Clinical and Sonographic Features of Mammary Paget's Disease.
Objective To summarize the clinical and sonographic features of mammary Paget's disease (MPD). Methods Totally 34 female patients with pathologically confirmed MPD were retrospectively recruited. According to diagnosis,the clinical data and sonographic findings were reviewed and analyzed. Results Among these 34 patients,7 patients had single MPD; in the remaining 27 patients,16 were accompanied by invasive ductal carcinoma (IDC),7 by ductal carcinoma in situ (DCIS),3 by both IDC and DCIS,and 1 by other pathologic types of carcinoma. Twenty-four patients presented with typical clinical features of MPD,whereas 10 patients had no typical features of MPD. Among the 24 patients with typical clinical features,ultrasound examinations showed that 11 had echoic abnormality in nipple-areolar complex,14 had lesions of breast,and 14 had microcalcifications. Among the 10 patients without typical clinical features,ultrasound examinations revealed echoic abnormality in nipple-areolar complex in 3 cases,breast lesions in 9 cases,and microcalcifications in 6 cases. Among the 14 patients with echoic abnormality in nipple-areolar complex,all of them presented as rich blood flow in nipple detected by color Doppler ultrasonography. Conclusions The main clinical feature of MPD is abnormalities in nipple-areolar complex. Sonography can recognize the echoic abnormalities of nipple and lesions of breast. Sonographer should be careful of the nipple-areolar complex when mass is found in breast.


PHLDA1 Modulates the Endoplasmic Reticulum Stress Response and is required for Resistance to Oxidative Stress-induced Cell Death in Human Ovarian Cancer Cells.
Objective: Pleckstrin homology-like domain family A member 1 (PHLDA1) has been implicated in the regulation of apoptosis in a variety of normal cell types and cancers. However, its precise pathophysiological functions remain unclear. Here, we examined the expression of PHLDA1 in human ovarian cancer (OvCa), the most lethal gynecologic malignancy, and investigated its functions in vitro. Materials and Methods: The expression of PHLDA1 was detected by reverse-transcription quantitative PCR (RT-qPCR), immunohistochemical analysis, or western blotting, silencing of PHLDA was achieved by shRNA, cell proliferation was detected by MTT assay, apoptosis was detected by flow cytometric analysis, PHLDA1 transcriptional activity was detected by dual luciferase reporter assay. Results: PHLDA1 mRNA levels were significantly higher in serous OvCa specimens compared with normal ovarian tissue, confirmed by immunohistochemical staining of PHLDA1 protein, which also indicated the expression was predominantly cytoplasmic. Bioinformatics analysis of publicly available datasets indicated that PHLDA1 expression in clinical specimens was significantly associated with disease stage, progression-free survival, and overall survival. In human OvCa cell lines, shRNA-mediated silencing of PHLDA1 expression enhanced apoptosis after exposure to oxidative stress- and endoplasmic reticulum stress-inducing agents. PHLDA1 silencing increased not the expression of anti-apoptotic or autophagy-related proteins, but the expression of ER stress response-associated proteins. Conclusion: PHLDA1 modulates the susceptibility of human OvCa cells to apoptosis via the endoplasmic reticulum stress response pathway.


Preserving Retinal Structure and Function with the Novel Nitroxide Antioxidant, DCTEIO.
Oxidative stress is a major contributor to progressive neurodegenerative disease and may be a key target for the development of novel preventative and therapeutic strategies. Nitroxides have been successfully utilised to study changes in redox status (biological probes) and modulate radical-induced oxidative stress. This study investigates the efficacy of DCTEIO (5,6-dicarboxy-1,1,3,3-tetraethyllisoindolin-2-yloxyl), a stable, kinetically-persistent, nitroxide-based antioxidant, as a retinal neuroprotectant. The preservation of retinal function following an acute ischaemic/reperfusion (I/R) insult in the presence of DCTEIO was quantified by electroretinography (ERG). Inflammatory responses in retinal glia were analysed by GFAP and IBA-1 immunohistochemistry, and retinal integrity assessed by histology. A nitroxide probe combined with flow cytometry provided a rapid technique to assess oxidative stress and the mitigation offered by antioxidant compounds in cultured 661W photoreceptor cells. DCTEIO protected the retina from I/R-induced damage, maintaining retinal function. Histological analysis showed preservation of retinal integrity with reduced disruption and disorganisation of the inner and outer nuclear layers. I/R injury upregulated GFAP expression, indicative of retinal stress, which was significantly blunted by DCTEIO. The number of 'activated' microglia, particularly in the outer retina, in response to cellular stress was also significantly reduced by DCTEIO, potentially suggesting reduced inflammasome activation and cell death. DCTEIO mitigated oxidative stress in 661W retinal cell cultures, in a dose-dependent fashion. Together these findings demonstrate the potential of DCTEIO as a neuroprotective therapeutic for degenerative diseases of the CNS that involve an ROS-mediated component, including those of the retina e.g. age-related macular degeneration and glaucoma.


Multistage pH-responsive codelivery liposomal platform for synergistic cancer therapy.
Small interfering RNA (siRNA) is utilized as a potent agent for cancer therapy through regulating the expression of genes associated with tumors. While the widely application of siRNAs in cancer treatment is severely limited by their insufficient biological stability and its poor ability to penetrate cell membranes. Targeted delivery systems hold great promise to selectively deliver loaded drug to tumor site and reduce toxic side effect. However, the elevated tumor interstitial fluid pressure and efficient cytoplasmic release are still two significant obstacles to siRNA delivery. Co-delivery of chemotherapeutic drugs and siRNA represents a potential strategy which may achieve synergistic anticancer effect. Herein, we designed and synthesized a dual pH-responsive peptide (DPRP), which includes three units, a cell-penetrating domain (polyarginine), a polyanionic shielding domain (ehG)n, and an imine linkage between them. Based on the DPRP surface modification, we developed a pH-responsive liposomal system for co-delivering polo-like kinase-1 (PLK-1) specific siRNA and anticancer agent docetaxel (DTX), D-Lsi/DTX, to synergistically exhibit anti-tumor effect. In contrast to the results at the physiological pH (7.4), D-Lsi/DTX lead to the enhanced penetration into tumor spheroid, the facilitated cellular uptake, the promoted escape from endosomes/lysosomes, the improved distribution into cytoplasm, and the increased cellular apoptosis under mildly acidic condition (pH 6.5). Moreover, both in vitro and in vivo study indicated that D-Lsi/DTX had a therapeutic advantage over other control liposomes. We provided clear evidence that liposomal system co-delivering siPLK-1 and DTX could significantly downregulate expression of PLK-1 and inhibit tumor growth without detectable toxic side effect, compared with siPLK-1-loaded liposomes, DTX-loaded liposomes, and the combinatorial administration. These results demonstrate great potential of the combined chemo/gene therapy based on the multistage pH-responsive codelivery liposomal platform for synergistic tumor treatment.


[Antiurolithic Activity of the Ethanolic Extract of Ayacuchano Propolis in Rats].
To determine the antiurolytic activity of the ethanolic extract of Ayacuchan propolis in a preventive model of urolithiasis in rats. A total of 45 male Sprague-Dawley albino rats were studied. The antiurolithic effect was analyzed in five groups of six animals each: blank, control (treated with 1 mL of 5% ethylene glycol and 1 mL of 5% ammonium chloride), and three experimental groups (treated with the ethanol extract of propolis at a daily dose of 250, 350, and 500 mg/kg, respectively). The drugs were administered by orogastric cannulation for 16 days. The diuretic effect was evaluated in 15 rats distributed in five groups: blank, control (treated with furosemide at 20 mg/kg), and three experimental groups (treated with the ethanol extract of propolis at daily doses of 250, 350, and 500 mg/kg, respectively). Urinary pH, urinary density, and sedimentation of calcium oxalate were measured. The presence of kidney stones was evaluated by examination of hematoxylin-eosin-stained histopathological sections under polarized light. The ethanolic extract of Ayacuchan propolis caused significant changes in the levels of uric acid, serum lactate dehydrogenase, pH, and urinary density in the three dose groups. The results of histological analysis indicated a lower presence of calcium oxalate crystals in kidney tubular cells in the group treated with 250 mg/kg. The diuretic effect in the group treated with 250 mg/kg was higher than that in the control group. The ethanolic extract of Ayacuchan propolis demonstrated antiurolytic activity in a preventive rat model of urolithiasis.


Endotoxin, coliform, and dust levels in various types of rodent bedding.
Endotoxins in grain dust, household dust, and animal bedding may induce respiratory symptoms in rodents and humans. We assayed the endotoxin, coliform, and dust levels in 20 types of rodent bedding. Endotoxin concentrations were measured by using a commercial test kit, coliform counts were determined by using conventional microbiologic procedures, and dust content was evaluated by using a rotating-tapping shaker. Paper bedding types contained significantly less endotoxin than did other bedding types; the highest levels of endotoxin were detected in hardwood and corncob beddings. The range of endotoxin content for each bedding type was: corncob bedding, 1913 to 4504 endotoxin units per gram (EU/g); hardwood bedding, 3121 to 5401 EU/g; corncob-paper mixed bedding, 1586 to 2416 EU/g; and paper bedding, less than 5 to 105 EU/g. Coliform counts varied from less than 10 to 7591 cfu/g in corncob beddings, 90 to 4010 cfu/g in corncob-paper mixed beddings, less than 10 to 137 cfu/g in hardwood beddings, and less than 10 cfu/g in paper beddings. Average dust content was less than 0.15% in all commercial bedding types. We conclude that paper bedding is the optimal bedding type for conducting LPS inhalation studies and that rodent bedding containing high levels of endotoxin may alter the results of respiratory and immunologic studies in rodents.


Influence of synchronized sleep on the biosynthesis of RNA in neuronal and mixed fractions isolated from rabbit cerebral cortex.
Adult male rabbits implanted with dural electrodes were injected intraventricularly with [3H]orotate and killed 1 h later. During the period of incorporation they were left undisturbed while their EEG activity was continuously monitored. In the fraction of neuronal perikarya prepared from cerebral cortex by a method developed by Satake and Abe in 1966, the relative content of radioactive RNA of the nuclear particulate showed a twofold increase in the transition from 0 to 100% synchronization. On the other hand, a slight but significant decline was observed in the corresponding cytoplasmic compartment. A marked increase in the relative content of radioactive RNA was similarly observed in the nuclear particulate prepared from the mixed cellular fraction. The corresponding cytoplasmic compartment showed a nonsignificant increase. These results indicate that during sleep neuronal nuclei accumulate newly synthetised RNA (presumably hnRNA) at a faster rate. Under the same conditions the process of RNA transfer to the cytoplasm (presumably rRNA) may be reduced. These effects may be only partly shared by other cerebral cells.


