Recovery of a dilated left ventricle after cessation of cocaine and HVAD™ explantation using a titanium plug.
The ultimate goal in the treatment of end-stage heart failure is the recovery of cardiac function following mechanical assistance of the left ventricle. The HVAD™ pump (HeartWare Inc.) left ventricular assist device (LVAD) can be explanted without resternotomy. This article demonstrates that the use of a custom-made mechanical plug (manufactured by INNOVO Solutions GmbH), which can be inserted into the LVAD's sewing ring, is feasible. This mechanical plug explicitly designed for device explantation is a viable alternative to the current standard of care. This article adopts a less invasive technique to explant the pump. The following case illustrates this technique.


Adult medulloblastoma: prognostic factors and response to therapy at diagnosis and at relapse.
Adult medulloblastoma is a rare tumor with few retrospective studies published so far. The role of adjuvant chemotherapy or chemotherapy at relapse is unclear. This study reports therapy and outcome in all adult (>or=16 years old) medulloblastoma (n=34) and supratentorial primitive neuroectodermal tumor (PNET) patients (n=2) treated in 2 neuro-oncological centers between 1976 and 2002. The median age was 24.5 years (range 16-76). After resection, 16 patients were treated with craniospinal radiotherapy alone, 20 patients also received adjuvant chemotherapy (8 vincristine, CCNU, cisplatin; 7 methotrexate alone or methotrexate/vincristine-based polychemotherapy; 5 other protocols). Median survival in the whole cohort was 126 months (2+ - 200+months). Five-year and 10-year survival rates were 79 % and 56%. Adjuvant chemotherapy was associated with a non-significant trend to prolonged survival (relative risk (RR) 1.89; p=0.068). The median progression-free survival (PFS) after primary therapy was 83 months. At relapse, 10 of 12 evaluable patients achieved a complete response upon second-line therapy. The median survival times from first (n=17) and second relapse (n=9) were 21 months (0-67+ months; 5/17 without second relapse) and 20 months (1-29 months). Cox regression analysis revealed the infiltration of the floor of the 4(th) ventricle at diagnosis as the only therapy-independent prognostic factor (RR 0.48; p=0.03). In conclusion, adjuvant chemotherapy may prolong survival in adult medulloblastoma patients. Moreover, second-line therapy may be beneficial for these patients. As in pediatric medulloblastoma patients, primary infiltration of the floor of the 4(th) ventricle indicates a poor prognosis.


Tamoxifen increases photodynamic therapeutic response of U87 and U25ln human glioma cells.
We tested the hypothesis that Tamoxifen (TMX), an inhibitor of protein kinase C (PKC), augments the cytotoxicity of photodynamic therapy (PDT) treatment of human (U87) and (U25ln) glioma cells. U87 and U25ln glioma cells were plated and treated with PDT using Photofrin as the sensitizer. Cells were treated with Photofrin at various doses and with various optical (632 nm) irradiation intensities 24 h later. Cells were also treated with Photofrin at a fixed dose alone and with various doses of Tamoxifen and subjected to laser treatment 24 h later. Tumor response was tested using the (3-94,5-dimethyl-2-yl)-2,5-diphenyl-tetrazolium (MTT) method. Total toxicity of U87 cells was achieved with PDT at all doses of Photofrin (1, 2.5, 5, 10 microg/ml) with irradiation densities equal to or greater than 200 mJ/cm2. Using an irradiation intensity of 100 mJ/cm2, U87 and U25ln cells were killed in a Photofrin dose-dependent manner. Significant cytotoxicity was detected with Photofrin doses of 5 microg/ml (p < 0.05) and 10 microg/ml (p < 0.001). Tamoxifen at a dose of 500 microg/ml and higher, significantly increased the toxicity of the PDT response with 5 microg/ml Photofrin and 100 mJ/cm2 (p < 0.05). In summary, our data demonstrate that Tamoxifen significantly enhances the Photofrin PDT activity of U87 and U25ln human glioma cells.


The association of weight, weight variability and socioeconomic situation among children.
We studied the association of body weight and weight variability among populations from different geographic, historic and socioeconomic background. We reanalyzed data from 833 growth studies of 78 different countries from 1920 to 2013. We used data from two age groups-infants (age 2 years) and juvenile (age 7 years)-and divided the studies into two geographic-socioeconomic groups. Multiple regressions showed significant interactions between weight, sex, historic year of study, continent and within-study standard deviation. Multiple regression revealed R(2)=0.256 (P<0.001) at age 2 years and R(2)=0.478 (P<0.001) at age 7 years. Although infants and juveniles in more affluent countries are heavier than children in less affluent countries (P<0.001), the within-study standard deviation of the two geographic-socioeconomic groups differs at age 7 years (P<0.001) but not at age 2 years (P>0.15). The general impression that prosperous conditions lead to growth improvements in height and weight appears to be true only at a large scale: wealthy countries have tall and heavy children. At small scale, the situation is different. Whereas economic and nutritional improvements can exhibit substantial effects in weight gains, the discrepancy between the within-population variation in height and weight strongly suggests that height gains and weight gains are subject to different regulations.


Exercise during pregnancy: knowledge and beliefs of medical practitioners in South Africa: a survey study.
There is compelling evidence for the benefits of regular exercise during pregnancy, and medical practitioners (MPs) can play an important role in changing antenatal health behaviours. The purpose of this study was to assess the knowledge, attitudes and beliefs of South African MPs towards exercise during pregnancy. A convenience sample of ninety-six MPs working in the private health care sector, including General Practitioners (n = 58), Obstetricians/Gynaecologists (n = 33) and other Specialists (n = 5), participated in this cross sectional, descriptive survey study. A 33-item questionnaire was distributed manually at medical practices and via email to an on-line survey tool. Descriptive statistics and frequency tables were calculated for all questions. Chi-squared and Fisher's exact statistical tests were used to determine the differences in response by age, speciality and years of practice (p < 0.05). The majority of practitioners (98%) believe that exercise during pregnancy is beneficial, and were knowledgeable on most of the expected benefits. Seventy-eight percent believed that providing exercise advice is an important part of prenatal care, however only 19% provided informational pamphlets and few (24%) referred to exercise specialists. A large majority (83%) were unaware of the recommended exercise guidelines. Although age and years of practice played no role in this awareness, practitioners who focussed on obstetrics and gynaecology were more likely to be aware of the current guidelines, than those in general practice (p < 0.001). Although the MPs were largely positive towards exercise during pregnancy, their advice did not always align with the current guidelines. Therefore, better dissemination of available research is warranted, to bridge the gap between clinical knowledge and current recommendations for physical activity promotion.


Bacillus thuringiensis delta-endotoxin: evidence that toxin acts at the surface of susceptible cells.
Enzymically activated delta-endotoxin of Bacillus thuringiensis covalently bound to Sephadex beads, has the same effect on insect cells in tissue culture as free toxin. The effect is prevented by antitoxin antibody and heat denaturation and is not due to a nonspecific protein effect, the beads, or toxin released from the beads. The toxin, therefore, probably acts at the cell surface.


Association of ADIPOQ gene polymorphisms and coronary artery disease risk: a meta-analysis based on 12 465 subjects.
Coronary artery disease (CAD) is one of the most common cardiovascular diseases and is a major cause of morbidity and mortality worldwide. Various researchers have investigated the role of ADIPOQ gene in the risk of CAD, yet their results have been inconsistent. To evaluate the association between ADIPOQ genetic polymorphisms and CAD risk, relevant studies published before October 2011 were identified by searching PubMed and EMBASE. Studies were selected using previously defined criteria. The strength of the relationship between the four single nucleotide polymorphisms (SNPs) of the ADIPOQ gene and CAD risk was assessed using odds ratios (ORs). A total of 12 465 subjects from 17 case-control studies were identified in the present study. Based on the relevant studies, it was determined that the risk of CAD was not associated with rs2241766 in any genetic model. Increased risk of CAD was associated with rs266729 in allele contrast (1.11, [1.03, 1.20]) and dominant genetic model (1.15, 95%CI: [1.05, 1.27]); increased risk of CAD was also associated with rs822395 in additive (1.63, 95%CI: [1.19, 2.22]) and recessive genetic model (1.71, 95%CI: [1.27, 2.30]). It was further determined that the rs1501299 polymorphism reduced the risk of CAD in the additive (0.80, 95%CI: [0.67, 0.94]) and recessive genetic model (0.81, 95%CI: [0.68, 0.95]). In the stratified analysis, significant associations were found in Asian subjects for rs266729 and in Caucasian subjects for rs1501299. There is an association between ADIPOQ gene polymorphisms and CAD risk. Different SNPs of the ADIPOQ gene have different associations with CAD risk, and appear to increase risk in individuals of Asian ethnicity while decrease the CAD risk in Caucasians. However, the overall strength of association was mild to moderate.


Phasic regulation of the ATP/P2X7 receptor signaling pathway affects the function of antigen-presenting cells in experimental autoimmune uveitis.
Purinergic ligand-gated ion channel 7 receptor (P2X7R) is a purine type P2 receptor that is expressed on a variety of immune cells. Recent studies have shown that P2X7R signaling is required to trigger an immune response, and P2X7R antagonist-oxidized ATP (oxATP) effectively blocks P2X7R activation. In this study, we investigated the effect of phasic regulation of the ATP/P2X7R signaling pathway on antigen-presenting cells (APCs) by constructing an experimental autoimmune uveitis (EAU) disease model. Our results demonstrated that APCs isolated from the 1st, 4th, 7th and 11th days of EAU presented antigen function and could stimulate the differentiation of naive T cells. Moreover, after stimulation by ATP and BzATP (a P2X7R agonist), antigen presentation, promoting differentiation and inflammation were enhanced. The regulation of the Th17 cell response was significantly stronger than that of the Th1 cell response. In addition, we verified that oxATP blocked the P2X7R signaling pathway on APCs, attenuated the effect of BzATP, and significantly improved the adoptive transfer EAU induced by antigen-specific T cells cocultured with APCs. Our results demonstrated that at an early stage of EAU, the ATP/P2X7R signaling pathway regulation of APCs was time dependent, and the treatment of EAU could be achieved by intervening in P2X7R function on APCs.


Psychological withdrawal and mental health during the COVID-19 pandemic: a longitudinal study.
The first objective was to track temporal changes in participants' mental health during the 2020 lockdown in Spain. Second, we tested whether age moderated the association between the use of psychological withdrawal and mental health over time. Design: Participants (N = 396, 74% women) completed three waves of a web-based survey during the lockdown. Age mean was 40.11 (sd = 12.66). Participants answered a set of sociodemographic data, the General Health Questionnaire (GHQ-12), and the Measures of Affect Regulation Scale (MARS). Disruptions and withdrawal were associated with more mental health symptoms (between 39% and 41% mental distress). Growth models showed that social dysfunction increased over time while dysphoric symptoms decreased. The use of withdrawal aggravated social dysfunction symptoms. Young people who use more withdrawal experienced more social dysfunction and dysphoria over time than those who used less withdrawal strategies. The differential trends in social dysfunction versus dysphoria symptoms suggest an adaptation process after the initial stress of the lockdown. Older age was correlated with less mental health problems and reflects age related improvements in emotional regulation.


