Cardiopulmonary physiological effects of diuretic therapy in preterm infants with chronic pulmonary hypertension.
Using targeted neonatal echocardiography (TNE) to examine cardiopulmonary physiological impact of diuretics in preterm infants with chronic pulmonary hypertension (cPH). Retrospective study comparing TNE indices pre- and ≤2 weeks (post) of initiating diuretic therapy in infants born <32 weeks gestational age with cPH. Twenty-seven neonates with mean gestational age, birthweight and interval between pre-post diuretic TNE of 27.0 ± 2.8 weeks, 859 ± 294 grams, and 7.8 ± 3.0 days respectively were studied. Diuretics was associated with improvement in pulmonary vascular resistance [pulmonary artery acceleration time (PAAT); 34.27(9.76) vs. 40.24(11.10)ms, p = 0.01), right ventricular (RV) ejection time:PAAT ratio [5.92(1.66) vs. 4.83(1.14), p < 0.01)], RV fractional area change [41.6(9.8) vs. 46.4(6.5%), p = 0.03)] and left ventricular myocardial performance index [0.55(0.09) vs. 0.41(0.23), p < 0.01)]. Post-treatment, frequency of bidirectional/right-to-left inter-atrial shunts decreased significantly (24% vs. 4%, p = 0.05). Primary diuretic treatment in neonates with cPH may result in improvement in PVR, RV and LV function and compliance.


Differences in Driving Outcomes Among Cognitively Normal African American and Caucasian Older Adults.
To examine the effect of race in driving performance and behavior prospectively among cognitively normal older adults. Cognitively normal participants (Clinical Dementia Rating 0), ≥ 65 years of age (n = 177) were selected from prospective, longitudinal studies at the Knight Alzheimer Disease Research Center at Washington University. Self-reported driving behavior (Driving Habits Questionnaire) and driving performance (road test) were annually assessed. Daily driving behavior data were collected using the Driving Real World In-Vehicle Evaluation System (DRIVES). Baseline differences between African Americans and Caucasians were tested using t tests and general linear models. Amyloid imaging and cerebrospinal fluid Alzheimer disease (AD) biomarkers were compared across groups. Linear mixed models examined change in daily driving behavior over time. Survival analyses tested time to a marginal or fail rating on the road test. There were no differences between African Americans (n = 34) and Caucasians (n = 143) in age, sex, education, or vascular risk factors. Baseline self-reported driving behavior and road test performance were largely similar for both races. Longitudinal analyses using the DRIVES data aggregated monthly showed that African Americans had a greater reduction in number of trips made per month, miles driven per month, and trips with aggressive behavior compared to Caucasians. These effects remained after controlling for AD biomarkers, age, education, and sex. In this sample of cognitively normal older adults, African Americans had a greater reduction of daily driving behavior compared to Caucasians. Observed racial differences may reflect differences in environmental/social factors, changes in cognition, and/or physical functioning.


The effectiveness of interventions for optometric referrals into the hospital eye service: A review.
Ophthalmic services are currently under considerable stress; in the UK, ophthalmology departments have the highest number of outpatient appointments of any department within the National Health Service. Recognising the need for intervention, several approaches have been trialled to tackle the high numbers of false-positive referrals initiated in primary care and seen face to face within the hospital eye service (HES). In this mixed-methods narrative synthesis, we explored interventions based on their clinical impact, cost and acceptability to determine whether they are clinically effective, safe and sustainable. A systematic literature search of PubMed, MEDLINE and CINAHL, guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), was used to identify appropriate studies published between December 2001 and December 2022. A total of 55 studies were reviewed. Four main interventions were assessed, where two studies covered more than one type: training and guidelines (n = 8), referral filtering schemes (n = 32), asynchronous teleophthalmology (n = 13) and synchronous teleophthalmology (n = 5). All four approaches demonstrated effectiveness for reducing false-positive referrals to the HES. There was sufficient evidence for stakeholder acceptance and cost-effectiveness of referral filtering schemes; however, cost comparisons involved assumptions. Referral filtering and asynchronous teleophthalmology reported moderate levels of false-negative cases (2%-20%), defined as discharged patients requiring HES monitoring. The effectiveness of interventions varied depending on which outcome and stakeholder was considered. More studies are required to explore stakeholder opinions around all interventions. In order to maximise clinical safety, it may be appropriate to combine more than one approach, such as referral filtering schemes with virtual review of discharged patients to assess the rate of false-negative cases. The implementation of a successful intervention is more complex than a 'one-size-fits-all' approach and there is potential space for newer types of interventions, such as artificial intelligence clinical support systems within the referral pathway.


Assessment of the Reliability of the Serbian Version of the Sickness Impact Profile Questionnaire in Patients with Chronic Viral Hepatitis.
Health-related quality of life (HRQL) of chronic patients has been researched as the ultimate goal of modern treatment of chronic diseases to improve patients'quality of life. The objective was to assess the reliability of the Serbian version of the Sickness Impact Profile (SIP) questionnaire on the sample of patients with chronic viral hepatitis. The research covered 102 patients with chronic hepatitis (47 type B and 55 type C). The assessment of the reliability of the SIP questionnaire was performed by testing the internal consistency of the questions by calculating the Cronbach's alpha coefficient. The factor analysis was used to assess whether the grouping of the questions within dimensions matches the distribution of the questions in the original English version of the questionnaire administered to U.S. patient population. The Cronbach's alpha coefficient for the entire questionnaire is 0.925, 0.869 for the physical dimension, and 0.857 for the psychosocial dimension. After running a factor analysis of the psychosocial dimension, "emotional instability" was extracted as the key factor, confirming the results of previous research. Compared with the English version of the questionnaire, the Cronbach's alpha coefficient of the Serbian version does not diverge significantly, whereas the factor analysis confirms the classification of the questionnaire into two dimensions. Our study has shown that the Serbian version of the SIP questionnaire is a reliable tool for assessing the HRQL of patients with chronic hepatitis B and C before starting treatment.


Yoga as a treatment for vasovagal syncope: A systematic review and meta-analysis.
Yoga therapy is being used for vasovagal syncope (VVS). However, there is no sufficient evidence. We aimed to evaluate the effect of yoga as an adjunct to the standard therapy on patients with recurrent VVS. Electronic databases were systematically searched to collect studies assessing the clinical effects of yoga along with guideline-directed treatment in patients with recurrent VVS. The outcomes were the number of VVS attacks and quality of life (QoL) assessment by Syncope Functional Status Questionnaire (SFSQ) scores at 12 months. We used the Mantel- Haenszel random-effects model to calculate the mean difference (MD) and 95% confidence interval (CI). We used The Cochrane Collaboration Risk of Bias Tool and Newcastle-Ottawa Scale for risk of bias assessment. Four studies were included, two RCTs and two observational studies. The total of participants was 309, with a mean age of 36.4 ± 13.5 years. The male participants represented 141 (45.6%) being males. The baseline syncope burden was 3.5 ± 2.38 episodes over 15.6 ± 12.8 months. Yoga therapy significantly reduced the number of episodes of syncope and presyncope compared to the control group (MD -1.86; 95% CI -3.30, -0.43; P = 0.01). Nevertheless, yoga therapy did not show significant improvement in the QoL assessed by SFSQ scores (MD -30.69; 95% CI -62.22,0.83; P = 0.06). Yoga therapy is a useful lifestyle intervention that can reduce the frequency of syncope and presyncope among patients with recurrent VVS. However, higher-quality RCTs are needed to confirm our results.


From incomplete to complete systemic lupus erythematosus; A review of the predictive serological immune markers.
Systemic lupus erythematosus (SLE) is a complex and heterogeneous autoimmune disease. A main challenge faced by clinicians is early identification of SLE, frequently resulting in diagnostic delay. Timely treatment, however, is important to limit disease progression, and prevent organ damage and mortality. Often, patients present with clinical symptoms and immunologic abnormalities suggestive of SLE, while not meeting classification criteria yet. This is referred to as incomplete SLE (iSLE). However, not all these patients will develop SLE. Therefore, there is need for predictive biomarkers that can distinguish patients at high risk of developing SLE, in order to allow early treatment. This article reviews the current literature on immunological changes in patients with stages preceding SLE, focusing on autoantibodies, type-I and -II interferons, and the complement system. We also provide an overview of possible predictive markers for progression to SLE that are applicable in daily clinical practice.


Surgical and functional outcomes of Retzius-sparing robotic-assisted radical prostatectomy versus conventional robotic-assisted radical prostatectomy in patients with biopsy-confirmed prostate cancer. Are outcomes worth it? Systematic review and meta-analysis.
Radical prostatectomy is the standard of care for prostate cancer. Retzius-sparing robotic-assisted radical prostatectomy (RS-RARP) is being widely adopted due to positive functional outcomes compared to conventional robotic-assisted radical prostatectomy (c-RARP). Concerns regarding potency, oncological outcomes, and learning curve are still a matter of debate. Following Preferred Instrument for Systematic Reviews and Meta-Analysis guidelines and PROSPERO registration CRD42023398724, a systematic review was performed in February 2023 on RS-RARP compared to conventional c-RARP. Outcomes of interest were continence recovery, potency, positive surgical margins (PSM), biochemical recurrence (BCR), estimated blood loss (EBL), length of stay (LOS), operation time and complications. Data were analyzed using R version 4.2.2. A total of 17 studies were included, totaling 2751 patients, out of which 1221 underwent RS-RARP and 1530 underwent c-RARP. Continence was analyzed using two definitions: zero pad and one safety pad. Cumulative analysis showed with both definitions statistical difference in terms of continence recovery at 1 month (0 pad odds ratio [OR] = 4.57; 95% confidence interval [CI] = [1.32-15.77]; Safety pad OR = 13.19; 95% CI = [8.92-19.49]), as well as at 3 months (0 pad OR, 2.93; 95% CI = [1.57-5.46]; Safety pad OR = 5.31; 95% CI = [1.33-21.13]). Continence recovery at 12 months was higher in the one safety pad group after RS-RARP (OR = 4.37; 95% CI = [1.97-9.73]). The meta-analysis revealed that overall PSM rates without pathologic stage classification were not different following RS-RARP (OR = 1.13; 95% CI = [0.96-1.33]. Analysis according to the tumor stage revealed PSM rates in pT2 and pT3 tumors are not different following RS-RARP compared to c-RARP (OR = 1.46; 95% CI = [0.84-2.55]) and (OR = 1.41; 95% CI = [0.93-2.13]), respectively. No difference in potency at 12 months (OR = 0.98; 95% CI = [0.69-1.41], BCR at 12 months (OR = 0.99; 95% CI = [0.46-2.16]), EBL (standardized mean difference [SMD] = -0.01; 95% CI = [-0.31 to 0.29]), LOS (SMD = -0.01; 95% CI = [-0.48 to 0.45]), operation time (SMD = -0.14; 95% CI = [-0.41 to 0.12]) or complications (OR = 0.9; 95% CI = [0.62-1.29]) were observed. Our analysis suggests that RS-RARP is safe and feasible. Faster continence recovery rate is seen after RS-RARP. Potency outcomes appear to be similar. PSM rates are not different following RS-RARP regardless of pathologic stage. Further quality studies are needed to confirm these findings.


