Human pulvinar units, spontaneous activity and sensory-motor influences.
Unit activity was recorded from the pulvinar nucleus (Pu) in human patients undergoing stereotaxic surgery. Thirty-six units (12 isolated and 12 pairs recorded with the same microelectrode) with a signal-to-noise ratio greater than 5, a stable amplitude, and a sustained discharge rate for more than 1 min, were selected for processing. The following functions were calculated with a digital computer to characterize discharge patterns: interval, autocorrelation and peristimulus time histograms for spikes, cross-correlation histograms between spikes of a pair, and autocorrelation functions and averages of the EEG. In spontaneous conditions, about half of the units fired in rhythmic bursts at the same or half the frequency of the Pu EEG. Most non-rhythmic units showed a "Poisson-like' interval histogram indicating a random firing pattern. Some non-rhythmic units revealed a periodic cross-correlation with the rhythmic Pu EEG, indicating that spikes tend to fire at a preferred phase of the rhythm. About half of the units showed phasic firing rate changes during voluntary movements. In most cells a discharge rate increase was observed. One unit also responded to passive movements of the fingers. Of the neurons tested, 2 out of 3 showed firing rate modulation during voluntary movements of the jaw as well as of the contralateral hand. The above units also increased the impulse rate after visual stimulation. Convergence of the effects of voluntary movements, and visual and auditory stimulation, was demonstrated in one unit. These results indicate the participation of the Pu in sensory-motor integrative functions.


Motion sickness susceptibility during rotation at 30 rpm in free-fall parabolic flight.
Free fall per se whether in parabolic or orbital flight may be regarded as a "partial" motion environment with respect to eliciting motion sickness, requiring an additional component to render this environment "complete" or stressful. Parabolic flight in toto falls in the category of a "complete" motion environment in that some persons became motion sick with head fixed and eyes closed. In the present experiment we selected subjects who were symptom free or nearly symptom free in the KC-135 with head fixed. All tests were conducted with the subject rotating at 30 rpm in a rotating litter chair, and comparisons were made between head-fixed and head-moving conditions (right-left) in the free-fall phase of parabolic flight and under simulated free-fall phases in the laboratory. With head fixed most subjects were insusceptible; with head moving left-right susceptibility was slightly higher in the laboratory than aloft. An additional comparison was made correlating susceptibility in the free-fall phases of parabolic flight with susceptibility to experimental motion sickness in Skylab. In both situations cross-coupled angular accelerations were generated by executing head and body movements out of the plane of rotation. In parabolic flight 9 of 15 subjects reached an endpoint just short of frank motion sickness. In the Skylab workshop all eight of the astronauts tested were symptom free at the end of the test. The explanation for the difference in susceptibility rests in two factors: (1) Basic susceptibility in free fall is lower than on the ground, and (2) in Skylab the astronauts who needed to adapt had achieved this goal prior to the first test on Mission-Day 8.


A biomechanical study of osseointegrated patient-matched additively manufactured implant for treatment of thumb amputees.
Thumb amputations leads to 50 % loss in hand functionality. To date, silicone vacuum prosthesis and autologous transplantation are the most adopted treatment solutions: nevertheless, vacuum prostheses lack in stability and cause skin issue and surgical treatment is not always accepted by patients. Osseointegrated implants were demonstrated to enhance stability, restore osseoperception and increase the time of prosthesis use. Thumb amputations present varying stump sizes: a standard size implant cannot address specificity of each patient, while a patient matched solution can meet surgeon requirements, by geometrical features of implant. The fixture presented in the current paper is the first additively manufactured patient matched osseointegrated implant for the treatment of thumb amputees. The current work aims to verify and validate a predictive finite element model (FEM) for mechanical strength of the presented fixture. FEM was demonstrated to correctly evaluate the mechanical strength of patient matched device. Minimum strength requirements were calculated in different core diameters: FEM were experimentally validated. Safety factor of 1.5 was guaranteed. Finally, considerations on performance of the prototype were carried out by means of insertion tests in Sawbones and axial pull-out force assessment. Cadaver tests to evaluate the entire procedure and production process are ongoing.


Low rate of COVID-19 seroconversion in health-care workers at a Department of Infectious Diseases in Sweden during the later phase of the first wave; a prospective longitudinal seroepidemiological study.
Background: Health-care workers are at risk of contracting and transmitting SARS-CoV-2. The aim of this study was to investigate the prevalence of SARS-CoV-2 IgG antibodies and the rate of seroconversion in an environment with high exposure to SARS-CoV-2. Methods: 131 health-care workers at the Department of Infectious Diseases in Västerås, Sweden, were included in the study. Abbott's SARS-COV-2 IgG immunoassay was used with a signal cut-off ratio of ≥1.4. Every third week from the beginning of May, blood samples were drawn, and the participants completed a questionnaire regarding symptoms consistent with COVID-19 and the result of any SARS-CoV-2 PCR performed since the last sampling occasion. Participants with IgG antibodies against SARS-CoV-2 were re-sampled only on the sixth and last occasion. Results: At the start of the study, 18 (15%) participants had SARS-CoV-2 IgG antibodies. At the end, 25 (19%) of 131 participants were seropositive. One case of asymptomatic infection was detected, and two cases with PCR-confirmed COVID-19 did not develop IgG antibodies. Conclusion: The low rate of seroconversion during the study suggests that it is possible to prevent transmission of SARS-COV-2 in a high-exposure environment. Compliance with adequate infection control guidelines is the likely explanation of our findings.


The role of anxiety sensitivity and mindful attention in anxiety and worry about bodily sensations among adults living with HIV/AIDS.
The current study examined cognitive factors that may be relevant to understanding anxiety and worry about bodily sensations among an HIV/AIDS population. Specifically, this investigation tested the main and interactive effects of anxiety sensitivity and mindful attention on anxious arousal, bodily vigilance, interoceptive fear, and HIV symptom distress among 164 adults with HIV/AIDS. Results indicated that anxiety sensitivity was positively related to anxious arousal, bodily vigilance, and interoceptive fear, but not HIV symptom distress. Mindful attention was negatively related to anxious arousal, interoceptive fear, and HIV symptom distress, but not bodily vigilance. These main effects for anxiety sensitivity and mindful attention were evident after controlling for disease stage, years with HIV, and demographic variables. There were no interactive effects between anxiety sensitivity and mindful attention. Results are discussed in terms of the clinical implications for identifying and treating anxiety and worry about bodily sensations among adults with HIV/AIDS. Limitations of this study include the use of cross-sectional data and self-report assessments.


Photoreceptor specific guanylate cyclases in vertebrate phototransduction.
Two membrane bound guanylate cyclases are expressed in vertebrate photoreceptor cells. They serve a key function in photoreceptor physiology as they synthesize the intracellular transmitter of photoexcitation guanosine 3',5'-cyclic monophosphate (cGMP). Both cyclases named ROS-GC1 and ROS-GC2 form a subclass of membrane bound cyclases and differ in many aspects from hormone peptide receptor guanylate cyclases. One unique feature is their regulation by three small Ca2+-binding proteins called GCAPs. These regulatory proteins sense changes in the cytoplasmic Ca2+-concentration [Ca2+] during illumination and activate ROS-GCs when the [Ca2+] decreases below the value in a dark adapted cell of 500-600 nM. Recent work has identified the target regions of GCAP-1 in ROS-GC1. In addition to GCAPs several other proteins including aktin, tubulin, a glutamic-acid-rich protein and a GTPase accelerating protein (RGS9) were found to interact with ROS-GC1 and probably form a multiprotein complex.


Characterization of parasporin gene harboring Indian isolates of Bacillus thuringiensis.
Bacillus thuringiensis (Bt) is popularly known as insecticidal bacterium. However, non-insecticidal Bt strains are more extensively available in natural environment than the insecticidal ones. Parasporin (PS) is a collection of genealogically heterogeneous Cry proteins synthesized in non-insecticidal isolates of Bt. An important character generally related with PS proteins is their strong cytocidal activity preferentially on human cancer cells of various origins. Identification and characterization of novel parasporin protein which are non-hemolytic and non-insecticidal but having selective anticancer activity raise the possibility of a novel application of Bt in medical field. In the present study, seven new indigenous isolates (T6, T37, T68, T98, T165, T186, and T461) of Bt showed variation in colony morphology, crystal characters and protein profiles with each other. Out of the seven new isolates screened for parasporin (ps) and cry genes, two of the new indigenous isolates (T98 and T186) of Bt showed the presence of ps4 gene. Partial ps4 gene was cloned from the two new isolates and the sequence of partial ps4 gene showed high homology with its holotype ps4Aa1. These two isolates were characterized based on the proteolytic processing of the inclusion proteins and the proteolytic products were found to be comparable to the PS4 reference strain A1470. The two isolates of Bt did not show toxicity toward Spodoptera litura and Helicoverpa armigera. Based on the results of this study, it can be concluded that the isolates T98 and T186 are parasporin producers.


Transfer-Learning Deep Radiomics and Hand-Crafted Radiomics for Classifying Lymph Nodes from Contrast-Enhanced Computed Tomography in Lung Cancer.
Positron emission tomography (PET) is currently considered the non-invasive reference standard for lymph node (N-)staging in lung cancer. However, not all patients can undergo this diagnostic procedure due to high costs, limited availability, and additional radiation exposure. The purpose of this study was to predict the PET result from traditional contrast-enhanced computed tomography (CT) and to test different feature extraction strategies. In this study, 100 lung cancer patients underwent a contrast-enhanced 18F-fluorodeoxyglucose (FDG) PET/CT scan between August 2012 and December 2019. We trained machine learning models to predict FDG uptake in the subsequent PET scan. Model inputs were composed of (i) traditional "hand-crafted" radiomics features from the segmented lymph nodes, (ii) deep features derived from a pretrained EfficientNet-CNN, and (iii) a hybrid approach combining (i) and (ii). In total, 2734 lymph nodes [555 (20.3%) PET-positive] from 100 patients [49% female; mean age 65, SD: 14] with lung cancer (60% adenocarcinoma, 21% plate epithelial carcinoma, 8% small-cell lung cancer) were included in this study. The area under the receiver operating characteristic curve (AUC) ranged from 0.79 to 0.87, and the scaled Brier score (SBS) ranged from 16 to 36%. The random forest model (iii) yielded the best results [AUC 0.871 (0.865-0.878), SBS 35.8 (34.2-37.2)] and had significantly higher model performance than both approaches alone (AUC: p < 0.001, z = 8.8 and z = 22.4; SBS: p < 0.001, z = 11.4 and z = 26.6, against (i) and (ii), respectively). Both traditional radiomics features and transfer-learning deep radiomics features provide relevant and complementary information for non-invasive N-staging in lung cancer.