Nurses and Doctors Heroes? A Risky Myth of the COVID19 Era.
Recent newspapers reports have named health professionals as "heroes". This is surprising, because in the last few decades, doctors and nurses have been taken into account by mass media only to describe cases of misconduct or of violence. This change was due to the coronavirus pandemic scenario that has produced fear in the population and the need for an alleged "savior". This need for health professionals seen as heroes is also disclosed by the fact that even politicians have abdicated to their role in favor of the healthcare "experts" to whom important decisions on social life during this pandemic have been delegated, even those decisions that fall outside of the specific health field. This commentary is a claim to framing the job of caregivers in its correct role, neither angel nor devil, but allied to the suffering person, that the image of "heroes" risks to overshadow.


Development and validation of a standardized tool for reporting retinal findings in abusive head trauma.
To develop and validate a robust standardized reporting tool for describing retinal findings in children examined for suspected abusive head trauma. A prospective interobserver and intraobserver agreement study. An evidence-based assessment pro forma was developed, recording hemorrhages (location, layer, severity) and additional features. Eight consultant pediatric ophthalmologists and 7 ophthalmology residents assessed a series of 105 high-quality RetCam images of 21 eyes from abusive head trauma cases with varying degrees of retinal hemorrhage and associated findings. The pediatric ophthalmologists performed a repeat assessment of the randomized images. The images were observed simultaneously with standardized display settings. Interobserver and intraobserver agreement was assessed using free-marginal multirater kappa, intraclass correlation coefficients, and concordance coefficients. Almost-perfect interobserver agreement was observed for residents and pediatric ophthalmologists recording the presence and number of fundus hemorrhages (intraclass correlation coefficients 0.91 and 0.87, respectively) and the location of hemorrhages (concordance coefficients 0.86 and 0.85, respectively). Substantial agreement was observed by both groups regarding size of hemorrhage (concordance coefficients 0.73 and 0.76), moderate agreement for hemorrhage morphology (concordance coefficients 0.53 and 0.52), and other findings (concordance coefficients 0.48 and 0.59). Intraobserver agreement for pediatric ophthalmologists varied by question, ranging from substantial to perfect for the presence, number, location, size, and morphology of fundus hemorrhage. We have developed and validated a standardized clinical reporting tool for ophthalmic findings in suspected abusive head trauma, which has excellent interobserver and intraobserver agreement among consultant specialists and residents. We suggest that its use will improve standardized clinical reporting of such cases.


Enhancement of drug sensitivity of human malignancies by epidermal growth factor.
We have previously shown that epidermal growth factor (EGF) enhances the in vitro and in vivo sensitivity of human ovarian carcinoma 2008 cells to cisplatin. EGF was found to enhance selectively the in vivo toxicity of cisplatin to 2008 cell xenografts without altering the toxicity of cisplatin to non-malignant target tissues such as the kidney or bone marrow. We now show that recombinant human EGF (rhEGF) enhances the cisplatin sensitivity of cell lines representative of many other types of malignancies in addition to ovarian carcinoma, including cancers of the head and neck, cervix, colon, pancreas and prostate, as well as non-small-cell carcinoma of the lung. In addition, rhEGF was found to sensitise cells to other platinum-containing drugs and several other classes of chemotherapeutic agents. rhEGF sensitised 2008 cells not only to cisplatin, but also to carboplatin and tetraplatin, as well as taxol, melphalan and 5-fluorouracil. We conclude that modulation of drug sensitivity by rhEGF is observed in cell lines representative of many human malignancies and for multiple classes of chemotherapeutic agents, indicating that it alters one or more components of the cellular damage response that are both common between cell lines and classes of drugs and fundamental to survival.


Implementing a care model for the older person.
This second in a three-part series shows how to use the Caring For and Caring About model in practice. Part 1, published last week, described the model; part 3, to be published online on 10 April, shows how to manage care using existing resources.


Changes in the mitochondrial membrane potential in endothelial cells can be detected by Raman microscopy.
The role of mitochondria goes beyond their capacity to create molecular fuel and includes e.g. the production of reactive oxygen species and the regulation of cell death. In endothelial cells, mitochondria have a significant impact on cellular function under both healthy and pathological conditions. Endothelial dysfunction contributes to the development of various lifestyle diseases and the key players in their pathogenesis are among others vascular inflammation and oxidative stress. The latter is very closely related to mitochondrial dysfunction; however, it is not straightforward. First, because mitochondria are small cellular structures, and second, it requires a sensitive method to follow the subtle biochemical changes. For this purpose, Raman microscopy (RM) was used here, which is considered a high-resolution method and can be applied in situ, usually as a non-labeled technique. In this work, we show that RM can not only locate mitochondria in the cell but also track their functional changes. Moreover, we test if labeling cells with Raman probes (Rp) can improve the specificity and sensitivity of RM (compared to conventional labeled techniques such as fluorescence, and the non-labeled Raman technique). MitoBADY Rp was used to detect changes in mitochondrial membrane potential as an indicator of mitochondrial activity, e.g. hyperpolarization or distortion of the proton gradient in the intermembrane space (depolarization). Thus, we show and compare RM, in the form of a label and non-labeled, to such a subtle cellular analysis.


Xanthogranulomatous pyelonephritis infected with the Providencia stuartii: a case report and literature review.
Xanthogranulomatous pyelonephritis (XGP) is a rare and severe chronic inflammatory disease of the renal parenchyma, which is most commonly associated with super-infections by bacteria such as E. coli, Proteus mirabilis, and occasionally Pseudomonas species. Herein, we present a rare case of a patient with XGP infected with Providencia stuartii. Initially, the patient refused nephrectomy and underwent holmium laser lithotripsy and right ureteral stenting, followed by meropenem treatment of 7 days. Relapse occurred in the third month after discharge from the hospital, due to which she underwent a radical nephrectomy. The diagnosis of XGP is confirmed by histopathology. The standard treatment for XGP is antibiotic therapy and radical nephrectomy, but partial nephrectomy may be appropriate in select cases.


Overexpression of growth hormone affects alternatively spliced IGF-I mRNA expression in oMt1a-oGH transgenic mice.
Restorative growth hormone (GH) treatment of hypophysectomized rats differentially enhances the transcription of alternative IGF-I mRNA classes in liver. The goal of the present study was to determine the effects of GH overexpression on various classes of hepatic IGF-I mRNA in GH transgenic mice. Unstimulated oMt1a-oGH transgenic mice had low levels of transgene expression, and therefore were used to determine the effects of long-term, slightly elevated GH levels on the abundance on each alternative IGF-I mRNA class. The acute effects of high GH levels on the expression of alternative IGF-I mRNA were studied by gavaging transgenic mice with 25 mM zinc sulfate to activate oMt1a-oGH transgene expression. Long-term, low levels of oGH transgene expression in unstimulated transgenic mice resulted in a 73% down regulation of IGF-I 2Ea mRNA but not 1Ea and 2Eb mRNA. Acute stimulation of transgene expression triggered a rapid, 240% increase in 1Ea mRNA levels within 4 hours of transgene expression while 2Ea mRNA was down regulated to nearly non-detectable levels by 6 hours. IGF-I 2Eb mRNA was not affected by the short-term GH elevation. Our results showed that IGF-I 1Ea and 2Ea mRNA were differentially regulated by chronic low or acute high levels of GH. These results suggest that the regulation of IGF-I 1Ea and 2Ea mRNA transcription involve different postreceptor molecules and/or feedback mechanisms.


The cell-assembled extracellular matrix: A focus on the storage stability and terminal sterilization of this human "bio" material.
The Cell-Assembled extracellular Matrix (CAM) is an attractive biomaterial because it provided the backbone of vascular grafts that were successfully implanted in patients, and because it can now be assembled in "human textiles". For future clinical development, it is important to consider key manufacturing questions. In this study, the impact of various storage conditions and sterilization methods were evaluated. After 1 year of dry frozen storage, no change in mechanical nor physicochemical properties were detected. However, storage at 4 °C and room temperature resulted in some mechanical changes, especially for dry CAM, but physicochemical changes were minor. Sterilization modified CAM mechanical and physicochemical properties marginally except for hydrated gamma treatment. All sterilized CAM supported cell proliferation. CAM ribbons were implanted subcutaneously in immunodeficient rats to assess the impact of sterilization on the innate immune response. Sterilization accelerated strength loss but no significant difference could be shown at 10 months. Very mild and transient inflammatory responses were observed. Supercritical CO2 sterilization had the least effect. In conclusion, the CAM is a promising biomaterial since it is unaffected by long-term storage in conditions available in hospitals (hydrated at 4 °C), and can be sterilized terminally (scCO2) without compromising in vitro nor in vivo performance. STATEMENT OF SIGNIFICANCE: In the field of tissue engineering, the use of extracellular matrix (ECM) proteins as a scaffolding biomaterial has become very popular. Recently, many investigators have focused on ECM produced by cells in vitro to produce unprocessed biological scaffolds. As this new kind of "biomaterial" becomes more and more relevant, it is critical to consider key manufacturing questions to facilitate future transition to the clinic. This article presents an extensive evaluation of long-term storage stability and terminal sterilization effects on an extracellular matrix assembled by cells in vitro. We believe that this article will be of great interest to help tissue engineers involved in so-called scaffold-free approaches to better prepare the translation from benchtop to bedside.


The principles of augmenting the cardiac output in adults.
Augmentation of the patient's cardiac output to optimize tissue oxygenation is a primary role of intensive and cardiac care nurses. This involves three approaches: the use of intravenous colloids and occasionally crystalloids, creating a passive stretching of the myocardium to increase cardiac output, the use of inotropic agents which directly stimulate the heart and finally and less commonly the use of cardiac assist devices, notably the intra aortic balloon pump. The choice of method will be dictated by the presenting clinical data and the perceived benefits to the patient of each approach. The role of nurses as part of the health care team is to practice safe, informed care, through an understanding of both the advantages and disadvantages of each approach to the clinical scenario encountered. This paper contains exploration of each of the three principles with a case study approach, allowing the reader to consider a variety of presenting clinical data and appropriate haemodynamic manipulation.