Controversies in ocular trauma classification and management: review.
Ocular trauma is a topic of unresolved controversies and there are continuous controversial and debatable management strategies for open-globe injuries (OGIs). International classification of ocular trauma proposed almost 15 years ago needs to be reviewed and to be more robust in predicting the outcome in the setting of OGIs. Anterior segment trauma involves controversies related to patching for corneal abrasion, corneal laceration repair, and medical management of hyphema. Timing of cataract surgery and intraocular lens implantation in the setting of trauma is still debated worldwide. There are unresolved issues regarding the management of OGIs involving the posterior segment. Timing of vitrectomy has been and will continue to be debated by proponents of early versus delayed intervention. The use of prophylactic cryotherapy and scleral buckle is still practiced differently throughout the world. The role of intravitreal antibiotics in posterior segment trauma in the absence of infection is still debated. Similarly, the use of vitrectomy versus vitreous tap in the setting of traumatic endophthalmitis is not fully resolved. In optic neuropathy, the role of intravenous methylprednisolone versus conservative management is always debated and still there are no evidence-based guidelines about the beneficial role of pulse steroid therapy. The role of optic canal decompression in the setting of acute traumatic optic neuropathy is also not conclusive. Orbital and adnexal trauma has been shown to adversely affect the outcome of OGI patients but both lids and orbital injury are not taken as preoperative variables in international ocular trauma classification. The timing of intervention in blow-out fracture is still debated. The pediatric age group, owing to the high risk of amblyopia and intraocular inflammation as well as strong vitreoretinal adhesions, has to be managed by different principles. Although the risk of sympathetic ophthalmia is very rare, it is always one of the key debated issues while managing traumatized eyes with no light perception vision. Prospective, controlled clinical studies are not possible in the OGI setting and this article reviews pertinent data regarding these management issues and controversies, and provides recommendations for treatment based on the available published data and the authors' personal experience.


Anti-Müllerian Hormone Concentrations for Determining Resumption of Sertoli Cell Function following Removal of a 4.7 mg Deslorelin Implant in Tomcats.
Background: Deslorelin implant use in cats is a medical alternative to surgical sterilization, and due to its prolonged efficacy, its use has shown growing interest in the veterinary community. In the case of breeding facilities, its removal is often requested for the early restoration of testicular function. As anti-Müllerian hormones (AMH) in males is dependent of testosterone secretion, its assay may determine the restoration of testicular steroid secretion. An average of 3 weeks has been already described for tomcats' testicular function resumption after implant removal, but information about AMH concentrations in deslorelin-treated tomcats is lacking. Methods: Fourteen tomcats were treated for temporary suppression of fertility with a 4.7 mg deslorelin implant, which was surgically removed after 3, 6 or 9 months (n = 6, 4 and 4 tomcats, respectively). A general clinical and reproductive check with a gonadorelin stimulation test for testosterone determination was performed before deslorelin implant administration. After implant removal, tomcats' testicles were ultrasonographically checked for volume determination every 1-2 weeks with observation of the glans penis (presence or absence of spikes) and blood collection to assay both testosterone and AMH concentrations. Results: AMH concentrations increased significantly during the deslorelin treatment from 20.95 ± 4.97 ng/mL to 82.41 ± 14.59 ng/mL (p < 0.05). Following implant removal, AMH concentrations progressively decreased to pre-treatment levels, with a value of 28.42 ± 7.98 ng/mL on the third week post-removal where testosterone secretion was again detected. Conclusions: Even if a big variability of AMH concentrations exists between male individuals, resumption of tomcats' testicular function following a deslorelin treatment can be determined by AMH assay.


[Retrospective analysis of cell-free fetal DNA prenatal testing of maternal peripheral blood].
To assess the value of non-invasive prenatal testing (NIPT) for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies, chromosomal microdeletions and microduplications using cell-free fetal DNA from peripheral blood samples of pregnant women. A total of 15 237 pregnant women who had undergone NIPT testing at the Maternity and Child Health Care Hospital of Zaozhuang from February 2015 to December 2021 were enrolled in this study. For those with a high risk by NIPT, amniotic fluid samples were collected for G-banding chromosomal karyotyping analysis and chromosomal microarray analysis to verify the consistency of NIPT with results of prenatal diagnosis. All of the women were followed up by telephone for pregnancy outcomes. Among the 15 237 pregnant women, 266 (1.75%) were detected with a high risk for fetal chromosomal abnormality were detected. Among these, 79 (29.7%) were at a high risk for T21, 26 (9.77%) were at a high risk for T18, 9 (3.38%) were at a high risk for T13, 74 (27.82%) were at a high risk for sex chromosome aneuploidies, 12 (4.51%) were at a high risk for other autosomal aneuploidies, and 66 (24.81%) were at a high risk for chromosomal microdeletions or microduplications. 217 women had accepted invasive prenatal diagnosis and respectively 50, 13, 1, 25, 1 and 18 were confirmed with T21, T18, T13, sex chromosome aneuploidies, autosomal aneuploidies and microdeletions/microduplications, and the positive predictive values were 75.76%, 68.42%, 11.11%, 40.32%, 10% and 35.29%, respectively. For 13 042 women (85.59%), the outcome of pregnancy were successfully followed up. During the follow-up, one false negative case of T21 was discovered. No false positive cases for T13 and T18 were found. NIPT has a sound performance for screening T13, T18 and T21, and is also valuable for screening other autosomal aneuploidies, sex chromosome aneuploidies and chromosomal microdeletions/microduplications.


Bendamustine--a new approach to the treatment of advanced hepatocellular carcinoma?
Therapeutic options for advanced hepatocellular carcinoma (HCC) are limited. Bendamustine, a bifunctional cytostatic agent with mainly alkylating effect may be an alternative. Five HCC cell lines were incubated in vitro with five different concentrations of bendamustine. In addition, cell lines Huh-7 and HepG2 were tested in a chimeric mouse model. In vitro treatment with bendamustine resulted in an IC( 50 )<6 microg/mL in two, <12 microg/mL in one, and 12-23 microg/mL in two cell lines. In vivo, bendamustine reduced significantly tumor volume in chimeric mice. Bendamustine demonstrated significant tumor growth inhibition both in vitro and in vivo at concentrations that can be reached in the plasma. The potential role of bendamustine therapy for HCC and its tolerability in impaired liver function is currently subject of a phase II study.


Apurinic and/or apyrimidinic endonuclease activity in ataxia telangiectasia cell extracts.
The possibility that the increased sensitivity of ataxia telangiectasia towards ionizing radiation is related to a DNA-repair deficiency has been examined further. When compared to unaffected controls, 6 lines of fibroblast cells derived from ataxia patients demonstrated a slightly reduced endonucleolytic activity (165 +/- 12 units vs. 214 +/- 28 units) towards apurinic and/or apyrimidinic sites as determined in a "nicking" assay.


Neurite-like outgrowth from CNS explants may not always be of neuronal origin.
In living explants of the developing CNS 'true' neurites (neuronal processes) may appear virtually indistinguishable from the processes of radial and Bergmann glia. This inability to clearly distinguish the phenotype of responsive 'neurites' in the living state has profound implications for the interpretation of responses to 'neurite-promoting' substances. Labeling techniques, specific for intermediate filament proteins that are characteristic of neurons and neuroglia, should always be used to supplement morphologic observations on neurite-like outgrowth from living CNS explants.


Cancer histotypes and trends in Azare, Northeast Nigeria: impact of diagnostic support disparity in data reporting.
Definitive, affordable, and timely diagnosis of cancer is key to providing data for surveillance and control programmes. Care disparities have been shown to contribute to poorer survival, especially in resource-constrained populations. Here, we describe the profile of histologically diagnosed cancers in our hospital and highlight the possible effects of inadequate diagnostic support on data reporting. We designed a retrospective cross-sectional descriptive study to review histopathology reports archived at the Department of Pathology of our hospital spanning from January 2011 to December 2022. Cases diagnosed as cancer were retrieved and classified by systems, organs and histology types alongside the patient's age and gender. The trend in the volume of pathology requests and the corresponding malignant diagnosis yield over the period was also documented. Data generated were analyzed statistically using appropriate statistics and presented as proportions and means, with the level of statistical significance set at p < 0.05. There were 488 cancers out of 3,237 histopathology requests received within the study period. Of these 316 (64.7%) were females. Overall mean age was 48.8 ± 18.6 years with a peak age at the sixth decade, females being significantly younger (46.1 versus 53.5 years; p < 0.001). The top five cancers were breast (22.7%), cervical (12.7%), prostate (11.7%), skin (10.7%) and colorectal cancers (8%). Among females, breast, cervical and ovarian cancers predominated, whereas prostate, skin and colorectal cancers, were commonest among males in decreasing order. Paediatric malignancies accounted for 3.7% of all the cases, most being small round blue cell tumours. The volume of pathology requests rose remarkably from 95 cases in 2014 to 625 cases in 2022 with a corresponding increase in cancer case diagnoses. Cancer subtypes and ranking in this study are similar to those from urban populations in Nigeria and Africa, despite the low number of cases recorded. Efforts to reduce the disease burden are warranted.


