Neurocognitive function of lymphoma patients after treatment with chemotherapy.
Acta Oncol. 2016 Jun 22;:1-5
Authors: Wouters H, Baars JW, Schagen SB
BACKGROUND: Chemotherapy has been shown to cause brain changes and to compromise cognitive function in cancer survivors. Knowledge about this matter is of vital importance for good clinical practice and insights into neurological aging. However, most studies have been conducted among breast cancer patients. Less is known about the effects of chemotherapy on the cognitive function of lymphoma patients.
MATERIAL AND METHOD: We studied patients with non-Hodgkin or Hodgkin lymphoma who had been treated with standard dose chemotherapy or with supplementary high dose chemotherapy when standard dose chemotherapy had been unsuccessful. Age- and sex-matched relatives and friends were invited to participate as control participants. All participants underwent a cognitive examination with a battery of validated neuropsychological tests.
RESULTS: Matching of patients with control participants was found to be successful. Regression analysis did not reveal worse cognitive functioning of patients (N = 106) compared to matched controls (N = 53) on the overall group level (All Bonferroni-Holm corrected p-values >0.05). However, a subgroup of 16% of patients had deviant performance according to a chance-corrected criterion based on Ingraham and Aiken’s probability curves, i.e. 1.5 standard deviations below the norm on three of 14 tests. Exploratory analyses showed that this subgroup of patients was lower educated and had lower estimated premorbid intelligence.
CONCLUSION: Chemotherapy may compromise the function of the brain in a subgroup of lymphoma patients. We hypothesize protection of the brain by ‘cognitive or brain reserve’ as a possible explanation.
PMID: 27333078 [PubMed – as supplied by publisher]
Posted in Acta Oncol
Discrepancy and Disliking Do Not Induce Negative Opinion Shifts.
PLoS One. 2016;11(6):e0157948
Authors: Takács K, Flache A, Mäs M
Both classical social psychological theories and recent formal models of opinion differentiation and bi-polarization assign a prominent role to negative social influence. Negative influence is defined as shifts away from the opinion of others and hypothesized to be induced by discrepancy with or disliking of the source of influence. There is strong empirical support for the presence of positive social influence (a shift towards the opinion of others), but evidence that large opinion differences or disliking could trigger negative shifts is mixed. We examine positive and negative influence with controlled exposure to opinions of other individuals in one experiment and with opinion exchange in another study. Results confirm that similarities induce attraction, but results do not support that discrepancy or disliking entails negative influence. Instead, our findings suggest a robust positive linear relationship between opinion distance and opinion shifts.
PMID: 27333160 [PubMed – as supplied by publisher]
Posted in PLoS One
Introduction – Granulomatosis with polyangiitis (GPA) is characterized by the presence of anti-neutrophil cytoplasmic autoantibodies (ANCA). However, several observations support the involvement of T cells and especially effector memory T cells (TEM cells) in the pathogenesis as well. Comprising the T cell lineage are also regulatory T cells (Tregs), a T cell subset that has been shown to have impaired suppressive function in GPA patients. It is hypothesized that this dysfunction might be caused by their capacity to differentiate into IL-17-producing Tregs in the context of a pro-inflammatory cytokine environment. Tregs are characterized by the expression of the transcription factor FoxP3 of which at least one isoform exists that lacks the second exon ((FoxP3Δ2). Previous research suggests that FoxP3Δ2 Tregs produce higher levels of IL-17 and that the proportion of these cells is increased in GPA patients. Recently, a new immune modulating therapy has been developed directed at blocking Kv1.3 potassium channels to inhibit activation of (pathogenic) TEM cells and their IL-17 production. No data is available on the effects of Kv1.3 blockade on IL-17 production of Tregs and their suppressive function. It has been shown that deletion of the Kv1.3 gene biases CD4+ T cells towards an immunoregulatory phenotype. Therefore, this study investigated the effects of inhibiting Kv1.3-channels on the phenotype and suppressive function of Tregs in GPA patients.
Materials and methods – Phenotyping of Tregs was performed on whole blood samples of 8 GPA patients in remission, 1 active GPA patient and 10 healthy controls. Samples were stimulated with and without the Kv1.3-channel blocker ShK-186 and phenotypes were determined using flowcytometry. Samples were stained for surface markers (CD4, CD8, CD45RO) and intracellularly for IL-17, and the transcription factors (FoxP3, FoxP3exon2). Additionally, isolated peripheral blood mononuclear cells (PBMCs) were cultured in a Th17-polarizing environment containing IL-6 and IL-23 and analysed at day 1, 4 and 6. To study the suppressive capacity, sorted Tregs and responder T cells (Tresp) were co-cultured in different ratios with various stimulation techniques.