[Orthodontic planning in treatment of single dental disharmonies of the anterior segment].
The Authors examined epidemiology and diagnosis of dental discrepancy in frontal teeth. An accurate orthodontic planning for its treatment is suggested. Bolton index and Ballard and Wylie diagram are considered illustrating their usefull in evaluating proportional dimensions in upper and lower dental arches.


Generation and analysis of the thiazide-sensitive Na+ -Cl- cotransporter (Ncc/Slc12a3) Ser707X knockin mouse as a model of Gitelman syndrome.
Gitelman syndrome (GS) is characterized by salt-losing hypotension, hypomagnesemia, hypokalemic metabolic alkalosis, and hypocalciuria. To better model human GS caused by a specific mutation in the thiazide-sensitive Na(+) -Cl(-) cotransporter (NCC) gene SLC12A3, we generated a nonsense Ncc Ser707X knockin mouse corresponding to human p.Ser710X (c.2135C>A), a recurrent mutation with severe phenotypes in Chinese GS patients. Compared with wild-type or heterozygous littermates, homozygous (Hom) knockin mice fully recapitulated the phenotype of human GS. The markedly reduced Ncc mRNA and virtually absent Ncc protein expression in kidneys of Hom mice was primarily due to nonsense-mediated mRNA decay (NMD) surveillance mechanisms. Expression of epithelial Na(+) channel (Enac), Ca(2+) channels (Trpv5 and Trpv6), and K(+) channels (Romk1 and maxi-K) were significantly increased. Late distal convoluted tubules (DCT) volume was increased and DCT cell ultrastructure appeared intact. High K(+) intake could not correct hypokalemia but caused a further increase in maxi-K but not Romk1 expression. Renal tissue from a patient with GS also showed the enhanced TRPV5 and ROMK1 expression in distal tubules. We suggest that the upregulation of TRPV5/6 and of ROMK1 and Maxi-K may contribute to hypocalciuria and hypokalemia in Ncc Ser707X knockin mice and human GS, respectively.


Evidence for GABAB-mediated mechanisms in experimental generalized absence seizures.
Experimental absence seizures are characterized by the fact that they are exacerbated by both direct and indirect GABA agonists. To date most of the studies that have examined this phenomenon have utilized GABAA agonists. We assessed the effect of a GABAB agonist, baclofen and a specific GABAB antagonist in two pharmacological models of absence seizures in rodent after using either gamma-hydroxybutyrate or pentylenetetrazole to induce the bilaterally synchronous spike wave discharges that typify absence seizures in rodent. Baclofen markedly prolonged and the GABAB antagonist attenuated or blocked the experimental absence seizures in both models. These data suggest a role for GABAB-related mechanisms in the pathogenesis of generalized absence seizures and raise the possibility that GABAB antagonists may have therapeutic potential as antiabsence drugs.


Multi-regional circuits underlying visually guided decision-making in Drosophila.
Visually guided decision-making requires integration of information from distributed brain areas, necessitating a brain-wide approach to examine its neural mechanisms. New tools in Drosophila melanogaster enable circuits spanning the brain to be charted with single cell-type resolution. Here, we highlight recent advances uncovering the computations and circuits that transform and integrate visual information across the brain to make behavioral choices. Visual information flows from the optic lobes to three primary central brain regions: a sensorimotor mapping area and two 'higher' centers for memory or spatial orientation. Rapid decision-making during predator evasion emerges from the spike timing dynamics in parallel sensorimotor cascades. Goal-directed decisions may occur through memory, navigation and valence processing in the central complex and mushroom bodies.


Non-invasive evaluation of the pathological and functional characteristics of chronic kidney disease by diffusion kurtosis imaging and intravoxel incoherent motion imaging: comparison with conventional DWI.
To explore the diagnostic performance of diffusion kurtosis imaging (DKI) and incoherent intravoxel movement (IVIM) in evaluating the clinical and pathological characteristics in chronic kidney disease (CKD) compared to conventional diffusion-weighted imaging (DWI). Forty-nine CKD patients and 24 healthy volunteers were included in this retrospective study from September 2020 to September 2021. All participants underwent MRI examinations before percutaneous renal biopsy. Coronal T2WI, axial T1WI and T2WI, and DWI (including IVIM and DKI) sequences obtained in one scan. We measured the apparent diffusion coefficient (ADC), true diffusion coefficient (Dt), pseudo-diffusion coefficient (Dp), perfusion fraction (fp), mean kurtosis (MK), and mean diffusivity (MD) values. One-way analysis of variance, correlation analysis, and receiver operating characteristic curve analysis were used in our study. Cortex and medulla ADC, MK, Dt, fp were significantly different between the healthy volunteers and CKD stages 1-2 (all p < 0.05). All diffusion parameters showed significant differences between CKD stages 1-2 and CKD stages 3-5 (all p < 0.05). Except for the uncorrelation between MDMedulla and vascular lesion score, all other diffusion parameters were low-to-moderately related to clinical and pathological indicators. fpMedulla was the best parameter to differentiate healthy volunteers from CKD stages 1-2. MKCortex was the best parameter to differentiate CKD stages 1-2 from that CKD stages 3-5. Renal cortex and medulla fp, Dt, and MK can provide more valuable information than ADC values for the evaluation of clinical and pathological characteristics of CKD patients, and thus can provide auxiliary diagnosis for fibrosis assessment and clinical management of CKD patients. IVIM and DKI can provide more diagnostic valuable information for CKD patients than conventional DWI.


Combined Arthroscopic Bankart Repair and Coracoid Process Transfer to Anterior Glenoid for Shoulder Dislocation in Rugby Players: Evaluation Based on Ability to Perform Sport-Specific Movements Effectively.
To evaluate the outcomes of a combination of an arthroscopic Bankart repair and an open Bristow procedure in relation to the subjective quality of performance in movements that are typical in rugby. Forty shoulders in 38 players who underwent surgery for traumatic anterior instability of the shoulder were reviewed. In all cases, arthroscopic Bankart repair was followed by a Bristow procedure, with preservation of the repaired capsular ligaments, during the same operation. The mean age at the time of surgery was 21 years. Patients were asked to describe common rugby maneuvers (tackle, hand-off, jackal, and saving) preoperatively and postoperatively as "no problem," "insufficient," or "impossible." There were no recurrent dislocations at a mean follow-up of 30.5 months. The mean Rowe score improved significantly from 65.0 (range, 55 to 75) to 97.5 (range, 95 to 100) (P < .001) after surgery. Preoperatively, regarding the tackling motion, none of the patients reported having no problem, whereas the ability was described as insufficient for 23 shoulders and impossible for 17 shoulders. Postoperatively, no problem with tackling was reported for 36 shoulders, whereas insufficiency was reported for 4. The results for the hand-off, jackal, and saving maneuvers were similar (P < .001). No patient rated any of the motions as impossible postoperatively. This combined surgical procedure clearly is effective in preventing recurrent dislocation in rugby players; however, some players complained of insufficiency in the quality of their play when they were tackling or performing other rugby-specific movements. Level IV, case series.


Generation of virus specific cytotoxic T cells in vitro. III. Spleen cells stimulated by viral antigens generate alloreactive cytotoxic T cells.
Cytotoxic T lymphocytes (CTL) from DBA/2 strain mice primed with Sendai virus (SV) in vivo were activated by secondary stimulation of spleen cells with viral antigens in vitro and analyzed for their target antigen specificity. These effector cells lysed syngeneic Sendai virus infected target cells, marginally a variety of non-infected targets and had a strong cytotoxic effect on H-2b targets. Studies on the antigenic requirements revealed that all SV preparations which generated specific CTL also induced the alloreactive populations. Similar results were found in the response to Newcastle disease virus (NDV) and some influenza A viruses; all these viruses were mitogenic for lymphocytes. Experiments on the cellular requirements indicated that virus specific and alloreactive cells can be separated by their requirements for help and for restimulation. By competition experiments both activities could be attributed to clearly separable T cell subpopulations. The induction mechanism of alloreactive T cells by viral antigens is discussed.


An osteogenesis/angiogenesis-stimulation artificial ligament for anterior cruciate ligament reconstruction.
To solve the poor healing of polyethylene terephthalate (PET) artificial ligament in bone tunnel, copper-containing bioactive glass (Cu-BG) nanocoatings on PET artificial ligaments were successfully prepared by pulsed laser deposition (PLD). It was hypothesized that Cu-BG coated PET (Cu-BG/PET) grafts could enhance the in vitro osteogenic and angiogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and in vivo graft-bone healing after anterior cruciate ligament (ACL) reconstruction in a goat model. Scanning electron microscope and EDS mapping analysis revealed that the prepared nanocoatings had uniform element distribution (Cu, Ca, Si and P) and nanostructure. The surface hydrophilicity of PET grafts was significantly improved after depositing Cu-BG nanocoatings. The in vitro study displayed that the Cu-BG/PET grafts supported the attachment and proliferation of rBMSCs, and significantly promoted the expression of HIF-1α gene, which up-regulated the osteogenesis-related genes (S100A10, BMP2, OCN) and angiogenesis-related genes (VEGF) in comparison with PET or BG coated PET (BG/PET) grafts which do not contain Cu element. Meanwhile, Cu-BG/PET grafts promoted the bone regeneration at the graft-host bone interface and decreased graft-bone interface width, thus enhancing the bonding strength as well as angiogenesis (as indicated by CD31 expression) in the goat model as compared with BG/PET and pure PET grafts. The study demonstrates that the Cu-containing biomaterials significantly promote osteogenesis and angiogenesis in the repair of bone defects of large animals and thus offering a promising method for ACL reconstruction by using Cu-containing nanobioglass modified PET grafts. It remains a significant challenge to develop an artificial graft with distinct osteogenetic/angiogenetic activity to enhance graft-bone healing for ligament reconstruction. To solve these problems, copper-containing bioactive glass (Cu-BG) nanocoatings on PET artificial ligaments were successfully prepared by pulsed laser deposition (PLD). It was found that the prepared Cu-BG/PET grafts significantly stimulated the proliferation and osteogenic/angiogenic differentiation of bone marrow stromal cells (BMSCs) through activating HIF-1α/S100A10/Ca2+ signal pathway. The most important is that the in vivo bone-forming ability of Cu-containing biomaterials was, for the first time, elucidated in a large animal model, revealing the enhanced capacity of osteogenesis and angiogenesis with incorporation of bioactive Cu element. It is suggested that the copper-containing biomaterials significantly promote osteogenesis and angiogenesis in large animal defects and thus offering a promising method for ACL reconstruction by using Cu-containing nanobioglass modification of PET grafts, paving the way to apply Cu-containing biomaterials for tissue engineering and regenerative medicine.


