Chromatin structure modulates transcription factor binding to the mouse mammary tumor virus (MMTV) promoter.
The MMTV promoter contains a complex hormone responsive region (HRR) upstream of a binding site for the transcription factor nuclear factor I (NFI). Hormonal induction of MMTV expression requires the integrity of both the HRR and the NFI binding site. However, in vitro NFI acts as a basal transcription factor on the MMTV promoter that does not cooperate but rather competes with the hormone receptors in terms of binding to MMTV-DNA. Fragments that contain the HRR and the NFI binding site have been reconstituted into mononucleosomes. Steroid hormone receptors bind efficiently to these nucleosomes, NFI does not. Therefore it has been postulated that the chromatin structure may be responsible for the inability of NFI to bind to the chromosomally organized inactive MMTV promoter. In vivo DNaseI and methidium-propyl-EDTA-Fe(II) (MPE) digestion pattern indicate the presence of a nucleosome covering the HRR and the NFI binding site. Genomic footprinting shows that in vivo the rotational setting of the MMTV promoter DNA in this nucleosome is identical to that previously reported for reconstituted nucleosomes in which the major grooves of the NFI half palindromes are facing towards the histone octamer and appear not to be accessible to NFI. These results indicate that MMTV promoter sequences are determining nucleosome positioning in vivo and supports the concept that rotational positioning of DNA in this nucleosome constitutively represses the MMTV promoter.


Muscle hypertrophy with neuropathy.
A patient with insidious onset of weakness, muscle atrophy and true hypertrophy, and sustained spasms is described. The spasms, initially mistaken to be myotonic, were shown electromyographically to result from sustained activity of the muscle fibres. An additional clinical manifestation verified myographically, was impaired reciprocal inhibition. Also, the patient had thick peripheral nerves and very slow motor (but normal sensory) nerve conduction. Histologic examination of sural nerve biopsy revealed large vacuoles within Schwann cells containing unidentified material, as well as onion-bulb formations. The possibility of a metabolic error resulting in storage of an abnormal material within Schwann cells is assumed.


A review of simulation platforms in surgery of the temporal bone.
Surgery of the temporal bone is a high-risk activity in an anatomically complex area. Simulation enables rehearsal of such surgery. The traditional simulation platform is the cadaveric temporal bone, but in recent years other simulation platforms have been created, including plastic and virtual reality platforms. To undertake a review of simulation platforms for temporal bone surgery, specifically assessing their educational value in terms of validity and in enabling transition to surgery. Systematic qualitative review. Search of the Pubmed, CINAHL, BEI and ERIC databases. Assessment of reported outcomes in terms of educational value. A total of 49 articles were included, covering cadaveric, animal, plastic and virtual simulation platforms. Cadaveric simulation is highly rated as an educational tool, but there may be a ceiling effect on educational outcomes after drilling 8-10 temporal bones. Animal models show significant anatomical variation from man. Plastic temporal bone models offer much potential, but at present lack sufficient anatomical or haptic validity. Similarly, virtual reality platforms lack sufficient anatomical or haptic validity, but with technological improvements they are advancing rapidly. At present, cadaveric simulation remains the best platform for training in temporal bone surgery. Technological advances enabling improved materials or modelling mean that in the future plastic or virtual platforms may become comparable to cadaveric platforms, and also offer additional functionality including patient-specific simulation from CT data.


Analysis of multiparasitism by Eupelmus vuilleti (Craw) (Eupelmidae) and Dinarmus basalis (Rond) (Pteromalidae) in the presence of one of their common hosts, Bruchidius atrolineatus (Pic) (Coleoptera Bruchidae).
Bruchidius atrolineatus (Pic) is a tropical beetle (Coleoptera Bruchidae) that develops during the larval and pupal stages in the seeds of a legume Vigna unguiculata (Walp). Two species of Hymenoptera, Dinarmus basalis (Rond) and Eupelmus vuilleti (Craw), solitary ectoparasitoids of the larvae and pupae of B. atrolineatus, were introduced successively in the presence of their hosts, varying the interval between the two introductions. When D. basalis females were introduced 24 h, 3 days or 7 days after E. vuilleti, multiparasitism was low. The females had low fecundity, and their eggs were not distributed randomly over the different available hosts. When E. vuilleti females were introduced second, they oviposited on the different hosts availabe and did not avoid multiparasitism. The presence of hosts already parasitised by D. basalis increased the reproduction of E. vuilleti, and the fecundity of the females was higher than in control batches with E. vuilleti alone. E. vuilleti seems capable of detecting the ovipositor shafts drilled by the D. basalis females, and by introducing its own ovipositors killing the D. basalis eggs or larvae. When interspecific competition was occurring the number of E. vuilleti adults emerging from the seeds was no different from that observed in control batches with E. vuilleti alone, and there were always fewer D. basalis adults than in control batches (D. basalis alone). This interspecific competition reduces the influence of the two parasitoids in the biological control of bruchid populations.


Comprehensive approach of methods for microstructural analysis and analytical tools in lignocellulosic biomass assessment - A review.
The trend in the modern world is to replace fossil fuels with green energy sources in order to reduce their environmental impact. The biorefinery industry, within this premise, needs to establish quantitative and qualitative analytical methods to better understand lignocellulosic biomass composition and structure. This paper presents chemical techniques (chromatography, thermal analysis, HRMS, FTIR, NIR, and NMR) and physicochemical techniques (XRD, optical and electron microscopy techniques - Confocal fluorescence, Raman, SPM, AFM, SEM, and TEM) for the microstructural characterization of lignocellulosic biomass and its derivatives. Each of these tools provides different and complementary information regarding molecular and microstructural composition of lignocellulosic biomass. Understanding these properties is essential for the design and operation of associated biomass conversion processing facilities. PAT, monitored in real-time, ensures an economical and balanced mass-energy process. This review aimed to help researchers select the most suitable analytical technique with which to investigate biomass feedstocks with recalcitrant natures.


Rapid LC-MS/MS detection of different carbapenemase types in carbapenemase-producing Enterobacterales.
Klebsiella pneumoniae carbapenemase (KPC)-2, metallo-beta-lactamases (MBL), and oxacillinase (OXA)-48-like carbapenemases are considered the most important carbapenemases. In vitro studies have demonstrated that the carbapenemase activity of KPC-2 and MBL can be inhibited by 3-aminophenylboronic acid and ethylenediaminetetraacetic acid (EDTA), respectively. Understanding the carbapenemase types expressed in carbapenem-resistant Enterobacterales (CRE) is of great significance to clinical therapies. Liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS) is fast, stable, and specific; and is considered the gold standard method for measuring small molecules. In this study, we developed carbapenemase inhibition tests combined with LC-MS/MS to rapidly identify carbapenemase types. A total of 295 clinical isolates were examined, including 212 KPC-2 producers, 29 MBL producers, 15 OXA-48-like producers, 3 KPC-2 + OXA-232 producers, and 36 carbapenem-sensitive strains. We used LC-MS/MS to determine the carbapenemase types by measuring the ratio of the hydrolyzed meropenem peak areas in the presence and absence of different inhibitors. The sensitivity and specificity of LC-MS/MS in detecting single KPC-2 producers were 97.64% and 100.00%, respectively, and 96.55% and 100.00% for MBL producers, respectively. In addition, the sensitivity and specificity of LC-MS/MS in detecting single OXA-48-like producers were both 100.00% when extending incubation time up to 2.5 h. LC-MS/MS showed excellent agreement in detecting carbapenemase types using the modified carbapenem inactivation (mCIM)/EDTA-carbapenem inactivation assay (eCIM) (kappa = 0.93 for serine carbapenemases and kappa = 0.98 for MBL carbapenemases). In this study, LC-MS/MS demonstrated excellent detection of different carbapenemase types, showing potential reliability in future clinical applications.


Dynamics in cognition and health-related quality of life in grade 2 and 3 gliomas after surgery.
The focus of clinical management and research in gliomas has been on survival, but the interest in the treatment effects on cognition and health-related quality of life (HRQoL) is emerging. The primary aim of this study was to investigate the dynamics in cognition after brain tumor surgery for astrocytomas and oligodendrogliomas grade 2 and 3. The secondary aim was to investigate the association of postoperative changes in cognition with changes HRQoL. In this observational study, 48 patients operated for an astrocytoma or oligodendrogliomas, grade 2 or 3, at the Department of Neurosurgery, Uppsala, Sweden, 2016-2021, were included. Cognitive and language skills were assessed with a selected test battery and HRQoL was patient-reported as assessed with RAND-36 pre- and approximately 3 months postoperatively. There was a significant postoperative decrease in attention span and verbal learning, but the patients improved in the test for visual memory. There was no change in visual attention, executive function, verbal memory, visual organization and construction, verbal fluency, and confrontation naming. The RAND-36 variables physical function, role physical, general health, vitality, and social functioning decreased significantly after surgery. Patients operated for tumor recurrence exhibited greater deterioration in attention and a greater extent of resection correlated with a less pronounced decrease in verbal memory, but there were otherwise weak associations between the dynamics in cognition and patient-, tumor-, and treatment-variables. A decline in cognitive variables was not associated with worse HRQoL. Although both several cognitive and HRQoL domains deteriorated postoperatively, these changes did not correlate with each other. This highlights the complexity of cognitive and HRQoL dynamics in the early postoperative phase.


Initial management of pelvic and femoral fractures in the multiply injured patient.
The management of polytrauma patients is clinically challenging and requires a multi-disciplinary team approach. The immediate and definitive operative care of fractures represents the optimal treatment for polytrauma patients with orthopedic injuries. Early orthopedic intervention in long bone fractures and pelvic ring injuries has been shown to decrease pulmonary complications, improve hemodynamic stability, reduce ventilator time, and facilitate early patient mobilization. These factors decrease mortality and improve outcomes for patients with multiple injuries.


In vivo functions of integrins: lessons from null mutations in mice.
The integrin family (Hynes, R.O., 1992. Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69, 11-25) is composed of at least 24 heterodimers formed from eight beta subunits and 18 alpha subunits. Thus far, mice expressing null mutations of seven of the eight beta subunits and 13 of the 18 known alpha subunits have been generated, With only a few exceptions, the phenotypes of each of the knockout lines are quite distinct. Studies utilizing integrin knockout mice and cells derived from these mice have provided considerable and sometimes surprising insights into unique functions of individual members of this family.