The With Or Without Olecranon K-wire (WOW OK) Trial of tension band wire fixation versus cerclage fixation without K-wires in displaced stable olecranon fractures: study protocol for a randomized controlled trial.
Displaced olecranon fractures with a stable elbow joint are classified as Mayo type 2a or 2b and are commonly operated with tension band wiring, i.e. two K-wires and a cerclage. Retrospective studies have reported fewer reoperations and complications with cerclage fixation alone when compared to tension band wiring, though with similar long-term results. We decided to compare tension band wiring to cerclage fixation of displaced, stable olecranon fractures in adults in a randomized controlled trial. All patients ≥ 18 years old with Mayo type 2a and 2b fractures presenting at Skåne University hospital will be eligible for study inclusion, unless exclusion criteria are met. Two hundred participants will be included and randomized 1:1 to cerclage fixation or tension band wiring. Outpatient physiotherapist follow-up appointments will be scheduled at 2 and 6 weeks and at 3, 12, and 36 months at the Dept. of Orthopaedics. A lateral view radiograph of the elbow will be analysed at 6 months. The primary outcome of our study is the rate of reoperations. Secondary outcomes are complication rates, severity of complications, and patient-reported outcome measures (QuickDASH, Short Musculoskeletal Function Assessment, pain level, and patient satisfaction). The sample size was calculated to give 80% power for detecting a statistically significant difference in reoperation rates (with alpha-value 0.05), based on a previous retrospective study. Reoperation and complication rates after tension band wiring of olecranon fractures are high. Treatment of these injuries is debated, and several ongoing trials compare tension band wiring with plate fixation, suture fixation, and non-operative treatment. As data from retrospective studies indicate that cerclage fixation may be superior to tension band wiring, we see a need for a randomized controlled trial comparing these methods. The WOW-OK Trial aims to obtain level-1 evidence that may influence treatment choice for this type of fracture. ClinicalTrials.gov NCT05657899 . Registered on 16 November 2022. The trial complies with SPIRIT and CONSORT guidelines. The SPIRIT figure is found in Table 2.


Health-related Quality of Life and Postural Changes of Spinal Alignment in Female Adolescents Associated With Back Pain in Adolescent Idiopathic Scoliosis: A Prospective Cross-sectional Study.
A prospective cross-sectional study. To identify risk factors for chronic back pain and back pain at rest in adolescent idiopathic scoliosis (AIS) patients, particularly focusing on the psychological backgrounds of the patients and on postural changes of radiographical parameters for spinal alignment. Back pain has been recognized as a relatively common condition in AIS. However, the effect of patients' psychological backgrounds and dynamic changes of spinal alignment on back pain are unclear. One hundred two consecutive female AIS patients (mean age, 14.1 yrs [range, 10-18]) who first visited our outpatient clinic between July 2013 and December 2017 were included. Using SRS-22r questionnaire, the presence of chronic back pain and back pain at rest and the scores of self-image and mental health were evaluated. Using full-length standing and supine posteroanterior radiographs, parameters related to curve profiles and coronal global balance were measured, and postural changes of these parameters were calculated. From full-length standing lateral radiographs, sagittal spinal and spino-pelvic alignment parameters were also measured. Multivariate logistic regression analysis was performed to identify risk factors for back pain. The prevalence of chronic back pain was 22.5% and that of back pain at rest was 25.5%. Poor self-image and mental health scores in SRS-22r were identified as risk factors for chronic back pain. Higher Risser grade, poor self-image score, large postural changes of apical vertebral translation at the main thoracic curve, and hyperlordosis in the lumbar spine were identified as risk factors for back pain at rest. Psychological distress and large postural changes of spinal alignment played an important role in the occurrence of back pain. Physicians should pay more attention to mental healthcare of AIS patients as well as to radiographical assessments of curve severity for better health-related quality of life. 4.


Round window electrocochleography before and after cochlear implant electrode insertion.
Previous reports have documented the feasibility of utilizing electrocochleographic (ECoG) responses to acoustic signals to assess trauma caused during cochlear implantation. The hypothesis is that intraoperative round window ECoG before and after electrode insertion will help predict postoperative hearing preservation outcomes in cochlear implant recipients. Prospective cohort study. Intraoperative round window ECoG responses were collected from 31 cochlear implant recipients (14 children and 17 adults) immediately prior to and just after electrode insertion. Hearing preservation was determined by postoperative changes in behavioral thresholds. On average, the postinsertion response was smaller than the preinsertion response by an average of 4 dB across frequencies. However, in some cases (12 of 31) the response increased after insertion. The subsequent hearing loss was greater than the acute loss in the ECoG, averaging 22 dB across the same frequency range (250-1,000 Hz). There was no correlation between the change in the ECoG response and the corresponding change in audiometric threshold. Intraoperative ECoG is a sensitive method for detecting electrophysiologic changes during implantation but had limited prognostic value regarding hearing preservation in the current conventional cochlear implant patient population where hearing preservation was not intended. 2b Laryngoscope, 126:1193-1200, 2016.


A Phase II Trial of AZD6244 (Selumetinib, ARRY-142886), an Oral MEK1/2 Inhibitor, in Relapsed/Refractory Multiple Myeloma.
AZD6244 is a MEK1/2 inhibitor with significant preclinical activity in multiple myeloma cells. This phase II study used a two-stage Simon design to determine the AZD6244 response rate in patients with relapsed or refractory multiple myeloma. AZD6244 (75 mg) was administered orally, twice a day, continuously for 28-day cycles. Response was evaluated after three cycles. Thirty-six patients received therapy. The median age was 65 years (range: 43-81) and the median number of prior therapies was 5 (range: 2-11). The most common grade 3 and 4 toxicities included anemia, neutropenia, thrombocytopenia, diarrhea, and fatigue. Three deaths occurred possibly related to AZD6244 (2 due to sepsis, 1 due to acute kidney injury). After AZD6244 discontinuation, three additional deaths occurred due to disease progression. The response rate (CR + PR) was 5.6% with a mean duration of response of 4.95 months and median progression-free survival time of 3.52 months. One patient had a very good partial response (VGPR), 1 patient had a partial response, 17 patients had stable disease, 13 patients had progressive disease, and 4 patients could not be assessed for response. Pharmacodynamic studies revealed variable effects on bone marrow CD138(+) cell MEK1/2 and ERK1/2 phosphorylation. The best clinical response, a prolonged VGPR, occurred in a patient with an MMSET translocation. Single-agent AZD6244 was tolerable and had minimal activity in this heavily pretreated population.


Increasing the stability of sacB transcript improves levansucrase production in Bacillus subtilis.
To develop a strategy to increase the stability of transcripts of structural genes expressed under the control of sacR, the leader region of Bacillus subtilis levansucrase gene. Insertion of Shine Dalgarno like sequences in the 5'-untranslated sacR region controlling the expression of sacB. Depending on the number of stabilizing sequences inserted and the position of these sequences with respect to the translation start codon, it was observed that the mRNA stability and the final protein production could be increased or decreased. This mRNA stabilization can be used to increase exocellular protein production in the degU32 (Hy) mutant. This approach can be applied to the expression of heterologous genes of biotechnological interest.


Prevalence of advance directives and impact on advanced life support in out-of-hospital cardiac arrest victims.
To evaluate the prevalence of advance directives and their impact on the management of out-of-hospital cardiac arrest (OHCA) victims. We analyzed data extracted from the French national registry of adult OHCA patients (RéAC). The data concerned the emergency medical services (EMS) of a Paris suburb over the period 01/01/2013 to 30/11/2015. The primary endpoint was the prevalence of advance directives. Secondary endpoints were the characteristics of the population, of cardiac arrest, and of basic life support as well as outcomes in patients with or without advance directives. Advance directives were available for 148/1985 (7.5%) of OHCA patients. Advanced life support was given to 35 patients with directives and 941 patients without (24% vs. 51%, p <0.0001) with no significant difference in the characteristics of the support provided. Spontaneous recovery of cardiac activity was observed in 5 patients with directives and in 217 patients without (14% vs. 23%, p=0.3). Among patients with advance directives, only one was admitted to hospital. He/she died within 24h of admission. Advance directives were accessed by EMS for 7.5% OHCA patients. Despite their availability, advanced life support was provided to 24% of patients.


Increased expression of interleukin-6 (IL-6) gene transcript in relation to IL-6 promoter hypomethylation in gingival tissue from patients with chronic periodontitis.
DNA methylation of the cytokine genes may play a role in the pathogenesis of periodontitis. The aim of this study is to evaluate whether the alteration of interleukin-6 (IL-6) gene promoter methylation in the gingival tissue (GT) and peripheral blood (PB) is unique to chronic periodontitis (CP). DNA isolated from the GT and PB of 25 patients with (CP) and 20 healthy controls (H) was modified with sodium bisulfite and analyzed for IL-6 promoter methylation with direct sequencing. The levels of IL-6 mRNA and serum IL-6 protein were evaluated by a quantitative reverse transcription polymerase chain reaction and an enzyme-linked immunosorbent assay. The CP group showed that the overall methylation rates of IL-6 promoter that contained 19 cytosine-guanine dinucleotide (CpG) motifs were significantly decreased in GT in comparison to PB (p<0.001), which was significantly negatively correlated with the probing depth (p=0.003). The GT and PB of the H group displayed similar overall methylation rates. No significant difference was observed in the methylation rates at each CpG in GT in comparison to the PB in both groups. The levels of IL-6 mRNA in the GT and PB and serum IL-6 of the two groups were comparable. The ratio of IL-6 mRNA in the GT relative to the PB was significantly higher in the CP group than in the H group (p=0.03). The increased expression of IL-6 gene transcription may be related to IL-6 promoter hypomethylation in the GT from CP patients.


Natural imidazole alkaloids as antibacterial agents against Pseudomonas syringae pv. actinidiae isolated from kiwi endophytic fungus Fusarium tricinctum.
Kiwi (Actinidia chinensis) plants are severely destroyed by canker disease which is caused by the bacterium Pseudomonas syringae pv. actinidiae (Psa). This program tries to find anti-Psa agents among secondary metabolites of endophytic fungi from kiwi plant itself. The chemical investigation on one kiwi endophytic fungi, Fusarium tricinctum, resulted in the isolation of nine new imidazole alkaloids, fusaritricines A-I (1-9) together with seven known analogues (10-16). The structures of new compounds were established by extensive spectroscopic methods. Compounds 2, 3, 9, and 13 showed good antibacterial activity against Psa with MIC values between 25 and 50 μg/mL. It is suggested that imidazole alkaloids should be potential anti-Psa agents.


An alternative interpretation of residual feed intake by phenotypic recursive relationships in dairy cattle.
There has been increasing interest in residual feed intake (RFI) as a measure of net feed efficiency in dairy cattle. Residual feed intake phenotypes are obtained as residuals from linear regression encompassing relevant factors (i.e., energy sinks) to account for body tissue mobilization. By rearranging the single-trait linear regression, we showed a causal RFI interpretation underlying the linear regression for RFI. It postulates recursive effects in energy allocation from energy sinks on dry matter intake, but the feedback or simultaneous effects are nonexistent. A Bayesian recursive structural equation model was proposed for directly predicting RFI and energy sinks and estimating relevant genetic parameters simultaneously. A simplified Markov chain Monte Carlo algorithm was described. The recursive model is asymptotically equivalent to one-step linear regression for RFI, yet extends the analytical capacity to multiple-trait analysis.