Inflammaging: The ground for sarcopenia?
Sarcopenia is a progressive skeletal muscle disease that occurs most commonly in the elderly population, contributing to increased costs and hospitalization. Exercise and nutritional therapy have been proven to be effective for sarcopenia, and some drugs can also alleviate declines in muscle mass and function due to sarcopenia. However, there is no specific pharmacological treatment for sarcopenia at present. This review will mainly discuss the relationship between inflammaging and sarcopenia. The increased secretion of proinflammatory cytokines with aging may be because of cellular senescence, immunosenescence, alterations in adipose tissue, damage-associated molecular patterns (DAMPs), and gut microbes due to aging. These sources of inflammaging can impact the sarcopenia process through direct or indirect pathways. Conversely, sarcopenia can also aggravate the process of inflammaging, creating a vicious cycle. Targeting sources of inflammaging can influence muscle function, which could be considered a therapeutic target for sarcopenia. Moreover, not only proinflammatory cytokines but also anti-inflammatory cytokines can influence muscle and inflammation and participate in the progression of sarcopenia. This review focuses on the effects of TNF-α, IL-6, and IL-10, which can be detected in plasma. Therefore, clearing chronic inflammation by targeting proinflammatory cytokines (TNF-α, IL-1, IL-6) and the inflammatory pathway (JAK/STAT, autophagy, NF-κB) may be effective in treating sarcopenia.


Dapsone-induced agranulocytosis-possible involvement of low-activity N-acetyltransferase 2.
Dapsone-induced agranulocytosis is a rare but potentially fatal adverse drug reaction (ADR). A 45-year-old male Caucasian patient developed agranulocytosis caused by dapsone (diamino-diphenyl sulfone), which he was prescribed for leukocytoclastic vasculitis. Patient's treatment consisted of termination of dapsone, antibiotic therapy, and granulocyte colony-stimulating factor leading to prompt improvement of symptoms and normalization of laboratory blood values. Diagnostic evaluation revealed methemoglobinemia and excluded glucose-6-phosphate dehydrogenase deficiency. Pharmacogenetics testing showed that he was a carrier of NAT2 *5/*6 genotype, predisposing to low activity of the N-acetyltransferase 2 enzyme. This was the first and only ADR to dapsone reported in Croatia. In total, there have been 73 ADR to dapsone recorded worldwide, including only four cases of agranulocytosis.


Aspects of DNA repair and nucleotide pool imbalance.
Evidence that optimum repair depends on adequate pools of deoxynucleotide triphosphates (dNTPs) comes from the study of pyrimidine auxotrophs of Ustilago maydis. These strains are sensitive to UV light and X-rays, and for pyr1-1 it has been shown that the intracellular concentration of dTTP is reduced about 7-fold. Evidence has been published that DNA repair synthesis may require higher concentrations of dNTPs, than chromosome replication. The survival curve of pyr1-1 after UV-treatment, and split dose experiments with wild-type cells, provide evidence for an inducible repair mechanism, which probably depends on genetic recombination. Although inducible repair saves cellular resources, it has the disadvantage of becoming ineffective at doses which are high enough to inactivate the repressed structural gene(s) for repair enzymes. To ensure survival it is vital for organisms to preserve the integrity of their DNA, and this is accomplished both by accurate replication and by repair. It is clear that a wide variety of repair mechanisms have evolved to remove lesions which arise either spontaneously (such as the deamination of cytosine to uracil) or as a result of damage from external agents. Nevertheless, it would be incorrect to assume that all species require all possible pathways of repair. It is now well established that the accuracy of DNA and protein synthesis depends on proof-reading or editing mechanisms (for a review, see Ref. 5). These consume energy and may slow down the rate of synthesis, therefore organisms must invest metabolic resources to achieve any given level of accuracy. Optimum accuracy levels will evolve from the balance between error avoidance in macromolecular synthesis and physiological efficiency in growth and propagation [11, 12, 22].(ABSTRACT TRUNCATED AT 250 WORDS)


Identification of precursor-product relationships in kinetic studies involving radiolabeled tracer molecules.
In radiotracer studies, the estimation of turnover time usually depends on the assumption of steady-state compartmental precursor-product (SCP) behaviour in the pools being studied. Deviation from SCP behaviour is currently measured from the extent of hysteresis, R, in an 'area plot': a plot of the time-integrated difference between precursor and product specific activities (spec. act.) against product spec. act. We propose two approaches to evaluating the statistical significance of apparent deviations from SCP behaviour in experimental data. The first constructs the sampling distribution of R. The second compares the variance in replicate data with the value of the objective function minimized in the least squares estimation of product turnover time. We show that this test closely approximates a variance ratio (F) test. Applied to [methyl-3H]choline and [14C]acetate tracer data from lung phospholipid pools in eupneic and hyperpneic rats, the analysis rejects SCP relationships between lamellar bodies and two subfractions of alveolar lavage material.


Determination of chlorpheniramine maleate in tablets by second-derivative absorption spectrophotometry.
A rapid method for the determination of chlorpheniramine maleate in tablets using second-derivative absorption spectrophotometry is described. The method has the advantage of requiring simple sample preparation and having accuracy comparable to the official acid-alkaline solvent extraction procedure. Results of recovery tests were close to 100%.


Correlations between DWI, IVIM, and HIF-1α expression based on MRI and pathology in a murine model of rhabdomyosarcoma.
To investigate the correlation between DWI, intravoxel incoherent motion (IVIM), and hypoxia-inducible factor 1-alpha (HIF-1α) expression in a nude mouse model of rhabdomyosarcoma based on imaging and pathological comparisons. Human rhabdomyosarcoma-derived (RD) cells were inoculated into the right thigh muscle of 20 BALB/c female nude mice. Mice were imaged using 3.0 Tesla MRI system. T1 -weighted imaging, T2 -weighted imaging, DWI, and IVIM images were obtained. ADW4.7 (GE Healthcare, ChicagoAQ34, IL, USA) was used for image processing of ADC, Dslow , Dfast , and f values. All parameter values were independently analyzed by 2 observers. Immunohistochemistry of HIF-1α was performed. We used a specific image-pathology comparison method to ensure correct overlap between the image plane and the pathological section. Mann-Whitney U test or independent sample t test, Pearson or Spearman correlation test, the intragroup correlation coefficient, Kolmogorov-Smirnov test, and receiver operating characteristic curve were used. The correlation between DWI and intravoxel incoherent motion parameter values and HIF-1α expression was determined. There were 10 mice in the low-expression group and 7 in the high-expression group. The ADC and Dslow values were negatively correlated with HIF-1α with correlation coefficients of -0.491 and - 0.702 (P = 0.045 and 0.002). The f value positively correlated with HIF-1α expression (r = 0.485, P = 0.048). ADC, Dslow , and f were significantly different between the high-HIF-1α expression tumors and the low-HIF-1α expression tumors. ADC showed the best predictive performance among all parameters (area under the curve = 0.652, sensitivity = 83.3%, specificity = 63.6%). The parameter values of DWI and intravoxel incoherent motion can be used to evaluate the expression of HIF-1α in rhabdomyosarcoma. ADC, Dslow , and f value showed correlation with the expression of HIF-1α.


Chronic cyanosis due to persistent left superior vena cava draining into the left atrium in the absence of a coronary sinus.
We report a rare case of a 5-year-old child who presented with chronic hypoxemia and a normal cardiac examination, and was found to have a persistent left superior vena cava draining directly into the left atrium. The coronary sinus was absent. This case introduces a contradiction to the generally accepted concept that this anomalous connection can only occur in the presence of a partly or completely unroofed coronary sinus. High index of suspicion is required to include this pathology in the differential diagnosis for a patient with persistent cyanosis with normal cardiac examination.


Steady-state pharmacokinetics of carvedilol and its enantiomers in patients with congestive heart failure.
Carvedilol is a relatively new drug with beta- and alpha 1-receptor blocking activity and antioxidant effects recently approved for the treatment of congestive heart failure (CHF). An ascending, multiple-dose study was completed in 20 male patients with stable New York Heart Association (NYHA) Class III or IV CHF. The pharmacokinetics of carvedilol, S(-)-carvedilol, R(+)-carvedilol, and the active metabolites of carvedilol was assessed at steady state after twice-daily oral administration of carvedilol for 7 days at 6.25, 12.5, 25, and 50 mg doses. Carvedilol exhibited stereoselective pharmacokinetics in CHF patients with dose-proportional increases in steady-state plasma concentrations of carvedilol and its enantiomers. Mean AUC and Cmax values for carvedilol were up to twofold higher in patients with Class IV CHF as compared to those with Class III CHF. Steady-state plasma concentrations of the active metabolites also increased in a dose-proportional manner and were typically 10% or less of that observed for carvedilol. In general, carvedilol was adequately tolerated by adult male CHF patients at the dose levels (6.25-50 mg) evaluated in this study as adverse events were consistent with those frequently observed in patients with CHF.


Enhanced photocatalytic degradation of toxic contaminants using Dy2O3-SiO2 ceramic nanostructured materials fabricated by a new, simple and rapid sonochemical approach.
The present study is on the fabrication of new photocatalytic nanocomposites (Dy2O3-SiO2) employing a basic agent, tetraethylenepentamine (Tetrene), through a simple, efficient and, quick sonochemical approach. The features of the fabricated photocatalytic nanocomposite were examined employing a variety of microscopic and spectroscopic methods such as XRD, EDS, TEM, FTIR, DRS, and FESEM. The outcomes of morphological studies demonstrated that by proper tuning of sonication time and ultrasonic power (10 min and 400 W), a porous nanocomposite composed of sphere-shaped nanoparticles with a particle size in the range of 20 to 60 nm could be fabricated. The energy gap for the binary Dy2O3-SiO2 nanophotocatalyst was determined to be 3.41 eV, making these nanocomposite favorable for removing contaminants. The photocatalytic performance of the optimal nanocomposite sample was tested for photodecomposition of several contaminants including erythrosine, thymol blue, eriochrome black T, Acid Red 14, methyl orange, malachite green, and Rhodamine B. The binary Dy2O3-SiO2 nanophotocatalyst exhibited superior efficiency toward the decomposition of the studied contaminants. It was able to degrade the erythrosine pollutant more effectively (92.9%). Optimization studies for the photocatalytic decomposition of each contaminant demonstrated that the best performance could be achieved at a specific amount of contaminant and nanocatalyst. Trapping experiments illustrated that hydroxyl radicals were more effectively involved in the decomposition of contaminant molecules by Dy2O3-SiO2 nanophotocatalyst.