In Silico Identification and Biological Evaluation of Antioxidant Food Components Endowed with IX and XII hCA Inhibition.
The tumor-associated isoenzymes hCA IX and hCA XII catalyze the hydration of carbon dioxide to bicarbonate and protons. These isoforms are highly overexpressed in many types of cancer, where they contribute to the acidification of the tumor environment, promoting tumor cell invasion and metastasis. In this work, in order to identify novel dual hCA IX and XII inhibitors, virtual screening techniques and biological assays were combined. A structure-based virtual screening towards hCA IX and XII was performed using a database of approximately 26,000 natural compounds. The best shared hits were submitted to a thermodynamic analysis and three promising best hits were identified and evaluated in terms of their hCA IX and XII inhibitor activity. In vitro biological assays were in line with the theoretical studies and revealed that syringin, lithospermic acid, and (-)-dehydrodiconiferyl alcohol behave as good hCA IX and hCA XII dual inhibitors.


"You Can Change the World With a Haircut": Evaluating the Feasibility of a Barber-led Intervention for Men of Black and Ethnic Minority Heritage to Manage High Blood Pressure.
People of Black, Asian and minority ethnic (BAME) heritage have a higher-than-average incidence of, and mortality from hypertension and stroke. Therefore, it is important to identify new settings for engaging people at risk of high blood pressure (BP). This feasibility study aimed to evaluate if barbers in a London borough can support and educate men of BAME heritage to manage their BP. Following UK Medical Research Council guidance, the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework was used to guide study objectives and feasibility outcomes. We collaborated with 8 barbers who were part of an existing BAME barber network. Barbers were trained online (1.5 h) and face-to-face (3 h) to provide BP healthcare advice and take customers BP readings. Qualitative field notes were collected to assess how best to recruit and train barbers, and to understand how to maintain motivation and retention of barbers. BP readings were recorded between June 2021 and March 2022. Both online and face-to-face training were effective, however, greater focus on how to start conversations about BP with clients was needed. We found that motivation, incentivization and regular contact with barbers were important for recruitment, retention, and sustained BP measurement. Obtaining BP readings was challenging due to client concerns about recording their data and the impracticalities of recording results. We captured 236 BP recordings, of which 39 (16.53%) were over 140/90 mmHg; of these, 5 were over 180/100 mmHg. The combined data showed that educating barbers to take BP readings and deliver healthcare advice about BP is a viable intervention for rollout in a large-scale study. It has demonstrated the need to identify strategies to motivate barbers for sustained recruitment and retention, as well as further efforts to build trust among customers for long-term BP surveillance.


[Interaction of polymorphonuclear leukocytes, bradykinin and carragenin. Transference reaction in the rat].
1. Injected in the paw of the rat, polymorphonuclear leucocytes do not increase the oedematogen action of bradykinin, but increase the action of lambda carrageenan. 2. This potentiation of carrageenan action is not modified when PG biosynthesis in leucocytes is inhibited by indomethacin or aspirin. It does not appear in rats previously treated by indomethacin or aspirin. 3. Our results suggest that rat polymorphonuclear leucocytes increase the inflammatory reaction, when they are stimulated by carrageenan, by the release of a phospholipase A2 activity which induces PG biosynthesis in rat paw tissues.


Midland non-invasive ventilation score: a tool to predict non-invasive ventilation failure in people with acute hypercapnic respiratory failure.
Use of non-invasive ventilation (NIV) in patients with hypercapnic respiratory failure has clear benefits over invasive ventilation. Existing risk prediction models are complex and difficult to apply in the acute setting. We developed the Midland NIV score comprising only five parameters for use to predict NIV failure (in-hospital death or intubation) at initiation. Individuals with Midland NIV score of ≤11 (average 13% NIV failure) may be suitable for general ward care, compared to intensive care for those with Midland NIV score ≥12 (average 66% NIV failure rate). Prospective external validation is required.


Different (13)CO(2) recovery of orally administered [1-(13)C]- and [8-(13)C] triolein in postprandial humans: an effect of phosphoenolpyruvate-carboxykinase (EC 188.8.131.52) in peripheral tissues?
In this study the conversion of orally administered [1-(13)C]- and [8-(13)C]triolein to CO(2) was compared in normal postprandial human subjects (3 female, 3 male). After an overnight fast the subjects consumed hourly meals of a liquid formula diet over 12 h (8.3% of the predicted 24 h resting energy expenditure/h). 90 min after the first meal on one occasion a bolus of [1-(13)C]triolein was given and in the repeat study the same subject received [8-(13)C]triolein. The order of isotope substrate was randomized. Isotope ratio mass spectrometry analysis of breath samples an recorded CO(2) production rate resulted in a significant 1.31 times greater (13)CO(2) recovery of [1-(13)C]triolein compared to [8-(13)C]triolein within 7.5 h. 10 h after bolus the significant difference disappeared. The different (13)CO(2) recovery is probably due to a different metabolic fate of (13)C at odd and even numbered carbon positions in the fatty acid chain caused by beta-oxidation, citric acid cycle and the phosphoenolpyruvate carboxykinase (EC 184.108.40.206) reaction in peripheral tissues. A contribution of a chain shortening in peroxisomes seems unlikely.


What do the 2011 American Heart Association guidelines tell us about prevention of cardiovascular disease in women?
The 2011 Update of the American Heart Association's Cardiovascular Disease Prevention Guideline for Women is designed to help women and their physicians understand cardiovascular Disease (CVD) risks and undertake practical steps that are most effective in preventing heart disease and stroke. Defining a woman's risk status and improving her adherence to preventive lifestyle behaviors and medications is the best strategy to lower the burden of CVD in women.


Iatrogenic Kaposi sarcoma of the small bowel in Crohn's disease following short-term use of immunomodulators: a case report and review of the literature.
Kaposi sarcoma is a vascular tumor highly related to human herpesvirus-8 and Kaposi sarcoma-associated herpesvirus. Kaposi sarcoma usually manifests as skin or mucosal lesions; involvement in visceral organs such as the gastrointestinal tract is rare. Kaposi sarcoma can occur in immunocompromised patients receiving immunosuppressive therapy, in which case it is known as iatrogenic Kaposi sarcoma or drug-induced Kaposi sarcoma. Intestinal Kaposi sarcoma in patients with inflammatory bowel disease is extremely rare. A 46-year-old East Asian male with recently diagnosed Crohn's disease was administered azathioprine and prednisolone; however, the patient complained of persistent abdominal pain and diarrhea following treatment. Endoscopy revealed small bowel Kaposi sarcoma. The patient was treated with systemic chemotherapy successfully without relapse. This is the fifth case of Kaposi sarcoma developed over the small intestine in a patient with Crohn's disease following administration of immunomodulators. Additionally, this case indicated that even short-term immunomodulator use can induce Kaposi sarcoma in patients with inflammatory bowel disease. Thus, in patients with inflammatory bowel disease, if symptoms are aggravated or do not abate after immunomodulators prescription, and before intending to upgrade immunomodulators, endoscopy should be considered. Finally, chemotherapy can also be considered if both medication withdrawal and surgical intervention are not feasible.


Factors associated with Korean adolescent's e-cigarette use by the severity level of generalized anxiety disorder (GAD-7).
The use of e-cigarette among Korean adolescents is spreading with alarming rapidity, but it has not been studied along with the severity level of GAD-7. This study aims to identify adolescents' e-cigarette use and its associated factors among four different anxiety groups using the problem behavioral theory (PBT). A cross-sectional secondary dataset was retrieved from the 2020 Korea Youth Risk Behavior Survey. Of the total sample of 54,948, four anxiety groups were formed: minimal (score 0-4; n = 36,711), mild (score 5-9; n = 12,138), moderate (score 10-14; n = 4143), and severe (score above 15; n = 1965). A total of 11 variables were selected based on the PBT domains. Descriptive analysis, Chi-square, ANOVA, univariate analysis, and multiple linear regression analysis were performed. E-cigarette use was the highest in the order of severe, mild, moderate, and minimal. While cigarette use was associated with vaping in all anxiety groups, adolescents with minimal or mild anxiety levels were more likely to be influenced by tobacco accessibility and other behavior system factors such as sexual intercourse, alcohol use, and smartphone addiction. Meanwhile, secondhand smoke exposure in public areas was only associated with those with severe anxiety levels, and secondhand smoke exposure at school was a significant factor in all anxiety groups except for those with moderate anxiety levels. Due to the nature of cross-sectional dataset, the study could not draw causal links between vaping and other identified factors, include all the necessary PBT components. These findings underscore the need to consider different levels of anxiety when addressing the problems related to vaping among Korean adolescents.


The role of biomarkers in cancer clinical trials.
To review strategies to incorporate biomarkers into screening studies, and prevention and therapeutic clinical trials. Published research articles. The incorporation of biomarkers into cancer clinical trials has been an important advancement in the last two decades of cancer research and has been critical to increasing our understanding of cancer across the spectrum from early lesions to frank cancers. While the incorporation of biomarkers into studies may increase the significance of the results, they also increase cost and a burden on research subjects. It is important for nurses to have an understanding of both the science and the implications of the biomarkers.


Variability of ovarian follicular growth in natural menstrual cycles.
Variation of ovarian follicular growth has been found to be too great for conventional statistical methods to provide valuable information when this growth has been related to menstrual age or peak volume day. A method that relates follicular growth to its start (follicular growth age) is presented. With the use of this dating method, variability of follicular growth was found to be within limits that could be handled by simple methods. Follicular volume growth followed a sigmoid-shaped curve and was well described by our growth equation.


A Holistic Self-learning Approach for Young Adult Depression and Anxiety Compared to Medication-Based Treatment-As-Usual.
A package of biopsychosocial services for young adults experiencing psychological distress was evaluated and compared to usual outpatient psychiatric care. Young adults (18-25) with moderate-to-severe symptoms of depression and/or anxiety (n = 26) were enrolled in a 13-week intervention consisting of nutritional coaching and multi-vitamin supplements, weekly educational and peer support groups, and a modest financial stipend to engage with physical or expressive activities. A comparison group (n = 13) continued with their usual medication-based outpatient care. Program participants reported significantly improved depression, anxiety, severity of distress, overall quality of life, and empowerment over 4 months, with progress maintained or further improved at 2-month follow-up. No evidence of change on any outcome was observed for comparison group participants. Although long-term impacts on mental health trajectories and reliance on psychotropic medications remain unknown, a holistic self-learning approach is a viable alternative to standard outpatient psychiatric care for young adults.