Targeted Endoplasmic Reticulum Localization of Storage Protein mRNAs Requires the RNA-Binding Protein RBP-L.
The transport and targeting of glutelin and prolamine mRNAs to distinct subdomains of the cortical endoplasmic reticulum is a model for mRNA localization in plants. This process requires a number of RNA-binding proteins (RBPs) that recognize and bind to mRNA cis-localization (zipcode) elements to form messenger ribonucleoprotein complexes, which then transport the RNAs to their destination sites at the cortical endoplasmic reticulum. Here, we present evidence that the rice (Oryza sativa) RNA-binding protein, RBP-L, like its interacting RBP-P partner, specifically binds to glutelin and prolamine zipcode RNA sequences and is required for proper mRNA localization in rice endosperm cells. A transfer DNA insertion in the 3' untranslated region resulted in reduced expression of the RBP-L gene to 10% to 25% of that in the wild-type. Reduced amounts of RBP-L caused partial mislocalization of glutelin and prolamine RNAs and conferred other general growth defects, including dwarfism, late flowering, and smaller seeds. Transcriptome analysis showed that RBP-L knockdown greatly affected the expression of prolamine family genes and several classes of transcription factors. Collectively, these results indicate that RBP-L, like RBP-P, is a key RBP involved in mRNA localization in rice endosperm cells. Moreover, distinct from RBP-P, RBP-L exhibits additional regulatory roles in development, either directly through its binding to corresponding RNAs or indirectly through its effect on transcription factors.


Phasins, Multifaceted Polyhydroxyalkanoate Granule-Associated Proteins.
Phasins are the major polyhydroxyalkanoate (PHA) granule-associated proteins. They promote bacterial growth and PHA synthesis and affect the number, size, and distribution of the granules. These proteins can be classified in 4 families with distinctive characteristics. Low-resolution structural studies and in silico predictions were performed in order to elucidate the structure of different phasins. Most of these proteins share some common structural features, such as a preponderant α-helix composition, the presence of disordered regions that provide flexibility to the protein, and coiled-coil interacting regions that form oligomerization domains. Due to their amphiphilic nature, these proteins play an important structural function, forming an interphase between the hydrophobic content of PHA granules and the hydrophilic cytoplasm content. Phasins have been observed to affect both PHA accumulation and utilization. Apart from their role as granule structural proteins, phasins have a remarkable variety of additional functions. Different phasins have been determined to (i) activate PHA depolymerization, (ii) increase the expression and activity of PHA synthases, (iii) participate in PHA granule segregation, and (iv) have both in vivo and in vitro chaperone activities. These properties suggest that phasins might play an active role in PHA-related stress protection and fitness enhancement. Due to their granule binding capacity and structural flexibility, several biotechnological applications have been developed using different phasins, increasing the interest in the study of these remarkable proteins.


Standardization of Pulmonary Embolism Evaluation and Management Through Implementation of a Pulmonary Embolism Response Team: A Single-Center Experience at Brooke Army Medical Center.
Pulmonary embolism (PE) is associated with significant rates of morbidity and mortality. Management of PE is complex, and adverse patient events are not uncommon. Brooke Army Medical Center (BAMC) is among several select institutions that have implemented multidisciplinary pulmonary embolism response teams (PERTs) to improve PE outcomes. PERT structure varies among institutions and often involves specialty expertise from a variety of departments within the hospital. PE response teams aim to improve the diagnosis and treatment for patients with acute PE. Here, we report our initial experience with this intervention. We developed a multidisciplinary PERT and implemented a standardized algorithm to guide the evaluation, management, and disposition of patients with acute PE. Patients with PE were identified in the pre-PERT period (2015-2017) and the post-PERT period (2020-2021). A retrospective analysis of clinical characteristics, management strategies, and outcomes was performed for both cohorts. A total of 68 patients with acute PE were analyzed, 38 patients before PERT adoption, and 30 patients post-PERT. Baseline characteristics between the two cohorts were similar. A statistically significant increase in the evaluation for right ventricle dysfunction was noted in the post-PERT cohort, with 80% of patients having pro-brain natriuretic peptide labs obtained compared to 47% in the pre-PERT cohort (P = .005). Furthermore, 97% of patients in the post-PERT cohort had a transthoracic echocardiogram compared to 55% in the pre-PERT cohort (P = .0001). Six patients in the pre-PERT cohort underwent catheter-directed thrombolysis, compared to zero in the post-PERT cohort (P = .006). There were no differences in other treatment modalities. There was no statistically significant difference in length of stay between the two cohorts. To our knowledge, this is the first report describing the successful implementation of a PERT at a military treatment facility to guide the evaluation, management, and treatment of PE. The implementation of the PERT improved the appropriate diagnostic evaluation for patients with intermediate-risk PE and reduced the use of non-guideline-based catheter-directed thrombolysis. This initiative serves as an example of what could be applied across other military treatment facilities within the Defense Health Agency.


A Dome-Shaped Aerosol Box for Protection During a Pandemic.
With the rise of COVID-19, the use of aerosol boxes when interacting with COVID-19 patients has increased. However, their use has been controversial. We have been involved in the development of a dome-shaped aerosol containment device with negative pressure (DAWN), an aerosol box that can maintain negative pressure inside at all times. There are two types of DAWN: one is mounted on a bed (bed type) and the other is mounted on a stretcher (stretcher type). Each device has its own characteristics and can be selected depending on the situation. The bed type has enough space inside to allow procedures to be performed easily. The stretcher type can be attached to a stretcher and can maintain negative pressure when the patient is being moved. Due to the negative pressure structure and easy change of nonwoven fabric adopted in both types of DAWN, it is expected to prevent the scattering of aerosol when it is removed, which is a problem of conventional aerosol boxes. DAWN will contribute to reducing the enormous psychological stress of medical personnel who treat infections, and will contribute to reducing aerosol dispersion.


Intensive Exercise Training Improves Cardiac Electrical Stability in Myocardial-Infarcted Rats.
Moderate exercise training has been shown to decrease sudden cardiac death post myocardial infarction. However, the effects of intensive exercise are still controversial. Fourteen myocardial-infarcted rats were divided into sedentary (n=8) and intensive training groups (n=6) and 18 sham control rats to sedentary (n=10) and intensive training groups (n=8). Heart rate variability was obtained at weeks 1 and 8. The inducibility of ventricular tachycardia/fibrillation was assessed in a Langendorff system. Fast Fourier transforms were applied on the recorded ventricular tachycardia/fibrillations. Training reduces low to high frequency ratio of heart rate variability at week 8 compared with that at week 1 (P<0.05). In isolated hearts, the probability for ventricular tachycardia/fibrillation was decreased from 4.5±0.8% in sedentary controls to 1.56±0.2% in intensive training controls (P<0.05) and from 13.5±2.1% in the sedentary group to 5.4±1.2% in the intensive training group (P<0.01). Moreover, the pacing current required for ventricular fibrillation induction in the trained groups was increased following exercise (P<0.05). Fast Fourier transform analysis of ECG findings revealed an exercise-induced ventricular fibrillation transition from a narrow, single-peak spectrum at 17 Hz in sedentary controls to a broader range of peaks ranging from 13 to 22 Hz in the intensive training controls. Intensive exercise in infarcted rats leads to reduced ventricular fibrillation propensity and is associated with normalization of refractoriness and intrinsic spatiotemporal electrical variations.


Temporal dynamics of figure-ground segregation in human vision.
The segregation of figure from ground is arguably one of the most fundamental operations in human vision. Neural signals reflecting this operation appear in cortex as early as 50 ms and as late as 300 ms after presentation of a visual stimulus, but it is not known when these signals are used by the brain to construct the percepts of figure and ground. We used psychophysical reverse correlation to identify the temporal window for figure-ground signals in human perception and found it to lie within the range of 100-160 ms. Figure enhancement within this narrow temporal window was transient rather than sustained as may be expected from measurements in single neurons. These psychophysical results prompt and guide further electrophysiological studies.


Evolutionary grass roots for odor recognition.
Considerable evidence supports the idea that odorant recognition depends on specific sequence variations in olfactory receptor (OR) proteins. Much of this emerges from in vitro screens in heterogenous expression systems. However, the ultimate proof should arise from measurements of odorant thresholds in human individuals harboring different OR genetic variants, a research vein that has so far been only scantly explored. The study of McRae et al., published in this issue of Chemical Senses, shows how the recognition of a grassy odorant depends on specific OR interindividual sequence changes. It provides a clear relevant example for the impact of genetics on olfaction and is an excellent portrayal of the power of human genomics to decipher olfactory perception.


Sampling for formaldehyde in workplace and ambient air environments--additional laboratory validation and field verification of a passive air monitoring device compared with conventional sampling methods.
Results of three extensive plant field tests using both area and personal sampling and involving 51 sets of comparison samples show the Du Pont Pro-Tek Formaldehyde Badge to have excellent correlation with three commonly used formaldehyde monitoring methods. In addition, comprehensive laboratory validation tests are reported which confirm an overall accuracy of +/- 9.6 to +/- 11.6% for the badge over an exposure range of 0.12-6.8 ppm. Laboratory test data are also included showing that the badge: (1) meets NIOSH and OSHA accuracy requirements of less than or equal to +/- 25% down to 1.6 ppm-hours (200 ppb) for an 8-hour TWA exposure; (2) is capable of accurately sampling for 15-minute exposures; and (3) is not affected by pressure or relative humidity variations.


In-person and online social participation and emotional health in individuals with multiple sclerosis.
Individuals with multiple sclerosis (MS) sometimes have barriers to social participation. The advent of the internet has created online support systems for social participation such as websites for individuals with MS. However, minimal research has been conducted about determinants of individuals' in-person and online social participation or how types of social participation contribute to emotional well-being. The present study aims are: (1) to assess the role of access to resources and other determinants as enabling in-person and online social participation, and (2) to analyze the association between social participation and emotional health of individuals with MS. The sample consisted of 508 individuals diagnosed with relapsing/remitting or secondary/progressive MS. Data from NARCOMS registry and data from original questionnaire on determinants of social participation and emotional health were merged. Logistic and linear regression analyses were performed. Individuals with access to the internet were more likely to participate online with friends (OR 5.47, p < .001) and the community (OR 47.7, p < .001). Individuals who regularly participate in in-person social participation with friends reported being happier (B = .38, p < .001), less depressed (B = -2.01, p < .001), and less anxious (B = -1.21, p < .001) than those who did not. However, there was no evidence of a relationship between emotional health and online social participation. Increasing access to in-person social participation with friends will likely have the most positive impact on emotional health. Future research should examine the aspects of online participation that are helpful or harmful.