Prediction of HIV-1 protease inhibitor resistance by Molecular Modeling Protocols (MMPs) using GenMol software.
This paper investigates the contribution of Molecular Modeling to (i) predict and (ii) understand more fundamentally HIV drug resistance. Based on a new automated GenMol module, these goals are approached by Molecular Modeling Protocols (MMPs), respectively, (i) the Molecular Modeling Phenotype Protocol (MMPP) and (ii) the Molecular Modeling Phenotype-Genotype Protocol (MMGPP). Section 2 recalls clinical practice with a reference case study and Section 3 presents atomistic simulation tools. Section 4 is the heart of the paper. In Section 4.1, MMPP drug resistance prediction is based on correlations between fold resistances versus binding energies on 2959 HIV-1 complexes with 6 protease inhibitors. Based on a drug sensitivity twofold criterion, modeling prediction is able to replace long and costly phenotype tests. In Section 4.2, MMGPP enlightens drug resistance by investigating steric and energetic residues/inhibitor interaction. Section 5 gives a synthesis on modeling contribution to drug resistance prediction. In conclusion, the most promising trend consists of MMP automats that are able to suggest a real time diagnosis taking into account the history of each patient, to enrich databases and to develop therapy strategy and new drugs.


The Women's Health Initiative Memory Study (WHIMS): a trial of the effect of estrogen therapy in preventing and slowing the progression of dementia.
Evidence from animal, human cross-sectional, case-control, and prospective studies indicate that hormone replacement therapy (HRT) is a promising treatment to delay the onset of symptoms of dementia. The Women's Health Initiative Memory Study (WHIMS) is the first double-masked, randomized, placebo-controlled, long-term clinical trial designed to test the hypothesis that HRT reduces the incidence of all-cause dementia in women aged 65 and older. WHIMS, an ancillary study to the Women's Health Initiative (WHI) funded by the National Institutes of Health, will recruit a subgroup of women aged 65 and older from among those enrolling in the HRT trial of the WHI. The WHI clinical centers and 10 affiliated satellites plan to enroll approximately 8300 women into WHIMS over a 2-year period. Participants will be followed annually for 6 years, receiving cognitive assessments via the Modified Mini-Mental State (3MS) Examination. Women who screen positively for cognitive impairment on the basis of an educational and age-adjusted 3MS cutpoint proceed to more extensive neuropsychological testing and neurologic evaluation. Each woman suspected to have dementia then undergoes a series of laboratory tests that confirm the clinical diagnosis and classify the type of dementia. WHIMS is designed to provide more than 80% statistical power to detect a 40% reduction in the rate of all-cause dementia, an effect that could have profound public health implications for older women's health and functioning.


Gemcitabine, vinorelbine and prednisone for refractory or relapsed aggressive lymphoma, results of a phase II single center study.
The optimum therapy for patients with relapsed or refractory aggressive non-Hodgkin's lymphomas (NHL) not qualifying for platinum-based and/or high-dose chemotherapy is not known. We conducted a prospective phase II study evaluating a regimen consisting of gemcitabine (1 g/m2, days 1 and 8), vinorelbine (30 mg/m2, days 1 and 8) and prednisone (100 mg/day, days 1-8) (GVP) given every 21 days. Fifteen patients with a median age of 68 years and a median of three previous therapies were enrolled. Diagnoses included B lymphoblastic (n=1), diffuse large B cell (n=10), anaplastic large T cell (n=2) and peripheral T-cell NHL (n=2). The median international prognostic index score was 3 (six patients with a score of 4 or 5). Five patients achieved a complete remission and three patients a partial remission. The median overall survival was 13.8 months, and the median time to next treatment was 4.4 months. Haematological toxicities of World Health Organisation grades 3/4 were leucopenia in 58%, thrombocytopenia in 33% and anaemia in 17% of all courses. Three patients had grade 3 infections. There was no treatment-related mortality. GVP shows substantial activity in poor prognosis relapsed or refractory aggressive lymphomas and is generally well tolerated, but haematological toxicity is dose limiting.


Search for human tumour viruses by transfection: uptake of melanoma and Epstein-Barr virus DNA by human cells.
In a model system, consistent transfection of chick embryo fibroblasts (CEF) by DNA from the XC cell line occurred, with recovery of infectious Rous sarcoma virus. The techniques were then applied in attempts to recover possible human tumour viruses. Even with various modifications of the XC technique, DNA from three human malignant melanoma cell lines failed to infect adult or foetal human fibroblasts, although melanoma DNA was taken up into nuclei of target cells. XC DNA did not transfect human foetal fibroblasts and melanoma DNA was ineffective in CEF. DNA from the Raji (Epstein-Barr virus non-producer) and QIMR-WIL (producer) lymphoblastoid cell lines did not transfect human cord blood lymphocytes or amnion cells. These broadly applicable techniques therefore failed to recover EB virus, the putative melanoma retrovirus, or other potential tumour virus.


The motion aftereffect reloaded.
The motion aftereffect is a robust illusion of visual motion resulting from exposure to a moving pattern. There is a widely accepted explanation of it in terms of changes in the response of cortical direction-selective neurons. Research has distinguished several variants of the effect. Converging recent evidence from different experimental techniques (psychophysics, single-unit recording, brain imaging, transcranial magnetic stimulation, visual evoked potentials and magnetoencephalography) reveals that adaptation is not confined to one or even two cortical areas, but occurs at multiple levels of processing involved in visual motion analysis. A tentative motion-processing framework is described, based on motion aftereffect research. Recent ideas on the function of adaptation see it as a form of gain control that maximises the efficiency of information transmission at multiple levels of the visual pathway.


Animal model for tendinopathy.
Tendinopathy is a common motor system disease that leads to pain and reduced function. Despite its prevalence, our mechanistic understanding is incomplete, leading to limited efficacy of treatment options. Animal models contribute significantly to our understanding of tendinopathy and some therapeutic options. However, the inadequacies of animal models are also evident, largely due to differences in anatomical structure and the complexity of human tendinopathy. Different animal models reproduce different aspects of human tendinopathy and are therefore suitable for different scenarios. This review aims to summarize the existing animal models of tendinopathy and to determine the situations in which each model is appropriate for use, including exploring disease mechanisms and evaluating therapeutic effects. We reviewed relevant literature in the PubMed database from January 2000 to December 2022 using the specific terms ((tendinopathy) OR (tendinitis)) AND (model) AND ((mice) OR (rat) OR (rabbit) OR (lapin) OR (dog) OR (canine) OR (sheep) OR (goat) OR (horse) OR (equine) OR (pig) OR (swine) OR (primate)). This review summarized different methods for establishing animal models of tendinopathy and classified them according to the pathogenesis they simulate. We then discussed the advantages and disadvantages of each model, and based on this, identified the situations in which each model was suitable for application. For studies that aim to study the pathophysiology of tendinopathy, naturally occurring models, treadmill models, subacromial impingement models and metabolic models are ideal. They are closest to the natural process of tendinopathy in humans. For studies that aim to evaluate the efficacy of possible treatments, the selection should be made according to the pathogenesis simulated by the modeling method. Existing tendinopathy models can be classified into six types according to the pathogenesis they simulate: extracellular matrix synthesis-decomposition imbalance, inflammation, oxidative stress, metabolic disorder, traumatism and mechanical load. The critical factor affecting the translational value of research results is whether the selected model is matched with the research purpose. There is no single optimal model for inducing tendinopathy, and researchers must select the model that is most appropriate for the study they are conducting. The critical factor affecting the translational value of research results is whether the animal model used is compatible with the research purpose. This paper provides a rationale and practical guide for the establishment and selection of animal models of tendinopathy, which is helpful to improve the clinical transformation ability of existing models and develop new models.


Cardiac arrhythmias in the differential diagnosis of epilepsy.
Symptomatic attacks or seizures associated with cardiac arrhythmias may cause difficulty in differential diagnosis. Two patients are reported in whom disturbances of cardiac conduction induced attacks which clinically resembled attacks of psychogenic and epileptic origin and were abolished after implantation of a demand-type pacemaker. A third patient is described who had epileptic seizures resulting in cardiac arrhythmias. In the differential diagnosis of these cases, simultaneous ambulatory EEG and ECG recording was essential.


On the Relationship Between Sun Exposure and All-Cause Mortality.
Increasing sun exposure is related to lower prevalence of death in cardiovascular disease (CVD), type 2 diabetes, and other noncancer non-CVD. In this chapter we aim to make a short update on the knowledge regarding sun exposure and all-cause mortality. Data support the hypothesis that low sun exposure habits are a major risk factor for all-cause mortality. Low sun exposure is related to an increased risk of death due to CVD and noncancer/non-CVD, and a minor reduction in risk of cancer. Active sun exposure habits have a dual effect; it increases the incidence of skin cancer, but also improves the prognosis in terms of all-cause mortality. In a low solar intensity region, we should carefully assess both risk and benefits of sun exposure in order to obtain balanced recommendations.


Anti-Candida albicans activity of Pichia anomala as determined by a growth rate reduction assay.
Killer toxin activity of Pichia anomala WC65 appeared fungicidal for P. bimundalis WC38 and fungistatic for Candida albicans RC1. Inhibitory activity against sensitive C. albicans showed a linear relationship between toxin concentrations and the inverse of the reduced growth rates. The plot of toxin concentrations against growth rates was hyperbolic, as is characteristic of saturation kinetics. Sensitivity of C. albicans to the toxin decreased with increased cell age. The measurement of growth rate reduction provided a simple and accurate method for quantitation of toxin.


Novel biphasic traffic of endocytosed EGF to recycling and degradative compartments in lacrimal gland acinar cells.
The purpose of this study was to delineate the traffic patterns of EGF and EGF receptors (EGFR) in primary cultured acinar epithelial cells from rabbit lacrimal glands. Uptake of [(125)I]-EGF exhibited saturable and non-saturable, temperature-dependent components, suggesting both receptor-mediated and fluid phase endocytosis. Accumulation of [(125)I] was time-dependent over a 120-min period, but the content of intact [(125)I]-EGF decreased after reaching a maximum at 20 min. Analytical fractionation by sorbitol density gradient centrifugation and phase partitioning indicated that within 20 min at 37 degrees C [(125)I] reached an early endosome, basal-lateral recycling endosome, pre-lysosome, and lysosome. Small components of the label also appeared to reach the Golgi complex and trans-Golgi network. Intact [(125)I]-EGF initially accumulated in the recycling endosome; the content in the recycling endosome subsequently decreased, and by 120 min increased amounts of [(125)I]-labeled degradation products appeared in the pre-lysosomes and lysosomes. Confocal microscopy imaging of FITC-EGF and LysoTrackerRed revealed FITC enriched in a dispersed system of non-acidic compartments at 20 min and in acidic compartments at 120 min. Both confocal immunofluorescence microscopy and analytical fractionation indicated that the intracellular EGFR pool was much larger than the plasma membrane-expressed pool at all times. Cells loaded with [(125)I]-EGF released a mixture of intact EGF and [(125)I]-labeled degradation products. The observations indicate that in lacrimal acinar cells, EGFR and EGF-EGFR complexes continually traffic between the plasma membranes and a system of endomembrane compartments; EGF-stimulation generates time-dependent signals that initially decrease, then increase, EGF-EGFR traffic to degradative compartments.