Unusual dual genital duct remnants in true hermaphroditism.
A case of true hermaphroditism is reported in which a 46,XY karyotype was associated with a testis and an ovotestis. The dual presence of a Fallopian tube and a vas deferens on the side of the ovotestis is documented as a previously unreported finding.


Surgery after Neoadjuvant Chemotherapy: A Clip-Based Technique to Improve Surgical Outcomes, a Single-Center Experience.
This study aims to describe the surgical management of breast cancer patients after neoadjuvant chemotherapy, with attention to the impact on surgical outcomes of a clip-based marking technique. Patients who underwent NACT at the Breast Unit of the A. O Ordine Mauriziano of Turin from January 2018 and had a surgical intervention by January 2022 were included. Data on the feasibility of clip insertion, after-treatment visibility, and successful removal during surgery were collected prospectively. Surgical outcomes in terms of breast-conserving surgery and axillary dissection reduction were described. In 51 patients who had surgery after NACT, 55 clips were placed (34 breast and 21 axillary clips). Ultrasound visibility of the clips was optimal (91%) as well as preoperative localization and retrieval within the surgical specimen. Moreover, the use of the clip positively affected surgical outcomes. In our study, clip insertion allowed to avoid mastectomy and axillary dissection in patients with a complete radiological response. In our findings, the use of breast and/or lymph node clips has proved to be a simple and effective method to improve surgical conservative management of breast cancer patients after NACT.


[Aftercare and adjuvant therapy for advanced renal cell carcinoma].
Specialist care following (nephron-sparing) kidney surgery serves to detect postoperative complications and to monitor kidney function and cardiovascular health. From an oncological point of view, the early detection of local and contralateral recurrences as well as (single) distant metastases in the early disease stages is paramount. This enables the option of metastasis-directed surgery to delay systemic therapies. On the other hand, the early detection of distant metastases can facilitate the initiation of necessary systemic therapies. In general, nephron-sparing surgery is recommended as the first-line treatment of choice for localized renal tumors. Current guidelines recommend a risk-adapted follow-up based on histopathological criteria (pT, pN or R status). For patients with intermediate and high-risk findings, aftercare should be intensified. In addition to routine blood tests, cross-sectional imaging using contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) remain the method of choice. Recently presented results of the phase III KEYNOTE-564 study on the adjuvant therapy with the programmed cell death 1 (PD1) inhibitor pembrolizumab in clear cell, locally advanced renal cell carcinoma (≥ pT1 GII and or ≥ N+) or oligometastatic renal cell carcinoma without evidence of distant metastases (e.g., after metastasis surgery < 1 year after nephrectomy) demonstrated an advantage in terms of disease-free survival compared to follow-up alone. However, overall survival results are pending. Other potentially effective adjuvant concepts including atezolizumab, nivolumab/ipilimumab, everolimus or pembrolizumab/belzutifan are currently being investigated in clinical trials.


Social status modifies estradiol activation of sociosexual behavior in female rhesus monkeys.
Estrogen (E2) has activational effects on sexual motivation and mitigating effects on anxiety-like behaviors that can be attenuated with chronic exposure to psychosocial stress. Some studies suggest that this attenuation can be overcome by higher doses of E2, while others show that chronic psychosocial stress may alter the mechanisms of E2 function, thus reducing any positive benefit from higher doses of E2. To determine the interaction between psychosocial stress and E2 dose on behavior, we examined the scope of attenuation across a suite of socioemotional behaviors, including reproduction, affiliation, aggression, submission, and anxiety-like behaviors on 36 ovariectomized female rhesus monkeys. Females were exposed to graded psychosocial stress, established by an intrinsic female dominance hierarchy, where subordinate animals receive high amounts of harassment. Our data show that E2 dose-dependently increased sexual motivation and male-affiliation in dominant (e.g. low-stress) females, while subordinate females showed no positive effects of E2, even at higher doses. In addition, contact aggression was attenuated in dominant females, while non-contact aggression was attenuated in both dominant and middle-ranking females. These results suggest that the stress-induced attenuation of E2's activational effects on sexual behavior and affiliation with males may not be overcome with higher doses of E2. Furthermore, the observed behavioral consequences of psychosocial stress and E2 dose may be dependent on the behaviors of all the females in the social-group, and better resolution on these effects depends on isolating treatment to individuals within the group to minimize alterations in social-group interactions.


[Relation of lymphatic microvessel density detected by monoclonal antibody D2-40 with VEGF-C expression in breast cancer].
To investigate the relationship of lymphatic micovessel density (LMVD) detected by monoclonal antibody D2-40) with the VEGF-C expression in human breast cancer. Tissue samples of 102 breast cancers, 25 breast fibroadenomas and 10 normal breasts were collected. Immunohistochemical staining was used to detected the lymphatic micovessels with monoclonal antibody D2-40. The expression of VEGF-C was detect by SP immunohistochemistry, and VEGF-C mRNA by hybridization in situ. In 102 breast cancers, the positive rate of D2-40 was 76.5% (78/102), higher than that in the breast fibroadenomas. LMVD in the periphery of breast cancer was 30.1 lymphatic microvessels per x 100 field of vision, which was significantly higher than that in the central area of the tumors (P = 0.000). The LMVD in the periphery of the breast cancers was correlated with the number of metastatic lymph nodes (r = 0.964, P < 0.01). The positive rates of VEGF-C protein and mRNA were 55.9% (57/102) and 59.8% (61/102), respectively, significantly higher than that in the breast fiberoadenomas and normal breast tissues (chi2 = 11.653, P = 0.003; chi2 = 10.345, P = 0.006), and were significantly correlated with the status of lymph node metastasis, clinical stage and the expressions of c-erbB-2 and p53 protein (P < 0.05). Both of VEGF-C protein and mRNA were significantly correlated with LMVD detected by D2-40 (P < 0.05), especially with the LMVD in the periphery of breast cancers (P < 0.05). The monoclonal antibody D240 can be used to detect the lymphatic endothelium in human breast cancer. The lymphatic microvessel density in the periphery of breast cancer is correlated with the lymph node metastasis and expression of VEGF-C. Therefore, VEGF-C may play a significant role in the lymphangiogenesis leading to metastasis of breast cancer.


Extracellular ATP and zinc are co-secreted with insulin and activate multiple P2X purinergic receptor channels expressed by islet beta-cells to potentiate insulin secretion.
It is well established that ATP is co-secreted with insulin and zinc from pancreatic beta-cells (beta-cells) in response to elevations in extracellular glucose concentration. Despite this knowledge, the physiological roles of extracellular secreted ATP and zinc are ill-defined. We hypothesized that secreted ATP and zinc are autocrine purinergic signaling molecules that activate P2X purinergic receptor (P2XR) channels expressed by beta-cells to enhance glucose-stimulated insulin secretion (GSIS). To test this postulate, we performed ELISA assays for secreted insulin at fixed time points within a "real-time" assay and confirmed that the physiological insulin secretagogue glucose stimulates secretion of ATP and zinc into the extracellular milieu along with insulin from primary rat islets. Exogenous ATP and zinc alone or together also induced insulin secretion in this model system. Most importantly, the presence of an extracellular ATP scavenger, a zinc chelator, and P2 receptor antagonists attenuated GSIS. Furthermore, mRNA and protein were expressed in immortalized beta-cells and primary islets for a unique subset of P2XR channel subtypes, P2X(2), P2X(3), P2X(4), and P2X(6), which are each gated by extracellular ATP and modulated positively by extracellular zinc. On the basis of these results, we propose that, within endocrine pancreatic islets, secreted ATP and zinc have profound autocrine regulatory influence on insulin secretion via ATP-gated and zinc-modulated P2XR channels.


Direct effects of exercise on kynurenine metabolism in people with normal glucose tolerance or type 2 diabetes.
Systemic kynurenine levels are associated with resistance to stress-induced depression and are modulated by exercise. Tryptophan is a precursor for serotonin and kynurenine synthesis. Kynurenine is transformed into the neuroprotective catabolite kynurenic acid by kynurenine aminotransferases (KATs). PGC-1α1 increases KAT mRNA and induces kynurenic acid synthesis. We tested the hypothesis that skeletal muscle PGC-1α1/KAT-kynurenine pathway is altered by exercise and type 2 diabetes. Skeletal muscle and plasma from men with normal glucose tolerance (n = 12) or type 2 diabetes (n = 12) was studied at rest, after acute exercise and during recovery. Tryptophan, Kynurenine and kynurenic acid plasma concentration were measured as well as mRNA of genes related to exercise and kynurenine metabolism. mRNA expression of KAT1, KAT2 and PPARα was modestly reduced in type 2 diabetic patients. In response to exercise, mRNA expression of KAT4 decreased and PGC-1α1 increased in both groups. Exercise increased plasma kynurenic acid and reduced kynurenine in normal glucose tolerance and type 2 diabetic participants. Plasma tryptophan was reduced and the ratio of [kynurenic acid] * 1000/[kynurenine] increased in both groups at recovery, suggesting an improved balance between neurotoxic and neuroprotective influences. Tryptophan and kynurenine correlated with body mass index, suggesting a relationship with obesity. Acute exercise directly affects circulating levels of tryptophan, kynurenine and kynurenic acid, providing a potential mechanism for the anti-depressive effects of exercise. Furthermore, exercise-mediated changes in kynurenine metabolism are preserved in type 2 diabetic patients. Copyright © 2016 John Wiley & Sons, Ltd.


The accuracy of mammography alone and in combination with clinical examination and cytology in the detection of breast cancer.
The accuracy of mammography alone and in combination with clinical examination and aspiration cytology was assessed in 402 patients who attended the Early Diagnostic Unit of the Royal Marsden Hospital, London. The sensitivities of mammography, clinical examination and cytology in identifying breast cancer were 76.9%, 81.7% and 63.5% respectively; the specificities of each test were 90.0%, 87.6% and 99.3%. The calculated sensitivity was increased to 96.2% if one positive test out of the three was regarded as an indication to undertake breast biopsy. If this approach was adopted the number of breast cancers missed would be two out of 104 and the yield of positive biopsies would be approximately one in four (27.6%). The implications of proceeding to breast biopsy on the basis of a single positive test are discussed.