The role of glucocorticoids in sodium retention in cirrhotic patients: a double blind, randomized, crossover study.
Cirrhotic patients have an increased ratio of urinary cortisol to cortisone metabolites, indicating decreased renal 11-β-hydroxysteroid dehydrogenase type-2 activity. This suggests that cortisol--by activation of the mineralocorticoid receptor--may contribute to the abnormal sodium retention evident in cirrhosis. The aim was to elucidate the role of glucocorticoids in sodium retention in decompensated cirrhotic patients. A randomized, double-blind, placebo-controlled, crossover study was performed in nine patients with alcoholic cirrhosis of the liver. A washout interval of 14 days separated the two periods. After a basal period of 36 h, dexamethasone (0.5 mg every 6 h) or placebo was given for two days. Urine was collected for 12 h periods, and the concentrations of sodium, potassium, creatinine, cortisol and cortisol metabolites were determined. Blood samples for hemoglobin, glucose, sodium, potassium, creatinine, aldosterone and cortisol were obtained daily. Dexamethasone treatment decreased S-cortisol 92.3% (82.9-93.4%) (median and range) compared with that in the basal period. Natriuresis (dexamethasone--placebo) increased 55.1 (-26.4-168.7) mmol/day (median and range). No statistically significant differences (dexamethasone--placebo) were found in changes in body weight (0.00 (-0.45-2.20) kg/day), diuresis (0.56 (-0.35-1.43) L/day) or mean arterial pressure (8.33 (-16.0-41.3) mmHg) (median and range) in reference to the preceding 24 h basal period. These results indicate that endogenous glucocorticoids contribute to the sodium retention in patients with alcoholic cirrhosis of the liver.


Uterine Sarcomas: The Latest Approaches for These Rare but Potentially Deadly Tumors.
Uterine sarcomas are rare malignant uterine neoplasms that are responsible for a large majority of uterine cancer-associated deaths. The subtypes include leiomyosarcomas, endometrial stromal tumors, and adenosarcomas. Standard treatment includes complete surgical resection. Adjuvant treatment with chemotherapy, hormonal therapy, or radiation may be considered in patients with high-risk disease. However, because the ability of adjuvant treatment to improve overall survival in patients with uterine sarcomas is unclear, there is no standard recommendation regarding adjuvant therapy. The risk in forgoing chemotherapy is that uterine sarcomas have a tendency to develop distant recurrences. Many cytotoxic agents have been investigated in clinical trials in an attempt to identify an effective treatment that can improve the course of this disease. Adjuvant radiation appears to improve local control but has no significant impact on survival. In this review we discuss preoperative diagnosis and the role of pathology, and we summarize the current literature regarding the management of uterine sarcomas.


HIV-1 seropositive women in the Philippines: pregnancy outcome and perinatal transmission of HIV-1.
Annual surveillance studies were initiated in 1985 to determine the incidence and prevalence of HIV-1 infection in female prostitutes registered through the Social Hygiene Clinic System of the Philippine Department of Health. All of the confirmed HIV-1 seropositive women detected in the above surveys who could be contacted were followed up about every three months to monitor their clinical and immunological status. Since we regularly interviewed and examined these HIV-1 seropositive women, we were able to note the occurrence of pregnancies following HIV diagnosis. By September 1990, 54 HIV-1 seropositive women (aged 18-35) detected from the above surveys had been interviewed and examined. Twenty-six of these HIV-1 positive women had a total of 37 pregnancies. Eight were pregnant at the time of HIV diagnosis: three term deliveries, one premature delivery (PD) at eight months, three abortions, and one lost to follow-up while still pregnant. Five of these eight had repeat pregnancies: two term deliveries, two abortions, and one lost to follow-up while pregnant. Eighteen other women became pregnant one or more times after HIV diagnosis: seven term deliveries, 13 abortions, two PDs, one ectopic pregnancy terminated, one currently pregnant, and one lost to follow-up during pregnancy. There was no clear indication from clinical examinations and CD4+ cell counts that pregnancy exacerbated the course of HIV-1 related disease in these women. One of the 12 term infants has died and eight have developed non-specific findings that are suggestive but not diagnostic of HIV infection.2+ strongly seropositive by both ELISA and Western blot assay at 16 months.


Controlled trial of H1 antagonists in the treatment of chronic idiopathic urticaria.
The efficacy of astemizole, diphenhydramine, and hydroxyzine hydrochloride in the treatment of chronic idiopathic urticaria was evaluated in this 3-month double-blind, randomized, parallel group study. Thirty-six adult patients were randomly assigned, 13 to the astemizole group (10 mg daily), 12 to the diphenhydramine group (25 mg t.i.d.), and 11 to the hydroxyzine hydrochloride group (25 mg t.i.d.). Demographic data were statistically similar for all variables assessed in the three treatment groups. Seven (58%) of the diphenhydramine patients withdrew before the end of the study, six because of lack of efficacy and one because of drowsiness. Two (18%) of the hydroxyzine hydrochloride patients withdrew, one because of lack of efficacy and one because of drowsiness. Two patients (15%) in the astemizole group withdrew, one because of adverse reaction, and the other because of lack of efficacy. Mean total symptom scores and mean individual symptom scores were lower in the astemizole group than in the other two groups. Wheal area measurements (0.1 mg/mL histamine challenge) decreased more in the astemizole and hydroxyzine hydrochloride groups than in the diphenhydramie group (P = .02). With regard to symptoms, 12/13 patients in the astemizole group improved clinically during their treatment period, versus 8/11 in the hydroxyzine hydrochloride group and 5/12 in the diphenhydramine group. The mean time to first observed therapeutic effect (maintained for three consecutive days) was 5.5 days in the astemizole group, 10.9 days in the hydroxyzine hydrochloride group, and 7.2 days in the diphenhydramine group. In this study, astemizole was as effective as hydroxyzine in patients treated for chronic idiopathic urticaria.


[Therapy of primary pulmonary arterial hypertension: current status].
Primary pulmonary hypertension is a rare disease with a median survival of only 2.8 years after diagnosis. In this review article the minimal diagnostic workup is summarized and pathophysiological concepts are discussed. Therapeutic options today include oral anticoagulation, which has a proven survival effect. Furthermore, in a selected subgroup of patients, vasodilators may be effective in lowering pulmonary vascular resistance and pulmonary arterial pressure. Among these, prostacyclin and the calcium antagonists nifedipine and diltiazem are the most promising treatments. It is mandatory to perform an acute drug trial under close monitoring of pulmonary and systemic pressures as well as cardiac output before starting vasodilator treatment. In the majority of patients there will be no improvement, but possibly deleterious hemodynamic effects. Long term trials with both nifedipine and prostacyclin indicate a significant survival effect in those patients who initially respond to this treatment. Lung transplantation remains the only treatment option for patients with uncontrollable pulmonary hypertension.


Association between recurrent concussion and late-life cognitive impairment in retired professional football players.
Cerebral concussion is common in collision sports such as football, yet the chronic neurological effects of recurrent concussion are not well understood. The purpose of our study was to investigate the association between previous head injury and the likelihood of developing mild cognitive impairment (MCI) and Alzheimer's disease in a unique group of retired professional football players with previous head injury exposure. A general health questionnaire was completed by 2552 retired professional football players with an average age of 53.8 (+/-13.4) years and an average professional football playing career of 6.6 (+/- 3.6) years. A second questionnaire focusing on memory and issues related to MCI was then completed by a subset of 758 retired professional football players (> or = 50 yr of age). Results on MCI were then cross-tabulated with results from the original health questionnaire for this subset of older retirees. Of the former players, 61% sustained at least one concussion during their professional football career, and 24% sustained three or more concussions. Statistical analysis of the data identified an association between recurrent concussion and clinically diagnosed MCI (chi = 7.82, df = 2, P = 0.02) and self-reported significant memory impairments (chi = 19.75, df = 2, P = 0.001). Retired players with three or more reported concussions had a fivefold prevalence of MCI diagnosis and a threefold prevalence of reported significant memory problems compared with retirees without a history of concussion. Although there was not an association between recurrent concussion and Alzheimer's disease, we observed an earlier onset of Alzheimer's disease in the retirees than in the general American male population. Our findings suggest that the onset of dementia-related syndromes may be initiated by repetitive cerebral concussions in professional football players.


A Comprehensive Investigation toward the Indicative Proteins of Bladder Cancer in Urine: From Surveying Cell Secretomes to Verifying Urine Proteins.
Urine is an ideal material to study the cancer-related protein biomarkers in bladder, whereas exploration to these candidates is confronting technique challenges. Herein, we propose a comprehensive strategy of searching the urine proteins related with bladder cancer. The strategy consists of three core combinations, screening the biomarker candidates in the secreted proteins derived from the bladder cancer cell lines and verifying them in patient urines, defining the differential proteins through two-dimensional electrophoresis (2DE) and isobaric tags for relative and absolute quantitation (iTRAQ) coupled with LC-MS/MS, and implementing quantitative proteomics of profiling and targeting analysis. With proteomic survey, a total of 700 proteins were found with their abundance of secreted proteins in cancer cell lines different from normal, while 87 proteins were identified in the urine samples. The multiple reaction monitoring (MRM)-based quantification was adapted in verifying the bladder cancer related proteins in individual urine samples, resulting in 10 differential urine proteins linked with the cancer. Of these candidates, receiver operating characteristic analysis revealed that the combination of CO3 and LDHB was more sensitive as the cancer indicator than other groups. The discovery of the bladder cancer indicators through our strategy has paved an avenue to further biomarker validation.


Performance of the Atom 235 syringe infusion pump under hyperbaric conditions.
Inotrope-dependent patients may become haemodynamically unstable during treatment in the hyperbaric chamber. One possible cause is altered performance of infusion devices. We tested six Atom 235 syringe infusion pumps under hyperbaric conditions of 2.8 atmospheres absolute in a multiplace chamber using a gravimetric method. There was a small but significant reduction in infused volume during a thirty-minute period including compression time. We concluded that altered inotrope delivery may explain at least some of the haemodynamic instability sometimes seen, although a physiologic effect of hyperbaric treatment cannot be excluded.