Results – IL-17 production of memory CD4+ T cells in GPA patients was significantly reduced after incubation with ShK-186 and normalized to the level of healthy controls after stimulation. Differences in phenotype of Tregs were found between healthy controls and GPA-patients in remission, with significantly less full-length FoxP3 and higher amounts of FoxP3Δ2, albeit statistically not significant. FoxP3Δ2 Tregs were significantly more prone to IL-17 production, that could be effectively reduced after incubation with ShK-186. ShK-186 also diminished IL-17 production in PBMCs cultured in Th17 promoting conditions. No functional assay could be established to test the suppressive capacity of Tregs.
Conclusion – ShK-186 effectively reduced IL-17 production in both total memory CD4+ T cells as well as memory Tregs from GPA patients in vitro, in which IL-17 production was preferentially found in memory Tregs expressing FoxP3Δ2.
Introduction: High recurrence rates and poor antibiotic bone penetration make that posttraumatic osteomyelitis of the tibia remains a challenge for every trauma surgeon. General principles of implant removal, reaming of the canal, debridement of affected tissues, and administration of local and systemic antibiotics are widely accepted. However, consensus on the best local antibiotic therapy has not yet been reached. In recent years several new forms of local antibiotic therapy have been described. One of these is the antibiotic cement rod. The hypothesis was that after proper debridement, low-dose antibiotic cement rods in combination with systemic antibiotics are effective in treating active osteomyelitis of the tibia.
Patients and methods: Data was collected retrospectively from all patients who were treated with an antibiotic cement rod at the University Medical Centre Utrecht between 2009 and 2015. Patients with a follow-up below 12 months were excluded. All patients were treated using low-dose antibiotic cement rods, handmade in the operating room, combined with systemic antibiotic therapy. After two weeks the cement rods were either removed or replaced depending on intraoperative culture results. The most important outcomes of this retrospective study were: recurrence of infection, infection control, and union.
Results: Eighteen consecutive patients (14 male, 4 female) with a mean age of 44 years (range 16-72) were included. At a mean follow-up of 34 months (range 12-73), 33 cement rods were placed in 22 admissions (mean 1.8 per patient). The mean time of cement rod treatment was 40 days. Four patients (22%) showed recurrence of infection. After further treatment, infection control was achieved in all patients. Sixteen out of eighteen patients achieved a united fracture at last follow-up. Of the cultures taken upon rod removal 22% was positive.
Conclusion: This study indicates that the use of low-dose antibiotic cement rods is effective in procuring infection control and union in the treatment of posttraumatic osteomyelitis of the tibia. With regard to the recurrence rate, the use of a low-dose antibiotic cement rod seems less effective than previously reported cement rod studies using high-dose antibiotic cement rods.
Introduction: Fluid resuscitation is considered to be the cornerstone of shock treatment. Question is to which extend is the fluid therapy contributing to oxygen transport and from what point is the fluid responsible for edema formation and thereby counteracting with the therapy? Materials and methods: This is a single-center prospective observational study among three categories of patients: cardiac surgery, sepsis patients and healthy volunteers. Of all the subjects recordings were made with the in-vivo-microscope Cytocam-IDF® to assess the microcirculation. There were BIVA- measurements performed and all the vital signs and fluid balance were recorded. Results: 106 subjects were enrolled, 52 cardiothoracic patients, 29 sepsis patients and 25 healthy volunteers. Of both the cardiothoracic patients and sepsis patients, the total vessel density (TVD) was significantly lower than that of the healthy volunteers (p = 0.009). In the cardiothoracic patient group there is a weak correlation between fluid balance and TVD (rs = 0.31 and p = 0.023). This correlation is not found in the other patient group. The BIVA measurements showed a weak correlation between the combined results of the BIVA measurement and fluid balance. No correlation was found between the BIVA-measurement and reduction of the TVD. Conclusion: A weak or no correlation between fluid balance and the decrease of TVD was found. No further increase of the TVD with higher fluid balances could indicate an optimal fluid balance by particular illnesses. The TVD could thus function as a start and stop sign for fluid resuscitation with an optimum of 21mm2/mm2. This is ground for further research.
Introduction: The development of an artificial bioengineered larynx will undoubtedly
alleviate suffering and restore the quality of life to a great extend for those who have lost their
own larynx due to trauma or cancer. This research is intended to investigate the prediction of
a voluntary cough using surface electromyography (EMG) of intercostal and diaphragm
muscles, in order to develop control algorithms for an EMG controlled artificial larynx.
Methods: Surface EMG of intercostal and diaphragm muscles as well as breathing and cough
flow rates were measured in twelve healthy subjects. EMG onset was compared to voluntary
cough exhalation onset and also to 0.1 second before onset of voluntary cough exhalation.