A unique hormonal recognition feature of the human glucagon-like peptide-2 receptor.
Glucagon-like peptides (GLP-1 and GLP-2) are two proglucagon-derived intestinal hormones that mediate distinct physiological functions through two related receptors (GLP-1R and GLP-2R) which are important drug targets for metabolic disorders and Crohn's disease, respectively. Despite great progress in GLP-1R structure determination, our understanding on the differences of peptide binding and signal transduction between these two receptors remains elusive. Here we report the electron microscopy structure of the human GLP-2R in complex with GLP-2 and a Gs heterotrimer. To accommodate GLP-2 rather than GLP-1, GLP-2R fine-tunes the conformations of the extracellular parts of transmembrane helices (TMs) 1, 5, 7 and extracellular loop 1 (ECL1). In contrast to GLP-1, the N-terminal histidine of GLP-2 penetrates into the receptor core with a unique orientation. The middle region of GLP-2 engages with TM1 and TM7 more extensively than with ECL2, and the GLP-2 C-terminus closely attaches to ECL1, which is the most protruded among 9 class B G protein-coupled receptors (GPCRs). Functional studies revealed that the above three segments of GLP-2 are essential for GLP-2 recognition and receptor activation, especially the middle region. These results provide new insights into the molecular basis of ligand specificity in class B GPCRs and may facilitate the development of more specific therapeutics.


Apoptosis inhibiting factor Bcl-xL might be the crucial member of the Bcl-2 gene family in colorectal cancer.
Since the role of the Bcl-2 gene family has been only poorly investigated in colorectal cancer, we have examined the expression of the apoptosis blockers Bcl-xL and Bcl-2, as well as the proapoptotic factors Bax and Bak. Northern blot analysis and immunohistochemistry were performed on normal and cancerous colonic tissue from 12 patients. In colorectal cancer, Bcl-xL immunoreaction was stronger than in normal controls, and 83% of the cancers had increased Bcl-xL mRNA expression. The median densitometric Bcl-xL values were 3.4-fold higher in carcinomas (P<0.005). In contrast to the normal colon, colorectal carcinomas often lack any Bcl-2 immunostaining, and Bcl-2 mRNA was not detectable by Northern blots either. Bax was not obviously altered in colorectal cancer, either at the protein level or at the mRNA level compared to the normal control colon. Bak mRNA expression exhibited a wide variation in carcinomas, but was somewhat decreased in comparison to the controls. Of these members of the Bcl-2 gene family, Bcl-xL seems to play a major role in colorectal tumorigenesis and disease progression. An agonistic effect might have caused the tendency for reduced Bak expression. The Bcl-2/Bax regulation system of cell homeostasis seems to be of lesser importance.


Adjuvant therapeutic decisions in elderly breast cancer patients: the role of chemotherapy in a retrospective analysis.
Decisions on the type of adjuvant treatment in older breast cancer patients are challenging. Side effects of chemotherapy have to be weighed against life expectancy, comorbidities, functional status, and frailty on the basis of studies usually excluding patients over 69 years. To aid this decision, we analyzed a database of 6000 unselected patients and of those evaluated elderly primary breast cancer patients with hormone receptor-negative tumors from 1963 until 2003 in respect of survival data depending on adjuvant treatment. A total of 131 elderly (i.e., >65 years) patients were observed retrospectively for a median of 72 months. Patients received breast-conserving therapy or mastectomy and adjuvant radiotherapy, chemotherapy, and endocrine therapy. Data were collected from a hospital-intern database. Median age at diagnosis was 72 years. Mostly, tumors were small (81 % T1, 17 % T2) but of unfavorable grading (40 % G2, 35 % G3). Lymph nodes were positive in 42 %. Mastectomy was performed in 65 %. While 42 % of patients received radiotherapy, only 10 % were treated with chemotherapy. Patients with G2 and G3 tumors (p = 0.027), younger women (p = 0.012), and patients with positive lymph node status (p < 0.0001) more likely received chemotherapy. Recurrence-free survival was longer in patients without chemotherapy (37 vs. 29 months, p = 0.234). Overall survival was non-significantly shorter in patients who received chemotherapy (59 vs. 81 months, p = 0.131). In this analysis, adjuvant chemotherapy was not associated with improved survival, presumably caused by an a priori poor prognosis of these patients. For an aging society more data are urgently needed to help selecting and personalizing adjuvant treatment within subgroups of breast cancer in older women.


Supermolecular nanovehicles co-delivering TLR7/8-agonist and anti-CD47 siRNA for enhanced tumor immunotherapy.
Cancer immunotherapy is the most promising method for tumor therapy in recent years, among which the macrophages play a critical role in the antitumor immune response. However, tumor-associated macrophages (TAMs) usually display the tumor-promoting M2 phenotype rather than the tumor-killing M1 phenotype. Moreover, the over-expressed CD47 on tumor cells severely hinders the function of macrophages by blocking the CD47/SIRPα pathway. Herein, a nano-assembly system of CHTR/siRNA was constructed through the host-guest interaction of a hyperbranched amino-functionalized β-cyclodextrin and immune agonist imiquimod (R848), while CD47 siRNA was loaded inside through electrostatic interaction. The Toll-like receptor (TLR) 7/8 agonist R848 can "re-educate" macrophages from the protumoral M2 phenotype to antitumoral M1 phenotype, while CD47 siRNA can down-regulate the "don't eat me" CD47 signal on the surface of cancer cells and enhance the phagocytosis of cancer cells by macrophages. Through the dual regulation of TAMs, the immunosuppressive tumor microenvironment was relieved, and the host-guest drug-carrying system resulted in synergistic immunotherapy effect on tumors and inhibited tumor growth. The facile self-assembly of nanodrug offers a new strategy in co-delivery of multiple therapeutic agents for cascade cancer immunotherapy.


[Reliability of retinography for the detection of hypertensive retinopathy in Primary Care].
High blood pressure is one of the most prevalent diseases in general adult population. Its importance lies in the complications it causes in target organs such as kidney, heart, brain and eye. The aim of this work is to evaluate the agreement in the evaluation and interpretation of retinographies of hypertensive patients by family doctors and ophthalmologists. This is a multicentric cross-sectional study in which 976 hypertensive patients from 50 to 70 years old were involved. They were participants of the «Investigating Silent Strokes in Hypertensives: a Magnetic Resonance Imaging Study» (ISSYS project) carried out in primary care centers of Barcelona and who agreed to undergo retinography. Six family physicians and 2 ophthalmologists evaluated the presence of retinal lesions through the Keith-Wagener-Barker criteria. The inter/intra-observer Kappa concordance of the evaluations was analyzed. The evaluation of the retinographies under the usual conditions of clinical practice obtained a high subjective component with slight and fair intra-observer concordance values in the Keith-Wagener-Barker criteria. Only the assessment of the microaneurysms showed a moderate concordance and the ratio artery/vein was the worst concordant. The evaluation of the retinographies in habitual conditions of clinical practice has a high subjective component that is reflected in slight and fair inter-intraobserver concordance values. The use of objective reading systems in the assessment of retinography in hypertensive patients would be useful.


Experimental and computational approach for the evaluation of the biomechanical effects of dental bridge misfit.
Dental bridges supported by osseointegrated implants are commonly used to treat the partially or completely edentulous jaw. The bridges are manufactured in metal alloy using a sequence of technological steps which well match the requirement to get custom overstructures but does not guarantee geometrical and dimensional tolerances. Dentists often experience that a perfect fit of the bridge with the abutments is almost impossible to achieve. When a misfitting bridge is forced on the abutments, deformations may occur inducing a permanent preload at the fixture-bone interface and the greater the misfit the greater is the preload and the risk of implant failure. This work gives an evaluation of the biomechanical effects induced by a misfitting bridge when forced on two supporting dental implants. The strains induced in the bridge have been measured using two purposely designed and fabricated experimental devices allowing different types of misfit. FEM 3D models of the bridge and of the bridge anchored to the bone by implants have been developed. The former has been validated by simulating the same loading conditions as in the experimental tests and comparing the bridge strains. Both models have been used for the evaluation of the stress induced in the bridge and at the fixture-bone interface by bridge length errors. The results show that the method may help to estimate the stress distribution in the bridge and bone as a consequence of different dental bridge misfits.


Evidence for various degrees of motional freedom of the "boundary" lipid in cytochrome oxidase.
The cytochrome oxidase-lipid complex from beef heart mitochondria after various degrees of lipid extraction has been studied by electron spin resonance spectroscopy using spin labelled fatty acids and phospholipids. With cytochrome oxidase at the lowest lipid content (below 0.2 mg/mg of protein) i.e. at the level sometimes referred to as the "boundary" lipid, with spin labelled fatty acids an immobilized spectrum is observed. However, when spin labelled phospholipids are used under the same conditions, a mobile component is also observed. A quantitative estimation of the spectral components by computer analysis has been performed. The difference in behaviour of the spin labelled fatty acids and phospholipids suggest that the part of the residual lipid of the complex, which in some conditions is apparently immobilised, may exhibit in other conditons a considerably high degree of mobility.


Invited Comment on: "Hyaluronic Acid Gel Injection for the Treatment of Tear Trough Deformity: A Multicenter, Observational, Single-Blind Study." by Alberto Diaspro et al.
From this article of Diaspro and colleagues, we can safely conclude that it proves that HA fillers are an effective treatment of tear troughs. A full analysis of the face in general, and the peri-orbital area in particular, is essential to select the right candidates for this treatment. A thorough knowledge of the anatomy is essential to do this selection and to avoid possibly serious complications.Level of evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Inflammatory rheumatic diseases and the risk of drug use disorders: a register-based cohort study in Sweden.
To investigate the association between chronic inflammatory rheumatic diseases (CIRD) and drug use disorder (DUD). Individuals aged ≥ 30 years in 2009 that met the following conditions were included: residing in the Skåne region, Sweden, with at least one healthcare contact in person and no history of DUD (ICD-10 codes F11-F16, F18-F19) during 1998-2009 (N = 649,891). CIRD was defined as the presence of rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), or systemic lupus erythematosus. Treating CIRD as a time-varying exposure, we followed people from January 1, 2010 until a diagnosis of DUD, death, relocation outside the region, or December 31, 2019, whichever occurred first. We used flexible parametric survival models adjusted for attained age, sociodemographic characteristics, and coexisting conditions for data analysis. There were 64 (95% CI 62-66) and 104 (88-123) incident DUD per 100,000 person-years among those without and with CIRD, respectively. CIRD was associated with an increased risk of DUD in age-adjusted analysis (hazard ratio [HR] 1.77, 95% CI 1.49-2.09). Almost identical HR (1.71, 95% CI 1.45-2.03) was estimated after adjustment for sociodemographic characteristics, and it slightly attenuated when coexisting conditions were additionally accounted for (1.47, 95% CI 1.24-1.74). Fully adjusted HRs were 1.49 (1.21-1.85) for RA, 2.00 (1.38-2.90) for AS, and 1.58 (1.16-2.16) for PsA. More stringent definitions of CIRD didn't alter our findings. CIRD was associated with an increased risk of DUD independent of sociodemographic factors and coexisting conditions. Key Points • A register-based cohort study including 649,891 individuals aged≥30 residing in the Skåne region, Sweden, was conducted. • Chronic inflammatory rheumatic diseases were associated with higher risks of drug use disorder independent of sociodemographic factors and coexisting conditions.