Candidates of Genomic Tests in HR+/HER2- Breast Cancer Patients With 1-2 Positive Sentinel Lymph Node Without Axillary Lymph Node Dissection: Analysis From Multicentric Cohorts.
The genomic tests such as the MammaPrint and Oncotype DX test are being gradually applied for hormone receptor positive/HER-2 negative (HR+/HER2-) breast cancer patients with up to three positive axillary lymph nodes (ALNs). The first results from RxPONDER trial suggested that Oncotype DX could be applied to patients with 1-2 positive sentinel lymph nodes (SLNs) without axillary lymph node dissection (ALND), which constituted 37.4% of the intent-to-treat population. However, there was no distinctive research on how to apply genomic tests precisely to HR+/HER2- patients with 1-2 positive SLNs without ALND. The purpose was to construct a nomogram using the multi-center retrospective data to predict precisely which HR+/HER2- candidates with 1-2 positive SLNs could be subjected to genomic tests (≤ 3 positive lymph nodes). We conducted a retrospective analysis of 18,600 patients with stage I-III breast cancer patients treated with sentinel lymph node biopsy (SLNB) in Shandong Cancer Hospital, Fudan University Shanghai Cancer Center, and West China Hospital. The univariate and multivariate logistic regression analysis was conducted to identify the independent predictive factors of having ≤ 3 positive nodes among patients with 1-2 positive SLNs. A nomogram was developed based on variables in the final model with p<0.05. Calibration of the nomogram was carried out by internal validation using the bootstrap resampling approach and was displayed using a calibration curve. The discrimination of the model was evaluated using the ROC curve. Based on the database of the three institutions, a total of 18,600 breast cancer patients were identified undergoing SLNB between May 2010 and 2020. Among the 1817 HR+/HER2- patients with 1-2 positive SLNs undergoing ALND, 84.2% harbored ≤ 3 totals metastatic ALNs. The multivariate logistic regression analysis identified imaging abnormal nodes (OR=0.197, 95%CI: 0.082-0.472), the number of positive SLNs (OR=0.351, 95%CI: 0.266-0.464), the number of negative SLNs (OR=1.639, 95%CI: 1.465-1.833), pathological tumor stage (OR=0.730, 95%CI: 0.552-0.964), and lympho-vascular invasion (OR=0.287, 95%CI: 0.222-0.398) as independent predictors for the proportion of patients with ≤ 3 total metastatic ALNs (all p<0.05). These five predictors were used to create a predictive nomogram. The AUC value was 0.804 (95%CI: 0.681-0.812, p<0.001). The calibration curve showed a satisfactory fit between the predictive and actual observation based on internal validation with a bootstrap resampling frequency of 1000. The nomogram based on the multi-centric database showed a good accuracy and could assist the oncologist in determining precisely which HR+/HER2- candidates with 1-2 positive SLNs without ALND could perform genomic tests. In the era of SLNB and precision medicine, the combined application of genomic tests and SLNB could provide patients with a better strategy of dual de-escalation management, including the de-escalation of both surgery and systemic treatment.


Plasmid-mediated quinolone resistance in typhoidal Salmonellae: a preliminary report from South India.
Fluoroquinolones are the drugs extensively employed for the treatment of Salmonella infections. Over the couple of decades that have elapsed since the introduction of fluoroquinolones, resistance to these agents by Enterobacteriaceae family members has become common and widespread. Although fluoroquinolone resistance is mediated by genomic DNA (deoxyribonucleic acid) as well as plasmid DNA, the plasmid-mediated quinolone resistance (PMQR) facilitates higher level resistance by interacting with genomic mechanism and is capable of horizontal spread. During a period of 1-year, 63 typhoidal Salmonellae were isolated from 14,050 blood cultures and one parietal wall abscess. 36 (56.25%) were Salmonella Typhi and 27 (42%) were Salmonella Paratyphi A. They were all screened for resistance by the disc diffusion method and their minimum inhibitory concentrations were determined using agar dilution, broth dilution and E-strip method. Ciprofloxacin resistant isolates were screened for PMQR determinants by polymerase chain reaction assay. All the 63 isolates were resistant to nalidixic acid. Among the 36 S. Typhi isolates 20 were resistant to ciprofloxacin, of which 14 carried the plasmid gene qnrB and one carried the aac(6')-Ib-cr gene. qnrA and qnrS genes were not detected. Ciprofloxacin resistance was not seen in any of the S. Paratyphi A isolates. The antibiotic sensitivity pattern of typhoidal Salmonellae shows an increasing trend of PMQR. The allele B of qnr gene was found to be the predominant cause of PMQR in this study.


Adnexal torsion presenting as an acute abdomen in a patient with bilateral cystic teratoma of the ovary.
Benign cystic teratomas are the most common ovarian neoplasms in women. Teratomas are usually benign, unilateral, and most often found in young and premenopausal women. Most are 5 cm to 10 cm in diameter when diagnosed, and on sectioning, they usually contain thick sebaceous material, tangled hair, and various dermal structures. One of the major complications seen in cystic teratoma is torsion, a partial or complete twisting of the ovarian suspensary pedicle causing severe pain, nausea, and tissue necrosis. The patient described had bilateral cystic teratomas, one uncommonly large and torsed, causing an acute abdomen. Discussion includes the diagnosis, operative management, and postoperative findings.


[Hereditary non-allergic angioneurotic edema and the complement system (author's transl)].
By way of example of a patient and his family and by means of the literature, the present knowledge of pathogenesis and therapy of hereditary non-allergic angioneurotic edema has been reviewed.


Lung eosinophilic inflammation and airway hyperreactivity are enhanced by murine anaphylactic, but not nonanaphylactic, IgG1 antibodies.
Chronic airway inflammation is a fundamental feature of bronchial asthma, which is characterized by the accumulation and activation of inflammatory cells, such as mast cells and eosinophils, that are tightly regulated by TH2 cytokines and chemokines. Recently, we demonstrated, in a murine model of asthma with immunosuppressed mice reconstituted with antigen-specific IgE or IgG1 antibodies, that IgE, but not IgG1, participates in potentiation of airway inflammation and induction of airway hyperreactivity (AHR). The IgG1 antibody, however, did not elicit passive cutaneous anaphylactic reactions, which was in contrast to IgE. Because 2 types of murine IgG1 have been demonstrated with regard to anaphylactic activity, the present experiments were undertaken to determine the role of anaphylactic and nonanaphylactic IgG1 antibodies in the development of antigen-induced eosinophilia and AHR in this model. Dinitrophenyl-conjugated, heat-coagulated hen's egg white was implanted in immunosuppressed mice reconstituted with anaphylactic or nonanaphylactic IgG1. Intratracheal challenge with aggregated dinitrophenyl-ovalbumin was performed on day 14, and lung inflammatory and mechanical parameters were evaluated after 48 hours. Our results demonstrated that reconstitution of immunosuppressed mice with anaphylactic IgG1 antibodies in contrast to nonanaphylactic IgG1 antibodies potentiates their ability to have pulmonary eosinophilic inflammation and AHR. IL-5 and eotaxin levels in bronchoalveolar lavage fluid from anaphylactic IgG1-reconstituted mice were also higher than those in nonanaphylactic IgG1-reconstituted mice. These results indicate that the anaphylactic property of murine IgG1 molecules is essential for their capacity to enhance lung eosinophilic inflammation and to induce AHR.


The normal location of the fetal conus medullaris.
In vivo studies of the location of the normal conus medullaris in infancy and childhood have been extended to the fetus utilizing sonography. This prospective study of 33 fetuses showed that the fetal conus medullaris can be visualized in the prone fetus as early as 19 menstrual weeks. By the time the conus medullaris was observed sonographically, its location was within the normal adult range, thus refuting the commonly held notion that the conus medullaris ascends to adult levels sometime in childhood. Our results suggest that a fetal spinal cord termination level of L2-L3 or higher should be considered within normal limits. A termination level of L3 is indeterminate and requires neonatal evaluation. A termination level of L3-L4 or lower is abnormal and should instigate a careful sonographic search for associated abnormalities.


Loss of interface pressure in various compression bandage systems over seven days.
Manufacturers' instructions of multi-component compression bandage systems inform that these products can remain up to 7 days during the therapy of venous leg ulcer. This implies that the pressure needed will be sustained during this time. The present research investigated the persistence of pressure of compression systems over 7 days. All 6 compression systems available in Germany at the time of the trial were tested on 35 volunteering persons without signs of venous leg disease. Bandaging with short-stretch bandages was included for comparison. Pressure was measured by using PicoPress®. Initially, all products showed sufficient resting pressure of 40 mm Hg checked with a pressure monitor, except for one system in which the pressure fell by at least 23.8%, the maximum being 47.5% over a period of 7 days. The currently available compression systems are not fit to keep the required pressure. Optimized products need to be developed.


Comprehensive study of serine/arginine-rich (SR) gene family in rice: characterization, evolution and expression analysis.
As important regulators of alternative splicing (AS) events, serine/arginine (SR)-rich proteins play indispensable roles in the growth and development of organisms. Until now, the study of SR genes has been lacking in plants. In the current study, we performed genome-wide analysis on the SR gene family in rice. A total of 24 OsSR genes were phylogenetically classified into seven groups, corresponding to seven subfamilies. The OsSR genes' structures, distribution of conserved domains, and protein tertiary structure of OsSR were conserved within each subfamily. The synteny analysis revealed that segmental duplication events were critical for the expansion of OsSR gene family. Moreover, interspecific synteny revealed the distribution of orthologous SR gene pairs between rice and Arabidopsis, sorghum, wheat, and maize. Among all OsSR genes, 14 genes exhibited NAGNAG acceptors, and only four OsSR genes had AS events on the NAGNAG acceptors. Furthermore, the distinct tissue-specific expression patterns of OsSR genes showed that these genes may function in different developmental stages in rice. The AS patterns on the same OsSR gene were variable among the root, stem, leaf, and grains at different filling stages, and some isoforms could only be detected in one or a few of tested tissues. Meanwhile, our results showed that the expression of some OsSR genes changed dramatically under ABA, GA, salt, drought, cold or heat treatment, which were related to the wide distribution of corresponding cis-elements in their promoter regions, suggesting their specific roles in stress and hormone response. This research facilitates our understanding of SR gene family in rice and provides clues for further exploration of the function of OsSR genes.