Chicken anemia virus VP1 negatively regulates type I interferon via targeting interferon regulatory factor 7 of the DNA-sensing pathway.
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway plays a vital role in sensing viral DNA in the cytosol, stimulating type I interferon (IFN) production and triggering the innate immune response against DNA virus infection. However, viruses have evolved effective inhibitors to impede this sensing pathway. Chicken anemia virus (CAV), a nonenveloped ssDNA virus, is a ubiquitous pathogen causing great economic losses to the poultry industry globally. CAV infection is reported to downregulate type I IFN induction. However, whether the cGAS-STING signal axis is used by CAV to regulate type I IFN remains unclear. Our results demonstrate that CAV infection significantly elevates the expression of cGAS and STING at the mRNA level, whereas IFN-β levels are reduced. Furthermore, IFN-β activation was completely blocked by the structural protein VP1 of CAV in interferon stimulatory DNA (ISD) or STING-stimulated cells. VP1 was further confirmed as an inhibitor by interacting with interferon regulatory factor 7 (IRF7) by binding its C-terminal 143-492 aa region. IRF7 dimerization induced by TANK binding kinase 1 (TBK1) could be inhibited by VP1 in a dose-dependent manner. Together, our study demonstrates that CAV VP1 is an effective inhibitor that interacts with IRF7 and antagonizes cGAS-STING pathway-mediated IFN-β activation. These findings reveal a new mechanism of immune evasion by CAV.


TSA-induced JMJD2B downregulation is associated with cyclin B1-dependent survivin degradation and apoptosis in LNCap cells.
Histone deacetylase (HDAC) inhibitors are emerging as a novel class of anti-tumor agents and have manifested the ability to induce apoptosis of cancer cells, and a significant number of genes have been identified as potential effectors responsible for HDAC inhibitor-induced apoptosis. However, the mechanistic actions of these HDAC inhibitors in this process remain largely undefined. We here report that the treatment of LNCap prostate cancer cells with HDAC inhibitor trichostatin A (TSA) resulted in downregulation of the Jumonji domain-containing protein 2B (JMJD2B). We also found that the TSA-mediated decrease in survivin expression in LNCap cells was partly attributable to downregulation of JMJD2B expression. This effect was attributable to the promoted degradation of survivin protein through inhibition of Cyclin B1/Cdc2 complex-mediated survivin Thr34 phosphorylation. Consequently, knockdown of JMJD2B enhanced TSA-induced apoptosis by regulating the Cyclin B1-dependent survivin degradation to potentiate the apoptosis pathways.


A laparoscopic one anastomosis gastric bypass with wrapping versus nonwrapping fundus of the excluded part of the stomach to treat obese patients (FundoRingOAGB trial): study protocol for a randomized controlled trial.
Laparoscopic one anastomosis gastric bypass (LOAGB) is a simple variation of gastric bypass and has gained worldwide popularity with clinical outcomes similar to laparoscopic Roux-en-Y gastric bypass (LRYGB) for weight loss and management of comorbidities. However, biliary reflux to the esophagus negates the benefits of LOAGB. In addition, weight gain after LOAGB and after LRYGB is a major problem in bariatric surgery. The aim of this article is to describe the design and protocol of a randomized controlled trial comparing the outcomes of two methods of LOAGB: experimental method with wrapping versus standard method nonwrapping fundus of the excluded part of the stomach to prevent weight regain and biliary reflux after LOAGB. The study was designed as a single-center prospective, interventional, randomized controlled trial. Masking: None (open label). Allocation: randomized. Enrollment: 100 obese patients. The relevant ethics committee approved the trial protocol. The endpoints (body mass index, bile reflux in the esophagus, other reflux symptoms) will be assessed presurgery and postsurgery (12, 24, and 36 months postoperatively). With its 3-year follow-up time, this RCT will provide important data on the impact of wrapping the fundus of the excluded part of the stomach to prevent weight regain and biliary reflux after LOAGB. ClinicalTrials.gov NCT04834635 . Registered on 8 April 2021.


Exploring the synergies between digital finance and clean energy: a case study of green bond spillover effects.
The impact of digital finance on green bonds and clean energy sources is analyzed. So, the primary objective of this study is to create a unique time-varying causality test to identify the relationship between ecological consciousness and green technology, clean energy, and digital currency. The China region was established using data from 2001 to 2019. A dynamic connection model with spillover is employed to further guarantee stability. The empirical findings reveal that the clean energy to digital finance index (30.544%) and the clean energy to green economy index (30.544%) are the sources for the spillover shocks analysis. because the overall dynamic connection of assets throughout time is affected by financial events. For every additional percentage point that renewable energy sources are employed, long-term environmental costs are lowered by 0.68%. And yet, the transition from renewable energy to digital finance has been characterised by increasing instability and causal significance as it has advanced. The organizational environment is shown to have the second-greatest influence on the growth of the green bond market, behind the state of the local economy and environmental governance. Increasing the marketability of clean energy securities requires stable, predictable legislation that improves our knowledge of the risk profile of these investments.


Does Time to Aseptic Failure After Primary Total Hip Arthroplasty Affect Clinical and Patient-Reported Outcomes?
Evidence on the effects of time-to-failure from primary total hip arthroplasty (THA) to aseptic first-revision on clinical results and patient-reported outcome measures (PROMs) is scarce. Therefore, we sought to compare demographics, operative times, lengths of stay, discharge dispositions, 90-day readmissions, re-revision rates, mortalities, and PROMs between early and late aseptic THA revisions. This study is a retrospective review of a prospectively collected institutional database of all elective hip procedures. In total, 572 patients who underwent aseptic revision after primary THA from August 2015 to December 2018 were analyzed. Patients were stratified into either early revision (<3-years; n = 176) or late revision (≥3-years; n = 396) cohorts. Significantly more patients were revised earlier for bone-related (ie, periprosthetic fractures) (22.7% versus 8.3%) or other various complications (19.9% versus 5.8%), whereas more late revisions were performed to treat implant-related failures (6.8% versus 37.1%), respectively. Operative time was significantly shorter in early versus late revisions (133 versus 157 minutes). A significantly higher delta-change/improvement from baseline/preoperative to 1-year postoperative was found for hip disability and osteoarthritis outcome score physical function (HOOS-PS), veterans-RAND-12 physical and mental components (VR-12-PCS and MCS, respectively) of early revisions. However, HOOS-PS and HOOS-Pain at 1-year of follow-up were significantly worse in early revisions. With exception of operative time, time-to-failure had no significant influence on clinical results. Despite greater improvements on PROMs from preoperative to postoperative, patients undergoing early revisions after primary THA perceive significantly higher levels of pain and worse physical functionality at 1-year of follow-up.


Structure of linkage region between ribitol teichoic acid and peptidoglycan in cell walls of Staphylococcus aureus H.
The cell walls of Staphylococcus aureus H were found to contain mannosamine in an amount (28.1 nmol/mg) comparable to the content of muramic acid 6-phosphate. The acidic polymer fraction obtained by heating the cell walls at pH 2.5 was shown to contain mannosamine and glycerol in addition to the components of ribitol teichoic acid. Mild alkali treatment of this polymer fraction followed by gel filtration resulted in separation of a disaccharide N-acetylmannosaminyl(1 leads to 4)N-acetylglucosamine and the ribitol teichoic acid moiety that contained glycerol. Smith degradation of the reduction product from the same polymer fraction gave a fragment characterized as (1,2-ethylene-diol phosphate)-(glycerol phosphate)3-N-acetylmannosaminyl(1 leads to 4)N-acetylxylosaminitol. Thus, the ribitol teichoic acid chain in the cell walls is probably linked to peptidoglycan through a linkage unit, (glycerol phosphate)3-N-acetylmannosaminyl(1 leads to 4)N-acetylglucosamine.


Occipital nerve pulsed radiofrequency treatment: a multi-center study evaluating predictors of outcome.
Occipital neuralgia (ON) is a challenging condition for which there is no reference standard for treatment. The purpose of this study was to provide outcome data on the largest study to date evaluating pulsed radiofrequency (PRF) for ON and to determine whether any demographic, clinical, or treatment characteristics are associated with success. Retrospective data analysis was conducted in 102 subjects evaluating the effect of myriad factors on treatment success. This study was conducted in academic civilian and military pain treatment centers. One hundred and two consecutive patients with a primary diagnosis of ON were treated with PRF of the greater and/or lesser occipital nerve. A positive primary outcome was predefined as ≥50% pain relief lasting at least 3 months. The secondary outcome measure was procedural satisfaction. Fifty-two (51%) patients experienced ≥50% pain relief and satisfaction with treatment lasting at least 3 months. Variables associated with a positive outcome included a traumatic inciting event (65.7% success rate; P=0.03), lower diagnostic block volumes (odds ratio [OR]: 0.72; 95% confidence interval [CI]: 0.62-0.82; P<0.0001), and employment of multiple rounds of PRF (OR: 2.95; 95% CI: 1.77-4.92; P<0.0001). Factors correlating with treatment failure included extension of pain anterior to the scalp apex (OR: 0.32; 95% CI: 0.14-0.73; P=0.006) and ongoing secondary gain issues (OR: 0.19; 95% CI: 0.11-0.33; P<0.0001). PRF may provide intermediate-term benefit in ON to a significant proportion of refractory cases. Careful attention to selection criteria and treatment parameters may further improve treatment outcomes.


The ELY-1 locus controls a di-allelic alloantigenic system on equine lymphocytes.
The ELY-1 locus controls the expression of a polymorphic cell surface antigen of equine lymphocytes which was detected using antibodies generated by alloimmunization with peripheral blood lymphocytes. The ELY-1 antigens were not detected on erythrocytes or platelets by absorption experiments. The two alleles, which have been designated ELY-1.1 and ELY-1.2, are expressed codominantly and appear to constitute a closed system at the population level. In family studies, the ELY-1 antigens segregated as products of an autosomal locus not linked to the major histocompatibility complex (MHC) of the horse. In the complement mediated lymphocyte microcytotoxicity test, antisera to the ELY-1 antigens selectively killed peripheral blood lymphocytes which did not express surface immunoglobulin. The ELY-1 antigens may be useful markers for equine T cells when assayed in this fashion. Three alloantisera were used in immune precipitation of iodinated and solubilized cell surface proteins from peripheral blood lymphocytes. Electrophoresis of the precipitates in sodium dodecyl sulphate (SDS)-polyacrylamide gels demonstrated strong bands in the Mr 180-190K range that were shared in the three different preparations. These results suggest that the ELY-1 allospecificities are expressed on an equine equivalent of the murine T200 molecule.