Protective potential of piroxicam on human peripheral blood mononuclear cells against the suppressive capacity of glioblastoma cell lines.
Dexamethasone, a common medication used in the treatment regimen of glioblastoma, has broad inhibitory effects on the immune responses. Here, in an in vitro study, we examined the effects of piroxicam, a potent substitute for dexamethasone, on peripheral blood mononuclear cells (PBMCs) co-cultured with two glioblastoma cell lines, U-87 MG and A-172 cells. MTT assay was used to determine the proliferation of PBMCs treated with piroxicam, or dexamethasone. In addition, to evaluate the effects of drugs on the cell cycle distribution, DNA content per cell was analyzed in PBMCs and A-172 cell lines using flow cytometry. Oxidative parameters, including superoxide dismutase-3 (SOD3) activity and total anti-antioxidant capacity, lactate dehydrogenase (LDH) activity, as well as IFN-γ and TGF-β levels were measured in PBMCs alone or in the presence of cell lines using ELISA. Unlike dexamethasone, piroxicam showed a protective effect on PBMCs against both glioblastoma cell lines. Furthermore, while dexamethasone reduced the proliferation of PBMCs, piroxicam had no adverse effect on the proliferation. Cell cycle analysis showed a reduction in the G2/M phase in piroxicam-treated A-172 cells. Additionally, dexamethasone limited the cell cycle progression by increasing the fraction of PBMCs in G0/G1. Interestingly, after co-culturing piroxicam-treated PBMCs with cell lines, a remarkable rise in the LDH activity was observed. Although not significant, piroxicam partially decreased TGF-β levels in both cell lines. Our findings suggested a protective effect of piroxicam, but not dexamethasone, on PBMCs against inhibitory mechanisms of two glioblastoma cell lines, U-87 and A-172 cells.


Nanoscale imaging of the conoid and functional dissection of its dynamics in Apicomplexa.
Members of the Apicomplexa phylum are unified by an apical complex tailored for motility and host cell invasion. It includes regulated secretory organelles and a conoid attached to the apical polar ring (APR) from which subpellicular microtubules emerge. In coccidia, the conoid is composed of a cone of spiraling tubulin fibers, two preconoidal rings, and two intraconoidal microtubules. The conoid extrudes through the APR in motile parasites. Recent advances in proteomics, cryo-electron tomography, super-resolution, and expansion microscopy provide a more comprehensive view of the spatial and temporal resolution of proteins belonging to the conoid subcomponents. In combination with the phenotyping of targeted mutants, the biogenesis, turnover, dynamics, and function of the conoid begin to be elucidated.


Association of Prostate Cancer Risk Variants with TMPRSS2:ERG Status: Evidence for Distinct Molecular Subtypes.
Numerous genetic variants have been confirmed as prostate cancer risk factors. These variants may confer susceptibility to the development of specific molecular alterations during tumor initiation and progression. The TMPRSS2:ERG gene fusion occurs in roughly 50% of prostate cancers. Genetic risk variants may influence the development of this fusion. We sought to determine whether prostate cancer risk variants are differentially associated with TMPRSS2:ERG fusion-positive and negative cancer. In the Health Professionals Follow-up Study and Physicians' Health Study Tumor Cohort, we evaluated the associations of 39 prostate cancer risk SNPs with TMPRSS2:ERG fusion status, measured by ERG protein expression. Logistic regression was performed to generate OR and 95% confidence intervals. The primary outcome was ERG(+) (n = 227) versus ERG(-) (n = 260) prostate cancer. A secondary outcome was ERG(+) or ERG(-) cancer versus controls without cancer. Six of 39 SNPs were significantly associated (P < 0.05) with ERG(+) versus ERG(-) disease. Three SNPs were exclusively associated with the risk of ERG(+), one with risk of ERG(-), and two with associations trending in opposite directions for ERG(+) and ERG(-) Only two significant SNPs would be expected by chance. Prostate cancer genetic risk variants are differentially associated with the development of ERG(+) and ERG(-) prostate cancer. Our findings suggest the molecular process of prostate carcinogenesis may be distinct for men with different underlying genetic predisposition. When examining risk factors for prostate cancer, the integration of molecular subtypes may enhance understanding of the etiology of this disease. Cancer Epidemiol Biomarkers Prev; 25(5); 745-9. ©2016 AACR.


Adenomatoid tumor: immunohistological features suggesting a mesothelial origin.
Four adenomatoid tumors of the epididymis were evaluated immunohistologically for the expression of intermediate filaments and endothelial cell markers, factor VIII-related antigen and binding of Ulex europaeus I-lectin (UEA I). Immunofluorescence microscopy showed a strong reaction with antikeratin but not with anti-vimentin antibodies, indicating that adenomatoid tumor cells contain epithelial but not mesenchymal type of intermediate filaments. No staining of tumor cells was seen with anti-FVIII-related antigen antibodies or with fluorochrome-coupled UEA I. The results support the mesothelial, non-endothelial origin of adenomatoid tumors.


Quantitative assessment of diagnostic radiation doses in adult blunt trauma patients.
Many emergency departments and trauma centers utilize extensive radiologic studies during the assessment of trauma patients. A point of concern arises about the possible biological effects of these cumulative radiation doses. The objective of this study is to determine the amount of ionizing radiation received by adult blunt trauma patients at a Level I trauma center during the first 24 hours of their care. This nonconcurrent case series reviewed the first 100 consecutive adult blunt trauma patients who presented to a Level I trauma center in 2006. All patients met hospital standards for the less acute major triage criteria. Individual radiation dose reports calculated by the computed tomography (CT) scanner were used to determine the radiation doses from each CT procedure. Standardized tables were used to determine radiation dose for plain radiographs. The median effective dose of radiation (millisieverts) was calculated for the first 24 hours of hospitalization. A total of 100 eligible patients presented between January 1, 2006, and March 20, 2006. Eighty-six patients had complete radiologic records available. The median age was 32 years, with an intraquartile range of 23 to 46 years; the median Injury Severity Score was 14, with an intraquartile range of 9 to 29; and the median number of CT scans was 3, with an intraquartile range of 3 to 4. The median effective total dose of ionized radiation was 40.2 mSv, with an intraquartile range of 30.5 to 47.2 mSv. A dose of 40.2 mSv is the equivalent of approximately 1,005 chest radiographs. Trauma patients meeting the less acute major triage criteria are exposed to clinically important radiation doses from diagnostic radiographic imaging during the first 24 hours of their care.


Preoperative Submucosal Injection of Carbon Nanoparticles Improves Lymph Node Staging Accuracy in Rectal Cancer after Neoadjuvant Chemoradiotherapy.
The aim of this study was to evaluate the association between the number of nodes harvested and the rate of node positivity, and to evaluate the effect of carbon nanoparticles (CNPs) in improving lymph node detection and staging accuracy in patients who received neoadjuvant chemoradiotherapy (NCRT) followed by curative resection. Between September 2008 and June 2014, 152 consecutive rectal cancer patients treated with NCRT and curative resection were included. Forty-five patients underwent preoperative submucosal injection of CNPs (CNP group); the other patients underwent surgery only (control group). The relationship between the number of lymph nodes harvested and the rate of node positivity was investigated. A comparison of the number of harvested lymph nodes and the node positivity rate between the 2 groups was also performed. The lymph nodes in the CNP group were analyzed in detail. The rate of node positivity increased gradually from 8.6% in patients with 1 to 5 nodes assessed to 37.8% in patients with 17 to 44 nodes assessed. The number of lymph nodes harvested was an independent risk factor for node positivity (p = 0.036). The mean number of lymph nodes retrieved in the CNP group was more than in the control group (21.1 vs 8.0, p = 0.000). The percentage of patients with positive lymph nodes was lower than in the control group (19.6% vs 35.6%, p = 0.037). In the CNP group, of 58 metastatic lymph nodes, 45 (77.6%) were dyed. Of 37 metastatic lymph nodes smaller than 5 mm, 33 (89.2%) were dyed. More precise oncologic prognosis assessment was provided for patients with rectal cancer after NCRT by increasing the number of lymph nodes counted using a dye-tracing method, indicating that the use of CNPs is beneficial.


Distance analysis helps to establish characteristic motifs in intron sequences.
Computer-assisted sequence analysis was applied to detect the most apparent nonrandom sequence motifs in eukaryotic introns. We describe in detail a method, which we call distance analysis, that we applied to the extensive study of 405 eukaryotic intron sequences. We observed very strong two-base periodicities for almost all tetranucleotides that are tandem repeats of nonhomopolymeric dinucleotides (the exception was GCGC and CGCG). We also observed, by using a fixed-point alignment method, that these periodic sequence motifs belong to large clusters of dinucleotides repeated tandemly as many as 15-35 times, which corresponds to the cluster lengths of 30-70 bases. We did not observe two-base periodicity of tetranucleotides in the collections of either 262 spliced eukaryotic exons or 107 bacterial genes. Instead, these sequences displayed strong three-base periodicity of some other tetranucleotides. These findings suggest that introns and exons display distinct sequence properties that can be used for mapping purposes.


Intracellular Temperature Sensing: An Ultra-bright Luminescent Nanothermometer with Non-sensitivity to pH and Ionic Strength.
Luminescence thermometry usually suffer from cellular complexity of the biochemical environment (such as pH and ionic strength), and thus the accuracy and reliability of the determined intracellular temperature are directly affected. Herein, a photoluminescent nanothermometer composed of polymer encapsulated quantum dots (P-QD) has been developed. And the prepared nanothermometer exhibits some advantages: such as non-sensitivity to pH and ionic strength, as well as high detection sensitivity and ultrahigh reversibility. The intracellular temperature was accurately determined under physiological conditions with different pH and ionic strength, and direct measurement of thermogenesis in individual cells has been achieved.


The staphylococcal exopolysaccharide PIA - Biosynthesis and role in biofilm formation, colonization, and infection.
Exopolysaccharide is a key part of the extracellular matrix that contributes to important mechanisms of bacterial pathogenicity, most notably biofilm formation and immune evasion. In the human pathogens Staphylococcus aureus and S. epidermidis, as well as in many other staphylococcal species, the only exopolysaccharide is polysaccharide intercellular adhesin (PIA), a cationic, partially deacetylated homopolymer of N-acetylglucosamine, whose biosynthetic machinery is encoded in the ica locus. PIA production is strongly dependent on environmental conditions and controlled by many regulatory systems. PIA contributes significantly to staphylococcal biofilm formation and immune evasion mechanisms, such as resistance to antimicrobial peptides and ingestion and killing by phagocytes, and presence of the ica genes is associated with infectivity. Due to its role in pathogenesis, PIA has raised considerable interest as a potential vaccine component or target.