Carbonaceous Nanomaterials for Phototherapy of Cancer.
Carbonaceous nanomaterials (CNMs) have drawn tremendous biomedical research interest because of their unique structural features. Recently, CNMs, namely carbon dots, fullerenes, graphene, etc, have been successful in establishing them as considerable nanotherapeutics for phototherapy applications due to their electrical, thermal, and surface properties. This review aims to crosstalk the current understanding of CNMs as multimodal compounds in photothermal and photodynamic therapies as an integrated approach to treating cancer. It also expounds on phototherapy's biomechanics and illustrates its relation to cancer biomodulation. Critical considerations related to the structural properties, fabrication approaches, surface functionalization strategies, and biosafety profiles of CNMs have been explained. This article provides an overview of the most recent developments in the study of CNMs used in phototherapy, emphasizing their usage as nanocarriers. To conquer the current challenges of CNMs, we can raise the standard of cancer therapy for patients. The review will be of interest to the researchers working in the area of photothermal and photodynamic therapies and aiming to explore CNMs and their conjugates in cancer therapy.


Genome-wide identification of Hami melon miRNAs with putative roles during fruit development.
MicroRNAs represent a family of small endogenous, non-coding RNAs that play critical regulatory roles in plant growth, development, and environmental stress responses. Hami melon is famous for its attractive flavor and excellent nutritional value, however, the mechanisms underlying the fruit development and ripening remains largely unknown. Here, we performed small RNA sequencing to investigate the roles of miRNAs during Hami melon fruit development. Two batches of flesh samples were collected at four fruit development stages. Small RNA sequencing yielded a total of 54,553,424 raw reads from eight libraries. 113 conserved miRNAs belonging to 30 miRNA families and nine novel miRNAs comprising nine miRNA families were identified. The expression of 42 conserved miRNAs and three Hami melon-specific miRNAs significantly changed during fruit development. Furthermore, 484 and 124 melon genes were predicted as putative targets of 29 conserved and nine Hami melon-specific miRNA families, respectively. GO enrichment analysis were performed on target genes, "transcription, DNA-dependent", "rRNA processing", "oxidation reduction", "signal transduction", "regulation of transcription, DNA-dependent", and "metabolic process" were the over-represented biological process terms. Cleavage sites of six target genes were validated using 5' RACE. Our results present a comprehensive set of identification and characterization of Hami melon fruit miRNAs and their potential targets, which provide valuable basis towards understanding the regulatory mechanisms in programmed process of normal Hami fruit development and ripening. Specific miRNAs could be selected for further research and applications in breeding practices.


Familial dilated (congestive) cardiomyopathy. Occurrence in two brothers and an overview of the literature.
Two young White brothers had dilated (congestive) cardiomyopathy. The elder came to autopsy after a chronic course of congestive cardiac failure, the younger underwent repeated cardiac catheterization and transvenous right ventricular endomyocardial biopsy specimens demonstrated histopathological features in keeping with a diagnosis of idiopathic dilated cardiomyopathy. These brothers may have the familial form of the disease, although post-viral myocarditis cardiomyopathy cannot be entirely excluded. The literature relating to familial dilated (congestive) cardiomyopathy is reviewed.


Breast reconstruction in previously irradiated patients using tissue expanders and implants: a potentially unfavorable result.
There exists a paucity of definitive information on the suitability of implant reconstructions in previously irradiated breast cancer patients. This controversial topic prompted a review of our prosthetic reconstructions in this select group of patients. A retrospective study of patients treated between 1976 and 1993 with lumpectomy and radiation therapy for early breast cancer revealed 67 patients with local recurrences. Nine of these patients (10 breasts) underwent a two-stage prosthetic reconstruction following a salvage mastectomy. The average age was 47.9 years. The mean dose of irradiation was 6,070 cGy. The average interval from radiation therapy to placement of a tissue expander was 4.6 years. In one patient (10%) the tissue expander extruded. The average follow-up for 8 patients (9 breasts) who underwent exchange to a permanent prosthesis was 5.1 years. In four reconstructions (40%) there was an uneventful postoperative course. Two cases (20%) were difficult to expand and the final result lacked projection. One patient (10%) developed an infection requiring removal of the permanent prosthesis. Two patients (20%) developed Baker class III or IV capsular contractures. Overall, in our group of 10 implant reconstructions, 60% of the patients resulted in either a complication or an unfavorable result.


Rapidly Simultaneous Determination of Six Effective Components in Cistanche tubulosa by Near Infrared Spectroscopy.
Quantitative determination of multiple effective components in a given plant usually requires a very large amount of authentic natural products. In this study, we proposed a rapid and non-destructive method for the simultaneous determination of echinacoside, verbascoside, mannitol, sucrose, glucose and fructose in Cistanche tubulosa by near infrared spectroscopy (NIRS). Near infrared diffuse reflectance spectroscopy (DRS) and high performance liquid chromatography (HPLC) were conducted on 116 batches of C. tubulosa samples. The DRS data were processed using standard normal variety (SNV) and multiplicative scatter correction (MSC) methods. Partial least squares regression (PLSR) was utilized to build calibration models for components-of-interest in C. tubulosa. All models were then assessed by calculating the root mean square error of calibration (RMSEC), correlation coefficient of calibration (r). The r values of all six calibration models were determined to be greater than 0.94, suggesting each model is reliable. Therefore, the quantitative NIR models reported in this study can be qualified to accurately quantify the contents of six medicinal components in C. tubulosa.


Comprehensive Prediction of Lipocalin Proteins Using Artificial Intelligence Strategy.
Lipocalin belongs to the calcyin family, and its sequence length is generally between 165 and 200 residues. They are mainly stable and multifunctional extracellular proteins. Lipocalin plays an important role in several stress responses and allergic inflammations. Because the accurate identification of lipocalins could provide significant evidences for the study of their function, it is necessary to develop a machine learning-based model to recognize lipocalin. In this study, we constructed a prediction model to identify lipocalin. Their sequences were encoded by six types of features, namely amino acid composition (AAC), composition of k-spaced amino acid pairs (CKSAAP), pseudo amino acid composition (PseAAC), Geary correlation (GD), normalized Moreau-Broto autocorrelation (NMBroto) and composition/transition/distribution (CTD). Subsequently, these features were optimized by using feature selection techniques. A classifier based on random forest was trained according to the optimal features. The results of 10-fold cross-validation showed that our computational model would classify lipocalins with accuracy of 95.03% and area under the curve of 0.987. On the independent dataset, our computational model could produce the accuracy of 89.90% which was 4.17% higher than the existing model. In this work, we developed an advanced computational model to discriminate lipocalin proteins from non-lipocalin proteins. In the proposed model, protein sequences were encoded by six descriptors. Then, feature selection was performed to pick out the best features which could produce the maximum accuracy. On the basis of the best feature subset, the RF-based classifier can obtained the best prediction results.


Interventions and their efficacy in controlling the spread of an epidemic: A numerical study.
The effect of interventions on the progression of an epidemic is studied by numerically modeling attributes, such as lockdowns and vaccinations within a stochastic, highly connected, mobile community using an agent-based model. Based on real life assumptions, we are able to gauge the effectiveness of various strategies to contain the spread of a disease through a population. The fine-tuning of control parameters makes the model coherent with real life scenarios and robust from a policy-maker's perspective.


Unfavorable outcome in patients with primary electrical disease who survived an episode of ventricular fibrillation.
Prognosis in patients with ventricular tachyarrhythmia without structural heart disease (primary electrical disease) has been described as excellent. However, prognosis may be less favourable in the subgroup surviving an episode of ventricular fibrillation. We prospectively followed 19 consecutive patients (age, 13 to 66 years; mean age, 33 years) who had survived an episode of documented ventricular fibrillation. Structural heart disease, preexcitation, and long QT syndromes were excluded by thorough cardiologic evaluation. All patients underwent 24-hour Holter monitoring, exercise testing, and programmed electrical stimulation according to a standardized protocol. Holter monitoring revealed episodes of ventricular tachyarrhythmia in 5 patients. Exercise testing reproducibly provoked ventricular tachycardia in 2 patients. Baseline programmed electrical stimulation yielded inducibility of rapid ventricular tachyarrhythmia in 10 patients (53%) and noninducibility in 9 (47%). Nine patients were discharged on antiarrhythmic drug therapy. A defibrillator was implanted in 10 patients. During 43-month follow-up (range, 5 to 85 months; median, 41 months), major arrhythmic events recurred in 7 patients (37%). Four of these patients had noninducibility at baseline programmed electrical stimulation. Two patients on antiarrhythmic drugs had recurrent cardiac arrest: one died suddenly and the other was successfully resuscitated from ventricular fibrillation and subsequently underwent defibrillator implantation. In the other 5 patients, termination of (pre)syncopal episodes was associated with defibrillator shocks. Termination of ventricular fibrillation was documented by Holter recording in one of these patients. Specific markers predictive of a recurrent event could not be identified, although 6 of 7 patients with recurrent events had experienced at least one episode of cardiac arrest or (pre)syncope before the index episode. Patients with primary electrical disease presenting with ventricular fibrillation are at high risk of recurrence of major arrhythmic events during long-term follow-up. Noninducibility at baseline study does not predict an uneventful course. Also, early defibrillator implantation should be considered in these patients.


Design, synthesis, and molecular modelling of pyridazinone and phthalazinone derivatives as protein kinases inhibitors.
The design and synthesis of pyridazinone and phthalazinone derivatives are described. Newly synthesized compounds were tested on a panel of four kinases in order to evaluate their activity and potential selectivity. In addition, the promising compounds were tested on four cancer cell lines to examine cytotoxic effects. The compounds inhibited DYRK1A and GSK3 with different activity. SAR analysis and docking calculations were carried out to aid in the interpretation of the results. Taken together, our findings suggest that pyridazinone and phthalazinone scaffolds are interesting starting points for design of potent GSK3 and DYRK1A inhibitors.