A cascaded fully convolutional network framework for dilated pancreatic duct segmentation.
Pancreatic duct dilation can be considered an early sign of pancreatic ductal adenocarcinoma (PDAC). However, there is little existing research focused on dilated pancreatic duct segmentation as a potential screening tool for people without PDAC. Dilated pancreatic duct segmentation is difficult due to the lack of readily available labeled data and strong voxel imbalance between the pancreatic duct region and other regions. To overcome these challenges, we propose a two-step approach for dilated pancreatic duct segmentation from abdominal computed tomography (CT) volumes using fully convolutional networks (FCNs). Our framework segments the pancreatic duct in a cascaded manner. The pancreatic duct occupies a tiny portion of abdominal CT volumes. Therefore, to concentrate on the pancreas regions, we use a public pancreas dataset to train an FCN to generate an ROI covering the pancreas and use a 3D U-Net-like FCN for coarse pancreas segmentation. To further improve the dilated pancreatic duct segmentation, we deploy a skip connection on each corresponding resolution level and an attention mechanism in the bottleneck layer. Moreover, we introduce a combined loss function based on Dice loss and Focal loss. Random data augmentation is adopted throughout the experiments to improve the generalizability of the model. We manually created a dilated pancreatic duct dataset with semi-automated annotation tools. Experimental results showed that our proposed framework is practical for dilated pancreatic duct segmentation. The average Dice score and sensitivity were 49.9% and 51.9%, respectively. These results show the potential of our approach as a clinical screening tool. We investigate an automated framework for dilated pancreatic duct segmentation. The cascade strategy effectively improved the segmentation performance of the pancreatic duct. Our modifications to the FCNs together with random data augmentation and the proposed combined loss function facilitate automated segmentation.


Body mass index and ischemic and hemorrhagic stroke: a prospective study in Korean men.
The association between obesity and stroke remains controversial, with earlier studies suggesting that differences might stem from heterogeneous stroke subtype compositions. The association between body mass index (BMI) and stroke subtypes was examined prospectively in a large cohort study. A total of 234 863 Korean men aged 40 to 64 years without substantial weight loss over 4 years after baseline examination in 1986 were divided into 8 categories of BMI and were followed up between 1991 and 2000 for fatal and nonfatal stroke events. There was a positive association across the whole range of BMI and ischemic stroke, with a confounder-adjusted hazard of 11% (95% CI, 1.09 to 1.12) for 1 kg/m2 higher BMI. A J-shaped association was observed between BMI and hemorrhagic stroke; groups with a higher BMI than the reference category (22 to 23 kg/m2) had significantly increased risks. Full adjustment for confounders and variables potentially on the causal pathway (ie, blood pressure, blood glucose, and cholesterol) attenuated the association between BMI and stroke subtypes only for those with BMI greater than the reference category. Exclusion of deaths during the first 8 years or stratified analysis according to smoking habit did not change the relation between BMI and stroke subtypes. BMI is a risk factor for both ischemic and hemorrhagic stroke but shows different relationships with each. When the total burden of stroke is considered, there is an urgent need to find better ways of reducing the trend toward growing obesity in both Western and Asian countries.


Association between Baseline Cognitive Score and Postoperative Delirium in Parkinson's Disease Patients following Deep Brain Stimulation Surgery.
Deep brain stimulation of the subthalamic nuclei (STN-DBS) is a standard treatment option for advanced Parkinson's disease (PD) patients. Delirium following DBS electrode implantation is common, by several studies, and cognitive impairment is a risk factor for developing postoperative delirium (POD). This prospective observational study was conducted to identify whether preoperative baseline cognitive status has an association with POD in PD patients undergoing DBS surgery. Preoperatively, neuropsychiatric and neuropsychological assessments of the patients were performed including clinical dementia rating (CDR) score, instrumental activities of daily living (IADL) score, mini-mental state exam (MMSE) score, Montreal cognitive assessment (MoCA) score, Hamilton anxiety (HAMA) and Hamilton depression (HAMD) scores, and numerical cancellation test. POD was identified by the confusion assessment method (CAM) twice per day on postoperative day 1 until discharge. Twenty-seven (21.6%) of 125 patients developed POD. Among the variables screened, age, CDR score, MMSE score, and HAMA score were indicated to be independent influence factors of POD. The cutoff score, AUC, sensitivity, and specificity of age, CDR score, MMSE score, and HAMA score associated with POD was 58.5, 0.751, 92.6%, 52.0%; 0.5, 0.848, 77.8%, 91.8%; 27.5, 0.827, 88.9%, 62.2%; and 12.5, 0.706, 85.2%, 54.1%, respectively. We observed age, CDR score, MMSE score, and HAMA score were independent influence factors of POD in PD patients who received DBS. It is necessary to assess the cognitive status of PD patients before surgery to identify high-risk patients.


Spinning-disc confocal microscopy in the second near-infrared window (NIR-II).
Fluorescence microscopy in the second near-infrared optical window (NIR-II, 1000-1350 nm) has become a technique of choice for non-invasive in vivo imaging. The deep penetration of NIR light in living tissue, as well as negligible tissue autofluorescence within this optical range, offers increased resolution and contrast with even greater penetration depths. Here, we present a custom-built spinning-disc confocal laser microscope (SDCLM) that is specific to imaging in the NIR-II. The SDCLM achieves a lateral resolution of 0.5 ± 0.1 µm and an axial resolution of 0.6 ± 0.1 µm, showing a ~17% and ~45% enhancement in lateral and axial resolution, respectively, compared to the corresponding wide-field configuration. We furthermore showcase several applications that demonstrate the use of the SDCLM for in situ, spatiotemporal tracking of NIR particles and bioanalytes within both synthetic and biological systems.


Rod outer segment membrane guanylate cyclase type 1 (ROS-GC1) gene: structure, organization and regulation by phorbol ester, a protein kinase C activator.
At present there are two recognized members of the ROS-GC subfamily of membrane guanylate cyclases. They are ROS-GC1 and ROS-GC2. A distinctive feature of this family is that its members are not switched on by the extracellular peptide hormones; instead, they are modulated by intracellular Ca2+ signals, consistent to their linkage with phototransduction. An intriguing feature of ROS-GC1, which distinguishes it from ROS-GC2, is that it has two Ca2+ switches. One switch inhibits the enzyme at micromolar concentrations of Ca2+, as in phototransduction; the other, stimulates. The stimulatory switch, most likely, is linked to retinal synaptic activity. Thus, ROS-GC1 is linked to both phototransduction and the synaptic activity. The present study describes (1) the almost complete structural identity of 18.5 kb ROS-GC1 gene; (2) its structural organization: the gene is composed of 20 exons and 19 introns with classical GT/AG boundaries; (3) the activity of the ROS-GC1 promoter assayed through luciferase reporter in COS cells; and (4) induction of the gene by phorbol ester, a protein kinase C (PKC) activator. The co-presence of PKC and ROS-GC1 in photoreceptors suggests that regulation of the ROS-GC1 gene by PKC might be a physiologically relevant phenomenon.


Three dimensional characterization of GaN-based light emitting diode grown on patterned sapphire substrate by confocal Raman and photoluminescence spectromicroscopy.
We performed depth-resolved PL and Raman spectral mappings of a GaN-based LED structure grown on a patterned sapphire substrate (PSS). Our results showed that the Raman mapping in the PSS-GaN heterointerface and the PL mapping in the InxGa1-xN/GaN MQWs active layer are spatially correlated. Based on the 3D construction of E2(high) Raman peak intensity and frequency shift, V-shaped pits in the MQWs can be traced down to the dislocations originated in the cone tip area of PSS. Detail analysis of the PL peak distribution further revealed that the indium composition in the MQWs is related to the residual strain propagating from the PSS-GaN heterointerface toward the LED surface. Numerical simulation based on the indium composition distribution also led to a radiative recombination rate distribution that shows agreement with the experimental PL intensity distribution in the InxGa1-xN/GaN MQWs active layer.


The use of ultrasound in the localisation of parathyroid glands in parathyroid disorders.
Eleven patients with clinical and biochemical evidence of primary hyperparathyroidism were studied with ultrasonography. In nine patients who were treated surgically, four had predictive ultrasound scans (44% consistency). There was no correlation between the transverse diameters of the glands, as measured from the scans, and either the pathologist's measurements or the mean protein-corrected serum calcium and parathormone (PTH) levels. The investigation failed to identify the only patient with parathyroid hyperplasia. The difficulties encountered and the reasons for the high number of both false positive and false negative scans are discussed. Five patients with parathyroid disorders associated with hyperplasia were also studied and in four patients the enlarged glands were identified. A variation in size between the glands in each patient was noted. No correlation between the total of the transverse diameters and either the protein-corrected serum calcium or PTH levels was found. Reduction in size of the glands in one patient occurred over a 12-month period on treatment and a role for ultrasonography in the follow-up of patients with secondary hyperparathyroidism is discussed.


Treatment of uremic pericarditis and pericardial effusion by augmented hemodialysis.
Six out of 21 patients attending maintenance hemodialysis had uremic pericarditis. Three patients had one or more recurrences of pericarditis while under regular intermittent dialysis. Two patients developed pericardial effusion and one of them had ascites. Augmented hemodialysis was successful in treating uremic pericarditis even in patients with pericardial effusion. The single instance of ascites was also controlled by augmented hemodialysis.