This time interval is to give the artificial larynx the time to close the bioengineered vocal
Results: In the 189 EMG of intercostal muscle detected voluntary coughs, 172 coughs (91%
[95% CI 86.9-95.1]) were detected before onset of cough exhalation and 128 coughs (67.7%
[95% CI 61-74.4]) 0.1 second before onset of cough exhalation. In the 158 EMG of
diaphragm muscle detected voluntary coughs, 149 coughs (94.3% [95% CI 90.7-97.9]) were
detected before onset of cough exhalation and 102 coughs (64.6% [95% CI 57.1-72.1]) 0.1
second before onset of cough exhalation. More coughs were detected before onset of cough
exhalation when combining EMG activity of intercostal and diaphragm muscles and
comparing this to intercostal muscle activity alone (183 coughs [96.8%, 95% CI 94.2-99.4] v
172 coughs, p=0.0294). When comparing the mentioned combination to diaphragm muscle
activity alone, the higher percentage detected coughs before cough exhalation onset was not
found to be significant (183 coughs v 149 coughs, p=0.295). In addition, more coughs were
detected 0.1 second before onset of cough exhalation with the mentioned combination of
EMG activity and comparing this to intercostal muscle activity alone (149 coughs [78.8%,
95% CI 73-84.6] v 128 coughs, p=0.0198) and to diaphragm muscle activity alone (149
coughs v 102 coughs, p=0.0038).
Conclusion: Results of findings have clearly illustrated that most voluntary coughs can
indeed be predicted based on combined EMG signals of intercostal and diaphragm muscles.
EMG signals of these two muscle groups will therefore be useful in controlling the
bioengineered vocal cords within the artificial larynx during a voluntary cough.
Background: The risk of cardiovascular complications is multifactorial. Therefore the treatment of a patient with an increased risk is based on all major risk factors in that patient. However, it is unknown which combination of risk factors cause the highest actual risk for cardiovascular complications in patients with hypertension, who are treated by the general practitioner, because of primary prevention of cardiovascular disease.
Objective: In this study, we investigate the risk factors that predict the development of cardiovascular complications in patients with hypertension and primary prevention of cardiovascular disease.
Methods: A retrospective cohort study was done at THOON B.V. Hengelo with three general practices concerning January 2007 until October 2015. There were 1344 patients enrolled, all treated for primary prevention in hypertension. Various search parameters have been investigated to reveal the predictors for the development of cardiovascular events. With those parameters a multivariate predictive model was developed.
Results: Off all patients, 26% developed a cardiovascular event. In the univariate analysis, thirteen risk factors with a significant relationship with time to develop an event were found. A multivariate model with six significant predictors was developed, in which age (Hazard Ratio (HR) 1,038 95% BI 1,027-1,050)), gender (HR 1,284 95% BI 1,023-1,612), weight (HR 1,009 95% BI 1,002-1,016), systolic blood pressure (HR 1,044 95% BI 0,993-1,098) and COPD (HR 2,166 95% BI 1,556-3,014) are significant predictive factors for time to develop a cardiovascular event. Therapy resistant hypertension at baseline will predict the development of a cardiovascular event too (HR 2,329 95% BI 1,597-3,396).
Conclusion: Age, gender, weight, systolic blood pressure and COPD are independent risk factors for the development of a cardiovascular event in patients with hypertension following a general practitioners’ primary prevention program for cardiovascular disease. Weight and systolic blood pressure are variables which could be acted on. Therefore it would be useful for general practitioners to focus on those factors in patients with hypertension and primary prevention of cardiovascular disease.
Introduction – During the study period, two major changes occurred that influenced the number
of pregnancies diagnosed with Down syndrome in the Netherlands. First was the considerable
increase in maternal age, which is a well-known risk factor for the development of Down
syndrome. Second was the increase in possibilities of prenatal screening and (invasive) prenatal
diagnosis for Down syndrome. When prenatal screening indicates an increased risk for a
pregnancy complicated with Down syndrome, a pregnant woman is eligible for prenatal
diagnosis. There are two forms of prenatal diagnosis to determine if a pregnancy is complicated
with Down syndrome: amniocentesis since 1974 and chorionic villus sampling since 1984.
In the early years of the study period, the major indication for prenatal diagnosis was a maternal
age of 36 years or older. Since 1991 the triple test is available; a prenatal screening test of
maternal serum to indicate the risk of a pregnant woman for a pregnancy with Down syndrome.
Since 2007 a national prenatal screening program is implemented in the Netherlands, in which
the combined test and a structural anomaly scan are offered to all pregnant women. From April
2014 a trial study is conducted in the Netherlands, with the offer of a non-invasive prenatal
screening test to pregnant women with an increased risk for Down syndrome. The non-invasive
prenatal test shows good results and has caused great expectations for the future of prenatal
screening and –diagnosis for Down syndrome.