Origin, nature, and some functional considerations of intraventricular macrophages, with special reference to the epiplexus cells.
Intraventricular macrophages encompass the supraependymal, free-floating, and epiplexus (Kolmer) cells; the supraependymal cells lie in close apposition to the ventricular ependyma, the epiplexus cells are closely associated with the choroid plexus epithelium, and the free-floating cells are at a variable distance from the epithelial surface. Although the three cell types are regarded as one cellular entity, the epiplexus cells preponderate. On scanning electron microscopy, the epiplexus cells display diverse morphological forms, ranging from round to bipolar to stellate, and bear a variable number of cytoplasmic processes. Transmission electron microscopy shows the presence of large numbers of lysosomes. The phagocytic nature of epiplexus cells is shown by their intense staining for nonspecific esterase and active uptake of tracers, e.g., horseradish peroxidase and rhodamine isothiocynate, administered intravenously or intraperitoneally. The mode of entry of these tracers in the cerebral ventricles is by way of transepithelial transport. In rats, the population of intraventricular macrophages increases steadily after birth until 17 days of age; thereafter, their cell population remains relatively unchanged. The early upsurge is attributed to proliferation of residential cells and/or influx of circulating monocytes/stromal macrophages through the process of "emperipolesis." The immunophenotypic features of intraventricular macrophages are consistent with other mononuclear phagocytes being immunoreactive for OX-42, OX-18, OX-6, and OX-1 and ED1 for the detection of CR3 receptors, MHC class I and II antigens, leucocyte common antigen, and macrophage antigen, respectively. The expression of these antigens is noticeably enhanced following the injection of lipopolysaccharide (LPS) into postnatal rats. Remarkably, the intraventricular macrophages are induced to express MHC class II (Ia) antigen after LPS or interferon-gamma injections. Furthermore, the expression of transferrin receptors as detected with OX-26 is also upregulated after these treatments. Epiplexus cells are also elicited to display a de novo expression of nitric oxide synthase-like immunoreactivity following intracerebral injection of LPS. They also respond vigorously to a single nonpenetrative blast. Results of our series of studies suggest that, besides their primary function as scavenger cells, the intraventricular macrophages partake in possible immunological responses and iron regulation in the ventricular system or the brain as a whole.


Facile synthesis of hierarchically nanostructured bismuth vanadate: An efficient photocatalyst for degradation and detection of hexavalent chromium.
Heterostructured nanomaterials can paid more significant attention in environmental safety for the detection and degradation/removal of hazardous toxic chemicals over a decay. Here, we report the preparation of hierarchically nanostructured shuriken like bismuth vanadate (BiVO4) as a bifunctional catalyst for photocatalytic degradation and electrochemical detection of highly toxic hexavalent chromium (Cr(VI)) using the green deep eutectic solvent reline, which allows morphology control in one of the less energy-intensive routes. The SEM results showed a good dispersion of BiVO4 catalyst and the HR-TEM revealed an average particle size of ca. 5-10 nm. As a result, the BiVO4 exhibited good photocatalytic activity under UV-light about 95% reduction of Cr(VI) to Cr(III) was observed in 160 min. The recyclability of BiVO4 catalyst exhibited an appreciable reusability and stability of the catalyst towards the photocatalytic reduction of Cr(VI). Also, the BiVO4-modified screen printed carbon electrode (BiVO4/SPCE) displayed an excellent electrochemical performance towards the electrochemical detection of Cr(VI). Besides, the BiVO4/SPCE demonstrated tremendous electrocatalytic activity, lower linear range (0.01-264.5 μM), detection limit (0.0035 μM) and good storage stability towards the detection of Cr(VI). Importantly, the BiVO4 modified electrode was also found to be a good recovery in water samples for practical applications.


Inhibition of L-Type Ca2+ Channels by TRPC1-STIM1 Complex Is Essential for the Protection of Dopaminergic Neurons.
Loss of dopaminergic (DA) neurons leads to Parkinson's disease; however, the mechanism(s) for the vulnerability of DA neurons is(are) not fully understood. We demonstrate that TRPC1 regulates the L-type Ca2+ channel that contributes to the rhythmic activity of adult DA neurons in the substantia nigra region. Store depletion that activates TRPC1, via STIM1, inhibits the frequency and amplitude of the rhythmic activity in DA neurons of wild-type, but not in TRPC1-/-, mice. Similarly, TRPC1-/- substantia nigra neurons showed increased L-type Ca2+ currents, decreased stimulation-dependent STIM1-Cav1.3 interaction, and decreased DA neurons. L-type Ca2+ currents and the open channel probability of Cav1.3 channels were also reduced upon TRPC1 activation, whereas increased Cav1.3 currents were observed upon STIM1 or TRPC1 silencing. Increased interaction between Cav1.3-TRPC1-STIM1 was observed upon store depletion and the loss of either TRPC1 or STIM1 led to DA cell death, which was prevented by inhibiting L-type Ca2+ channels. Neurotoxins that mimic Parkinson's disease increased Cav1.3 function, decreased TRPC1 expression, inhibited Tg-mediated STIM1-Cav1.3 interaction, and induced caspase activation. Importantly, restoration of TRPC1 expression not only inhibited Cav1.3 function but increased cell survival. Together, we provide evidence that TRPC1 suppresses Cav1.3 activity by providing an STIM1-based scaffold, which is essential for DA neuron survival.SIGNIFICANCE STATEMENT Ca2+ entry serves critical cellular functions in virtually every cell type, and appropriate regulation of Ca2+ in neurons is essential for proper function. In Parkinson's disease, DA neurons are specifically degenerated, but the mechanism is not known. Unlike other neurons, DA neurons depend on Cav1.3 channels for their rhythmic activity. Our studies show that, in normal conditions, the pacemaking activity in DA neurons is inhibited by the TRPC1-STIM1 complex. Neurotoxins that mimic Parkinson's disease target TRPC1 expression, which leads to an abnormal increase in Cav1.3 activity, thereby causing degeneration of DA neurons. These findings link TRPC1 to Cav1.3 regulation and provide important indications about how disrupting Ca2+ balance could have a direct implication in the treatment of Parkinson's patients.


Nonideal behavior of the intramolecular structure factor of dilute polymers in a theta solvent.
We study the configurational properties of single polymers in a theta solvent by Monte Carlo simulation of the bond fluctuation model. The intramolecular structure factor at the theta point is found to be distinctively different from that of the ideal chain. The structure factor shows a hump around q approximately 5/Rg and a dip around q approximately 10/Rg in the Kratky plot with Rg being the radius of gyration. This feature is apparently similar to that in a melt. The theoretical expression by the simple perturbation expansion to the first order in terms of the Mayer function can be fitted to the obtained structure factor quite well, but the second virial coefficient cannot be set to zero.


[Value of tumor biological prognostic factors in adjuvant therapy of node-negative breast cancer].
In an extensive meta-analysis it was shown that adjuvant therapy improves the course of the disease in breast cancer. This risk reduction was observed independent of the stage of disease in the same percentage in node-negative and node-positive patients. As a consequence, recommendations were given to offer all patients some kind of adjuvant therapy regardless of lymph node status. In node-negative disease, however, prognosis is assumed to be good in general, as about 70% are cured by locoregional surgery alone. Therefore it was alternatively suggested to select high-risk node-negative patients for adjuvant chemotherapy by a combination of different prognostic factors. Both, established and new prognostic factors should meet strict statistical and methodological requirements before clinical application to therapeutic decisions is justified. The malignant potential of solid tumors consists in their capacity for fast proliferation on the one hand and for invasion and metastasis on the other. Estimation of proliferation rate in breast cancer is now possible by determination of S-phase fraction, thymidine labelling index (TLI), or Ki-67 (MIB-1) antigen. Also steroid receptors (inverse correlation) and EGF-R show a high correlation with proliferation parameters; they can therefore be regarded as indirect indicators for proliferation. Unfortunately up to now none of these factors is of satisfactory clinical value for node negative breast cancer. Factors capable to quantify invasive and metastatic capacity of malignant cells should be even more suitable for estimation of prognosis, as mortality in the disease is predominantly based on occurrence of distant metastasis.(ABSTRACT TRUNCATED AT 250 WORDS)


Novel FEMASK-score, a histopathologic assessment for destructive Charcot neuropathic arthropathy, reveals intraneural vasculopathy and correlates with progression and best treatment.
Charcot neuropathic arthropathy is a debilitating, rapidly destructive degenerative joint disease that occurs in diabetic, neuropathic midfoot. Clinicoradiologic assessment for Charcot neuropathic arthropathy previously relied on Eichenholtz stage. There is limited histopathologic data on this entity. We wanted to independently develop a histopathologic scoring system for Charcot neuropathic arthropathy. Retrieval of surgical pathology midfoot specimens from Charcot patients (2012-2019) were analyzed to evaluate joint soft tissue and bone. Considering progression from large (≥half 40× hpf) to small (<half 40× hpf) periarticular bone fragments to resolution, we devised and applied a Charcot neuropathic arthropathy novel FEMASK-score (named after coauthors: Fanburg-Smith, Frauenhoffer, Flemming, Fritsche, Elfar, Murie, Aynardi, Stauch, Smith, King, and Klein): 0 (initial) = the observed intraneural arteriolosclerosis in all diabetic neuropathic patient specimens (not observed in other diabetic nerves); and finally scored with the most destruction observed: 1 = large bone fragments without host histiocytic response; 2 = mixed bone fragments with host histiocytic response; 3 = small minute bone spicules resorption to fibrosis. Eichenholtz stage and outcome were then compared. Forty-eight cases of Charcot neuropathic arthropathy included 34 males and 14 females, mean age 60.3 and age range 28-83 years, with clinical diabetes mellitus (predominantly Type II) and longstanding neuropathy. Elevated HbA1C, Eichenholtz stage, American Society of Anesthesia score, and Charlson comorbidity index indicated initial clinical amputation. Pathologic specimens varied from fixation tissue to amputation. In addition to neurotraumatic, neurovascular and inflammatory findings, a distinctive intraneural hyalinized arteriolosclerosis was observed. FEMASK-scores: 1 = 10%, 2 = 58%, and 3 = 32%. Score comparisons were 98% accurate compared with Eichenholtz and 98% reproducible among pathologists. FEMASK 2 and 3 correlate with clinical need for amputation. Our novel Charcot neuropathic arthropathy FEMASK-score classification, derived from the largest cohort of diabetic neuropathic specimens, is reproducible, explains pathophysiologic progression of destructive phase of Charcot, correlates with Eichenholtz, and predicts progression to or clinical need for amputation. The unique intraneural vasculopathy observed contributes to Charcot neuropathic arthropathy etiology.


Relevance of microbial symbiosis to insect behavior.
Microbial symbiosis is widespread among insects. This article reviews our understanding of insect behaviors relevant to commensalistic and mutualistic microbial symbiosis, which has received relatively less attention compared to insect behaviors in parasitic symbiosis. First, we review our knowledge of symbiont transmission behaviors by which the host insects maintain associations with beneficial microorganisms over generations. Some insects that extracellularly harbor mutualistic symbionts exhibit particularly sophisticated behaviors for vertical symbiont transmission. Next, we highlight notable studies on behavioral changes induced by symbiont infection. In the last decade, a number of studies have demonstrated or suggested that mutualistic or commensalistic symbiont infections affect their host behaviors. Finally, future directions regarding these research topics are discussed.


