane inlet mass spectrometry. Potential anammox rates in the two river sediments ranged from 0.11±0.07 to 6.79±1.28 μmol N m(-2) h(-1) and the remove of N by anammox accounted for 0.8±0.00% to 10.7±0.03% of total N2 production. Potential anammox rates varied spatially and temporally in the two rivers, with the highest and lowest mean anammox rates appearing during summer and early autumn and during winter, respectively. The variation of the percentage of anammox to total N2 production displayed the same trend with potential anammox rates. Water temperature and NO3(-) content in sediments were the main factors affecting anammox activity. Anammox bacteria were detected in sediment samples using barcode pyrosequencing. The 16S rRNA anammox gene sequences in the river sediments were affiliated with Candidatus Kuenenia, Candidatus Jettenia, and Candidatus Scalindua, among which C. Kuenenia dominated the anammox bacterial communities. Our results confirmed the presence of anammox bacteria but their role is relatively small in removing fixed N from freshwater river systems.


Association between 2D echocardiographic right atrial volume to left atrial volume (RAV/LAV) ratio and in-hospital prognosis in thrombolysed acute pulmonary thromboembolism patients.
Right atrial volume/Left atrial volume (RAV/LAV) ratio is a good hemodynamic parameter in acute pulmonary thromboembolism (PTE), whose prognostic ability by 2D echocardiography is not studied to date. We conducted a 27 month, prospective observational study on 55 eligible acute PTE thrombolysed (29: Tenecteplase; 26: Streptokinase) patients. The primary endpoint was a composite of in-hospital death and poor right ventricular reverse remodelling at the time of discharge. The incidence of primary end-point and death were 40% and 7.2% respectively. On regression analysis, RAV/LAV ratio was the only predictor of the primary endpoint, with an optimal cut-off of 3.8 (accuracy 75%).