Breast cancer screening interventions for Arabic women: a literature review.
Similar to other Middle Eastern countries, breast cancer is the most common cancer among women in Qatar with increasing incidence and mortality rates. High mortality rates of breast cancer in the Middle Eastern countries are primarily due to delayed diagnosis of the disease. Thus screening and early detection of breast cancer are important in reducing cancer morbidity and mortality. With the aim of updating knowledge on existing interventions and developing effective intervention programs to promote breast cancer screening in Arabic populations in Qatar, this review addresses the question: What interventions are effective in increasing breast cancer knowledge and breast cancer screening rates in Arabic populations in Arabic countries and North America? Systematic literature review was performed to answer the proposed question. As the result of the search, six research studies were identified and appraised. From the findings, we infer several insights: (a) a language-appropriate and culturally sensitive educational program is the most important component of a successful intervention regardless of the study setting, (b) multi-level interventions that target both women, men, health care professionals, and/or larger health care system are more likely to be successful than single educational interventions or public awareness campaigns, and (c) more vigorous, personal and cognitive interventions that address psychosocial factors are likely to be more effective than less personal and informative interventions. This review has important implications for health care providers, intervention planners, and researchers.


Effect of N-acetyltransferase 2 genetic polymorphism on 4,4'-methylenebis(2-chloroaniline)-induced genotoxicity and oxidative stress.
4,4'-Methylenebis(2-chloroaniline) or MOCA is an aromatic amine used primarily in polyurethane and rubber industry. MOCA has been linked to hepatomas in animal studies while limited epidemiologic studies reported the association of exposure to MOCA and urinary bladder and breast cancer. We investigated MOCA-induced genotoxicity and oxidative stress in DNA repair-deficient Chinese hamster ovary (CHO) cells stably transfected with human metabolizing enzymes CYP1A2 and N-acetyltransferase 2 (NAT2) variants as well as in rapid, intermediate, and slow NAT2 acetylator cryopreserved human hepatocytes. N-acetylation of MOCA was highest in UV5/1A2/NAT2*4 followed by UV5/1A2/NAT2*7B and UV5/1A2/NAT2*5B CHO cells. Human hepatocytes showed a NAT2 genotype-dependent response with highest N-acetylation in rapid acetylators followed by intermediate and slow acetylators. MOCA induced higher levels of mutagenesis and DNA damage in UV5/1A2/NAT2*7B compared to UV5/1A2/NAT2*4 and UV5/1A2/NAT2*5B cells (p < 0.0001). MOCA also induced higher levels of oxidative stress in UV5/1A2/NAT2*7B cells. MOCA caused concentration-dependent increase in DNA damage in cryopreserved human hepatocytes (linear trend p < 0.001) which was NAT2 genotype dependent i.e., highest in rapid acetylators, lower in intermediate acetylators, and lowest in slow acetylators (p < 0.0001). Our findings show that N-acetylation and genotoxicity of MOCA is NAT2 genotype dependent and suggest that individuals possessing NAT2*7B are at higher risk to MOCA-induced mutagenicity. DNA damage, and oxidative stress. They confirm significant differences in genotoxicity between the NAT2*5B and NAT2*7B alleles, both of which are associated with slow acetylator phenotype.


Evidence for the presence of numerous protein components in immature bovine dental enamel.
The proteins and peptides of immature enamel were extracted from freshly slaughtered bovine embryos in solutions containing protease inhibitors. No detectable differences were noted in the number of components, their overall amino acid composition, or molecular weights from the proteins and peptides extracted 12-16 h postmortem in solutions which contained no protease inhibitors. These data indicate that the large number of components found in developing bovine enamel is not due to proteolysis occurring during their isolation. Significant amounts of protein components having molecular weights greater than approximately 15,000 were not detected. Therefore, if the ameloblasts initially synthesize only a few high molecular weight protein species, the present data imply that in vivo degradation of the high molecular weight enamel proteins occurs very rapidly after their synthesis and precedes the massive loss of protein which accompanies the final stages of enamel mineralization and maturation.


Blunt Dissection: A Solution to Prevent Bile Duct Injury in Laparoscopic Cholecystectomy.
Laparoscopic cholecystectomy (LC) has been a standard operation and replaced the open cholecystectomy (OC) rapidly because the technique resulted in less pain, smaller incision, and faster recovery. This study was to evaluate the value of blunt dissection in preventing bile duct injury (BDI) in laparoscopic cholecystectomy (LC). From 2003 to 2015, LC was performed on 21,497 patients, 7470 males and 14,027 females, age 50.3 years (14-84 years). The Calot's triangle was bluntly dissected and each duct in Calot's triangle was identified before transecting the cystic duct. Two hundred and thirty-nine patients (1.1%) were converted to open procedures. The postoperative hospital stay was 2.1 (0-158) days, and cases (46%) had hospitalization days of 1 day or less, and 92.8% had hospitalization days of 3 days or less; BDI was occurred in 20 cases (0.09%) including 6 cases of common BDI, 2 cases of common hepatic duct injury, 1 case of right hepatic duct injury, 1 case of accessory right hepatic duct, 1 case of aberrant BDI 1 case of biliary stricture, 1 case of biliary duct perforation, 3 cases of hemobilia, and 4 cases of bile leakage. Exposing Calot's triangle by blunt dissection in laparoscopic cholecystectomy could prevent intraoperative BDI.


Oral and dental manifestations of celiac disease in children: a case-control study.
Celiac disease (CD) is an immune-mediated enteropathy. CD may also involve complications with the oral cavity, which can result in various dental and oral pathologies. There are currently a limited number of studies on the oral manifestation of CD. This study aims to compare the oral manifestations of children with CD against healthy controls in Saudi Arabia. This study includes 208 children aged 6-14 years, distributed equally into CD patients and healthy controls. A parent completed and validated the interview questionnaire, which included the child's personal information and medical history. A dental examination was undertaken to measure possible recurrent aphthous stomatitis (RAS), dental enamel defects (DEDs), dental caries experience, and dental malocclusion. Data were analyzed using descriptive statistics and bivariate and multivariate analysis. Two hundred and eight participants were included (104 CD patients and 104 controls). The mean age for CD patients was 10.67 ± 2.39 years and 10.69 ± 2.36 for the healthy controls. CD children had more RAS than controls (42.3% vs. 15.4%, P < 0.001) (OR = 4.03, 95% CI = 2.09-7.81) and more DEDs than healthy controls (70.2% vs. 34.6%, P < 0.001) (OR = 4.45, 95% CI = 2.48-7.97). No significant difference was found in the frequency of malocclusion between cases and controls. Saudi Arabian children with CD had a greater number of clinical findings of RAS and DEDs than healthy controls. Pediatric dentists should consider the possibility of CD in child patients presenting with RAS or DEDs.


Regulation of SGLT expression and localization through Epac/PKA-dependent caveolin-1 and F-actin activation in renal proximal tubule cells.
This study demonstrated that exchange proteins directly activated by cAMP (Epac) and protein kinase A (PKA) by 8-bromo (8-Br)-adenosine 3',5'-cyclic monophosphate (cAMP) stimulated [(14)C]-α-methyl-D-glucopyranoside (α-MG) uptake through increased sodium-glucose cotransporters (SGLTs) expression and translocation to lipid rafts in renal proximal tubule cells (PTCs). In PTCs, SGLTs were colocalized with lipid raft caveolin-1 (cav-1), disrupted by methyl-β-cyclodextrin (MβCD). Selective activators of Epac or PKA, 8-Br-cAMP, and forskolin stimulated expressions of SGLTs and α-MG uptake in PTCs. In addition, 8-Br-cAMP-induced PKA and Epac activation increased phosphorylation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NF-κB), which were involved in expressions of SGLTs. Furthermore, 8-Br-cAMP stimulated SGLTs translocation to lipid rafts via filamentous actin (F-actin) organization, which was blocked by cytochalasin D. In addition, cav-1 and SGLTs stimulated by 8-Br-cAMP were detected in lipid rafts, which were blocked by cytochalasin D. Furthermore, 8-Br-cAMP-induced SGLTs translocation and α-MG uptake were attenuated by inhibition of cav-1 activation with cav-1 small interfering RNA (siRNA) and inhibition of F-actin organization with TRIO and F-actin binding protein (TRIOBP). In conclusion, 8-Br-cAMP stimulated α-MG uptake via Epac and PKA-dependent SGLTs expression and trafficking through cav-1 and F-actin in PTCs.


3' adenylation determines mRNA abundance and monitors completion of RNA editing in T. brucei mitochondria.
Expression of the mitochondrial genome in protozoan parasite Trypanosoma brucei is controlled post-transcriptionally and requires extensive U-insertion/deletion mRNA editing. In mitochondrial extracts, 3' adenylation reportedly influences degradation kinetics of synthetic edited and pre-edited mRNAs. We have identified and characterized a mitochondrial poly(A) polymerase, termed KPAP1, and determined major polypeptides in the polyadenylation complex. Inhibition of KPAP1 expression abrogates short and long A-tails typically found in mitochondrial mRNAs, and decreases the abundance of never-edited and edited transcripts. Pre-edited mRNAs are not destabilized by the lack of 3' adenylation, whereas short A-tails are required and sufficient to maintain the steady-state levels of partially edited, fully edited, and never-edited mRNAs. The editing directed by a single guide RNA is sufficient to impose a requirement for the short A-tail in edited molecules. Upon completion of the editing process, the short A-tails are extended as (A/U) heteropolymers into structures previously thought to be long poly(A) tails. These data provide the first direct evidence of functional interactions between 3' processing and editing of mitochondrial mRNAs in trypanosomes.


Insights into heat-induced molecular-level interactions between wheat and common buckwheat proteins.
This study investigated the heat-induced interactions between wheat and buckwheat proteins by heating wheat proteins, buckwheat albumin, globulin, and mixtures of wheat flour with buckwheat albumin/globulin at 50, 65, 80, 95, and 100 °C. The results showed that the cross-linking reactions of wheat glutenin with buckwheat albumin and globulin initiated at 80 and 95 °C, respectively. Buckwheat albumin decreased the extractability of α-gliadin by 35 % at 95 °C and 5.9 % at 100 °C. The linkage of buckwheat globulin to wheat glutelin prevented part of the wheat gliadin from linking to glutelin, resulting in the extractability of α- and γ-gliadin increased by 8.6 % and 11 % at 95 °C, respectively. The chemical forces results indicated that interactions between wheat and buckwheat proteins were primarily driven by disulfide bonds and hydrophobic interactions. This study provides a theoretical basis for better regulating the wheat-buckwheat protein network to improve the quality of buckwheat-enriched products.