The integrin alpha IIb-beta 3, platelet glycoprotein IIb-IIIa, can form a functionally active heterodimer complex without the cysteine-rich repeats of the beta 3 subunit.
Integrin alpha IIb-beta 3 binds fibrinogen via the recognition sequence Arg-Gly-Asp-Ser (RGDS). We have used the baculovirus/insect cell expression system to study the structural requirements for the formation of a functionally active fragment of alpha IIb-beta 3. A tandem baculovirus transfer vector was constructed containing the cDNA coding for the heavy chain of human alpha IIb (alpha IIbH, amino acids 1-874) and the cDNA coding for a truncated form of human beta 3 (t beta 3; amino acids 1-469). Sf9 insect cells were infected with the corresponding baculovirus, and the produced soluble recombinant proteins were purified using an RGD-like affinity column. The bound receptor fragments were specifically eluted with RGDS and existed as a heterodimeric complex (rec alpha IIbH-t beta 3) with an apparent M(r) of 160,000. In an immunocapture assay, the monoclonal antibody pl-55, which only recognizes the functionally active form of alpha IIb-beta 3, bound to the purified complex. Rec alpha IIbH-t beta 3 specifically bound 125I-fibrinogen with an affinity comparable with that of purified platelet alpha IIb-beta 3. Electron micrographs of rotary-shadowed rec alpha IIbH-t beta 3 showed that the complex had the characteristic globular head, but the two rodlike tails were 4-6 nm shorter than those found in intact alpha IIb-beta 3. Thus, the cysteine-rich repeats of beta 3 are not required for assembly, stability, and functional activity of this integrin.


Effectiveness and Implementation of Evidence-Based Practices in Residential Care Settings.
Prompted by calls to implement evidence-based practices (EBPs) into residential care settings (RCS), this review addresses three questions: (1) Which EBPs have been tested with children and youth within the context of RCS? (2) What is the evidence for their effectiveness within such settings? (3) What implementation issues arise when transporting EBPs into RCS? Evidence-based psychosocial interventions and respective outcome studies, published from 1990-2012, were identified through a multi-phase search process, involving the review of four major clearinghouse websites and relevant electronic databases. To be included, effectiveness had to have been previously established through a comparison group design regardless of the setting, and interventions tested subsequently with youth in RCS. All outcome studies were evaluated for quality and bias using a structured appraisal tool. Ten interventions matching a priori criteria were identified: Adolescent Community Reinforcement Approach, Aggression Replacement Training, Dialectical Behavioral Therapy, Ecologically-Based Family Therapy, Eye Movement and Desensitization Therapy, Functional Family Therapy, Multimodal Substance Abuse Prevention, Residential Student Assistance Program, Solution-Focused Brief Therapy, and Trauma Intervention Program for Adjudicated and At-Risk Youth. Interventions were tested in 13 studies, which were conducted in different types of RCS, using a variety of study methods. Outcomes were generally positive, establishing the relative effectiveness of the interventions with youth in RCS across a range of psychosocial outcomes. However, concerns about methodological bias and confounding factors remain. Most studies addressed implementation issues, reporting on treatment adaptations, training and supervision, treatment fidelity and implementation barriers. The review unearthed a small but important body of knowledge that demonstrates that EBPs can be implemented in RCS with encouraging results.


Electroconvulsive stimulation reverses anhedonia and cognitive impairments in rats exposed to chronic mild stress.
Electroconvulsive therapy remains the most effective treatment for depression including a fast onset of action. However, this therapeutic approach suffers from some potential drawbacks. In the acute phase this includes amnesia. Electroconvulsive stimulation (ECS) has previously been shown to reverse a depression-like state in the chronic mild stress model of depression (CMS), but the effect of ECS on cognition has not previously been investigated. In this study the CMS model was used to induce a depressive-like condition in rats. The study was designed to investigate the acute effect of ECS treatment on working memory and the chronic effect of repeated ECS treatments on depression-like behavior and working memory. The results indicated that, in the acute phase, ECS treatment induced a working memory deficit in healthy controls unexposed to stress, while repeated treatments reversed stress-induced decline in working memory, as well as recovering rats submitted to the CMS paradigm from the anhedonic-like state. Like in the clinical setting, a single ECS exposure was ineffective in inducing remission from a depression-like state.


Cardiovascular risk stratification among individuals with obesity: The Coronary Artery Calcium Consortium.
The effectiveness of coronary artery calcification (CAC) for risk stratification in obesity, in which imaging is often limited because of a reduced signal to noise ratio, has not been well studied. Data from 9334 participants (mean age: 53.3 ± 9.7 years; 67.9% men) with BMI ≥ 30 kg/m2 from the CAC Consortium, a retrospectively assembled cohort of individuals with no prior cardiovascular diseases (CVD), were used. The predictive value of CAC for all-cause and cause-specific mortality was evaluated using multivariable-adjusted Cox proportional hazards and competing-risks regression. Mean BMI was 34.5 (SD 4.4) kg/m2 (22.7% Class II and 10.8% Class III obesity), and 5461 (58.5%) had CAC. Compared with CAC = 0, those with CAC = 1-99, 100-299, and ≥300 Agatston units had higher rates (per 1000 person-years) of all-cause (1.97 vs. 3.5 vs. 5.2 vs. 11.3), CVD (0.4 vs. 1.1 vs. 1.5 vs. 4.2), and coronary heart disease (CHD) mortality (0.2 vs. 0.6 vs. 0.6 vs. 2.5), respectively, after mean follow-up of 10.8 ± 3.0 years. After adjusting for traditional cardiovascular risk factors, CAC ≥ 300 was associated with significantly higher risk of all-cause (hazard ratio [HR]: 2.05; 95% CI: 1.49-2.82), CVD (subdistribution HR: 3.48; 95% CI: 1.81-6.70), and CHD mortality (subdistribution HR: 5.44; 95% CI: 2.02-14.66), compared with CAC = 0. When restricting the sample to individuals with BMI ≥ 35 kg/m2 , CAC ≥ 300 remained significantly associated with the highest risk. Among individuals with obesity, including moderate-severe obesity, CAC strongly predicts all-cause, CVD, and CHD mortality and may serve as an effective cardiovascular risk stratification tool to prioritize the allocation of therapies for weight management.


The retrograde response: when mitochondrial quality control is not enough.
Mitochondria are responsible for generating adenosine triphosphate (ATP) and metabolic intermediates for biosynthesis. These dual functions require the activity of the electron transport chain in the mitochondrial inner membrane. The performance of these electron carriers is imperfect, resulting in release of damaging reactive oxygen species. Thus, continued mitochondrial activity requires maintenance. There are numerous means by which this quality control is ensured. Autophagy and selective mitophagy are among them. However, the cell inevitably must compensate for declining quality control by activating a variety of adaptations that entail the signaling of the presence of mitochondrial dysfunction to the nucleus. The best known of these is the retrograde response. This signaling pathway is triggered by the loss of mitochondrial membrane potential, which engages a series of signal transduction proteins, and it culminates in the induction of a broad array of nuclear target genes. One of the hallmarks of the retrograde response is its capacity to extend the replicative life span of the cell. The retrograde signaling pathway interacts with several other signaling pathways, such as target of rapamycin (TOR) and ceramide signaling. All of these pathways respond to stress, including metabolic stress. The retrograde response is also linked to both autophagy and mitophagy at the gene and protein activation levels. Another quality control mechanism involves age-asymmetry in the segregation of dysfunctional mitochondria. One of the processes that impinge on this age-asymmetry is related to biogenesis of the organelle. Altogether, it is apparent that mitochondrial quality control constitutes a complex network of processes, whose full understanding will require a systems approach. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids.


Cardiovascular disease-risk factors in middle-aged osteopaenic women treated with calcium alone or combined to three nutrients essential to artery and bone collagen.
Recent research suggests that cardiovascular disease (CVD) and bone loss are functionally interwoven. This study examined the concomitant effects of a nutritional treatment of osteopaenia on CVD-risk factors. A 1-year placebo-controlled trial was conducted on middle-aged women with normal (group A) or low (groups B and C) bone mineral density. Subjects (n = 20 per group) took daily either a placebo, calcium carbonate alone or combined to a vitamin (C and B(6))-proline capsule, respectively. Urinary pyridoxic acid (used to assess treatment compliance), plasma homocysteine, serum lipids and lipoproteins were measured before and after nutritional intervention. Groups were comparable at baseline in most parameters of interest. No changes occurred in groups A and B. The 4%, 7% and 25% reductions of total cholesterol, LDL and triglycerides, and 14% elevation of HDL were all significant in group C. A trend toward reduction was observed for homocysteine in this group. Vitamins C (500 mg) and B(6) (75 mg) combined with proline had consistent beneficial effects on CVD-risk factors, whereas calcium alone did not. This study also underlined the importance of considering vitamin B(6) status as a potential CVD risk factor.


Site-selective DNA hydrolysis induced by a metal-free peptide nucleic acid-cyclen conjugate.
A metal-free artificial restriction DNA cutter which is composed of cyclen and classical peptide nucleic acid (PNA) was synthesized. Analysis of DNA cleavage products indicates the site-selective hydrolysis.


[Evaluation of radiological methods for detection of wood foreign body in animal model].
To determine the usefulness of different radiological methods in the diagnoses of wooden foreign bodies (FB). Eleven adult chickens were used. Each thigh received a puncture wound and in one of them a wooden splinter was introduced and left in place while in the contralateral it was introduced and removed (control group). After 7 days the animals where killed and the legs removed to be analyzed with conventional radiography (CR), ultrasonography (US), magnetic resonance and computed tomography. The results were viewed by 2 independent senior radiologists. Sensitivity was: CR--13.6%; US--63.6%; MR--59.1%; and CT--72.7%, with specificity of 100%, 100%, 95.5%, and 95.5%, respectively. The positive predictive value for CR and US was 100%, 95% for CT 95% and 93.8% for MR. CT had a negative predictive value of 78.3%, while US, MR, and CR had 73.7%, 70.1%, and 53.7%, respectively. The accuracy for CT was 84.1%, followed by US--81.8%, RM--77.3%, and CR--56.8%. Inflammatory reaction was histologically demonstrated in all thighs containing FB. CR showed a poor performance to detect wooden FB in chickens, while US and CT seem to be the best option, followed by RM.


Simplified Zone 2 Arch Repair Using a Trifurcated Graft for Acute Type A Dissection.
We report a simplified zone 2 arch repair using a trifurcated graft for acute type A aortic dissection. The right axillary artery is cannulated. After completion of proximal aortic repair using a 1-branched graft, a trifurcated graft is anastomosed to the ascending graft just above the proximal suture line or coronary buttons in case of Bentall procedure. Distal aortic anastomosis is performed at the zone 2 level under unilateral antegrade cerebral perfusion. Full cardiopulmonary bypass flow is resumed via the right axillary artery and ascending graft using both Y-shaped arterial limbs. The left common carotid and innominate arteries are sequentially anastomosed.