The role of 20-hydroxyecdysone and juvenile hormone in pupal commitment of the epidermis of the silkworm, Bombyx mori.
During the pupal metamorphosis in insects, cellular commitment for pupal differentiation must precede before its differentiation. The pupal commitment of Bombyx mori epidermis occurred from day 3 to day 6 last (5th) instar larvae in response to the gradual increase in ecdysteroid titer in the presence of a small amount of juvenile hormone (JH). Yet the concealed preparatory process of the commitment had begun in the newly synthesized 5th instar larval epidermis (approximately 6 h before the ecdysis) as a competence phase, in which pupal commitment in vitro was induced by 20-hydroxyecdysone (20E) but inhibited by JH. This competence phase continued until day 2 5th instar, and the decrease and increase in cellular sensitivity to JH and 20E, respectively, occurred gradually during this period. In early day 3, autonomous pupal commitment began in vitro and 20E stimulated the commitment, but JH could only partially prevent the commitment in both cases. This apparent reversible to irreversible transition ended in early day 6 by the completion of pupal commitment, when the cells completely lost their sensitivity to JH and no longer expressed the larval cuticle protein gene 30. The expression of the transcription factor, broad, closely followed the commitment, so that we could use this gene expression as a molecular marker for pupal commitment. These results indicate that exposure to 20E and loss of the sensitivity of the epidermal cells to JH are required for the completion of pupal commitment, and suggest that the unusually long process over 3 days could be due to the presence of the detectable JH during the commitment.


Primary Ewing's sarcoma of the petroclival bone.
A 17-year-old male presented with signs of raised intracranial tension and multiple cranial nerve dysfunction. Radiological imaging revealed an extradural calcified tumor involving the right petrous bone and adjacent clivus. The patient underwent extensive surgical debulking of the mass. Histopathological study revealed that the tumor was Ewing's sarcoma. Post-operative radio- and chemotherapy were administered. The patient's cranial nerve dysfunctions had recovered to some extend at 12 months' follow-up. Ewing's sarcoma arising from the skull base is an extremely rare lesion. The relevant literature on the subject is reviewed.


Interaction between external medium and haem pocket in myoglobin probed by low-temperature optical spectroscopy.
The visible absorption spectra of carbonmonoxymyoglobin in the temperature range 300 to 20 K are reported and compared with the analogous spectra of carbonomonoxyhaemoglobin. The temperature dependence of the zeroth, first and second moment of the observed bands is analysed to obtain information on the local dynamics in the proximity of the haem. Contrary to haemoglobin, the first moment of the observed bands in myoglobin is markedly affected by the solvent composition and its value saturates at temperatures at which the solvent undergoes the glass transition. These data indicate that solvent properties influence the haem pocket stereodynamics in myoglobin; moreover, the different behaviour between myoglobin and haemoglobin suggests that the process should involve the surfaces that are buried in the haemoglobin tetramer and exposed to the solvent in myoglobin, and/or the different protein compressibility.


Sequence enrichment profiles enable target-agnostic antibody generation for a broad range of antigens.
Phenotypic drug discovery (PDD) enables the target-agnostic generation of therapeutic drugs with novel mechanisms of action. However, realizing its full potential for biologics discovery requires new technologies to produce antibodies to all, a priori unknown, disease-associated biomolecules. We present a methodology that helps achieve this by integrating computational modeling, differential antibody display selection, and massive parallel sequencing. The method uses the law of mass action-based computational modeling to optimize antibody display selection and, by matching computationally modeled and experimentally selected sequence enrichment profiles, predict which antibody sequences encode specificity for disease-associated biomolecules. Applied to a phage display antibody library and cell-based antibody selection, ∼105 antibody sequences encoding specificity for tumor cell surface receptors expressed at 103-106 receptors/cell were discovered. We anticipate that this approach will be broadly applicable to molecular libraries coupling genotype to phenotype and to the screening of complex antigen populations for identification of antibodies to unknown disease-associated targets.


Colonization by multidrug-resistant bacteria in hematological patients undergoing hematopoietic stem cell transplantation and clinical outcomes: A single-center retrospective cohort study.
Bloodstream infections are a leading cause of death in patients who undergo hematopoietic stem cell transplantation (HSCT) and are more severe when caused by multidrug-resistant (MDR) bacteria. This study proposed to investigate if colonization by MDR bacteria negatively affects the clinical outcomes in hematological patients after HSCT, as well as to evaluate possible risk factors for death due to bacteremia by the same colonizing agent. A single-center retrospective cohort study was conducted with 405 hematological patients submitted to a single HSCT procedure between 2015 and 2021. Patients were classified as colonized (n = 132) or noncolonized (n = 273) based on the surveillance cultures from D-30 to D+30 of transplantation, and their relevant clinical and laboratory data were collected until D+100. Colonization by MDR bacteria increased blood culture positivity by all micro-organisms and also specifically by MDR bacteria, with a more pronounced effect when caused by carbapenemase-producing Klebsiella pneumoniae. Patients colonized with carbapenem-resistant K. pneumoniae had increased overall mortality (HR = 4.07, 95% CI 1.85-8.91, P = .0005) and had prolonged hospital length of stay in the context of autologous transplantation. Risk factors for death due to bacteremia by the same colonizing agent were neutropenia, colonization by carbapenem-resistant K. pneumoniae and use of high-dose total body irradiation in conditioning. Hematological patients colonized by MDR bacteria presented a higher incidence of bloodstream infections, and colonization by carbapenemase-producing K. pneumoniae was associated with reduced overall survival.


Stability of urinary glycosaminoglycans in patients with mucopolysaccharidoses.
The aim of this work is to investigate the degradation of urinary glycosaminoglycans (GAGs) at different storage temperatures, in order to identify whether frozen transportation to reference laboratories is necessary. An improved method for the determination of total GAGs with 1,9-dimethylmethylene blue (DMB) is presented. Urine samples of 37 patients suffering from mucopolysaccharidoses (MPS) were analyzed in this study (13 Hunter, 6 Maroteaux-Lamy, 6 Morquio, 6 Sanfilippo, 5 Hurler-Scheie, and 1 Sly). Stability was assayed at room temperature, 5 degrees C and -30 degrees C, and analyses were repeated for at least 15 days. Spectrophotometric quantitation of GAGs with DMB was used for all determinations, using a variable wavelength for quantitation. The concentration of urinary GAGs was stable for 10 days at room temperature, but it was found to be stable for more than 15 days at 5 degrees C and -30 degrees C. The stability of GAGs allows urine samples to be sent for quantitation at a clinical laboratory without the need to freeze samples, as this would not affect results. This issue is important for the rapid detection of MPS at hospitals or primary health care centres, where GAGs determination is not performed.


Neglect of quality-of-life considerations in intensive care unit family meetings for long-stay intensive care unit patients.
To examine the frequency with which quality of life and treatment limitation were discussed in formal family meetings for long-stay intensive care unit patients with high risk for mortality and morbidity. Descriptive observational study. Five intensive care units. One hundred sixteen family surrogate decisionmakers of long-stay intensive care unit patients who participated in an intensive communication system that aimed to provide weekly meetings with family decisionmakers. The structure of each meeting was to address medical update, patient preferences, treatment plan, and milestones for evaluating the treatment plan. None. We audiotaped initial family meetings for 116 family decisionmakers for a total of 180 meetings. On average, meetings were 24 mins long with a majority of time being devoted to nonemotional speech and little (12%) spent discussing patient preferences. Quality of life was discussed in 45% and treatment limitation in 23% of all meetings. Quality-of-life discussions were more likely to occur when patients were admitted to a medical intensive care unit (odds ratio [OR] 5.9; p = .005), have a family decisionmaker who is a spouse (OR 9.4; p = .0001), were older (OR 1.04; p = 01), have a shorter length of stay (OR 0.93; p = .001), and have a family decisionmaker who was a spouse (OR 5.1; p = .002). For those with a treatment limitation discussion, 67% had a do-not-resuscitate order, 40% were admitted to a medical intensive care unit, 56% had a family decisionmaker who had been their caregiver, and 48% of their family decisionmakers were their children. To guide discussion with families of the subset of intensive care unit patients with high risk of mortality and long-term morbidity, quality of life was not consistently addressed. Continued efforts to assist clinicians in routinely including discussions of quality-of-life outcomes is needed.


Dosimetric verification of complex radiotherapy with a 3D optically based dosimetry system: dose painting and target tracking.
The increasing complexity of radiotherapy (RT) has motivated research into three-dimensional (3D) dosimetry. In this study we investigate the use of 3D dosimetry with polymerizing gels and optical computed tomography (optical CT) as a verification tool for complex RT: dose painting and target tracking. For the dose painting studies, two dosimeters were irradiated with a seven-field intensity modulated radiotherapy (IMRT) plan with and without dose prescription based on a hypoxia image dataset of a head and neck patient. In the tracking experiments, two dosimeters were irradiated with a volumetric modulated arc therapy (VMAT) plan with and without clinically measured prostate motion and a third with both motion and target tracking. To assess the performance, 3D gamma analyses were performed between measured and calculated stationary dose distributions. Gamma pass-rates of 95.3% and 97.3% were achieved for the standard and dose-painted IMRT plans. Gamma pass-rates of 91.4% and 54.4% were obtained for the stationary and moving dosimeter, respectively, while tracking increased the pass-rate for the moving dosimeter to 90.4%. This study has shown that the 3D dosimetry system can reproduce and thus verify complex dose distributions, also when influenced by motion.


Diffusion Entropy: A Potential Neuroimaging Biomarker of Bipolar Disorder in the Temporal Pole.
Despite much research, bipolar depression remains poorly understood, with no clinically useful biomarkers for its diagnosis. The paralimbic system has become a target for biomarker research, with paralimbic structural connectivity commonly reported to distinguish bipolar patients from controls in tractography-based diffusion MRI studies, despite inconsistent findings in voxel-based studies. The purpose of this analysis was to validate existing findings with traditional diffusion MRI metrics and investigate the utility of a novel diffusion MRI metric, entropy of diffusion, in the search for bipolar depression biomarkers. We performed group-level analysis on 9 un-medicated (6 medication-naïve; 3 medication-free for at least 33 days) bipolar patients in a major depressive episode and 9 matched healthy controls to compare: (1) average mean diffusivity (MD) and fractional anisotropy (FA) and; (2) MD and FA histogram entropy-a statistical measure of distribution homogeneity-in the amygdala, hippocampus, orbitofrontal cortex and temporal pole. We also conducted classification analyses with leave-one-out and separate testing dataset (N = 11) approaches. We did not observe statistically significant differences in average MD or FA between the groups in any region. However, in the temporal pole, we observed significantly lower MD entropy in bipolar patients; this finding suggests a regional difference in MD distributions in the absence of an average difference. This metric allowed us to accurately characterize bipolar patients from controls in leave-one-out (accuracy = 83%) and prediction (accuracy = 73%) analyses. This novel application of diffusion MRI yielded not only an interesting separation between bipolar patients and healthy controls, but also accurately classified bipolar patients from controls.