Deuterium magnetic resonance of selectively deuterated cholesteryl esters in dipalmitoyl phosphatidylcholine dispersions.
Dispersions (50 wt% water) containing 95 mol% dipalmitoyl phosphatidylcholine/5 mol% deuterated cholesteryl palmitate (or stearate) were studied using 2H-NMR. Incorporation of ester into the phospholipid bilayer was found to be 0.5 mol% at 50 degrees C. From the profile of 2H quadrupolar splitting vs. chain position, support for an average conformation resembling a 'horseshoe' within the bilayer is obtained. Quadrupolar relaxation times T2e of approx. 250 microseconds and approx. 850 microseconds are measured for cholesteryl palmitate-2,2-d2 and cholesteryl palmitate-16,16,16-d3, respectively, which are less than one-half those obtained for the corresponding positions in dipalmitoyl-d62 phosphatidylcholine. This is ascribed to a slower rate of motion of the ester chain and/or an extra, slow motion of the molecule.


JNCC guidelines for minimising the risk of injury and disturbance to marine mammals from seismic surveys: We can do better.
The U.K.'s Joint Nature Conservation Committee 1998 guidelines for minimising acoustic impacts from seismic surveys on marine mammals were the first of their kind. Covering both planning and operations, they included various measures for reducing the potential for damaging hearing - an appropriate focus at the time. Since introduction, the guidelines have been criticised for, among other things: the arbitrarily-sized safety zones; the lack of shut-down provisions; the use of mitigation measures that introduce more noise into the environment (e.g., soft-starts); inadequate observer training; and the lack of standardised data collection protocols. Despite the concerns, the guidelines have remained largely unchanged. Moreover, increasing scientific recognition of the scope and magnitude of non-injurious impacts of sound on marine life has become much more widespread since the last revisions in 2010. Accordingly, here we present feasible and realistic recommendations for such improvements, in light of the current state of knowledge.


Clinical relevance of 1p and 19q deletion for patients with WHO grade 2 and 3 gliomas.
To assess the frequency of chromosomes 1p and 19q deletions in gliomas and to correlate 1p deletion with prognosis in patients with grade 2 and grade 3 gliomas independently of histologic subtype. We retrospectively evaluated 208 patients with WHO grade 2 and 3 gliomas who had 1p/19q molecular studies performed between 2000 and 2004. DNA was extracted from tumor tissue and germline material and evaluated by PCR using microsatellite markers for each chromosome. There were 113 men and 95 women with a median age at diagnosis of 40. Thirty-eight patients had a low-grade astrocytoma (A2), 58 low-grade oligodendroglioma (O2), 31 low-grade oligoastrocytoma (OA2), 21 anaplastic astrocytoma (A3), 37 anaplastic oligodendroglioma (O3), and 23 had an anaplastic oligoastrocytoma (OA3). Chromosome 1p analysis was performed in all patients and showed deletions in 105 patients (76% of O2, 42% of OA2, 21% of A2, 89% of O3, 17% of AO3, and 14% of A3). Chromosome 19q studies were performed in 118 patients and showed deletions in 46 (56% of O2, 45% of OA2, 27% of A2, 76% of O3, 11% of OA3 and 0% of A3). On multivariate analyses, chromosome 1p was a prognostic factor for prolonged PFS (HR = 1.75, P = 0.03) and OS (HR = 3.59, P = 0.02) in grade 2 gliomas but not for grade 3 (HR = 0.81, P = 0.7 for PFS; HR = 1.31, P = 0.7 for OS). Chromosome 1p deletion is a significant positive prognostic marker in diffuse, grade 2 gliomas regardless of histologic subtype.


[Unspecified gain of weight?].
In the case of a 49 year old patient, a weight gain of 37 kg occurred during the first weeks of the year 2003, accompanied by a painless increase in the diameter of the upper arms and thighs. This process did spontaneously cease in the summer of 2003, but weight reduction could not be achieved. The diagnosis of multiple symmetrical lipomatosis, also known as Launois-Bensaude syndrome, the first authors to describe the condition in detail in 1898, could be established due to the unique appearance of the patient. Typical features of the disease are the accumulation of multiple lipomata in the shoulder girdle, upper arms, thorax and thighs, whereas the face, the forearms and the shanks are typically excluded. The etiology of the disease is obscure, dietetic intervention is futile, surgical approaches are liposuction or excision of the lipomata. Cessation of alcohol consumption may also be helpful, since the condition is typically associated with present or past alcohol abuse. The disease is usually reported to be rare, but there is reason enough to assume, that it is frequently misdiagnosed as simple truncal obesity.


Accelerated inactivation of voltage-dependent K+ outward current in cardiomyocytes from thyroid hormone receptor alpha1-deficient mice.
Thyroid hormone affects the electrophysiologic properties of the heart. It is not known which of the different subtypes of thyroid hormone receptors mediate these effects. Using standard patch-clamp techniques, we studied time- and voltage-dependent properties of depolarization-activated K+ currents in ventricular heart cells isolated from mice lacking the thyroid hormone receptor alpha1 (TR alpha1) and compared these currents with those in respective wild-type cells. In both groups of cells, the time course of current decay could be described by two inactivating exponential components and a sustained current component. In TR alpha1-deficient cells, the total inactivation time course was accelerated due to both increase of the relative contribution of the fast component and shortening of the slow time constant. The peak amplitude of the total current was not altered. The main component of steady-state inactivation of the voltage-dependent K+ outward current was shifted to more hyperpolarized voltages by 7 mV in TR alpha1-deficient cells compared with that in wild-type cells. Under current-clamp conditions, action potential duration at 90% repolarization was prolonged in TR alpha1-deficient cells compared with that in wild-type cells by 3.6 msec. The resulting acceleration of the total inactivation time course is proposed to contribute to action potential prolongation and thus to the increased QTend-time observed previously on ECG of TR alpha1-deficient mice.


Vessel Wall Enhancement and Focal Cerebral Arteriopathy in a Pediatric Patient with Acute Infarct and COVID-19 Infection.
Herein, we report the findings of intracranial arterial wall enhancement, consistent with focal cerebral arteriopathy-inflammatory type, in a child presenting with acute infarct in the setting of coronavirus disease 2019 (COVID-19) infection. To our knowledge, this report provides the first description of vessel wall imaging findings in COVID-19-associated acute stroke.


Microscope-induced retinal phototoxicity in cataract surgery of short duration.
Microscope-induced retinal phototoxicity has been described after prolonged cataract surgery, usually in operations lasting longer than 100 minutes. The purpose of this study was to compare the features of microscope-induced retinal phototoxicity occurring in patients who underwent cataract surgery of short duration and long duration. A retrospective nonrandomized comparative trial. Thirty-four patients, whose medical records documented the development of phototoxic lesions in the retina as a result of cataract surgery, were divided into two groups: group A with 14 patients whose operating time was 30 minutes or less, and group B with 20 patients whose operating time was greater than 30 minutes. All patients underwent either phacoemulsification or extracapsular cataract extraction (ECCE) with implantation of an intraocular lens. The mean operating time was 23.1 minutes (range, 11-30 minutes) in group A, and 60.8 minutes (range, 34-123 minutes) in group B. Phacoemulsification was done more often in group A (P = 0.001) and ECCE in group B (P = 0.0003). A final refraction of +/- 1 D was achieved by 12 eyes (86%) in group A and by 12 eyes (60%) in group B (P = 0.11). The correlation between final refraction and duration of the operation was significant; the closer the final refraction approached to emmetropia, the shorter the duration of surgery (r = 0.53; P = 0.001). Diabetic retinopathy was more common in group A (P = 0.03). Phototoxic lesions of the retina may occur during cataract surgery even when the duration of the operation is short. The most relevant associated factors found in this study were correction approximating emmetropia and diabetic retinopathy.


Transgenic sickle cell trait mice do not exhibit abnormal thermoregulatory and stress responses to heat shock exposure.
There remains controversy over whether individuals with sickle cell trait (SCT) are vulnerable to health risks during physical activity in high temperatures. We examined thermoregulatory and stress-related responses to heat exposure in SCT and wild-type (WT) mice. No significant differences in core temperature (Tc) were observed between SCT and WT mice during heat exposure. There was no correlation between peak Tc during heat exposure and levels of hemoglobin S in SCT mice. Basal levels of circulating inflammatory and stress-related markers were not significantly different between SCT and WT mice. Although heat exposure caused significant increases in plasma interleukins 1β and 6, and 8-isoprostane in SCT and WT mice, no differences were found between SCT and WT mice with similar thermal response profiles during heat exposure. SCT mice had significantly higher expression of heat shock protein 72 in heart, liver and gastrocnemius muscle than WT mice under control and post-heat conditions. In conclusion, there is neither thermoregulatory dysfunction nor abnormal stress-related response in SCT mice exposed to moderate heat. The hemoglobin variant in mice is associated with altered tissue stress protein homeostasis.


Predictive models for the practical management of renal cell carcinoma.
The expanding availability of multiple therapeutic strategies and sequencing options for patients with renal cell carcinoma (RCC) has increased the importance of skilled individualized outcome estimation for patients. This need has driven the development of statistical models to guide patient management in a variety of common clinical settings, including the management of small renal masses, identification of patients with high-risk localized RCC requiring systemic therapy and selection of suitable targeted therapies in metastatic disease. With an increasing number of different predictive models described in the literature, identifying those models most relevant for practical use is challenging. In addition to statistical models based on clinical data, there has also been an evolution towards incorporation of molecular markers into predictive algorithms. These models also serve as important benchmarks for the researchers developing novel prognostic and predictive molecular biomarkers.


S100B overexpression increases behavioral and neural plasticity in response to the social environment during adolescence.
Genetic variants as well as increased serum levels of the neurotrophic factor S100B are associated with different psychiatric disorders. However, elevated S100B levels are also related to a better therapeutic outcome in psychiatric patients. The functional role of elevated S100B in psychiatric disorders is still unclear. Hence, this study was designed in order to elucidate the differential effects of S100B overexpression in interaction with chronic social stress during adolescence on emotional behavior and adult neurogenesis. S100B transgenic and wild-type mice were housed either in socially stable or unstable environments during adolescence, between postnatal days 28 and 77. In adulthood, anxiety-related behavior in the open field, dark-light, and novelty-induced suppression of feeding test as well as survival of proliferating hippocampal progenitor cells were assessed. S100B transgenic mice revealed significantly reduced anxiety-related behavior in the open field compared to wild-types when reared in stable social conditions. In contrast, when transgenic mice grew up in unstable social conditions, their level of anxiety-related behavior was comparable to the levels of wild-type mice. In addition, S100B overexpressing mice from unstable housing conditions displayed higher numbers of surviving newborn cells in the adult hippocampus which developed into mature neurons. In conclusion, elevated S100B levels increase the susceptibility to environmental stimuli during adolescence resulting in more variable behavioral and neural phenotypes in adulthood. In humans, this increased plasticity might lead to both, enhanced risk for psychiatric disorders in negative environments and improved therapeutic outcome in positive environments.