Regulation of macronutrient intake in termites: A dietary self-selection experiment.
Many animals have been shown to select among nutritionally complementary foods to reach a specific balance of nutrients that optimizes key life history traits. Nutritional ecology theory, however, predicts that an animal with a diet that is very stable in its composition, and with nutritional requirements that do not vary in their balance through time, would not need to display such mechanisms of regulation. Here we use the Australian termite Nasutitermes exitiosus as a model to test this prediction for the first time. We used the nutritional geometric framework to investigate the regulation of carbohydrate and protein, as well as the effects on foraging behaviour of protein type and group caste composition and size. Our results support the prediction of nutritional ecology, as termites failed to actively defend a well-defined macronutrient ratio. Termites maintained food collection relatively constant across protein type and group composition, and only appear to vary their collection by avoiding diets too rich in protein.


Antibodies and thermolabile opsonins in the phagocytosis of human red and white blood cells pretreated with formaldehyde.
Erythrophagocytosis is conditioned by serum immunoglobulins. The extent of phagocytosis depends on the haematocrit of the red cell suspension pretreated with formaldehyde. The higher the haematocrit value, the lower will be the extent of phagocytosis. Phagocytosis of white blood cells pretreated with formaldehyde by granulocytes and monocytes is conditioned mainly by a thermolabile fraction of the serum, probably the complement.


[Evaluation of stresses in different cingulum rest seats].
Both lingual and incisal rest seats are used on anterior teeth. Lingual rest seats are preferred since they are more acceptable esthetically and located closer to the centre of rotation of the tooth. Lingual rest seats can be prepared directly on the abutment teeth as grooves, shoulders or may require restorations such as crowns, inlays and prefabricated rest seats to provide proper contour. In this study, the stress induced by two conventionally applied rest seats were compared with that of the U shaped rest seats which were recently induced. As a result it is found that more uniform stress distribution occurred in U and inverted "v" type rest seat designs.


A seed tick infestation of the conjunctiva: Amblyomma americanum larva.
Ticks commonly infest humans but rarely bite the eyes. They are vectors of disease; therefore, rapid and complete removal is important. Their attachment can be so secure that removal is difficult or hazardous. We excised a larval form of Amblyomma americanum from a woodsman's conjunctiva.


[3+2] click chemistry approach to tetrazine containing polymers.
We report a [3+2] cycloaddition using 3,6-bis-propargyloxy-1,2,4,5-tetrazine and azides to synthesize energetic polymers containing 1,2,4,5-tetrazine within the scaffold. This work also includes [3+2] cycloaddition to crosslink azide containing glycidyl azide polymer (GAP). These reactions provide pathways for incorporation of 1,2,4,5-tetrazine into novel energetic materials using click-chemistry and provide an alternative polymer curing approach.


Rapid detection of oesophageal intubation: take care when using colorimetric capnometry.
Rapid detection of a misplaced endotracheal tube in the esophagus is crucial, especially in emergency situations. Hence, we have compared the ability of a colorimetric CO2 indicator (Colibri technology, CO2ntrol 1) and a capnography to differentiate oesophageal and tracheal intubation, with and without CO2 air in the esophagus. Fourteen otherwise healthy patients were intubated with an endotracheal tube in the trachea under general anesthesia. After a positive verification of this endotracheal tube and established mechanical ventilation a second endotracheal tube was placed in the esophagus. Both were initially ventilated four times, and expired CO2 was measured with a mainstream capnograph and a colorimetric indicator. In the remaining five patients CO2 containing air was inserted into the esophagus first and then ventilated four times. Both the colorimetric indicator and mainstream capnograph verified correct placement of the endotracheal tube from the first ventilation. When the tube was placed in the esophagus, both methods correctly showed that no CO2 was present. However, in patients (n=5) with CO2 installed in their esophagus, the colorimetric indicator, but not the capnograph, had readings showing that CO2 was present. This may cause a misinterpretation of correct tracheal placement. We found that in emergency situations where CO2 containing air may be present in the esophagus, capnography should be the preferred method of verifying endotracheal and not oesophageal intubation. The tested colorimetric CO2 indicator (Colibri technology, CO2ntrol 1) is very sensitive to low CO2 values. It may therefore falsely indicate correct endotracheal intubation, even when the tube is in the oesophageus.


A pathophysiological model of freezing of gait in Parkinson's disease.
Freezing of gait (FOG) is a common phenomenon in Parkinson's disease (PD) affecting over half of those in the advanced stages of the disease and often does not respond to standard drug therapies. This article proposes a possible mechanism by which this disorder of movement comes about. Co-ordinated neural activities are dependent on a series of parallel neuronal networks passing through the basal ganglia connecting and integrating functions. In healthy subjects, these competing, yet complementary, networks permit tight regulation in the broad domains of motor, cognitive, and limbic functions. In patients with PD, the loss of striatal dopamine coupled with the limited repertoire of the output nuclei within these pathways allows for an element of 'cross-talk' between competing inputs, which in turn could lead to a paroxysmal excessive inhibition of the thalamus and pedunculopontine nucleus triggering freezing of gait. It is further postulated that this phenomenon may be acting via a transient period of increased synchronization within the basal ganglia oscillations.


Waterpipe tobacco smoking and its human health impacts.
Waterpipe tobacco smoking (WTS, also known as hookah, shisha, narghile, and many other names) involves passing tobacco smoke through water prior to inhalation by the consumer. As the number of waterpipe smokers is rising rapidly, there is growing concern over the use of WTS, particularly as there has been a widely held misconception that WTS is free from health hazards. In reality, it is associated with a variety of adverse health outcomes on both a short- and long-term basis. Hence, it is desirable to develop advanced techniques for surveillance, intervention, and regulatory/policy frameworks specific to the production and use of waterpipe tobacco. This review is written to survey the types and extent of pollutants released from its use and their potential health risks. A review of the present regulation guidelines is also included.


Correction to "Effectiveness and Safety of Palbociclib plus Endocrine Therapy in Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: Real-World Results".
[This corrects the article on p. 26 in vol. 75, PMID: 34987260.].


Sequential object recognition deficits in normal readers.
The present work examined the relationship between sequential object recognition and variations in normal reading ability. A group of normal readers completed a battery of tests examining nonverbal intelligence, rapid-automatized naming, reading ability, and an attentional blink (AB) task in which they were asked to identify two sequential targets embedded amongst distractors. Consistent with previous studies, all participants showed a significant AB, with second-target identification improving as inter-target interval increased. More critically, low-normal readers showed a larger AB than high-normal readers. Considered in context with earlier work, these results imply that the ability to allocate capacity-limited processing resources to sequential visual inputs is linked to reading proficiency across the range of both disabled and normal readers.


Rotational magneto-acousto-electric tomography (MAET): theory and experimental validation.
We present a novel two-dimensional (2D) MAET scanner, with a rotating object of interest and two fixed pairs of electrodes. Such an acquisition scheme, with our novel reconstruction techniques, recovers the boundaries of the regions of constant conductivity uniformly well, regardless of their orientation. We also present a general image reconstruction algorithm for the 2D MAET in a circular chamber with point-like electrodes immersed into the saline surrounding the object. An alternative linearized reconstruction procedure is developed, suitable for recovering the material interfaces (boundaries) when a non-ideal piezoelectric transducer is used for acoustic excitation. The work of the scanner and the linearized reconstruction algorithm is demonstrated using several phantoms made of high-contrast materials and a biological sample.


Clinical-pathological discrepancies in critically ill patients with difficult premortem diagnoses.
The importance of autopsies is a common theme of discussions both in Brazil and around the world as it elucidates causes of death and has wide ranging social value. However this is a practice that is gradually being considered unnecessary and there have been a decline in the number of postmortems examinations. To compare clinical and pathological diagnosis in critically ill patients with difficult premortem diagnosis. All autopsy cases (total of 98) from any of the three general medical/surgical intensive care units (78 beds in total) affiliated to the medical school from January 2003 to December 2006 were analyzed. We analyzed the clinical and pathological diagnosis based on the Goldman criteria. In 49 (50%) cases, there were class I and II of Goldman. In contrast, only 30 (30.6%) had a complete agreement between premortem and postmortem diagnosis and were classified as class V. Infections had a significantly greater rate of concordant diagnosis than cardiovascular diseases. We found significant discrepancies between clinical and pathological findings, reinforcing the value of postmortem examination.


Voice Analysis in Post Tonsillectomy Patients.
The main aim of this study was to analyse the change in voice in terms of acoustic parameters and its perceptual impact in patients who have undergone tonsillectomy. A prospective study was conducted in our institution-JSS Hospital and JSS institute of speech and hearing, Mysore for a duration of 1 year (December 2015-December 2016). 50 post tonsillectomy cases were selected randomly and subjected to acoustic analysis. It was inferred that situation of vocal analysis and assessment for the vowels 'a', 'i' and 'u' under the categories hoarse, harsh and breathy remain more or less the same during preoperative stages, first preoperative follow up and the second post operative follow up. It was concluded that tonsillectomy did not appear to change the acoustic features of vowels remarkably. It was assumed that the subject may adjust the shape of the vocal tract to produce consistent speech sound after surgery using auditory feedback.


Automated image-based analysis of spatio-temporal fungal dynamics.
Due to their ability to grow in complex environments, fungi play an important role in most ecosystems and have for that reason been the subject of numerous studies. Some of the main obstacles to the study of fungal growth are the heterogeneity of growth environments and the limited scope of laboratory experiments. Given the increasing availability of image capturing techniques, a new approach lies in image analysis. Most previous image analysis studies involve manual labelling of the fungal network, tracking of individual hyphae, or invasive techniques that do not allow for tracking the evolution of the entire fungal network. In response, this work presents a highly versatile tool combining image analysis and graph theory to monitor fungal growth through time and space for different fungal species and image resolutions. In addition, a new experimental set-up is presented that allows for a functional description of fungal growth dynamics and a quantitative mutual comparison of different growth behaviors. The presented method is completely automated and facilitates the extraction of the most studied fungal growth features such as the total length of the mycelium, the area of the mycelium and the fractal dimension. The compactness of the fungal network can also be monitored over time by computing measures such as the number of tips, the node degree and the number of nodes. Finally, the average growth angle and the internodal length can be extracted to study the morphology of the fungi. In summary, the introduced method offers an updated and broader alternative to classical and narrowly focused approaches, thus opening new avenues of investigation in the field of mycology.