A Hollow-Core Photonic-Crystal Fiber-Optic Gyroscope Based on a Parallel Double-Ring Resonator.
A novel system structure of resonant fiber optical gyroscope using a parallel double hollow-core photonic crystal fiber ring resonator is proposed, which employs the double closed loop and reciprocal modulation-demodulation technique to solve the problem of the length mismatch between rings. This structure can suppress the residual amplitude modulation noise and laser frequency noise, essentially eliminating the influence of the Rayleigh backscattering noise and dramatically reduce the Kerr-effect-induced drift by three orders of magnitude. Thanks to its excellent noise suppression effect, the sensitivity of this novel system can approach the shot-noise-limited theoretical value of 8.94 × 10-7 rad/s assuming the length of the fiber ring resonator is 10 m.


Effect of chronic caffeine intake on choice reaction time, mood, and visual vigilance.
The stimulatory effects of acute caffeine intake on choice reaction time, mood state, and visual vigilance are well established. Little research exists, however, on the effects of chronic caffeine ingestion on psychomotor tasks. Therefore, the purpose of this study was to evaluate the effects of 5 days of controlled caffeine intake on cognitive and psychomotor performance. Three groups of 20 healthy males (age=22+/-3 years, mass=75.4+/-7.9 kg, body fat percentage=11.2+/-5.1%) twice completed a battery of cognitive and psychomotor tasks: after 6 days of 3 mg.kg(-1) day(-1) caffeine equilibration (Day 6), and after 5 days of experimental (0 [G0], 3 [G3], or 6 [G6] mg.kg(-1) day(-1)) caffeine intake (Day 11). Groups were randomized and stratified for age, mass, and body composition; all procedures were double-blind. Cognitive analyses involved a visual four-choice reaction time test, a mood state questionnaire, and a visual vigilance task. Experimental chronic caffeine intake did not significantly alter the number of correct responses or the mean latency of response for either the four-choice reaction time or the visual vigilance tasks. The Vigor-Activity subset of the mood state questionnaire was significantly greater in G3 than G0 or G6 on Day 11. All other mood constructs were unaffected by caffeine intake. In conclusion, few cognitive and psychomotor differences existed after 5 days of controlled caffeine ingestion between subjects consuming 0, 3, or 6 mg.kg(-1) day(-1) of caffeine, suggesting that chronic caffeine intake (1) has few perceptible effects on cognitive and psychomotor well-being and (2) may lead to a tolerance to some aspects of caffeine's acute effects.


Study on a pseudo-simulated moving bed with solvent gradient for ternary separations.
There is a trapping effect on the solute in the simulated moving bed (SMB) with solvent gradient. As the eluotropic strength of the liquid in zone II (between the extract-port and feed-port) is higher than that in zone III (between the feed-port and the raffinate-port), the solute can move forward in zone II but backward in zone III to be trapped in the two zones consequently. On this basis, a pseudo-SMB was proposed to separate the medium retained solute from a ternary mixture by selectively trapping the medium retained solute. Once the columns in zones II and III are saturated with the target solute, the solvent dissolving the feed is introduced at the feed-port to remove the least retained solute from the raffinate-port and the most retained solute from the extract-port. Finally, the target solute is recovered. A model simulation was used to investigate the behavior and performance of a system operating with this technology. The results showed that increasing the columns in zone III could trap more target solutes since the eluotropic strength decreased from zone II to zone III. Partial recovery in combination with incomplete purification could improve the separation performance in terms of the productivity and solvent consumption without losing purity.


Localization of A20 to a lysosome-associated compartment and its role in NFkappaB signaling.
A20 is a tumor necrosis factor (TNF)-inducible zinc finger protein that contains both ubiquitinating and deubiquitinating activities. A20 negatively regulates NFkappaB (nuclear factor kappaB) signaling induced by TNF receptor family and Toll-like receptors, but the mechanism of A20 action is poorly defined. Here we show that a fraction of endogenous and ectopically expressed A20 is localized to an endocytic membrane compartment that is in association with the lysosome. The lysosomal association of A20 requires its carboxy terminal zinc finger domains, but is independent of its ubiquitin-modifying activities. Interestingly, A20 mutants defective in membrane association also contain reduced NFkappaB inhibitory activity. These findings suggest the involvement of a lysosome-associated mechanism in A20-dependent termination of NFkappaB signaling.


Ciliogenesis and ciliation of the respiratory epithelium in the human fetal cartilaginous trachea.
Ciliogenesis of the respiratory epithelium in the human cartilaginous trachea start during the 12th week of gestation. Ciliary shafts are first seen under the scanning electron microscope during the 13th week. Unlike its membranous counterpart, ciliary shafts appear all over the epithelial surface at almost the same time. Epithelial cells destined to become ciliated cells first develop numerous long and thin microvilli. A process of individual cell extrusion and proliferation of neuroepithelial bodies around the carinal angle precede ciliation in the respiratory epithelium of the cartilaginous trachea. Epithelial cell differentiation patterns in both the cartilaginous and membranous trachea are different. The mechanisms involved in modulating cell differentiation are currently under investigation.


Signalling by senescent melanocytes hyperactivates hair growth.
Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration1. Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity. Here, using genetic mouse models of nevi2,3, we show that dermal clusters of senescent melanocytes drive epithelial hair stem cells to exit quiescence and change their transcriptome and composition, potently enhancing hair renewal. Nevus melanocytes activate a distinct secretome, enriched for signalling factors. Osteopontin, the leading nevus signalling factor, is both necessary and sufficient to induce hair growth. Injection of osteopontin or its genetic overexpression is sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescue enhanced hair growth induced by dermal nevus melanocytes. Osteopontin is overexpressed in human hairy nevi, and it stimulates new growth of human hair follicles. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue4, we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal. This finding identifies senescent cells and their secretome as an attractive therapeutic target in regenerative disorders.


High-frame rate four dimensional optoacoustic tomography enables visualization of cardiovascular dynamics and mouse heart perfusion.
Functional imaging of mouse models of cardiac health and disease provides a major contribution to our fundamental understanding of the mammalian heart. However, imaging murine hearts presents significant challenges due to their small size and rapid heart rate. Here we demonstrate the feasibility of high-frame-rate, noninvasive optoacoustic imaging of the murine heart. The temporal resolution of 50 three-dimensional frames per second provides functional information at important phases of the cardiac cycle without the use of gating or other motion-reduction methods. Differentiation of the blood oxygenation state in the heart chambers was enabled by exploiting the wavelength dependence of optoacoustic signals. Real-time volumetric tracking of blood perfusion in the cardiac chambers was also evaluated using indocyanine green. Taken together, the newly-discovered capacities offer a unique tool set for in-vivo structural and functional imaging of the whole heart with high spatio-temporal resolution in all three dimensions.


Hereditary neuropathy with liability to pressure palsies. Report of two families and review of the literature.
Clinical, neurophysiological and pathological investigations were carried out in 11 affected members of 2 families with hereditary neuropathy with liability to pressure palsies (HNPP). The observations were related to findings in 261 cases of 47 families published in the literature. It was concluded that HNPP is a nosological entity characterized by the following diagnostic criteria: (1) an autosomal dominant inheritance; (2) the clinical presentation of a recurrent mononeuropathy simplex or multiplex, frequently related to an inadequate trauma to peripheral nerves; (3) a significant slowing of motor and sensory conduction velocity in clinically affected, but also in clinically unaffected nerves; (4) characteristic morphological findings in sural nerve biopsy featuring "tomaculous" swellings of myelin sheaths, transnodal myelination and segmental demyelination. The pathogenesis of HNPP is not clear. Hypothetical explanations of the pathogenesis of HNPP are discussed.


Effects on post-prandial glucose and AGE precursors from two initial insulin strategies in patients with type 2 diabetes uncontrolled by oral agents.
Progressive β-cell dysfunction in Type 2 diabetes results in the need for insulin therapy in many patients. Yet the best regimen to prescribe to patients transitioning from oral anti-hyperglycemic drugs (OADs) is not clear. We sought to compare the effects of two standard initial insulin strategies (basal insulin alone versus premixed insulin) on post-prandial glucose metabolism and precursors of advanced glycation end-products in patients with type 2 diabetes suboptimally controlled on OADs. This was a 6-month, open-label, single-center study using a cross-over design. 14 subjects were randomized to one of two protocols: once daily insulin glargine or twice-daily 75%/25% neutral protamine lispro/lispro mix. At 12 weeks, the subjects were crossed-over to the opposite protocol. During each period, insulin doses were titrated to target fasting blood glucose of 90-110 mg/dL. At baseline and after the two 12-week treatment periods, subjects were studied in the Clinical Research Center; they consumed three liquid mixed isocaloric meals at 4-h intervals, and glucose, free fatty acids (FFA), lipids, and α-dicarbonyls (3-deoxyglucosone [3-DG] and methylglyoxal [MG]) were measured before and after each meal. Patient data were analyzed in the context of their assigned insulin strategy groups. Both insulin regimens led to a significant improvement in glycemic profiles, including fasting glucose and HbA1c, compared to baseline. However, mean post-prandial glucose was lower with lispro mix than with glargine (153 ± 36 vs. 199 ± 49 mg/dL, respectively; P=0.001). Likewise, there was a reduction in both fasting (48 ± 13 vs. 57 ± 19, P=0.047) and post-prandial (53 ± 19 vs. 63 ± 23; P=0.007) 3DG levels with lispro mix as compared to glargine. No differences were noted in MG concentrations. In type 2 diabetes patients failing OAD therapy, an initial insulin regimen of twice daily premixed insulin results in significantly improved post-prandial glucose levels as well as a reduction in a precursor of AGEs. The effect of these two initial insulin regimens on long-term diabetic complications requires further study.