Encapsulation of coenzyme Q10 in a simple emulsion-based nutraceutical formulation and application in cheese manufacturing.
Coenzyme Q10 (CoQ10) was encapsulated successfully in a nutraceutical formulation composed of calcium caseinate, flaxseed oil and lecithin. The effect of CoQ10 on the physico-chemical stability of emulsions was compared to emulsions without CoQ10. According to ATR-FTIR analysis, emulsions were found to be more stable in the presence of CoQ10. The emulsion with CoQ10 was used as a functional cream in the cheese making process. The retention rate of CoQ10, composition and cheese yield were also determined. Quantification of CoQ10 by HPLC showed that the retention of this lipophilic agent into cheese matrix was 93% and equivalent to the total lipid retention. Protein retention and cheese yield were not affected by the addition of the functional cream. For the first time, CoQ10 has been encapsulated in a cheese matrix, hence demonstrating that CoQ10 could be used in the development of functional cheeses.


Stress and Learning in Pupils: Neuroscience Evidence and its Relevance for Teachers.
Our understanding of how stress affects primary school children's attention and learning has developed rapidly. We know that children experience differing levels of stressors (factors that cause stress) in their environments, and that this can influence how they respond to new stressors when they occur in educational contexts. Here, we review evidence showing that stress can increase children's attention and learning capacities in some circumstances but hinder them in others. We show how children differ in their attention and learning styles, dependent on stress levels: for example, more highly stressed children may be more distracted by superficial features and may find it harder to engage in planning and voluntary control. We review intervention research on stress management techniques in children, concentrating on psychological techniques (such as mindfulness and stress reappraisal), physiological techniques (such as breathing exercises) and environmental factors (such as reducing noise). At the current time, raising teachers' awareness of pupils' differing stress responses will be an important step in accommodating the differing needs of children in their classrooms.


Association of folate metabolism-related genetic polymorphisms with susceptibility to breast cancer: A protocol for a systematic review and meta-analysis.
Breast cancer has recently become one of the most common causes of cancer-related deaths, and several studies have suggested that genetic polymorphisms in the folate metabolism pathway may be associated with susceptibility to breast cancer, although their results have been inconsistent or inconclusive. Therefore, the aim of this meta-analysis was to obtain accurate, consistent conclusions regarding the potential associations of genetic polymorphisms in the folate metabolism pathway with the risk of breast cancer, based on case-controlled studies. From the beginning of database establishment through May 2021, we indexed and searched domestic and foreign databases, including the Chinese National Knowledge Infrastructure, Web of Science, VIP and BioMedical Database of China, PubMed, EMBASE, Wanfang database, and the Cochrane Library. To determine the effects of folate metabolism-related genetic polymorphisms on breast cancer risk, we used Stata version 16.0 to analyze all data and calculated variable odds ratios and 95% confidence intervals. The findings of the current meta-analysis are going to be presented to peer-reviewed journals for publication when the analysis is completed. The meta-analysis will summarize the association of genetic polymorphisms in the folate metabolism pathway with breast cancer. May 26, 2021.osf.io/25r48. (https://osf.io/25r48/).


Comparison of classroom instruction and independent study in body mechanics.
This study was designed to determine which method of instruction in body mechanics results in the higher subsequent use of the techniques taught. Two groups were formed from nursing personnel at a rural general medical-surgical hospital in the southwestern United States. Subjects from the direct care nursing staff were randomly assigned to one of the two groups. One group attended two hours of classroom instruction in body mechanics, while the other completed an independent study module. Subjects were pre- and posttested using the Work-Related Body Mechanics Evaluation (Carlton, 1987) while performing a standardized lifting task in the clinical setting. Using analysis of covariance, no significant differences were found in the posttest scores of the two groups.


Long-term survival of Shiga toxin-producing Escherichia coli in cattle effluents and environment: an updated review.
Shiga toxin-producing Escherichia coli (STEC) are one of the most important emergent foodborne pathogens. STEC are common as colonizers in the intestine of healthy cattle and are spread into the environment by fecal shedding or following the surface application of farm effluent on soil. The bacteria can be transmitted to humans through food, such as inadequately cooked ground beef or unpasteurized milk. During the last decade, a wide variety of environmentally related exposures have emerged as new routes of transmission. Major outbreaks due to the consumption of raw fruits and vegetables or accidental ingestion of soil or water contaminated by STEC have been increasingly reported. STEC survival in cattle effluents, soil, plants and water is discussed in the light of new knowledge regarding both biotic and abiotic factors which may affect their survival or enhance their dissemination in the environment. The ability to persist in cattle production environments contributes to the contamination and recontamination of cattle, as well as for human infection. Consequently, effective control strategies must be considered on cattle farms, in order to limit entry of STEC cells into the environment.


Optimal control of transitions between nonequilibrium steady states.
Biological systems fundamentally exist out of equilibrium in order to preserve organized structures and processes. Many changing cellular conditions can be represented as transitions between nonequilibrium steady states, and organisms have an interest in optimizing such transitions. Using the Hatano-Sasa Y-value, we extend a recently developed geometrical framework for determining optimal protocols so that it can be applied to systems driven from nonequilibrium steady states. We calculate and numerically verify optimal protocols for a colloidal particle dragged through solution by a translating optical trap with two controllable parameters. We offer experimental predictions, specifically that optimal protocols are significantly less costly than naive ones. Optimal protocols similar to these may ultimately point to design principles for biological energy transduction systems and guide the design of artificial molecular machines.


Hormonal contraception: venous and arterial disease.
The aim of this review was to evaluate whether the biological and epidemiological evidence is concordant in suggesting that levonorgestrel (LNG)-based hormonal contraceptives (HCs) are safer than newer formulations with regard to their effect on the cardiovascular system. A narrative review was carried out of the modification of risk factors for venous thromboembolism (VTE) and arterial diseases induced by different HCs. Limits and concordance with epidemiological data were addressed. The data indicate general concordance between modifications of risk factors and epidemiology of VTE, with LNG-based HCs showing lower risk compared with most new formulations. Evidence for drospirenone (DRSP)-containing HCs is conflicting. LNG-based HCs are less favourable than HCs containing non-androgenic progestins, particularly DRSP, on risk factors for arterial events. Epidemiological studies do not consistently show a difference in arterial disease outcomes between different HCs; however, by evaluating women up to the age of 50, they do not take into consideration the time lag necessary for atherosclerosis to develop. As a consequence of the different risk factors involved, and the different time lags between HC use and the manifestation of VTE or arterial diseases, the available epidemiological data do not give a reliable estimate of the cardiovascular risk associated with the use of different HCs. LNG-based HCs are safer than newer HCs as regards VTE risk, but biological data indicate that they are less favourable, particularly than HCs containing DRSP, on risk factors for atherosclerosis. Because of the limits of actual epidemiological evidence regarding arterial disease, modifications of arterial risk factors should be taken into consideration when considering individual long-term safety of HC use.


Live Cell Microscopy: A Physical Chemistry Approach.
Probing dynamics of intracellular components using physical chemistry techniques is a remarkable bottom-up approach for understanding the structures and functions of a biological cell. In this "Feature Article", we give an overview on local polarity, solvation, viscosity, acid-base property, red-ox processes (thiol-disulfide exchange), and gene silencing at selected intracellular components inside a live cell. Significant differences have been observed between cancer cells and their noncancer counterparts. We demonstrate that thiol-disulfide exchange, calcium oscillation, and gene silencing are manifested in time dependence of fluorescence intensity. We show that fluorescent gold nanoclusters may be used in drug delivery (e.g., doxorubicin) and selective killing of cancer cells. Further, we discuss dynamics and structural changes of DNA quadruplexes and i-motifs, induced by different external conditions (e.g., pH) and additives (e.g., K+ and other target specific small molecules). We demonstrate that peptidomimetic analogues have high specificity over double-stranded DNA for binding with i-motifs and G-quadruplexes. These results may have significant biological implications.


Reference ranges and Z-scores for fetal cardiac measurements from two-dimensional echocardiography in Asian population.
Currently available fetal echocardiographic reference values are derived mainly from North American and European population studies, and there is a lack of reference z-score for fetal echocardiographic measurement in Asian populations. The aim of this study was to establish normal ranges of echocardiographic measurements and z-scores in healthy Asian fetuses. A total of 575 healthy pregnant Taiwanese with an estimated gestational age from 14 to 38 weeks were enrolled voluntarily for this observational study. Standard two-dimensional echocardiography was performed to obtain measurements of the cardiac chambers and great arteries of the developing fetuses. In contrast to past studies, our sample was more evenly distributed for estimated gestational age (p<0.001). We present percentile graphs for 13 fetal echocardiographic measurements from the knowledge of estimated gestational age, biparietal distance, head circumference, abdominal circumference, and femur length. Most cardiac structures and developmental markers had linear models as the best-fitting, except for transverse aortic isthmus by estimated gestational age and transverse ductus arteriosus by femur length. Our findings indicate that estimated gestational age was generally the best model for fetal heart development, while head circumferences could be used as an optimal developmental marker to predict left atrium, right atrium, right ventricle, pulmonary annulus, and ductus arteriosus. Lastly, we developed nomograms for each of the 13 fetal heart measurements by each developmental markers. This is the first study providing echocardiographic reference ranges and nomograms for Asian fetuses. Computing z-scores from nomograms helps in standardizing comparisons and adds additional prognostic information to the diagnosis of congenital heart disease.