Mindfulness and shooting performance in biathlon. A prospective study.
The aim of the study was to examine the temporal relationship between facets of sport-specific dispositional mindfulness (i e., Awareness, Refocusing, Nonjudgemental attitude) and shooting performance in actual competitions, in a population of 25 elite biathlon athletes. Findings indicated that mindfulness facets were positively associated with shooting performance, with higher levels of Awareness, Refocusing, and Awareness being related to better shooting performance in competitions. In spite of the fact that the explained variance was quite small, even a minor shooting performance enhancement may increase an athlete's chance of winning a biathlon competition.


Cocaine and habit training cause dendritic spine rearrangement in the prelimbic cortex.
Successfully navigating dynamic environments requires organisms to learn the consequences of their actions. The prelimbic prefrontal cortex (PL) formulates action-consequence memories and is modulated by addictive drugs like cocaine. We trained mice to obtain food rewards and then unexpectedly withheld reinforcement, triggering new action-consequence memory. New memory was disrupted by cocaine when delivered immediately following non-reinforcement, but not when delayed, suggesting that cocaine disrupted memory consolidation. Cocaine also rapidly inactivated cofilin, a primary regulator of the neuronal actin cytoskeleton. This observation led to the discovery that cocaine also within the time of memory consolidation elevated dendritic spine elimination and blunted spine formation rates on excitatory PL neurons, culminating in thin-type spine attrition. Training drug-naive mice to utilize inflexible response strategies also eliminated thin-type dendritic spines. Thus, cocaine may disrupt action-consequence memory, at least in part, by recapitulating neurobiological sequalae occurring in the formation of inflexible habits.


1H NMR spectroscopic identification of protonable sites in cryptolepines with C-11 substituents containing two amino functionalities.
Knowledge of protonable sites and acid dissociation constants of cryptolepine derivatives having C-11 substituents containing two amino functionalities is of great importance to the understanding of the mechanism of their antimalarial action, which may contribute to their further development as drug candidates. In this work, we applied (1)H NMR titration to investigate the acid-base characteristics of these polyprotic compounds in the pH range 3-13. We identified three acid-base equilibria with most acid dissociation constants (pK(a)*) being greater than 10.5, which prevented us from using the potentiometric method. Overall, (1)H NMR titration was sensitive and suitable for the determination of pK(a) values for these drug leads.


Hepatitis C virus genotype distribution in Egyptian diabetic patients: a preliminary study.
There is controversy regarding whether a specific hepatitis C virus (HCV) genotype is associated with diabetes mellitus. This study aimed to investigate HCV genotype distribution in diabetics and its relation to some clinical and laboratory variables in HCV-positive diabetic versus non-diabetic Egyptians in East Delta. The study included 100 HCV-positive patients of which 66 were diabetic in addition to 35 healthy adults as a control group. Clinical assessment, laboratory measurements of plasma glucose, insulin, C-peptide, C-reactive protein (CRP), tumour necrosis factor-α (TNF-α) and liver functions (alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT)) as well as HCV genotype determination were done, and AST/platelet ratio index (APRI) and Homoeostasis Model of Assessment-Insulin Resistance (HOMA-IR) were calculated. The main results were the presence of HCV genotype 3, in 31.8% of the diabetic group and in 26.5% of the non-diabetic group, while the remainder of cases had genotype 4, the predominant genotype in Egypt. This is the first report of the presence of HCV genotype 3 in about 30% of an Egyptian cohort. However, there was no significant difference in genotype distribution between both groups. Further, there were significantly higher values of HOMA-IR, insulin and C-peptide in HCV-positive groups in comparison to the control group, while TNF-α was significantly higher in the HCV-positive diabetic group. However, there were no significant differences between both genotypes regarding these parameters. Although this study reveals for the first time the presence of HCV genotype 3 in a significant percentage of a group of Egyptian patients, where the majority were diabetic, the association between diabetes and certain HCV genotypes could not be confirmed on the basis of our findings. Hence, taking into consideration the impact of such a finding on the treatment decisions of those patients, further studies are warranted to explore these findings to a greater extent.


Thermal sensitivity in healthy subjects is decreased by a central mechanism after TNS.
Using the thermal sense as a model for nociception, the effects of conventional and acupuncture-like transcutaneous nerve stimulation (TNS) were tested on thresholds for warm and cold sensation in 8 healthy subjects. Photic stimulation did not change the thermically neutral zone (the warm-cold difference limen) from that seen under baseline conditions. However, the thermal difference limen usually increased with both types of TNS. The effect was ipsi- as well as contralateral, implying that a central inhibitory mechanism is activated by conventional and acupuncture-like TNS.


Analysis of structural specificity in antibody-antigen reactions by capillary electrophoresis with laser-induced fluorescence detection.
A rapid and simple procedure for screening antibodies for binding to an antigen is proposed. A fluorescent hapten-dye conjugate was prepared by labeling the amino moiety of the hapten with a commercially available reactive cyanine dye, Cy5 (excitation maximum: 650 nm, emission maximum: 670 nm). A fixed amount of the Cy5-hapten was titrated with serial dilution of the antibody. Each of the titration mixture was analyzed by capillary electrophoresis (25 cm x 20 microns column) monitored by laser-induced fluorescence (laser: 10 mW helium-neon, 632.8 nm). Free and antibody-bound Cy5-hapten were analyzed simultaneously on the electropherogram. Competitive immunoassay of hapten was demonstrated with low-end sensitivity of 5.10(-8) M, about 10x more sensitive than the present drug screening methods. Using morphine as an example, the screening of various antibodies (from different vendors) and cross-reactivity of morphine analogues using the present procedure will be discussed.


The processes of case management: a review of the evaluation of a pilot study for elderly people in Hong Kong.
This paper is based on research into case management that aimed to evaluate the processes of the introduction of case management for elderly people into the community nursing services in Hong Kong. The Hospital Authority in Hong Kong introduced a pilot Case Management scheme into the Community Nursing Services. A research project was therefore developed to evaluate this case management model. The processes were measured through information gained from group interviews, daily diaries and weekly activity sheets. The roles and work practices of the Care Coordinators and Case Managers are described and the benefits of case management to patients, carers and nurses are highlighted. Difficulties are also discussed and good practices are identified. Staff in the hospital and community need time to get used to the model of case management and to the accompanying documentation. The role of the case manager needs to be clearly dilineated.


Working from home and positive/negative experiences due to social distancing as interacting factors of depressive symptoms during the COVID-19 pandemic in a Chinese general population.
This study investigated the associations between some factors related to working from home status (WFHS) and positive/negative experiences due to social distancing and their interactions effects on depressive symptoms during the COVID-19 pandemic. A random population-based telephone survey interviewed income-earning adults in the Hong Kong general population during April 21-28, 2020 (n = 200). Mild to severe depression (according to PHQ-9) was reported by 12% of the participants. The prevalence of WFHS categories was 14% for 3-7 days and 13% for ≥ 8 days (past 2 weeks). The multivariable regression analysis showed that, social isolation (β = 0.36; p < 0.001), relaxation feeling in daily life (β = - 0.22; p = 0.002), and WFHS ≥ 8 days (β = 0.15; p = 0.027), but not perceived huge inconvenience and improved family relationship, were associated with depressive symptoms. Statistically significant interaction effects were found. Some positive experiences buffered the potential harms of some negative experiences of social distancing on depressive symptoms; WFHS ≥ 8 days significantly moderated the risk/protective effects of social isolation, improved family relationship, and relaxation feeling on depressive symptoms. Social distancing is double-edged. Positive experiences should be maximized while negative experiences be minimized, as both were directly and interactively associated with depression. Intensive but not mild to moderate (< 80%) WFHS may impact depressive symptoms negatively via its direct association with depression; it also moderated the associations between positive/negative experiences due to social distancing and depression. Further research is required to discern the inter-relationships among WFHS, positive/negative experiences of social distancing, and depression to better cope with the stressful pandemic.


The elucidation of the structure of the core part of the LPS from Plesiomonas shigelloides serotype O17 expressing O-polysaccharide chain identical to the Shigella sonnei O-chain.
Plesiomonas shigelloides O17 LPS contains the same O-antigenic polysaccharide chain as a causative agent of dysentery, Shigella sonnei. This polysaccharide can be used as a component of a vaccine against dysentery. Core part of the P. shigelloides O17 LPS was studied using NMR and mass spectrometry and the following structure was proposed: [structure : see text]. Significant similarity of the P. shigelloides O17 LPS core with the structure of the P. shigelloides O54 core was observed.


A glycoprotein from Spirometra erinaceieuropaei plerocercoids suppresses osteoclastogenesis and proinflammatory cytokine gene expression.
Various parasites modify the immune-reactions of the host. We have previously shown that crude excretory/secretory (ES) products from plerocercoids of Spirometra erinaceieuropaei, the plerocercoids of which cause sparganosis in humans, suppress the expression of tumor necrosis factor (TNF)-alpha and IL-1beta in lipopolysaccharide (LPS)-stimulated macrophages. As osteoclasts are cells of the monocyte/macrophage lineage, we hypothesised that ES products might suppress receptor activator of nuclear factor kappaB ligand-induced osteoclastogenesis. Crude ES products from plerocercoids suppressed osteoclastogenesis, judged by tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cell counting, and the mature osteoclast-specific gene expression (calcitonin receptor and TRAP). Second, we purified the inhibitory factor for osteoclastogenesis from the crude ES products. The factor was a trypsin-sensitive glycoprotein and had a relative molecular mass of 90 kDa. The glycoprotein, plerocercoid-immunosuppressive factor, from crude ES products could suppress the gene expression of TNF-alpha, IL-1beta and NO synthesis in LPS-stimulated RAW264.7 macrophages.


Nuclear Factor Erythroid-2 Like 1 (NFE2L1): Structure, function and regulation.
Nrf1 (also referred to as NFE2L1) is a member of the CNC-bZIP family of transcription factors that are characterized by a highly conserved CNC-domain, and a basic-leucine zipper domain required for dimerization and DNA binding. Nrf1 is ubiquitously expressed across tissue and cell types as various isoforms, and is induced by stress signals from a broad spectrum of stimuli. Evidence indicates that Nrf1 plays an important role in regulating a range of cellular functions including oxidative stress response, differentiation, inflammatory response, metabolism, and maintaining proteostasis. Thus, Nrf1 has been implicated in the pathogenesis of various disease processes including cancer development, and degenerative and metabolic disorders. This review summarizes our current understanding of Nrf1 and the molecular mechanism underlying its regulation and action in different cellular functions.