The significance of subdivisions of microscopically positive (R1) margins in colorectal cancer: A retrospective study of a national cancer registry.
Microscopically positive (R1) margins are associated with poorer outcomes in patients with colorectal cancer. However, little is known of the differential impact of subdivisions of R1 margins, be they to the primary tumour (R1tumour) or to lymph node metastases/tumour deposits (R1LNM). Patients treated for Stage III colorectal cancer from 1 January 2016 to 31 December 2019 were identified from the Danish national cancer registry. Patients were stratified into three groups according to margin status (R0 vs. R1tumour vs. R1LNM). The primary outcome was overall survival. In all, 4186 patients were included, comprising 3012 patients with colon cancer and 1174 patients with rectal cancer. The R1 resection rates were 16.5% and 18.2% in patients with colon and rectum cancer, respectively. In colon cancers, 3-year overall survival was reduced in patients with R1LNM (65.7%, 95% CI 62.8-68.6) or R1tumour margins (51.8%, 95% CI 47.3-56.3) compared with R0 resections (80.8%, 95% CI 79.9-81.6, P < 0.001). A similar impact on survival was seen in rectal cancers (R0, 84.2%, 95% CI 82.9-85.5; R1LNM, 72.2%, 95% CI 67.8-76.6; R1tumour, 56.6%, 95% CI 50.0-63.2, P < 0.001). Margin status was independently prognostic of survival in both colon (R1tumour, hazard ratio 2.08, 95% CI 1.50-2.89, P < 0.001; R1LNM, hazard ratio 1.48, 95% CI 1.11-1.97, P = 0.008) and rectal cancers (R1tumour, hazard ratio 2.35, 95% CI 1.42-3.90, P < 0.001; R1LNM, hazard ratio 1.54, 95% CI 0.95-2.48, P = 0.077). R1 subdivisions have distinct impacts on survival in Stage III colorectal cancer. Further focused research in these patient subgroups is warranted.


Transmural variation of myocardial attenuation measured with a clinical imager.
The objective of this study was to quantify the transmural variation in attenuation for the septal and lateral walls of the heart. Our approach was to utilize a commercially available ultrasonic imaging system to acquire images of excised sections of eight sheep hearts with an orientation similar to that encountered in the apical four-chamber view. The measured values (mean +/-SE) of the slope of attenuation for the transmural regions of the septum are: 1.40 +/-0.11, 0.99 +/-0.09, and 1.85 +/-0.16 (dB/cm/MHz) for the left subendocardial, midmyocardial, and right subendocardial zones, respectively. The analogous data from the lateral wall are: 1.42 +/-0.11, 0.83 +/-0.07, and 1.20 +/- 0.16 (dB/cm/MHz) for the subendocardial, midmyocardial, and subepicardial zones, respectively. These data demonstrate that ultrasonic attenuation associated with the septum and the lateral wall, when imaged in a manner similar to that of the apical four-chamber view, is anisotropic.


Arterial steroid receptors and their putative role in the mechanism of hypertension.
Data from clinical and experimental studies indicate that mechanism(s) for action of mineralocorticoids, other than renal, must be involved in the overall effect of mineralocorticoids on circulation--increased peripheral resistance and hypertension. We have postulated existence of such a mechanism in the arterial wall and have looked for the evidence for its presence. We have found high affinity, specific binders for mineralocorticoids, and glucocorticoids, with characteristics of steroid receptors, in the cytosol of rabbit aorta and femoral and carotid arteries. These binders possess physico-chemical properties of steroid receptors and, moreover, they translocate to cell nuclei (as steroid-receptor complexes) and bind to relatively specific "acceptor-sites" on nuclear chromatin. This provides evidence for the existence in the arterial wall of a molecular mechanism for a direct in situ action of mineralocorticoids and glucocorticoids. The mineralocorticoid receptors are not present in veins. We have also found that chronically elevated levels of 11-desoxycorticosterone (DOC) result in a marked increase in permeability of arterial smooth muscle cell membrane to sodium ions; this is in accord with findings of other investigators in the rat. This change presumably leads, through a chain of biochemical events, to increased arterial and arteriolar smooth muscle contractility, increased peripheral resistance and hypertension. Study is in progress to determine whether the effect of DOC on arterial smooth muscle cell-membrane permeability to electrolytes is elicited through the receptor-mediated mechanism for the in situ action of mineralocorticoids in the arterial wall. It is postulated that this mechanism is primarily responsible for "mineralocorticoid hypertension", but may well be instrumental also in pathogeneses of various other forms of hypertension, including "essential".


Evaluating the effect of cooking and gastrointestinal digestion in modulating the bio-accessibility of different bioactive compounds of eggs.
Eggs' nutritional value has been enhanced by enriching hen's diet with bioactive compounds, but factors influencing bio-accessibility are unspecified. This study investigated the effect of hen breed, diet enrichment, and cooking methods in modulating the egg compounds' bio-accessibility after gastrointestinal (GI) digestion. White Leghorn (WLH) and Rhode Island Red (RIR) hens were fed a corn-soybean-based diet enriched with flaxseed and carotenoids; eggs were collected, cooked, and subjected to simulated GI digestion. The results showed that egg proteins were equally digestible with no change in the degree of hydrolysis (DH). The linolenic fatty acid in enriched-cooked samples remained bio-accessible after GI digestion. The lutein bio-accessibility in enriched eggs decreased after GI digestion except in RIR fried sample. Eggs from WLH and RIR achieved similar peptide content after GI digestion. These results elucidate the bio-accessibility of different bioactive compounds in cooked eggs and the use of eggs as potential functional foods.


Fabrication, characterization and in vitro cell exposure study of zein-chitosan nanoparticles for co-delivery of curcumin and berberine.
For the first time, we synthesized the co-delivery nanopolymers using zein protein as the core and chitosan polysaccharide as the shell to deliver curcumin (Cur) and berberine (Ber) in MDA-MB-231 breast cancer cells. It has been shown that Cur and Ber altogether have synergistic effects on multiple cancers. Herein, the curcumin-zein-berberine-chitosan (Cur-Z-Ber-Ch) nanoparticles were fabricated and their organization procedure was reported. Physicochemical properties of synthesized nanoparticles were determined by Fourier transform infrared (FTIR) spectroscopy, XRD and fluorescence spectroscopy analyses. The nanoparticles included relatively small particles (d = 168.24 nm) with +36.76 mV zeta potential. The resulting nanoparticles had high entrapment efficiency (about 75%) for Cur and 60% for Ber. The Cur-Z-Ber-Ch nanoparticles represented ideal redispersibility and storage stability after 4 months. Drug release of the freeze-dried nanoparticles had pH-sensitive characteristic. In vitro cytoxicity assay demonstrated that Cur-Z-Ber-Ch nanoparticles induced elevated cytotoxic effect in MDA-MB-231 and A549 cancer cells. In vitro studies in MDA-MB-231 cells demonstrated that the Cur-Z-Ber-Ch nanoparticles could successfully increase cellular uptake and apoptosis with significant inhibition of IL-8 pro-inflammatory cytokines in comparison to the free Cur + Ber bioactive molecules. These bio-nanoparticles are the co-delivery vehicle for Cur and Ber which could be beneficial for participating them into pharmaceutical products.


The Impella Recover microaxial left ventricular assist device reduces mortality for postcardiotomy failure: a three-center experience.
We evaluated patient outcomes and complications associated with the microaxial Impella Recover left ventricular assist device (Impella Cardiosystems AG, Aachen, Germany) for postcardiotomy low-output syndrome. This low-cost device is inserted across the aortic valve through a 10-mm vascular graft sewn to the ascending aorta. Impella patients were compared with 198 patients treated with an intraoperative intra-aortic balloon pump between January 2000 and December 2002. Three risk scores were used: the Hausmann score, the Texas Heart Institute score, and the Cleveland intensive care unit score. Between September 2001 and March 2003, 24 patients were treated with the Impella Recover for low-output syndrome. Before device insertion, 21 could not be separated from cardiopulmonary bypass, and 3 had postoperative hemodynamic instability despite high-dose catecholamines. Sixteen were treated with the Impella and intra-aortic balloon pump and 8 with the Impella alone (no intra-aortic balloon pump because of peripheral vascular disease or because deemed unnecessary). No technical problems with device insertion occurred. Pump flow was 3.3 +/- 0.7 L/min at 28,000 +/- 4500 RPM. Support time was 61 +/- 56 hours (range, 7-228 hours). Four devices required repositioning. One device failed (leaking purge line) and was removed. Hemolysis was minimal (lactate dehydrogenase levels of 540 +/- 260 U/dL for Impella survivors). Mortality for Impella patients was 54% (13/24), similar to that for high-risk intra-aortic balloon pump patients (Hausmann score > or =2 [57%], intensive care unit score > or =2 [51%], Texas Heart Institute score > or =0.75 [55%], and cardiac index < or =2.3 [45%]). Cardiac output data were available in 19 Impella patients. Impella patients able to increase their cardiac output to 1 L/min or more above the pump flow of the Impella Recover had a 10% (1/10) mortality, versus 88% (8/9) in patients with a residual cardiac function of 1 L/min or less (P =.001). Comparison of high-risk intra-aortic balloon pump patients with Impella patients with residual cardiac function of 1 L/min or more showed a significant reduction in mortality, regardless of the high-risk definition used. Residual cardiac function was the strongest predictor of survival in Impella patients. The Impella Recover device provides 3 to 4 L/min flow. It improves survival in patients with low-output syndrome if the heart is able to pump 1 L/min or more above device flow.


New regression models to predict fat mass in intermediate-level male padel players.
Padel is a racquet team sport that has generated great interest in recent years, but the anthropometric and body composition characteristics of padel players have not widely been investigated. So, this study has a threefold aim: i) to draw two specific linear regression models to estimate fat mass from Dual X-ray Absorptiometry (DXA) to anthropometry or bioelectrical impedance analysis (BIA); ii) to provide a BIA-vector (BIVA) profile of intermediate level padel players; iii) to understand if anthropometric, body composition and handgrip strength differ among padel's roles. Participants were 15 padel players (26.66 ± 11.84 years, 71.6 ± 12.51 kg, 173.13 ± 7.63 cm) who competed in the same championship. DXA, anthropometry, BIA and vector analysis were assessed. The stepwise procedure for the best general linear model was performed. The one-way ANOVA was used to compare right and left-side players. The Bland-Altman method, concordance correlation and Pearson's correlation coefficients, and statistical power achieved were computed. The regression models achieved high goodness of fits in fat mass estimation (anthropometric adj. R2 = 0.984, BIA adj. R2 = 0.949) with four and two regressors, respectively. Padel players showed BIVA features close to teams' (D = 0.22) and power's (D = 0.37) sports. Also, no significant differences between left and right players were found in body composition and handgrip strength. This study provided novel and useful information on players' body profiles for coaches and trainers. Also, our resulting equations provide easy-to-assess field methods in the accurate estimation of players' body composition characteristics.