Relationships between ganglion cell dendritic structure and retinal topography in the cat.
The morphology of ganglion cell dendritic trees varies across the cat retina. Evidence is presented that the variation in two attributes of ganglion cell dendritic structure can be accounted for by specific aspects of the topography of the adult and developing retina. The first attribute considered was the displacement of the center of the dendritic field from the cell body in the plane of the retina. The results of this study provide evidence that most ganglion cell dendritic fields are displaced away from neighboring cells, i.e., down the retinal ganglion cell density gradient. Because of the systematic dendritic displacement locally, the centers of the dendritic fields are arranged in a more precise mosaic than are their cell bodies. The second attribute considered was the elongation and orientation of the dendritic fields. From approximately embryonic day 50 to postnatal day 10 the cat retina undergoes a process of maturation (reviewed by Rapaport and Stone: Neuroscience 11:289-301, '84) that begins at the area centralis and spreads over the retina in a horizontally elongated wave. We found that the elongation and orientation of retinal ganglion cell dendritic fields is significantly correlated with the shape of the wave of maturation. The orientation of a dendritic field is not predicted by the direction of its displacement nor is it directly related to the distribution of neighboring retinal ganglion cells. These results indicate that the displacement of a ganglion cell's dendritic field from its cell body results from mechanisms different from those responsible for the orientation of the dendritic field. Factors that may be responsible for these two attributes of ganglion cell dendritic morphology are discussed.


Clinical features, risk of mass enlargement, and development of endocrine hyperfunction in patients with adrenal incidentalomas: a long-term follow-up study.
To evaluate the risk of mass enlargement and endocrine function modification in patients with adrenal incidentaloma (AI). In this retrospective study, we examined clinical and hormonal characteristics of 310 patients with AI (200 females and 110 males; age: 58.3 ± 12.9 years), followed up for a median (interquartile range) of 31.4 months (13.0-78.6) and evaluated for possible modification in adrenal mass size and hormonal function. The hormonal evaluation included morning serum cortisol and plasma ACTH at 8 a.m., aldosterone, plasma renin activity/direct renin concentration, and 24-h urine metanephrines/normetanephrines. One microgram overnight dexamethasone suppression test (DST) was performed. Autonomous cortisol secretion (ACS) was diagnosed in the presence of cortisol after 1 mg DST > 5 μg/dl (138 nmol/l) or >1.8 and ≤5 μg/dl (50-138 nmol/l) and at least one of the following: (i) low ACTH; (ii) increased 24-h urinary-free cortisol; (iii) absence of cortisol rhythm; and (iv) post-LDDST cortisol level > 1.8 μg/dl (50 nmol/l). When there was no biochemical evidence of adrenal hormonal hyperactivity, AIs were classified as nonfunctioning (NFAIs). The mass was considered significantly enlarged when the size increase was more than 20% and at least 5 mm compared to baseline. At diagnosis, NFAIs were found in 209 patients, while ACS and overt adrenal hyperfunction were diagnosed in 81 and 20 patients, respectively. During follow-up, 3.3% and 1.5% of patients with NFAI developed subtle and overt endocrine hyperfunction, respectively, while a significant mass enlargement was observed in 17.7% of all AIs. The risk of developing ACS was significantly higher in patients with adenoma >28 mm (hazard ratio [HR] 12.4; 95% confidence interval [CI], 2.33-66.52, P = 0.003), in those with bilateral adrenal tumors (HR: 5.36; 95% CI, 1.17-24.48, P = 0.030), and with low/suppressed ACTH values (HR: 11.2, 95% CI 2.06-60.77; P = 0.005). The risk of mass enlargement was lower for patients in the fourth quartile of body mass index than those in the first quartile (HR 0.33; 95% CI, 0.14-0.78; P = 0.012). In patients with AI, the risk of developing hormonal hyperfunction and mass enlargement is overall low, although some tumor characteristics and anthropometric features might increase this risk. Taking account of all these aspects is important for planning a tailored follow-up in AI patients.


Environmental control of CO2-assimilation and leaf conductance in Larix decidua Mill. : I. A comparison of contrasting natural environments.
CO2-assimilation and leaf conductance of Larix decidua Mill. were measured in the field at high (Patscherkofel, Austria) and low (Bayreuth, Germany) elevation in Europe, and outside its natural range along an altitudinal gradient in New Zealand.Phenology of leaf and stem growth showed New Zealand sites to have much longer growing seasons than in Europe, so that the timberline (1,330 m) season was almost twice as long as at the Austrian timberline (1,950 m).The maximum rates of photosynthesis, A max, were similar at all sites after completion of leaf growth, namely 3 to 3.5 μmol m-2 s-1. Only the sun needles of the Bayreuth tree reached 3.5 to 5 μmol m-2 s-1. Light response curves for CO2-assimilation changed during leaf ontogeny, the slope being less in young than in adult leaves. The temperature optimum for 90% of maximum photosynthesis was at all sites similar between ca. 12-28°C for much of the summer. Only at the cooler high altitude timberline sites were optima lower at ca. 10-16°C in developing needles during early summer.A linear correlation existed between A max and leaf conductance at A max, and this showed no difference between the sites except for sun needles at Bayreuth.Leaf conductance responded strongly to light intensity and this was concurrent with the light response of CO2-uptake. A short-term and a long-term effect were differentiated. With increasing age maximum rates of CO2-uptake and leaf conductance at A max increased, whereas short-term response during changes in light declined. The stomata became less responsive with increasing age and tended to remain open. The stomatal responses to light have a significant effect on the water use efficiency during diurnal courses. A higher water use efficiency was found for similar atmospheric conditions in spring than in autumn.Stomata responded with progressive closure to declining air humidity in a similar manner under dissimilar climates. Humidity response thus showed insensitivity to habitat differences.From the diurnal course of gas-exchange stomata were more closed at timberline (1,330 m) than at lower elevations but this did not lead to corresponding site differences in CO2-exchange suggesting Larix may not be operating at high water use efficiency when air is humid.The main difference between habitats studied was in the time necessary for completion of needle development. Similarity in photosynthesis and leaf conductance existed between sites when tree foliage was compared at the same stage of development. Length of growing season and time requirement for foliar development appear to be a principle factor in the carbon balance of deciduous species. The evergreen habit may be more effective in counterbalancing the effects of cool short summers.


Rapid visual field constriction in a patient with retinitis pigmentosa and pituitary adenoma.
To report a case of pituitary adenoma in a patient with retinitis pigmentosa (RP) and consequent rapid constriction of the visual field in each eye, which is atypical for either of these pathologies. A 45-year old male, with a long-standing history of RP, presented with rapid vision loss over 3 months. Examination revealed a severe drop in visual acuity and significant progression of concentric visual field constriction in each eye compared to 3 months prior. MRI revealed a pituitary macroadenoma compressing the optic chiasm. The patient underwent endoscopic trans-sphenoidal resection of the tumor and experienced partial recovery of visual acuity but not visual field. The visual field deficit in this patient was atypical for pituitary adenoma or optic neuropathy. The pattern was most consistent with RP, but the rate of progression was not. In a patient with chiasmal pathology in the setting of pre-existing retinopathy, visual field progression may not be limited exclusively to the bitemporal regions. Rapid constriction of the visual field in a patient with RP should prompt a work-up for alternative etiologies which includes neuro-imaging.


Prognostic impact of sustained new-onset atrial fibrillation in critically ill patients.
The development of new-onset atrial fibrillation (AF) in critically ill patients may be associated with poor outcomes. However, it is unknown whether sustained new-onset AF contributes to worse outcome. The aim of this study was to assess whether sustained new-onset AF is associated with stroke and death and to look for a possible dose-response relationship between AF duration and death. In a prospective cohort study conducted in 32 intensive care units in Japan from 2017 to 2018, we enrolled adult patients with new-onset AF. We compared patients with AF duration longer than 48 h with those with AF duration shorter than 48 h. To assess a dose-response relationship between AF duration and hospital mortality, we conducted landmark analysis and time-dependent Cox regression analysis. Among a total of 423 new-onset AF patients, hospital mortality was 25%, and the incidence of in-hospital stroke was 4.6%. AF duration longer than 48 h was not independently associated with hospital mortality (adjusted odds ratio: 1.52; 95% Confidence Interval: 0.87-2.64). The incidence of in-hospital stroke was 7.6% in patients with AF duration longer than 48 h and 3.8% in those with AF duration shorter than 48 h (p = 0.154). When analyzing time more continuously, we observed a time-dependent association between AF duration and hospital mortality (p = 0.005 by landmark analysis and p = 0.019 by Cox analysis). Sustained new-onset AF was time-dependently associated with hospital mortality in ICU patients, albeit with some uncertainty since AF duration longer than 48 h was not independently associated with in-hospital death or stroke.


The Path Toward Fellow Designation in the Academy of Emergency Nursing: Understanding and Navigating the Process to Ensure Your Success.
The Academy of Emergency Nursing was established to honor emergency nurses who have made enduring and substantial contributions that have had significant impact and continue to advance the emergency nursing specialty. Nurses who have been recognized as having made enduring and substantial contributions to emergency nursing achieve fellow status in the Academy of Emergency Nursing and are conferred the credential, Fellow of the Academy of Emergency Nursing. Academy of Emergency Nursing Board Members want to dismantle any structural barriers, clarify any misunderstandings or mysteries, and support diverse candidates by providing clear and equitable resources about the path toward fellow designation and the application process. Therefore, the purpose of this article is to support interested persons in their path toward Academy of Emergency Nursing fellow designation and give explicit details of each section of the application to develop a shared understanding among potential applicants, sponsors, and Fellows of the Academy of Emergency Nursing.


Ecologic studies of solar UV-B radiation and cancer mortality rates.
Solar ultraviolet B (UV-B) radiation (280-320 nm) has been associated with reduced risk of cancer of the breast, colon, ovary, and prostate, as well as non-Hodgkin's lymphoma (NHL) through the production of vitamin D in papers extending back to 1980. Using data on the geographic distribution of cancer mortality rates in the US, another ten cancers have been added to the list for which UV-B/vitamin D is a risk reduction factor (Grant 2002b; submitted). These associations persist even after additional cancer risk and risk reduction factors such as smoking, urban or rural residence, Hispanic heritage, poverty, dietary factors, and use of nonsteroidal anti-inflammatory drugs are added to the analysis. As a further test of the protective role of UV-B radiation, an ecologic study of cancer mortality rates in Europe with UV-B radiation and dietary factors was conducted. Inverse correlations are found for UV-B radiation for a number of cancers, with those for bladder, breast, endometrial, ovarian, prostate, and renal cancer, and multiple myeloma and NHL having the strongest correlations in this and ongoing multicountry ecologic studies. These studies add further support for the role of UV-B radiation and vitamin D in reducing the risk of a large number of cancers.