Cognitive function and anxiety before and after surgery for asymptomatic unruptured intracranial aneurysms in elderly patients.
The prevalence of patients with asymptomatic unruptured intracranial aneurysms (UIAs) will likely increase as the general population ages. The goal of the present study was to prospectively assess cognitive function and anxiety before and after surgical repair of asymptomatic UIAs in patients ≥ 70 years. A total of 28 patients ≥ 70 years with UIAs underwent cognitive testing using the Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale (WMS), and the Rey-Osterrieth Complex Figure test (ROCF) 1 month before and 1 month after surgery. All patients also underwent anxiety testing at these time points using the State-Trait Anxiety Inventory. Group-rate analysis demonstrated that the performance intelligence quotient (IQ) and ROCF recall trial scores were significantly increased postoperatively, whereas there were no postoperative differences in verbal IQ, WMS, and ROCF copy trial scores. State anxiety scores were significantly decreased postoperatively, but there was no change in trait anxiety scores. Furthermore, a significant negative correlation was observed between changes in state anxiety scores and preoperative verbal IQ, performance IQ, and WMS. None of the patients developed postoperative cognitive functional impairments as demonstrated by event-rate analysis. Surgical treatment of UIAs does not impair cognitive function and results in improvement in state anxiety in elderly patients.


Dietary medium-chain α-monoglycerides increase BW, feed intake, and carcass yield in broilers with muscle composition alteration.
Glycerol monolaurate (GML), a member of medium-chain α-monoglycerides (MG), is proved to be beneficial for productive performance, feed efficiency, and health of broilers based on recent research. The present study aims to evaluate the effect of MG mixture rich in GML and glycerol monodecanoate on performance, intestinal development, serum parameters, carcass yield, and muscle composition in broilers. A total of 528 chicks were weighed and randomly assigned into 4 groups (22 chicks/replicate, 6 replicates/group) for a 56-d experiment. The control group received a basal diet containing 0 mg/kg MG (CON), and the treated groups fed basal diets containing 300 (MG300), 450 and 600 mg/kg MG. The results revealed that the BW (P < 0.05), ADG, and ADFI were notably increased in MG-containing groups during the finisher phase compared with the CON group. Remarkable intestinal improvements were observed in the duodenum and jejunum of MG-treated groups, but no statistical differences were obtained. Dietary MG significantly (P < 0.05) increased the serum high-density lipoprotein cholesterol, total protein, and superoxide dismutase content in broilers. Inclusion of 300 mg/kg MG in diet increased the eviscerated yield (P = 0.066), leg muscle (P < 0.01) and breast muscle yield (P = 0.083), and improved the fresh meat quality with reduced drip loss (P < 0.01) and pH decline (P < 0.01) compared with the CON group. Moreover, the saturated fatty acid (P = 0.073), flavor amino acid (P < 0.05), and total amino acid (P < 0.05) content was notably higher in the muscle of the MG300 group than that in the CON group. In summary, these findings revealed that mixed MG can be used as an effective and novel feed supplement to improve productive performance and quality of broilers.


Generalist predators and the importance of spatial density dependence.
The model examples in this paper illustrate that non-random spatial distributions of predation or parasitism by polyphagous natural enemies will not necessarily promote population persistence. The test of whether such responses are stabilizing requires the spatial distribution of predation to be examined over a range of total prey densities. As shown in Fig. 2, a contribution to stability will occur if average predation from each spatial response tends to be positively related to total prey density.


The risk of lower urinary tract symptoms five years after the first delivery.
To estimate the prevalence and 5-year incidence of lower urinary tract symptoms (LUTS) after the first delivery and to evaluate the impact of pregnancy per se and delivery per se on long-lasting symptoms. A longitudinal cohort study of 305 primiparae questioned a few days, 3 months, and 5 years after their delivery. The questionnaire used was tested and validated, and the questions were formulated according to the definitions of the International Continence Society (ICS). Maternal, obstetric, and neonatal data concerning every delivery and objective data concerning surgeries during the observation period were obtained from the records. From the sample of 278 women (91%) who responded 5 years after their first delivery, three subpopulations were defined: 1) women without initial LUTS before or during the first pregnancy or during the puerperal period, 2) women with onset of LUTS during the first pregnancy, and 3) women with onset of LUTS during the first puerperium. The risk of LUTS 5 years after the first delivery was examined using bivariate analyses. The obstetric variables in the bivariate tests with a significant association with long-lasting urinary incontinence were entered into a multivariate logistic regression. The prevalence of stress and urge incontinence 5 years after first delivery was 30% and 15%, respectively, whereas the 5-year incidence was 19% and 11%, respectively. The prevalence of urgency, diurnal frequency, and nocturia 5 years after the first delivery was 18%, 24%, and 2%, respectively, whereas the 5-year incidence was 15%, 20%, and 0.5%, respectively. The prevalence of all LUTS except nocturia increased significantly during the 5 years of observation. The risk of long-lasting stress and urge incontinence was related to the onset and duration of the symptom after the first pregnancy and delivery in a dose-response-like manner. Vacuum extraction at the first delivery was used significantly more often in the group of women with onset of stress incontinence during the first puerperium, whereas an episiotomy at the first delivery was performed significantly more often in the group of women with onset of stress incontinence in the 5 years of observation. The prevalence of urgency and diurnal frequency 5 years after the first delivery was not increased in women with symptom onset during the first pregnancy or puerperium compared with those without such symptoms. The frequency of nocturia 5 years after the first delivery was too low for statistical analysis. The first pregnancy and delivery may result in stress and urge incontinence 5 years later. Women with stress and urge incontinence 3 months after the first delivery have a very high risk of long-lasting symptoms. An episiotomy or a vacuum extraction at the first delivery seems to increase the risk. Subsequent childbearing or surgery seems without significant contribution. Long-lasting urgency, diurnal frequency, or nocturia cannot be predicted from onset during the first pregnancy or puerperium.


Implementation of an Office Ergonomics Program to Promote Musculoskeletal Health: A Case Study in Hong Kong.
OCCUPATIONAL APPLICATIONSAn office ergonomics program was implemented at a multinational company in Hong Kong. The FITS Model office ergonomics program included four components: (1) F: Furniture Evaluation and Selection, wherein the ergonomist conducted a walkthrough review of furniture and environmental settings; (2) I: Individual Workstation Assessment, in which the office ergonomics guideline and educational video were developed. An interactive individual ergonomics workstation assessment included a health survey, and the assessor provided immediate recommendations for changes to workstation setup; (3) T: Training and Education; and (4) S: Stretching Exercises and Rest Breaks, which entailed classroom training to promote office ergonomics principles and demonstrate office stretching exercises. A case study is described, included the steps to implement the program and highlights of the feedback from the project team gathered during mid-term and final evaluations. Lessons learned regarding program management and the limitations of the project intervention offer useful information for practitioners and companies.


Very early treatment with fluoxetine and reboxetine causing long-lasting change of the serotonin but not the noradrenaline transporter in the frontal cortex of rats.
Interactions of the serotonergic and noradrenergic system at different sites of the brain may be important for efficacy and side effects of antidepressant drugs. Further, serotonin and noradrenaline play a critical role in the development of neurons during brain maturation. To gain further insight how brain maturation and the two monoaminergic systems are influenced by drug treatment during early postnatal development, this animal study investigated possible effects on the noradrenaline and serotonin transporter density of the frontal cortex very early in postnatal life. Rats were treated from postnatal day 2 to 5 either with fluoxetine (5 mg/kg per day s.c.) or with reboxetine (10 mg/kg per day s.c.). At day 90 the serotonin and noradrenaline transporter density in the frontal cortex was measured by ligand binding assay. Fluoxetine treatment led to a significant long-lasting increase of serotonin (not noradrenaline) transporter density (Bmax = 1231 +/- 34) in the frontal cortex (compared with saline-treated controls (Bmax = 1112 +/- 58)). Reboxetine treatment (surprisingly) led to an even more enhanced serotonin transporter density (Bmax = 1322 +/- 46), while noradrenaline transporter density seemed to be unaffected. There were no significant differences for KD values. The results support the idea that serotonin seems to play an important role during early brain development. Moreover, drug-related modulation of the noradrenergic system during brain maturation seems to cross-influence the serotonergic system.


Prostate cancer screening uptake in Kenya: An analysis of the demographic and health survey.
Prostate cancer (PCa) screening is a cost-effective strategy to promote early detection and treatment. Understanding the determinants of PCa screening uptake would help policy makers to identify high-risk populations and ensure the cost-effectiveness of health promotion interventions. This study aims to estimate the prevalence of PCa screening uptake and assess its associated factors among Kenyan men. The study relied on data from the 2014 Kenya Demographic and Health Survey. Both descriptive and inferential analyses were performed. Firth logistic regression was employed using the "firthlogit" command in STATA. The adjusted odds ratio and 95% confidence interval were presented. Overall, the prevalence of PCa screening uptake was 4.4%. The odds of PCa screening uptake were high among men aged 50-54 [aOR= 2.08; CI= 1.23, 3.52], those who had health insurance coverage [aOR= 1.69; CI= 1.28, 2.23], those who read at least once in a week [aOR= 1.52; CI= 1.10, 2.10], and among those who watched TV at least once in a week [aOR= 1.73; CI= 1.18, 2.52]. Men who resided in the Eastern [aOR= 2.23; CI= 1.39, 3.60], Nyanza [aOR= 2.13; CI= 1.29, 3.53], and Nairobi [aOR= 1.97; CI= 1.01, 3.86] had a higher likelihood of getting screened for PCa. In conclusion, the uptake of PCa screening in Kenya is low. To ensure the cost-effectiveness of health-promoting interventions that aim to improve PCa screening uptake in Kenya, men without health insurance coverage should be targeted and prioritized. Increasing literacy rate, sensitization via television, and increasing the insurance coverage in the country would significantly contribute to a higher uptake of PCa screening. To improve the uptake of PCa screening, there would be a need to implement a national advocacy campaign that will sensitize Kenyan men about the need to undergo PCa screening. This national advocacy campaign to increase the uptake of PCa screening in Kenya must leverage mass media platforms.