Comparison of the bioactive potential of Roselle (Hibiscus sabdariffa L.) calyx and its by-product: Phenolic characterization by UPLC-QTOF MSE and their anti-obesity effect in vivo.
The aim of the present study was to evaluate extractable (EPP), non-extractable polyphenols (NEPP) and organic acid in Roselle by-product, as well as its potential health beneficial effects in obesity control and their complication in rats fed with high caloric diet. Roselle by-product showed a higher content of dietary fiber and NEPP than Roselle calix, which was was a better source of EPP (P < .05). The UPLC-QTOF MSE analysis allowed the tentative identification of 34 EPP, and 3 hydrolysable polyphenols (NEPP), and 2 organic acids in calyx and by-product. Rats fed with a high caloric diet supplemented with 4% of dietary fiber from by-products and Roselle calyx powder generated a reduction in body weight gain (10% and 14%), adipocytes hypertrophy (17% and 13%) and insulin resistance (48% and 59%) and hepatic steatosis (15% and 25%; respectively) compared with rats fed with a high caloric diet alone. Interestingly, even though Roselle by-product has low EPP contents showed comparable beneficial health effects than Roselle calyces. These effects could be associated with high content of dietary fiber and NEPP. Together, the results of the present study indicate that Roselle by-products could be a potential ingredient to develop functional foods against obesity and its complications.


Single amino acid substitutions in influenza haemagglutinin change receptor binding specificity.
The haemagglutinin (HA) glycoproteins of influenza virus membranes are responsible for binding viruses to cells by interacting with membrane receptor molecules which contain sialic acid (for review see ref. 1). This interaction is known to vary in detailed specificity for different influenza viruses (see, for example, refs 2-4) and we have attempted to identify the sialic acid binding site of the haemagglutinin by comparing the amino acid sequences of haemagglutinins with different binding specificities. We present here evidence that haemagglutinins which differ in recognizing either NeuAc alpha 2 leads to 3Gal- or NeuAc alpha 2 leads to 6Gal- linkages in glycoproteins also differ at amino acid 226 of HA1. This residue is located in a pocket on the distal tip of the molecule, an area previously proposed from considerations of the three-dimensional structure of the haemagglutinin to be involved in receptor binding.


Longitudinal Changes of Parafoveal Vessel Density in Diabetic Patients without Clinical Retinopathy Using Optical Coherence Tomography Angiography.
The purpose of this study was to identify the rate of parafoveal vessel density (VD) changes associated with the progression from non-diabetic retinopathy (NDR) to early stages of DR over a year. This longitudinal cohort study enrolled diabetic patients from the Guangzhou community in China. The patients with NDR at baseline were included and underwent comprehensive examinations at baseline and after 1 year. A commercial OCTA device (Triton Plus, Topcon, Tokyo, Japan) was employed to quantify the parafoveal VD in the superficial and deep capillary plexuses. The rates of change in parafoveal VD over time in the incident DR and NDR groups were compared after a year. A total of 448 NDR patients were included in the study. Among them, 382 (83.2%) were stable and 66 (14.4%) developed incident DR during the 1-year follow-up. The average parafoveal VD in the superficial capillary plexus (SCP) reduced significantly more quickly in the incident DR group than in the NDR group (-1.95 ± 0.45%/year vs. -0.45 ± 0.19/year, p = 0.002). The VD reduction rate for the deep capillary plexus (DCP) was not significantly different for the groups (p = 0.156). The incident DR group experienced a significantly faster reduction in parafoveal VD in the SCP compared with the stable group. Our findings further provide supporting evidence that parafoveal VD in the SCP may be used as an early indicator of the pre-clinical stages of DR.


Impact of exercise and/or dietary interventions, and their behaviour change techniques, on quality of life in middle-aged and older women following treatment for cancer: A systematic review.
Many middle-aged or older women are treated for cancer and their quality of life can be significantly impaired following treatment. Exercise and dietary interventions could address this. The aim of this review was to determine whether exercise and/or dietary interventions which are scaffolded by behaviour change theories and techniques are associated with improved quality of life in middle-aged and older women following cancer treatment. Secondary outcomes included self-efficacy, distress, waist circumference, and food variety. A search of CINAHL (EBSCOhost), Embase, MEDLINE (EBSCOhost), PsycINFO, PubMed and Scopus databases up to 17th November 2022 was conducted. A narrative summary was provided. Twenty articles discussing 18 independent randomised controlled trials/interventions were included, with a total of 1754 participants. No studies reported the outcomes of distress or food variety. Exercise and/or dietary interventions had mixed effects on quality of life, self-efficacy and waist circumference (positive effect: n = 4/14; n = 3/5; n = 4/7, respectively). Two-thirds of the interventions (exercise-only, n = 2; exercise and diet, n = 2) that demonstrated an improvement in quality-of-life scores were based upon Social Cognitive Theory. All studies that reported improvements in waist circumference employed combined exercise and dietary interventions, with individualised aspects for the dietary components. Exercise and/or dietary interventions could potentially enhance quality of life and self-efficacy, and reduce waist circumference, in middle-aged and older women treated for cancer. Although findings are currently mixed, avenues for the development of interventions include ensuring there is a theoretical underpinning and incorporating more behaviour change techniques in exercise and/or dietary interventions in this population.


Impairments in Peripheral Blood T Effector and T Regulatory Lymphocytes in Bipolar Disorder Are Associated with Staging of Illness and Anti-cytomegalovirus IgG Levels.
There is now evidence that, based on cytokine profiles, bipolar disorder (BD) is accompanied by simultaneous activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS), and that both components may be associated with the staging of illness. Nevertheless, no BD studies have evaluated the IRS/CIRS ratio using CD (cluster of differentiation) molecules expressed by peripheral blood activated T effector (Teff) and T regulatory (Treg) subpopulations. This study examined Teff/Treg subsets both before and after ex vivo anti-CD3/CD28 stimulation using flow cytometric immunophenotyping in 25 symptomatic remitted BD patients and 21 healthy controls and assessed human cytomegalovirus (HCMV)-specific IgG antibodies. BD is associated with a significantly lowered frequency of unstimulated CD3 + CD8 + CD71+ and CD4 + CD25 + FOXP3 and increased CD4 + CD25 + FOXP3 + CD152+ frequencies and with lowered stimulated frequencies of CD3 + CD8 + CD71+, CD4 + CD25 + FOXP3 + CD152+, and CD4 + CD25 + FOXP3 + GARP cells and, consequently, by an increased stimulated Teff/Treg ratio. Moreover, the number of manic, but not hypomanic or depressive episodes, is significantly and negatively associated with the stimulated proportions of CD3 + CD4 + CD154+, and CD69+ and CD71+ expression on CD4+ and CD8+ cells, while duration of illness (≥ 10 years) is accompanied by a depleted frequency of stimulated CD152+ Treg, and CD154+ and CD71+ CD4+ T cells. BD and anti-human cytomegalovirus (HCMV) IgG levels significantly interact to decrease the expression of CD4 + CD25 + FOXP+GARP T phenotypes. In conclusion, in BD patients, immune injuries, staging, and HCMV seropositivity interact and cause CIRS dysfunctions and exaggerated IRS responses, which play a key role in parainflammation and neuroaffective toxicity. HCMV seropositivity contributes to an immune-risk phenotype in BD.


Absence seizures in patients with localization-related epilepsy.
We studied the clinical features of 12 patients with localization-related epilepsy (LRE) associated with absence seizures (AS). AS did not appear in any patients before partial seizures (PS) were first observed. The interval between the onset of PS and AS ranged from 1 month to 7.2 years (mean 2.11 years). The duration of AS (mean 5 months) was short compared with that of PS (mean 3.8 years). Carbamazepine (CBZ) was used in seven patients at the onset of AS. It was discontinued in five but continued in the other two. AS was initially treated with valproate in ten patients. Three of them needed additional antiepileptic drugs: clonazepam in two patients and ethosuximide in one. All patients became free from AS after treatment for AS was started, whereas PS was relatively intractable. Generalized spike-and-waves were often observed before the onset of AS. The interval between the first appearance of generalized spike-and-waves and the onset of AS ranged from 1 to 53 months (mean 20 months). AS in patients with LRE will be relatively benign and transient, and will respond well to antiepileptic drugs.


Radiotherapy in the multidisciplinary treatment of liver cancer: a survey on behalf of the Italian Association of Radiation Oncology.
To report the results of the first Italian survey investigating the role of liver-directed radiotherapy in the multidisciplinary approach of primary and metastatic liver cancer. A 21-item, two-section questionnaire was sent to all Italian radiotherapy centers on June 2014. The two sections aimed at: (1) evaluating the presence of a multidisciplinary liver tumor board and describing the role of radiation oncologists within the latter, (2) analyzing Radiotherapy treatment details and differences between centers. A total of 37 centers completed the survey. A multidisciplinary liver tumor board was available in most centers (73 %), with a radiation oncologist routinely attending the latter in the majority of cases (85 %). Most of the respondents considered liver-directed Radiotherapy as the third line choice when other therapies were not indicated or technically suitable. 18 centers reported the use of liver-directed radiotherapy. The majority of centers started liver irradiation after 2010. The most adopted motion management strategy was abdominal compression. The most adopted GTV-CTV expansion was 0 and 5 mm for metastases and hepatocellular carcinoma, respectively. Stereotactic body radiotherapy was the technique of choice; several treatment schedules were registered, being 45 Gy in three fractions the most reported fractionation scheme. Dose was prescribed at the PTV margin in most cases. Liver-directed radiotherapy represents a new field of interest which is currently adopted by 10 % of all Italian Centers. The technical equipment seems adequate. The variations observed in the treatment regimens reflect the lack of a well-established standard schedule.


Functional dissociation of dual activities of glia maturation factor: inhibition of glial proliferation and preservation of differentiation by glial growth inhibitory factor.
Glial growth inhibitory factor (GGIF), derived from the culture medium of mouse neuroblastoma cell (NAs-1), lowered the DNA synthesis and cell multiplication of normal rat glioblasts induced by glia maturation factor (GMF). The inhibitory action of GGIF depended on the concentration of GMF in the culture medium, and was of an uncompetitive type on kinetic analysis. GGIF showed the inhibitory activity at a late stage of the G1 phase or early stage of the S phase. The factor, however, failed to inhibit the differentiation-promoting activity of GMF. The data strongly suggest that the dual activities of GMF, the promotion of glial proliferation and differentiation, may be elicited by mutually independent intracellular processes.