Synergistic interaction between Astragali Radix and Rehmanniae Radix in a Chinese herbal formula to promote diabetic wound healing.
Astragali Radix (AR) and Rehmanniae Radix (RR) are two traditional Chinese medicines widely used in China for treating diabetes mellitus and its complications, such as diabetic foot ulcer. In our previous study, a herbal formula NF3 comprising AR and RR in the ratio of 2:1 was found effective in enhancing diabetic wound healing in rats through the actions of tissue regeneration, angiogenesis promotion and inflammation inhibition. The aims of the present study were to investigate the herb-herb interaction (or the possible synergistic effect) between AR and RR in NF3 to promote diabetic wound healing and to identify the principal herb in the formula by evaluating the potencies of individual AR and RR in different mechanistic studies. A chemically induced diabetic foot ulcer rat model was used to examine the wound healing effect of NF3 and its individual herbs AR and RR. For mechanistic studies, murine macrophage cell (RAW 264.7) inflammation, human fibroblast (Hs27) proliferation and human endothelial cell (HMEC-1) migration assays were adopted to investigate the anti-inflammatory, granulation formation and angiogenesis-promoting activities of the herbal extracts, respectively. In the foot ulcer animal model, neither AR nor RR at clinical relevant dose (0.98g/kg) promoted diabetic wound healing. However, when they were used in combination as NF3, synergistic interaction was demonstrated, of which NF3 could significantly reduce the wound area of rats when compared to water group (p<0.01). For anti-inflammation and granulation formation, AR was more effective than RR in inhibiting lipopolysaccharide (LPS)-induced nitric oxide production from RAW 264.7 cells and promoting Hs27 fibroblast proliferation. In the aspect of angiogenesis promotion, only NF3 promoted cell migration of HMEC-1 cells. AR plays a preeminent role in the anti-inflammatory and fibroblast-proliferating activities of NF3. The inclusion of RR, however, is crucial for NF3 to exert its overall wound-healing as well as the underlying angiogenesis-promoting effects. The results of present study justified the combined usage of AR and RR in the ratio of 2:1 as NF3 to treat diabetic foot ulcer and illustrated that AR is the principal herb in this herbal formula.


Development of chicken intrafusal muscle fibers.
The first sign of developing intrafusal fibers in chicken leg muscles appeared on embryonic day (E) 13 when sensory axons contacted undifferentiated myotubes. In sections incubated with monoclonal antibodies against myosin heavy chains (MHC) diverse immunostaining was observed within the developing intrafusal fiber bundle. Large primary intrafusal myotubes immunostained moderately to strongly for embryonic and neonatal MHC, but they were unreactive or reacted only weakly with antibodies against slow MHC. Smaller, secondary intrafusal myotubes reacted only weakly to moderately for embryonic and neonatal MHC, but 1-2 days after their formation they reacted strongly for slow and slow-tonic MHC. In contrast to mammals, slow-tonic MHC was also observed in extrafusal fibers. Intrafusal fibers derived from primary myotubes acquired fast MHC and retained at least a moderate level of embryonic MHC. On the other hand, intrafusal fibers developing from secondary myotubes lost the embryonic and neonatal isoforms prior to hatching and became slow. Based on relative amounts of embryonic, neonatal and slow MHC future fast and slow intrafusal fibers could be first identified at E14. At the polar regions of intrafusal fibers positions of nerve endings and acetylcholinesterase activity were seen to match as early as E16. Approximately equal numbers of slow and fast intrafusal fibers formed prenatally; however, in postnatal muscle spindles fast fibers were usually in the majority, suggesting that some fibers transformed from slow to fast.


Low-Grade Ductal Carcinoma in situ Within a Fibroadenoma of the Breast: A Rare Case Report and Review of the Literature.
Ductal carcinoma in situ within a breast fibroadenoma is a rare malignancy with an incidence of only 0.02-0.125%. Imaging of low-grade ductal carcinoma in situ within a breast fibroadenoma shows no specific presentation. Therefore, pathology and immunohistochemistry are required for definitive diagnosis. Surgery is currently considered to be an effective treatment. There is no uniform clinical standard for postoperative adjuvant radiotherapy. A 60-year-old female patient underwent excisional biopsy on October 19, 2022. Pathology and immunohistochemistry confirmed the diagnosis of low-grade ductal carcinoma in situ within the fibroadenoma. Subsequently, breast-conserving surgery and sentinel lymph node biopsy were performed under general anesthesia with tracheal intubation, and no cancer metastasis was observed in the sentinel lymph nodes or incisional margins. Low-grade ductal carcinoma in situ within a breast fibroadenoma is an extremely rare malignancy, and clinicians should be familiar with its clinicopathological features and treatment methods. Multidisciplinary joint treatment is recommended to maximize the benefits to patients.


Implementation interventions to improve the management of non-specific low back pain: a systematic review.
Recommendations in clinical practice guidelines for non-specific low back pain (NSLBP) are not necessarily translated into practice. Multiple studies have investigated different interventions to implement best evidence into clinical practice yet no synthesis of these studies has been carried out to date. The aim of this study was to systematically review available studies to determine whether implementation interventions in this field have been effective and to identify which strategies have been most successful in changing healthcare practitioner behaviours and improving patient outcomes. A systematic review was undertaken, searching electronic databases until end of December 2012 plus hand searching, writing to key authors and using prior knowledge of the field to identify papers. Included studies evaluated an implementation intervention to improve the management of NSLBP in clinical practice, measured key outcomes regarding change in practitioner behaviour and/or patient outcomes and subjected their data to statistical analysis. The Cochrane Effective Practice and Organisation of Care (EPOC) recommendations about systematic review conduct were followed. Study inclusion, data extraction and study risk of bias assessments were conducted independently by two review authors. Of 7654 potentially eligible citations, 17 papers reporting on 14 studies were included. Risk of bias of included studies was highly variable with 7 of 17 papers rated at high risk. Single intervention or one-off implementation efforts were consistently ineffective in changing clinical practice. Increasing the frequency and duration of implementation interventions led to greater success with those continuously ongoing over time the most successful in improving clinical practice in line with best evidence recommendations. Single intervention or one-off implementation interventions may seem attractive but are largely unsuccessful in effecting meaningful change in clinical practice for NSLBP. Increasing frequency and duration of implementation interventions seems to lead to greater success and the most successful implementation interventions used consistently sustained strategies.


RVD2: an ultra-sensitive variant detection model for low-depth heterogeneous next-generation sequencing data.
Next-generation sequencing technology is increasingly being used for clinical diagnostic tests. Clinical samples are often genomically heterogeneous due to low sample purity or the presence of genetic subpopulations. Therefore, a variant calling algorithm for calling low-frequency polymorphisms in heterogeneous samples is needed. We present a novel variant calling algorithm that uses a hierarchical Bayesian model to estimate allele frequency and call variants in heterogeneous samples. We show that our algorithm improves upon current classifiers and has higher sensitivity and specificity over a wide range of median read depth and minor allele fraction. We apply our model and identify 15 mutated loci in the PAXP1 gene in a matched clinical breast ductal carcinoma tumor sample; two of which are likely loss-of-heterozygosity events. http://genomics.wpi.edu/rvd2/. firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


Effect of the Finnish Tube on the Voice of a Deaf Musician: A Case Report.
To verify the auditory-perceptual and acoustic effects of the semioccluded vocal tract exercise with Finnish tube on the vocal quality of a deaf musician. A seven-day protocol with Finnish tube was performed with guidance for its home replication twice a day. A 46-years-old man with profound bilateral sensorineural hearing loss, musician and composer participated. Before and after the application of the protocol had undergone tonal audiometry, nasofibrolaryngoscopy, acoustic analysis with Praat and auditory-perceptual evaluation of the voice with Voice Profile Analysis Scheme for Brazilian Portuguese. The postintervention auditory-perceptual analysis identified reduction of the deviation in lip spreading, extensive labial range, raised tongue body, pharyngeal expansion, nasal resonance, larynx height, larynx and vocal tract tension and irregularity, pitch, speech rate, and a better respiratory support. The maximum phonation time reduced, probably because of elimination of the abrupt vocal attack and tension, articulatory deviations, improvement in voicing and the absence of the use of expiratory reserve air. The fundamental frequency became lower, and the first, second, third, and fourth formants became higher. The jitter increased, and the shimmer reduced. The use of the Finnish tube might have facilitated the voicing sensations in the deaf musician, by enhancing the tactile-kinesthetic perception of the vocal tract and brought a greater source-filter interaction.


Green bond vs. Islamic bond: Which one is more environmentally friendly?
This research investigates the dynamic dependence and causality relationship of the S&P Kensho Clean Energy (CE) and Cleantech (CT) indices with two green bond indices, including the S&P Green Bond Index (GB) and Green Bond Select (GBS) indices, and four Islamic bond indices, including A-, AA-, AAA-, and BBB-graded Sukuk Indices. In the long- and medium-term, the dependence of CE and CT on Sukuk and green bond indices strengthens under normal or bearish market conditions based on quantile cross-spectral (coherency). Overall, among all alternative financing instruments, AA- and A-rated Sukuk indices and GBS indices have higher coherency with CE and CT. Furthermore, the direction of causality in the frequency domain is most commonly observed from Sukuk and bond indices to CT and CE. Once again, AA-rated, A-rated, and GBS have more significant causality effects on CT and CE for nearly all frequencies compared to other indices. These results present vital implications for both policymakers who want to advocate the development of environmentally friendly projects and investors who want to invest their capital in green economic activities in terms of diversifying and hedging their investments.


Of FOXes and Forgetful Worms.
Age-related cognitive decline is one of the most haunting aspects of human aging. In a recent publication, Coleen Murphy and colleagues (Kaletsky et al., 2016) describe the transcriptional program that maintains youthful function of aging neurons in the nematode worm.


Nothing to see here.
Based on one company's past poor publishing practices, a top-tier medical journal misguidedly stigmatizes any paper from industry.


Improvement in the endothelium-dependent relaxation in hypercholesterolemic rabbits treated with vitamin E.
The authors studied the time course of the vitamin E mediated improvement in endothelium-dependent relaxation in hypercholesterolemic rabbits. A total of 40 male New Zealand white rabbits were randomly assigned to hypercholesterolemic (control) and vitamin E treated groups. The latter group was further divided in three subgroups in accordance with the duration of the vitamin E treatment (2, 4 or 6 days) at the end of the experiment. The dose of vitamin E utilized was 50 IU/day administered once a day by gavage. All the rabbits were fed a diet supplemented with cholesterol (0.5%) and coconut oil (2%) for 4 weeks. At the end of this period, the animals were sacrificed and the aorta removed for determination of the cholesterol and malondialdehyde (MDA) contents. The relaxation of the aortic strips in response to acetylcholine was also studied. In addition, the cholesterol and MDA contents of native and oxidized LDL were measured. At the end of the 4th week, the MDA level was significantly reduced in native and oxidized LDL in the rabbits treated with vitamin E for 2 days, while in aortic tissue a reduction was seen after 4 days of treatment. Endothelium-dependent relaxation improved significantly after 6 days of vitamin E administration, and there was a reduction in the total plasma and aortic cholesterol levels during this same period. We conclude that vitamin E at a dose of 50 IU/day for 6 days improves the endothelium-dependent relaxation seen in hypercholesterolemic rabbits. This effect may be mediated through an antioxidant action on LDL particles and on the aortic arterial wall.