Injectable, macroporous scaffolds for delivery of therapeutic genes to the injured spinal cord.
Biomaterials are being developed as therapeutics for spinal cord injury (SCI) that can stabilize and bridge acute lesions and mediate the delivery of transgenes, providing a localized and sustained reservoir of regenerative factors. For clinical use, direct injection of biomaterial scaffolds is preferred to enable conformation to unique lesions and minimize tissue damage. While an interconnected network of cell-sized macropores is necessary for rapid host cell infiltration into-and thus integration of host tissue with-implanted scaffolds, injectable biomaterials have generally suffered from a lack of control over the macrostructure. As genetic vectors have short lifetimes in vivo, rapid host cell infiltration into scaffolds is a prerequisite for efficient biomaterial-mediated delivery of transgenes. We present scaffolds that can be injected and assembled in situ from hyaluronic acid (HA)-based, spherical microparticles to form scaffolds with a network of macropores (∼10 μm). The results demonstrate that addition of regularly sized macropores to traditional hydrogel scaffolds, which have nanopores (∼10 nm), significantly increases the expression of locally delivered transgene to the spinal cord after a thoracic injury. Maximal cell and axon infiltration into scaffolds was observed in scaffolds with more regularly sized macropores. The delivery of lentiviral vectors encoding the brain-derived neurotrophic factor (BDNF), but not neurotrophin-3, from these scaffolds further increased total numbers and myelination of infiltrating axons. Modest improvements to the hindlimb function were observed with BDNF delivery. The results demonstrate the utility of macroporous and injectable HA scaffolds as a platform for localized gene therapies after SCI.


pH-driven shifts in overall and transcriptionally active denitrifiers control gaseous product stoichiometry in growth experiments with extracted bacteria from soil.
Soil pH is a strong regulator for activity as well as for size and composition of denitrifier communities. Low pH not only lowers overall denitrification rates but also influences denitrification kinetics and gaseous product stoichiometry. N2O reductase is particularly sensitive to low pH which seems to impair its activity post-transcriptionally, leading to higher net N2O production. Little is known about how complex soil denitrifier communities respond to pH change and whether their ability to maintain denitrification over a wider pH range relies on phenotypic redundancy. In the present study, we followed the abundance and composition of an overall and transcriptionally active denitrifier community extracted from a farmed organic soil in Sweden (pH H2O = 7.1) when exposed to pH 5.4 and drifting back to pH 6.6. The soil was previously shown to retain much of its functioning (low N2O/N2 ratios) over a wide pH range, suggesting a high functional versatility of the underlying community. We found that denitrifier community composition, abundance and transcription changed throughout incubation concomitant with pH change in the medium, allowing for complete reduction of nitrate to N2 with little accumulation of intermediates. When exposed to pH 5.4, the denitrifier community was able to grow but reduced N2O to N2 only when near-neutral pH was reestablished by the alkalizing metabolic activity of an acid-tolerant part of the community. The genotypes proliferating under these conditions differed from those dominant in the control experiment run at neutral pH. Denitrifiers of the nirS-type appeared to be severely suppressed by low pH and nirK-type and nosZ-containing denitrifiers showed strongly reduced transcriptional activity and growth, even after restoration of neutral pH. Our study suggests that low pH episodes alter transcriptionally active populations which shape denitrifier communities and determine their gas kinetics.


Preliminary study to investigate the normal range of Ankle Brachial Pressure Index in young adults.
The aim of this study was to find the normal range of Ankle Brachial Pressure Index (ABPI) for healthy adults in the 20-40-year age group. The hypothesis was: there is no difference between the accepted normal value of ABPI (1.00) and the observed value of ABPI in healthy adults in the 20-40-year age group. Doppler ultrasound and ABPI calculations are used in the assessment of lower limb vascularity. Ankle Brachial Pressure Index is used as an indicator for the choice of nursing options for the treatment of chronic leg ulcers. Little research has been done to establish what the normal range of ABPI is in young healthy adults. This information has practical significance to the treatment of young adults who are prone to present with leg ulcers such as i.v. drug users. An observational survey was conducted with 24 healthy adults in the 20-40-year age range (who did not have a history of i.v. drug use). The study found that the ABPI ranged from 1.05 to 1.25 (mean = 1.14; SD 0.06). In addition, the study also found that there was a negative correlation between ABPI and observed brachial systolic pressure. A 'normal' ABPI should not be considered a fixed figure (1.00) and that ABPI may be dependant on an individual's blood pressure and possibly other factors. RELEVANCE TO CLINICAL PRACTICE. Ankle Brachial Pressure Index is a routine procedure undertaken when assessing the vascular supply to the lower legs. The results summarized in this paper will be useful to clinicians attempting to interpret ABPI results in young people.


Standardization of robotic right liver mobilization.
Since its introduction 2 decades ago, robotics has been increasingly used for resection of benign and malignant liver lesions. The robotic platform seems to preserve minimally invasive approach benefits, overcoming laparoscopy limitations. Robotic right liver mobilisation represents a key step for many robotic resections from non-anatomical resections of posterosuperior segments to right hepatectomy. We present here a standardized technique of right hepatic lobe mobilisation including technical steps and videos. Robotic resection provide all benefits of minimally invasive approaches in terms of preserving abdominal wall, early alimentation, reduced respiratory stress, associated with more ergonomic conditions for surgeon. We present our standardized and feasible right liver lobe mobilisation needed for posterosuperior resections to the right hepatectomy. The standardisation of right liver lobe represented our aim to provide a safe and reproducible initial step for many procedures to reduce the conversion rate and to improve the learning curve in young surgeons.


Acute leukaemia with a pure erythroid phenotype: under-recognized morphological and cytogenetic signatures associated universally with primary refractory disease and a dismal clinical outcome.
Pure erythroid leukaemia (PEL) is an extremely rare and aggressive subtype of acute myeloid leukaemia defined by the World Health Organization (WHO) as a neoplastic proliferation of immature cells committed exclusively to the erythroid lineage, comprising >80% of bone marrow cells and not meeting the criteria of other well-defined myeloid neoplasms. The aim of this study was to describe the clinicopathological features of acute leukaemias with a pure erythroid phenotype (ALPEP) irrespective of their WHO classification and to determine if ALPEP represents a distinct clinicopathological entity. We identified seven cases of ALPEP, in which immature cells fulfilled WHO morphological and immunophenotypical criteria for PEL. All patients except one were male, with a median age of 60 years. Three cases represented de novo PEL, three were therapy-related myeloid neoplasms and one was a blast phase of a myeloproliferative neoplasm. Extensive tumour necrosis was present in five cases (71%). Five cases with available modal karyotypes all demonstrated a complex karyotype involving the TP53 gene locus, with three cases (60%) also showing a monosomy 5 or deletion 5q and additional material on chromosome 19q13. All patients died of their disease, with a mean overall survival of 189 and 64.7 days in cases without and with necrosis on the initial biopsy, respectively. We describe previously unreported but relatively common findings of extensive tumour necrosis and recurring cytogenetic abnormalities in ALPEP. Our findings suggest strongly that ALPEP represents a distinct clinicopathological entity regardless of its WHO classification.


Vacuum sealing drainage as a pre-surgical adjunct in the treatment of complex (open) hand injuries: Report of 17 cases.
Few studies have been conducted to explore the use of the vacuum sealing drainage (VSD) technique in complex hand injuries. The aim of this study was to report outcomes in patients with complex hand injuries receiving VSD as a coadjuvant treatment prior to second-stage surgery. This case series study retrospectively reviewed the patients who underwent VSD for treatment of hand injuries. Inclusion criteria for the study were: (1) traumatic soft tissue defects of the hand and wrist, accompanied by different degrees of injury and exposure of bone, tendon, or blood vessel; (2) the wound surface of hand and wrist was seriously contaminated and direct wound closure was not possible; and (3) the soft tissues of hand and wrist were seriously lacerated or avulsed, and showed necrosis or acute infection. After debridement, one-stage and/or two-stage repairs using healthy adjacent tissues were performed and the wound was covered by the VSD materials. The non-cytotoxic polyethylene alcohol hydration seaweed salt foam was applied during the VSD treatment for its good biocompatibility. The drainage tube was connected to the vacuum equipment and the negative pressures were set at -60kPa to -40kPa. The VSD device was left in place for 5 to 7 days before removal. Either free skin grafting or skin flap transplantation was used for wound closure and/or reconstructive surgery. The hand injury severity score was used to assess wound severity. The surgical results were scored using the total active motion classification. A total of 17 patients (13 and 4 patients had major and severe hand injuries), averaging 33.8 years were included. During the study period, 6 patients with severe hand injuries were not treated with VSD for the following reasons: (1) hemodynamic instability (n=1); (2) impaired coagulation function (n=1); (3) uncontrollable hemorrhage on the wound surface (n=2); and (4) exposure of the main blood vessels after surgical repair (n=2). VSD treatment was performed for an average of 7.4 days (range, 6-14 days) and the duration of wound healing averaged 23 days (range, 20-43 days). Wound infection was not reported prior to second-stage surgery. Only one of 17 patients had superficial necrosis at the flap edge, for a success rate of 94%. Average follow-up was 8.7 months (range, 4-13 months). Twelve (71%) patients reported excellent or good, four (23%) reported fair, and one (6%) reported poor results. The VSD can effectively promote safe and rapid repair of local soft tissues with good prognosis.


[Immunization Against Measles at the Asylum Center Bielefeld, Germany: Vaccination Rate 73%, Refusal Rate 21].
The aim of this cross-sectional study was to identify the immunization rate as well as the refusals of at least one vaccination against measles by asylum seekers in the reception center (EAE) Bielefeld (a town in Germany). The findings represent a baseline for this asylum center before the implementation of mandatory immunizations against measles. This is a cross-sectional study. Lists with routinely collected management data were used to collect and analyze demographic information (age, gender, nationality) and data on vaccinations. Results In this study, data on 4606 asylum seekers based in the reception center (EAE) Bielefeld (01 January 2018-31 December 2018) were analyzed. These showed that 59% were male, 41% were female asylum seekers and 62% of them were under 30 years of age. The top ten countries of origin were: Turkey 15%, Syria 13%, Iraq 9%, Iran 9%, Nigeria 5%, Afghanistan 4%, Guinea 3%, Albania 3%, Somalia 3% and Pakistan 3%. Of the 4606 asylum seekers, 4326 were between 1 and 49 years of age; 3150 of them possessed at least one documented vaccination against measles. Thus, the immunization rate of measles vaccination was 73%. The immunization rate of measles vaccination related to different age cohorts ranged from 67% (1-4 years of age) to 78% (10-14 years of age). The following main reasons for non-vaccination against measles were identified: refusal (21%), being ill (2%), pregnancy (2%), "other" (1%). In EAE Bielefeld the immunization rate of measles vaccination was 73%. The main reason for non-immunization was refusal to be vaccinated (21% of the eligible asylum seekers). It is a matter of urgency that the immunization rate of EAE Bielefeld be increased. The planned statutory vaccination against measles and internal measures in the reception center will help closing immunization gaps. More studies involving numerous asylum reception centers are required to obtain national figures related to measles immunization of asylum seekers in Germany.