Modelling the impact of multiple sclerosis on life expectancy, quality-adjusted life years and total lifetime costs: Evidence from Australia.
To quantify life expectancy (LE), quality-adjusted life years (QALYs) and total lifetime societal costs for a hypothetical cohort of Australians with multiple sclerosis (MS). A 4-state Markov model simulated progression from no/mild to moderate and severe disability and death for a cohort of 35-year-old women over a lifetime horizon. Death risks were calculated from Australian life tables, adjusted by disability severity. State-dependent relapse probabilities and associated disutilities were considered. Probabilities of MS progression and relapse were estimated from AusLong and TasMSL MS epidemiological databases. Annual societal (direct and indirect) costs (2017 Australian dollars) and health-state utilities for each state were derived from the Australian MS Longitudinal Study. Costs were discounted at 5% annually. Mean (95% confidence interval (CI)) LE from age 35 years was 42.7 (41.6-43.8) years. This was 7.5 years less than the general Australian population. Undiscounted QALYs were 28.2 (26.3-30.0), a loss of 13.1 QALYs versus the Australian population. Discounted lifetime costs were $942,754 ($347,856-$2,820,219). We have developed a health economics model of the progression of MS, calculating the impact of MS on LE, QALYs and lifetime costs in Australia. It will form the basis for future cost-effectiveness analyses of interventions for MS.


Exosomal long noncoding RNAs - the lead thespian behind the regulation, cause and cure of autophagy-related diseases.
Recent advances in exosome biology have revealed significant roles of exosome and their contents in intercellular communication. Among various exosomal content, long non-coding RNAs (lncRNAs), which have a large size (˃ 200 nt) and lack protein coding potential, are known to play key roles in intercellular communication and novel biomarkers of various metabolic disorders. Moreover, long non-coding RNAs are often involved in the regulation of various cellular processes such as autophagy, apoptosis, cell proliferation. On the other hand, autophagy is the central regulating point that controls the various metabolic functions of the body. This process is known to prevent diseases and promote longevity. Therefore, the present review discusses the relationship between diseases and autophagy, and also look into the biological functions of exosome-associated lncRNAs in regulating autophagy. Furthermore, this review will summarize some of the studies that provide novel insights into the pathogenesis of autophagy-related diseases followed by the non-canonical roles played by autophagy and related proteins in the development of exosome biogenesis.


Formation of encrustations on indwelling urinary catheters in the elderly: a comparison of different types of catheter materials in "blockers" and "nonblockers".
In order to determine the effect of catheter materials on formation of encrustations in long-term indwelling urinary catheters in the elderly we performed a crossover study utilizing commercially available silicone, silicone-coated, teflon-coated and latex catheters that were left in place for 14 days. The study was conducted with #18 french catheters fitted with a 30 ml. balloon since smaller size catheters frequently fell out spontaneously. The distinction between patients who were "blockers" and "nonblockers" was found to be clinically useful since "nonblockers", who constituted about half the population, did well regardless of type of catheter material used. Formation of encrustations and blockage was significantly less in "blockers" with silicone than with teflon-coated or latex catheters. The more rapid flow-time through silicone catheters appears to be related to a larger bore. Although this study supports the use of silicone catheters for "blockers" on long-term drainage the results should not be interpreted to imply that they are preferable to other types of catheters for short-term use or to changing less expensive catheters more frequently when needed.


Relationship between endothelial cell loss and microcoaxial phacoemulsification parameters in noncomplicated cataract surgery.
To assess the relationship between postoperative endothelial cell loss and microcoaxial phaco parameters using Ozil IP (Alcon Laboratories, Inc, Fort Worth, TX) in noncomplicated cataract surgery. In this prospective observational study, 120 consecutive cases of cataract patients with different grades of nuclear hardness underwent microcoaxial phacoemulsification through a 2.2-mm clear corneal incision. An Alcon Infinity Vision System with Ozil IP (Alcon Laboratories) was used with an Ozil torsional handpiece and a Kelman-style 45° phacoemulsification tip. Patients underwent preoperative and postoperative central endothelial cell counts. The study included 120 cases of age-related cataract whose mean age (standard deviation [SD]) was 59.68 years (9.47). There was a highly statistically significant endothelial cell loss (P < 0.001). The endothelial cell loss ranged 11-1149 cells/mm(2) with a median (interquartile range) of 386 cells/mm(2) (184.5-686 cells/mm(2)). The percentage of postoperative ECLoss% ranged from 0.48% to 47.8% with a median (interquartile range) of 15.4% (7.2% to 26.8%). A significant positive correlation was found between the ECLoss% and different phaco parameters. The Spearman's rank-order correlation coefficient values, rho, (ρ) were as follows: CDE (ρ = 0.425), aspiration time (ρ = 0.176), and volume (ρ = 0.278). Also, ECLoss% was significantly correlated with the grade of nuclear opalescence (Kendall's tau τ = 0.42). Microcoaxial phacoemulsification was efficient in removing noncomplicated cataracts; however a statistically significant endothelial cell loss was noted, especially with increased nuclear hardness. This endothelial cell loss was mostly related to the increased cumulative dissipated energy (CDE), aspiration time, and volume of balanced salt solution used.


Lack of metabolic effects of a triphasic formulation containing norethindrone in normal women studied prospectively.
The glucose and insulin responses to oral glucose tolerance tests and lipid values in normal women taking a triphasic pill containing norethindrone (Ortho 7/7/7) were performed. After three months, no significant changes in these metabolic indices were found. These results confirm and expand the knowledge regarding the metabolic safety of norethindrone-containing triphasic formulations.


High-performance anion-exchange chromatography of proteins using aza-ether bonded silica-based phases.
The use of wide-pore silica-based hydrophilic aza-ether bonded phases for the chromatographic separation of proteins under anion-exchange conditions was studied. Polyether silanes containing terminal morpholine or piperazine derivatives are synthesized for attachment to the silica surface and provide a flexible approach to bonded phase design. In one instance, a quaternized amine support may be prepared by further derivatization of the methylpiperazine bonded phase. The supports provide high-performance anion-exchange chromatographic separations of proteins using gradients of increasing salt content, e.g., to 1.0 M sodium acetate at pH 7.0. The salt type and concentration can be varied to control protein retention while the buffer system used at pH 7.0 exerts a minimal influence on the separation. The anion exchangers may be reproducibly prepared and exhibit chromatographic retention stability at pH 7.5 for at least 2 months of operation. Acceptable capacity for protein on the bonded phase is demonstrated with high recovery of solute mass. The flexibility in anion exchanger design provides a probe of bonded ligand hydrophobic effects which can contribute in an undefined and deleterious manner to the desired ion-exchange separation. Taken together, these results provide a greater insight into the operating characteristics of anion exchangers, especially with regard to competing retention mechanisms.


DNAJB4 suppresses breast cancer progression and promotes tumor immunity by regulating the Hippo signaling pathway.
Breast cancer is the most common cancer worldwide. Low DNAJB4 expression levels are strongly correlated with poor prognosis in breast cancer patients. However, the molecular mechanism by which DNAJB4 regulates breast cancer progression is unclear. The expression of DNAJB4 was validated in human breast cancer tissues, normal human breast tissues, and breast cancer cell lines. CCK-8, colony-forming, and wound healing assays were used to assess the biological effect of DNAJB4 overexpression on cell proliferation and migration in MCF-7 cell lines. Bioinformatic analysis was used to identify the DNAJB4 related pathways in breast cancer. Epithelial-mesenchymal transition (EMT)-related biomarkers and Hippo pathway components were quantified by Western blots. Luciferase and Western blot assays were used to validate which miRNA regulates DNAJB4. In addition, the effects of DNAJB4 on in vivo tumor growth were assessed in xenograft models. DNAJB4 was expressed at low levels in human breast cancer tissues and breast cancer cell lines and correlated with poor prognosis. DNAJB4 overexpression significantly inhibited cell proliferation and migration in vitro by activating the Hippo pathway. The dual-luciferase assay showed that hsa-miR-183-5p targeted DNAJB4. Moreover, the effects of DNAJB4 could be reversed by miR-183-5p. In addition, the expression of DNAJB4 was strongly correlated with immune infiltration levels. Notably, DNAJB4 overexpression markedly enhanced CD4 + and CD8 + T cells and reduced PD-L1 levels in 4T1 tumors via the Hippo pathway, which retarded tumor growth in a subcutaneous xenograft tumor mouse model of 4T1 cells. The present study demonstrated that DNAJB4 overexpression inhibited the malignant biological behavior of breast cancer by regulating the Hippo pathway and tumor immunosuppressive environment.


Transcriptional regulation of triacylglycerol accumulation in plants under environmental stress conditions.
Triacylglycerol (TAG), a major energy reserve in lipid form, accumulates mainly in seeds. Although TAG concentrations are usually low in vegetative tissues because of the repression of seed maturation programs, these programs are derepressed upon the exposure of vegetative tissues to environmental stresses. Metabolic reprogramming of TAG accumulation is driven primarily by transcriptional regulation. A substantial proportion of transcription factors regulating seed TAG biosynthesis also participates in stress-induced TAG accumulation in vegetative tissues. TAG accumulation leads to the formation of lipid droplets and plastoglobules, which play important roles in plant tolerance to environmental stresses. Toxic lipid intermediates generated from environmental-stress-induced lipid membrane degradation are captured by TAG-containing lipid droplets and plastoglobules. This review summarizes recent advances in the transcriptional control of metabolic reprogramming underlying stress-induced TAG accumulation, and provides biological insight into the plant adaptive strategy, linking TAG biosynthesis with plant survival.


[Corrigendum] Activation of sonic hedgehog signaling enhances cell migration and invasion by induction of matrix metalloproteinase-2 and -9 via the phosphoinositide-3 kinase/AKT signaling pathway in glioblastoma.
Mol Med Rep 12: [Related article:] 6702–6710, 2015; DOI: 10.3892/mmr.2015.4229 After the publication of the article, it has been brought to the authors' attention by an interested reader that we had made an error regarding the presentation of certain data in the manuscript. The error relates to the presentation of Figs. 1 and 2 in the paper: The control panels for Fig. 1C [labelled 'cyclopamine (µM)'] and Figs. 2B and C [labelled 'rhSSH (µg/ml)'] were derived from the same image. The control U251 cells, featured in Fig. 1 and Figs. 2B and C, were treated without cyclopamine and rhSHH. Therefore, the U251 cells treated without cyclopamine and rhSHH were considered as a control group compared with U251 cells that were separately treated with cyclopamine or rhSHH, and these were photographed randomly. A new Fig. 2 is provided, which contains the correct data for the control panels for Figs. 2B and C.