New Paradigm for Nano-Bio Interactions: Multimolecular Assembly of a Prototypical Disordered Protein with Ultrasmall Nanoparticles.
Understanding the interactions between nanoparticles (NPs) and proteins is crucial for the successful application of NPs in biological contexts. Protein adsorption is dependent on particle size, and protein binding to ultrasmall (1-3 nm) NPs is considered to be generally weak. However, most studies have involved structured biomacromolecules, while the interactions of ultrasmall NPs with intrinsically disordered proteins (IDPs) have remained elusive. IDPs are abundant in eukaryotes and found to associate with NPs intracellularly. As a model system, we focused on ultrasmall gold nanoparticles (usGNPs) and tau, a cytosolic IDP associated with Alzheimer's disease. Using site-resolved NMR, steady-state fluorescence, calorimetry, and circular dichroism, we reveal that tau and usGNPs form stable multimolecular assemblies, representing a new type of nano-bio interaction. Specifically, the observed interaction hot spots explain the influence of usGNPs on tau conformational transitions, with implications for the intracellular targeting of aberrant IDP aggregation.


Structural and functional considerations of the cholinergic brainstem.
Cholinergic neurons of the brainstem have traditionally been associated with a role in wakefulness as part of the reticular activating system, but their function cannot be explained solely on the basis of their modulation of the brain state. Recent findings about their connectivity and functional heterogeneity suggest a wider role in behavior, where basal ganglia is at the center of their influence. This review focuses on recent findings that suggest an intrinsic functional organization of the cholinergic brainstem that is closely correlated with its connectivity with midbrain and forebrain circuits. Furthermore, recent evidence on the temporal structure of the activation of brainstem cholinergic neurons reveals fundamental aspects about the nature of cholinergic signaling. Consideration of the cholinergic brainstem complex in the context of wider brain circuits is critical to understand its contribution to normal behavior.


Integrating banana and ruminant production in the French West Indies.
Using a mechanistic model, we compared five alternative farming systems with the purpose of transforming monoculture (MON) banana farms into mixed farming systems (MFS) with ruminants feeding banana by-products (leaves, pseudostems and nonmarketable fruits) and forage from the fallow land. The paper presents the main structure of the model (land surface changes, available biomass for animals, stocking rates, productive or reproductive indicators), and impact assessment (change in farm productivity) is discussed. Five MFS with typical local ruminant production systems were used to compare MON to the strategies using forage from fallow and/or integrating Creole cattle (CC), Creole goats (CG) or Martinik sheep (MS) into banana farming. One hectare MON shifted into an MFS allows a stocking rate of 1,184, 285, and 418 kg of live weight per hectare for CC, CG and MS, respectively. Banana by-products seem to be better valorized by the CC scenario. However, parameters such as length of the cycle, local prices for cattle, goat and sheep meat, work time and farmer's skills in ruminant management may have been taken into account by the farmer when choosing the ruminant species to rear.


Coping Strategies in Elderly Colorectal Cancer Patients.
In Spain, 34,331 new cases of colorectal cancer were diagnosed in 2018 and 15,923 individuals died from this disease in the same year. The highest incidence of colorectal cancer is among individuals aged 65-75 years and the physiological consequences of aging, alongside the effects of the disease and its treatment, can exacerbate their physical deterioration and cognitive impairment and reduce their social relationships. The learning of coping strategies may help to improve the quality of life of patients after cancer diagnosis. To test the hypothesis that the utilization of coping strategies can improve the quality of life of elderly patients with colorectal cancer, PubMed and EBSCO databases were searched, up to 2021, using the following terms: "coping strategies and colorectal cancer" with "anxiety", "quality of life", "depression", "unmet needs", "optimism", "intimacy", "distress", "self-efficacy" and "self-esteem" with Boolean operators "AND", "OR". The literature search retrieved 641 titles/abstracts written in English. After an exhaustive analysis, only 7 studies met the inclusion criteria. Randomized evidence was scant and was reported only in 3/7 of the studies analyzed. Data from available randomized evidence support that patients improved on their depression and quality of life and felt more prepared to deal with their cancer. Coping strategies in patients with colorectal cancer were effective in improving patient adaptation to their new situation. Healthcare professionals working with these patients should receive training in this complementary treatment, to be able to conduct comprehensive care in order to improve the quality of life of these patients.


Disparities in fresh fruit and vegetable intake by sociodemographic and behavioural factors among adults in China.
To measure the associations of sociodemographic and behavioural factors with fruit and vegetable consumption among adults in China. A cross-sectional study. A 2015 wave of the China Health and Nutrition Survey. Totally, 11 910 adults aged 18 to 64 years. Adjusted log binomial regression analyses showed that adults with higher income levels had higher fruit intake than those with low income levels (medium income group, risk ratio (RR): 1·28; 95 % CI: 1·16, 1·41; high income group, RR: 1·58; 95 % CI: 1·43, 1·74). Current smokers had lower fruit intake than non-smokers (RR: 0·86; 95 % CI: 0·77, 0·96). Adults living in southern China had higher vegetable intake (RR: 1·88; 95 % CI: 1·76, 2·01) but lower fruit intake (RR: 0·85; 95 % CI: 0·79, 0·91) than adults in northern China. With increasing age, adults had higher fruit intake (50-64 years, RR: 1·20; 95 % CI: 1·09, 1·33; reference category 18-34 years) and higher vegetable intake (35-49 years, RR: 1·13; 95 % CI: 1·05, 1·22; 50-64 years, RR: 1·22; 95 % CI: 1·13, 1·31). Our findings identify a range of sociodemographic and behavioural factors associated with fruit and vegetable consumption among Chinese adults. They also point to the need for public health nutrition interventions for socially disadvantaged populations in China.


Basal motor activity of the distal colon: a reappraisal.
The significance of recent motor data on the distal colon in irritable bowel syndrome is obscured by methodological questions such as bowel preparation, variability and reproducibility of motor activity and segmental differences. Thirty subjects were studied after prior bowel cleansing with a water enema on two separate occasions 1 wk apart (10 with one bowel movement per day, 10 with two to three per week, and 10 with three to 12 per day). Two additional studies were performed in 10 of the subjects, one with and one without prior cleansing. The motility indices of the cleansed and unwashed colon were dissimilar. The motility index per 3 min varied markedly over 3 h, and the indices between the paired studies were rarely identical. Marked segmental differences were noted. The mean motility index per 3 min of the constipated and the diarrhea groups was significantly greater than that of normals only in the 15-cm segment. In view of these variables, caution should be exercised in the interpretation of basal motor activity of the distal colon.


Recurrent prenatal PIEZO1-related lymphatic dysplasia: Expanding molecular and ultrasound findings.
Generalized lymphatic dysplasia (GLD), characterized by lymphedema, lymphangiectasias, chylothorax, effusions, represents a recognized cause of fetal hydrops. We describe for the first time recurrent pregnancies showing different ultrasound presentations of lymphatic dysplasia. The first fetus displayed diffuse subcutaneous cysts and septations while the second one presented fetal hydrops. Exome sequencing results at 18 gestational weeks in the second pregnancy showed compound heterozygosity for two novel PIEZO1 variants, afterwards detected also in the first fetus and in the heterozygous parents. Both ultrasound and genetic findings expand the current knowledge of PIEZO1-related GLD. We suggest exome sequencing in hydropic fetuses with normal cytogenetics and in pregnancies with recurrent hydrops/lymphatic dysplasia.


A unique sialoglycopeptide growth regulator that inhibits mitogenic activity of a phorbol ester tumor promoter.
The ability of a naturally occurring cell surface sialoglycopeptide growth inhibitor to antagonize the induction of DNA synthesis by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) was studied with mouse 3T3 cells. The bovine sialoglycopeptide was shown to be a potent antagonist of TPA-induced DNA synthesis in confluent 3T3 cell cultures. Kinetic studies demonstrated that inhibition of TPA-induced DNA synthesis required the addition of the sialoglycopeptide within 15 min of TPA treatment. Addition of the sialoglycopeptide 30 min or longer after the cells were exposed to TPA did not block stimulation of DNA synthesis by TPA. The inhibition of TPA action was shown not to be restricted to DNA synthesis in 3T3 cultured cells since the sialoglycopeptide also inhibited TPA-induced ornithine decarboxylase (ODC, L-ornithine carboxylase, EC 18.104.22.168) activation in suspensions of mouse epidermal and 3T3 cells.


46,XX,-12,+der(12),rcp(3;12)(p25.1;p13.31)pat karyotype in a girl. Probable subregional assignment of glyceraldehyde-3-phosphate dehydrogenase locus to 12p13.1----p13.31 by exclusion mapping.
A female infant with partial trisomy 3p and a terminal deletion 12p, due to a paternal (3;12)(p25.1;p13.31) translocation is described. Normal glyceraldehyde-3-phosphate (GAPD) activity in the proposita tentatively excludes GAPD locus from the deleted segment. Therefore, the region for this locus is reduced to 12p13.1----p13.31.


Calcaneus fracture pattern and severity: Role of local trabecular bone density.
Calcaneus fracture is the most common tarsal bone fracture and is associated with external loads resulting from vehicle crashes, under body blasts, or sports. Almost 50% of weight bearing by the foot occurs through the calcaneus and its surgical fixation remains a challenging procedure. Postmortem human subjects were used to measure the regional trabecular BMD of the calcaneus. Mean age, height and weight of the included 14 specimens was 69 years, 177 cm and 80 kg respectively. Using a custom mode within Quantitative Computed Tomography clinical software; calcaneal trabecular BMD in the anterior and posterior regions was quantified. Tolerance data and calcaneus fracture patterns were also available for these specimens from previous tests. The posterior region of the calcaneus had a higher mean BMD (114 mg/cc) than the anterior region (81 mg/cc). These BMD differences also paralleled injury outcome of specimens from axial loading with 50% of specimens resulting in high severity anterior region calcaneal fractures and 36% of specimens resulting in low severity posterior calcaneal fractures. These findings may be reflective of the lower BMD in the anterior region, although the load was uniformly distributed across the plantar surface of the foot. Severity of fracture was greater (intraarticular/crush) in the anterior region as compared to fractures of the posterior region. The BMD ratio between anterior and posterior was significant (p = 0.02) between anterior region fractures and posterior region fractures. The ratio parameter may indicate that the disparity in trabecular BMD between anterior and posterior calcaneus regions is more important in predicting injury outcome than the absolute BMD value of each region.


Ophiobolins P-T, five new cytotoxic and antibacterial sesterterpenes from the endolichenic fungus Ulocladium sp.
Five ophiobolane sesterterpenes, ophiobolins P-T, and three known compounds, 6-epi-21,21-O-dihydroophiobolin G, 6-epi-ophiobolin G and 6-epi-ophiobolin K, were isolated from the acetone extract of the endolichenic fungus Ulocladium sp. by using OSMAC method. Their structures were elucidated on the basis of spectroscopic analysis. The absolute configuration of the 18,19-diol moieties in ophiobolin Q was assigned using the Frelek's method. The cytotoxic effects on KB and HepG2 cell lines, antibacterial activity against Bacillus subtilis, methicillin-resistant Staphylococcus aureus, and Bacille Calmette-Guerin were evaluated for all isolated compounds. Ophiobolin T and 6-epi-ophiobolin G exhibited the most potent cytotoxic activity against HepG2 with IC₅₀ of 0.24 and 0.37 μM, respectively. In antibacterial assay, ophiobolins P and T showed moderate antibacterial activity against B. subtilis and meticillin-resistant S. aureus. Ophiobolin T also displayed moderate antibacterial activity against the Bacille Calmette-Guerin strain.


Incorporating a β-hairpin sequence motif to increase intracellular stability of a peptide-based PROTAC.
Proteolysis targeting chimeras (PROTACs) have emerged as a new class of therapeutics that utilize the ubiquitin-proteasome system (UPS) to facilitate proteasomal degradation of "undruggable" targets. Peptide-based PROTACs contain three essential components: a binding motif for the target protein, a short amino acid sequence recognized by an E3 ligase called a degron, and a cell penetrating peptide to facilitate uptake into intact cells. While peptide-based PROTACs have been shown to successfully degrade numerous targets, they have often been found to exhibit low cell permeability and high protease susceptibility. Prior work identified peptides containing a β-hairpin sequence motif that function not only as protecting elements, but also as CPPs and degrons. The goal of this study was to investigate if a β-hairpin sequence could replace commonly used unstructured peptides sequences as the degron and the CPP needed for PROTAC uptake and function. The degradation of the protein Tau was selected as a model system as several published works have identified a Tau binding element that could easily be conjugated to the β-hairpin sequence. A series of time- and concentration-dependent studies confirmed that the βhairpin sequence was an adequate alternative CPP and degron to facilitate the proteasomemediated degradation of Tau. Microscopy studies confirmed the time-dependent uptake of the PROTAC and a degradation assay confirmed that the β-hairpin conjugated PROTAC had a greater lifetime in cells.


Successful Explantation of a Ball and Cage Mitral Valve Prosthesis 48 Years After Initial Implantation.
A 58-year-old female had undergone previous mechanical mitral replacement with a Starr-Edwards ball and cage valve (Edwards Lifesciences, Irvine, CA) at 11 years of age for rheumatic disease. The valve functioned well until pannus resulted in prosthetic valve stenosis with class IV dyspnea and pulmonary hypertension. She underwent reoperative mitral replacement with an On-X mechanical mitral prosthesis (Cryolife, Kennesaw, GA) 48 years after initial implantation. To our knowledge, this case represents the longest known implant period of a ball and cage mitral valve in the literature. This presentation highlights the durability of this historic prosthesis, along with the role of reoperative surgery decades after initial implantation.


Interleukin-11 (IL11) inhibits myogenic differentiation of C2C12 cells through activation of extracellular signal-regulated kinase (ERK).
Cancer-associated cachexia (CAC) is a multifactorial wasting syndrome characterized by loss of skeletal muscle. Interleukin-11 (IL11), one of the IL6 family cytokines, is highly expressed in various types of cancer including cancers frequently associated with cachexia. However, the impact of IL11 on muscle metabolism remains to be determined. Since one of the mechanisms of muscle wasting in cachexia is defective muscle regeneration due to impaired myogenic differentiation, we examined the effect of IL11 on the differentiation of C2C12 mouse myoblasts. Treatment of C2C12 cells with recombinant mouse IL11 resulted in decreased myotube formation. In addition, IL11 treatment reduced the protein and mRNA levels of myosin heavy chain (MHC), a marker of myogenic differentiation. Moreover, the levels of myogenic regulatory factors including myogenin and Mrf4 were significantly reduced by IL11 treatment. IL11 treatment increased the number of BrdU-positive cells and the level of phosphorylated retinoblastoma (Rb) protein, while the levels of p21Waf1 and p27Kip1 were reduced by IL11 treatment in differentiating C2C12 cells, suggesting that IL11 interferes with cell cycle exit during the early stages of myogenic differentiation. Consistent with this, IL11 treatment at the late stage of differentiation did not affect myotube formation and MHC expression. IL11 treatment resulted in an activation of ERK, STAT3, and AKT in differentiating C2C12 cells. However, only ERK inhibitors including PD98059 and U0126 were able to ameliorate the suppressive effect of IL11 on the expression of MHC and myogenin. Additionally, pretreatment with PD98059 and U0126 resulted in improved myotube formation and reduced BrdU staining in IL11-treated cells. Together, our results suggest that IL11 inhibits myogenic differentiation through delayed cell cycle exit in an ERK-dependent manner. To our knowledge, this study is the first to demonstrate an inhibitory role of IL11 in myogenic differentiation and identifies the previously unrecognized role of IL11 as a possible mediator of CAC.


Outcome Measures and Patient-Reported Metrics in Cancer Rehabilitation.
The current panorama of measurement tools for use in cancer rehabilitation is reviewed. For rehabilitation purposes, evaluating function is of the highest priority. From a patient-reported outcome (PRO) standpoint, SF-36 and EORTC-QLQ-C30 are in most common use in cancer rehabilitation research; these are quality of life measures that contain functional subdomains. Newer tools which are based on item response theory and have options for both computer assisted or short form (SF) administration, including the Patient-Reported Outcomes Measurement Information System (PROMIS) and Activity Measure for Post-acute Care (AMPAC) instruments, show increasing use, especially PROMIS Physical Function SF, and, recently, PROMIS Cancer Function Brief 3D, which has been validated in the cancer population, with domains of physical function, fatigue, and social participation, to track clinical rehabilitation outcomes. Evaluating objective measures of function in cancer patients is also crucial. Utilization of clinically feasible tools for cancer rehabilitation, to employ for both screening purposes and for monitoring of rehabilitation treatment efficacy, is an evolving area, much needed to promote further research and improved, consistent clinical care for cancer patients and survivors.


High-quality genomes of Paenibacillus spp. RC334 and RC343, isolated from a long-term forest soil warming experiment.
Paenibacillus spp. RC334 and RC343 were isolated from heated soil in a long-term soil warming experiment. Both genomes were 5.98 Mb and assembled as a single contig. We describe the assembly and annotation of the two high-quality draft genomes for these isolates here.


The glycolytic genes pfk and pyk from Lactobacillus casei are induced by sugars transported by the phosphoenolpyruvate:sugar phosphotransferase system and repressed by CcpA.
In Lactobacillus casei BL23, phosphofructokinase activity was higher in cells utilizing sugars transported by the phosphoenolpyruvate:sugar phosphotransferase system (PTS). The phosphofructokinase gene (pfk) was cloned from L. casei and shown to be clustered with the gene encoding pyruvate kinase (pyk). pfk and pyk genes are cotranscribed and induced upon growth on sugars transported by the PTS. Contrarily to the model proposed for Lactococcus lactis, where the global catabolite regulator protein (CcpA) is involved in PTS-induced transcription of pfk and pyk, a ccpA mutation resulted in a slight increase in pfk-pyk expression in L. casei. This weak regulation was evidenced by CcpA binding to a region of the pfk-pyk promoter which contained two cre sequences significantly deviated from the consensus. The PTS induction of pfk-pyk seems to be counteracted by the CcpA-mediated repression. Our results suggest that the need to accommodate the levels of pfk-pyk mRNA to the availability of sugars is fulfilled in L. casei by a PTS/CcpA-mediated signal transduction different from L. lactis.


Difficulty with the preceding visual search affects brain activity in the following resting period.
It has been well-documented that brain regions related to a task are activated during the task performance. We investigated whether brain activity and functional connectivity during the rest period are affected by the preceding task. Participants performed visual search tasks with three search conditions, which were followed by a rest period. During the rest period, participants were asked to look at the display that did not show any visual stimuli. In the result, brain activity in occipital and superior parietal regions would be deactivated by the preceding task during the rest period after visual search tasks. However, the activity of the inferior frontal gyrus during the rest period, which is also part of the attention network, was not affected by the brain activity during the preceding visual search task. We proposed a new model for explaining how the cognitive demands of the preceding visual search task regulate the attention network during the rest period after the task. In this model, the cognitive demand changes with task difficulty, which affects the brain activity even after removing the visual search task in the rest phase.


Mismatch negativity and low frequency oscillations in schizophrenia families.
Theta-alpha range oscillations have been associated with MMN in healthy controls. Our previous studies showed that theta-alpha activities are highly heritable in schizophrenia patients' families. We aimed to test the hypothesis that theta-alpha activities may contribute to MMN in schizophrenia patients and their family members. We compared MMN and single trial oscillations during MMN in 95 patients, 75 first-degree relatives, 87 controls, and 34 community subjects with schizophrenia spectrum personality (SSP) traits. We found that (1) MMN was reduced in patients (p<0.001) and SSP subjects (p=0.047) but not in relatives (p=0.42); (2) there were augmented 1-20 Hz oscillations in patients (p=0.02 to <0.001) during standard and deviant stimuli; (3) theta-alpha (5-12 Hz) oscillations had the strongest correlation to MMN in controls and relatives (ΔR(2)=21.4-23.9%, all p<0.001), while delta (<5 Hz) showed the strongest correlation to MMN in schizophrenia and SSP trait subjects; and, (4) MMN (h(2)=0.56, p=0.002) and theta-alpha (h(2)=0.55, p=0.004) were heritable traits. Low frequency oscillations have a robust relationship with MMN and the relationship appears altered by schizophrenia; and schizophrenia patients showed augmented low frequency activities during the MMN paradigm. The results encourage investigation of low frequency oscillations to elucidate the neurophysiological pathology underlying MMN abnormalities in schizophrenia.


Clinical evaluation and feasibility of changing intraoperative visibility with a novel viewing filter system for human eye.
The study was conducted to develop a new viewing system as a clinical prototype that enables visibility during surgery. The system was composed of several filters attached to the microscope. This nonrandomized, retrospective, observational case series study involved 33 eyes from 32 patients who presented with various diseases and underwent surgery. The authors evaluated the changes in visualization focusing on controlling intraoperative visibility under air infusion and enhancing Brilliant Blue G staining focusing a sharp-cut filter Y (SCY). Visibility was compared under various surgical conditions, including cataract surgery, both with and without this system. Quantitative analysis of changes in intraoperative reflection including halation under air infusion and Brilliant Blue G intensity was carried out using the International Commission on Illumination 1976 (L*, a*, b*) color space method. A SCY reduced the reflection and halation by a maximum of 69.6%, when compared with use of no filter under air infusion (P < 0.01). The color difference between Brilliant Blue G-stained and nonstained areas was improved by 127.8% relative to values with no filter and using SCY (P < 0.01) in macular hole cases. Furthermore, in cataract surgery with corneal opacity, improvement of visibility was observed by SCY insertion. The system improved intraoperative visibility under air infusion and the Brilliant Blue G staining intensity by use of SCY during vitrectomy.


Sucrose and ABA regulate starch biosynthesis in maize through a novel transcription factor, ZmEREB156.
Sucrose is not only the carbon source for starch synthesis, but also a signal molecule. Alone or in coordination with ABA, it can regulate the expression of genes involved in starch synthesis. To investigate the molecular mechanisms underlying this effect, maize endosperms were collected from Zea mays L. B73 inbred line 10 d after pollination and treated with sucrose, ABA, or sucrose plus ABA at 28 °C in the dark for 24 h. RNA-sequence analysis of the maize endosperm transcriptome revealed 47 candidate transcription factors among the differentially expressed genes. We therefore speculate that starch synthetic gene expression is regulated by transcription factors induced by the combination of sucrose and ABA. ZmEREB156, a candidate transcription factor, is induced by sucrose plus ABA and is involved in starch biosynthesis. The ZmEREB156-GFP-fused protein was localized in the nuclei of onion epidermal cells, and ZmEREB156 protein possessed strong transcriptional activation activity. Promoter activity of the starch-related genes Zmsh2 and ZmSSIIIa increased after overexpression of ZmEREB156 in maize endosperm. ZmEREB156 could bind to the ZmSSIIIa promoter but not the Zmsh2 promoter in a yeast one-hybrid system. Thus, ZmEREB156 positively modulates starch biosynthetic gene ZmSSIIIa via the synergistic effect of sucrose and ABA.


Selective mercury adsorption and enrichment enabled by phenylic carboxyl functionalized poly(pyrrole methane)s chelating polymers.
Mercury decontamination from water requires highly effective and efficient methods for maintaining public health and environmental protection. Herein, based on the coordination theory between functional groups and metal ions, we proposed phenylic carboxyl group-based poly(pyrrole methane)s (PPDCBAs) as highly efficient mercury removal materials for environmental remediation applications. It was found that PPDCBAs can efficiently adsorb and remove mercury(II) from aqueous solutions by functionalizing the molecular structure with phenylic carboxyl groups. Among the as-prepared PPDCBAs, poly[pyrrole-2, 5-diyl (4-carboxybenzylidane)] (PPD4CBA) with the carboxyl group at the para position can not only adsorb mercury over 1400 mg⋅g-1 but also achieve a 92.5 % mercury(II) uptake within 100 min by a very low dosage of 0.1 g⋅L-1. In addition, PPDCBAs exhibited excellent adsorption selectivity for mercury(II) compared with copper(II), cadmium(II), zinc(II) and lead(II). Furthermore, as determined by Fourier transform infrared (FT-IR) spectra, X-ray photoelectron spectroscopy (XPS) and the density functional theory (DFT) calculation, the mercury removal was found to be mainly dependent on the high density of chelating sites, the phenylic carboxyl moieties, which helped us to realize an ultra-trace amount mercury removal (from 10.8 μg⋅L-1 to 0.6-0.8 μg⋅L-1) for meeting drinking water standard requirements (1.0 μg⋅L-1).


Phytotoxicity of orellanine, a mushroom toxin.
Orellanine, a toxic principle of Cortinarius orellanus Fr., efficiently inhibited the photosynthetic activity of duckweed, Lemna minor L., at a concentration of 0.4 mM. A lower concentration (0.06 mM) blocked the O2 production in isolated spinach class A chloroplasts. However, no effect was observed on thylakoids (class C chloroplasts), showing that orellanine does not interfere with the chloroplastic electron transfer chain and that orellanine does not act like methylviologen (paraquat) in green plants, as previously suggested. An electrochemical study of orellanine and related compounds showed that orellanine can neither be reduced by electrons derived from H2O nor from NADPH, as is methylviologen in plant and animal cells, respectively.


Embryo disposition: choices made by patients and donor oocyte recipients.
To compare final embryo disposition between patients and donor oocyte recipients. Retrospective study. Private infertility practice. Patients undergoing IVF with embryo cryopreservation. None. Final cryopreserved embryo disposition. A total of 1,262 patients using autologous oocytes had 5,417 embryos cryopreserved. A majority either used their embryos (39%) or continued storage (35%). Of 364 patients, who did not use their remaining 1,406 embryos, 77 (21%) donated 290 embryos to other infertile couples, 41 (11%) donated 160 embryos for research, and 246 (68%) discarded 956 embryos. Concurrently, 272 donor oocyte recipients had 1,233 embryos cryopreserved. A majority either used their embryos (40%) or continued storage (23%). Of 110 recipients that did not use their remaining 455 embryos, 62 (56%) donated 280 embryos to other infertile couples, 6 (6%) donated 31 embryos for research, and 42 (38%) discarded 144 embryos. In our patient population, a higher proportion of patients with infertility ultimately used or stored their cryopreserved embryos for future reproduction compared with donor oocyte recipients. However, recipients were much more likely to donate to other infertile couples and less likely to discard their remaining embryos compared with patients.


Microcystin uptake and biochemical responses in the freshwater clam Corbicula leana P. exposed to toxic and non-toxic Microcystis aeruginosa: Evidence of tolerance to cyanotoxins.
We investigated the accumulation and adverse effects of toxic and non-toxic Microcystis in the edible clam Corbicula leana. Treated clams were exposed to toxic Microcystis at 100 μg of MC (microcystin)-LReq L-1 for 10 days. The experimental organism was then placed in toxin-free water and fed on non-toxic Microcystis for the following 10 days for depuration. Filtering rates (FRs) by C. leana of toxic and non-toxic Microcystis and of the green alga Chlorella vulgaris as a control were estimated. Adverse effects were evaluated though the activity of catalase (CAT), superoxide dismutase (SOD) and glutathione S-transferase (GST). Clam accumulated MCs (up to 12.7 ± 2.5 μg g-1 dry weight (DW) of free MC and 4.2 ± 0.6 μg g-1 DW of covalently bound MC). Our results suggest that although both toxic and non-toxic cyanobacteria caused adverse effects by inducing the detoxification and antioxidant defense system, the clam was quite resistant to cyanotoxins. The estimated MC concentration in C. leana was far beyond the World Health Organization's (WHO) provisional tolerable daily intake (0.04 μg kg-1 day-1), suggesting that consuming clams harvested during cyanobacterial blooms carries a high health risk.


Mercury and Selenium in Muscle and Target Organs of Scalloped Hammerhead Sharks Sphyrna lewini of the SE Gulf of California: Dietary Intake, Molar Ratios, Loads, and Human Health Risks.
Selenium and mercury were evaluated in muscle, liver, kidney, brain, and the stomach contents of juvenile scalloped hammerhead shark Sphyrna lewini. Se:Hg molar ratios were calculated. The average Hg levels in muscle ranged from 0.12 to 1.17 μg/g (wet weight); Hg was <0.39 μg/g in liver and kidneys and <0.19 μg/g in brain. The lowest value of Se was found in muscle (0.4 μg/g) and the highest in kidney (26.7 μg/g). An excess of Se over Hg was found, with Se:Hg molar ratios >1. Correlations were found for Hg in muscle with size, age, and weight, and also for Hg in liver with size, age, and weight. Hg in muscle was significantly positive correlated to Hg in brain as well as Hg in liver was correlated to Hg in kidney. The highest Hg in preys was for carangid fishes; scombrid and carangid fishes contributed with the highest Se levels. Results suggest that more than 98 % of the total Hg and 62 % of Se end up in muscle and might be affected by factors, such as geographical area, age, size, and feeding habits. The muscle of S. lewini should be consumed by people cautiously so as not to exceed the recommended intake per week.


A new surgical technique to treat refractory labial fusion in the elderly.
An elderly woman with refractory labial fusion was treated by labial separation. The subsequent raw area was covered by a rotational skin flap from the thigh. The flap was deroofed of epithelium proximally and tunnelled subcutaneously. The distal portion emerged to cover the raw clitoral area and this successfully prevented contraction and scarring.


Anterior collateral circulation in the primate eye.
Sequential microdissection and scanning electron microscopy of whole primate ocular lumenal methyl methacrylate corrosion castings were performed to determine the anatomic basis of collateral arterial blood flow to the anterior uvea. Collateral anastomoses were observed at three sites: (1) the episclera where the anterior ciliary arteries interconnect at the limbus to form the episcleral circle; (2) the ciliary muscle where anastomoses between the perforating anterior ciliary and long posterior ciliary arteries comprise the intramuscular circle, the most extensive of the three collateral arterial rings, and (3) the root of the iris where circumferentially oriented vessels derived from the intramuscular circle form the "major arterial circle". Of these, the "major arterial circle" is the most discontinuous. This multilevel collateral system probably accounts for the rarity of anterior segment ischemia following all but the most extensive extraocular muscle surgeries.


Moesin is a biomarker for the assessment of genotoxic carcinogens in mouse lymphoma.
1,2-Dibromoethane and glycidol are well known genotoxic carcinogens, which have been widely used in industry. To identify a specific biomarker for these carcinogens in cells, the cellular proteome of L5178Y mouse lymphoma cells treated with these compounds was analyzed by 2-dimensional gel electrophoresis (2-DE) and MALDI-TOF mass spectrometry (MS). Of 50 protein spots showing a greater than 1.5-fold increase or decrease in intensity compared to control cells on a 2-D gel, we focused on the candidate biomarker moesin. Western analysis using monoclonal rabbit anti-moesin confirmed the identity of the protein and its increased level of expression upon exposure to the carcinogenic compounds. Moesin expression also increased in cells treated with six additional genotoxic carcinogens, verifying that moesin could serve as a biomarker to monitor phenotypic change upon exposure to genotoxic carcinogens in L5178Y mouse lymphoma cells.