Purpose – This study gives an overview of the developments and trends of prenatal screening and
diagnosis for Down syndrome in the Northern Netherlands during the period 1981-2013, based
on the EUROCAT-NNL database.
Methods – The study included all cases with an ICD-code of 758.0 or Q90.0 for Down syndrome
with a date of delivery or termination of the pregnancy between January 1st 1981 and December
31 2013. The cases should be registered at EUROCAT-NNL before September 14th 2015 for the
inclusion in this study. Trends were analysed for prevalence rates, maternal age, prenatal
screening and –diagnosis and pregnancy outcome.
Results – In the period 1981-2013, 876 cases with Down syndrome were registered at
EUROCAT-NNL, resulting in a total birth prevalence of 16,0 per 10.000 births. The total birth
prevalence of Down syndrome increased and the live birth prevalence slightly decreased during
the study period. In our study population, median maternal age increased from 30,0 in 1981 to
35,0 in 2013 and the proportion of births to mothers ≥ 35 years of age has risen from 25,0% to
52,6% during the study period. The proportion of pregnancies in which Down syndrome was
prenatally detected and diagnosed, increased. The proportion of pregnancies resulting in
termination also increased.
Conclusion – The increase in the total birth prevalence may be attributed to the increase
Introduction: Metabolism of the inhibitory neurotransmitter Gamma-Aminobutyric acid
(GABA) occurs through the synchronous action of GABA-transaminase (GABA-T) and
succinic semialdehyde dehydrogenase (SSADH). Several hundred patients are diagnosed with
SSADH deficiency primarily suffering from epilepsia among other neurological symptoms.
However, these patients appear relatively protected against the development of metabolic
syndrome-related disorders. Since GABAergic mechanisms were shown to be active in
peripheral tissue as well, we hypothesized that this apparent metabolic protection is conferred
by the biological activities of GABA outside the central nervous system. Therefore, the aim
of the present study was to investigate the expression of GABA-metabolizing enzymes in
peripheral tissues and to provide an initial characterization of potential functional
consequences of reduced SSADH expression.
Method: A variety of mouse organs, human liver and a number of macrophages and
hepatocyte-derived cell lines were analyzed by means of qPCR for the expression of SSADH,
and other GABA metabolizing genes. Western blot was preformed to confirm SSADH protein
expression. SSADH was downregulated in HepG2 cells using an SSADH specific siRNA and
changes in mRNA expression of a number of genes involved in (chol)sterol metabolism were
Results: SSADH was expressed in mouse liver and adrenals, as well as in human liver and the
human liver cell lines IHH and HepG2. No expression was found in Kupffer cells, M1
macrophages, M2 macrophages and THP-1 cells. Complete knockdown of SSADH was
achieved in HepG2 cells using siRNA transfection. Interestingly, a significantly lower
CYP7A1 expression was observed in SSADH silenced cells compared with the scrambled
control, while the expression of other genes involved in cholesterol synthesis and uptake
Discussion: This study indicates that SSADH is expressed in hepatocytes where it appears to
be functionally associated with the expression of CYP7A1, a key enzyme for bile acid
synthesis. Decreased expression of CYP7A1, likely results in a higher relative contribution of
CYP8B1 driven bile acid synthesis, which is expected to lead to more cholic acid and
subsequently deoxycholic acid (DCA) production. In preclinical models, DCA was shown to
reverse high fat diet-induced weight gain and improve glucose tolerance. Thus, more DCA
production upon reduced SSADH expression could provide an explanation for the protective
effect of SSADH mutations against obesity and insulin resistance. However, this concept
needs to be tested in further in vivo studies.
Conclusion: This study demonstrates substantial expression of SSADH in hepatocytes and
suggests a potential link between GABA and bile acid metabolism, which could explain the
decreased incidence of metabolic syndrome-related disease observed in epileptic patients
Maryam Darvishian: Real-world influenza vaccine effectiveness De Wereldgezondheidsorganisatie raadt extra kwetsbare groepen zoals ouderen, zwangere …
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Reply to “Does the eyebrow sag with aging. An Anthropometric study of 95 Caucasians from 20 to 79 years of age.” (article of Bruneau S, Foletti JM, Muller S, Vercasson G, Lauwers F, Guyot L. Plast Reconstruct Surg 137: 305e, 2016.).
Plast Reconstr Surg. 2016 Jun 10;
Authors: van der Lei B, Fechner MF
PMID: 27307321 [PubMed – as supplied by publisher]
Chemphyschem. 2016 Jun 16;
Authors: Browne WR, Woolley A, Hu D
PMID: 27309568 [PubMed – as supplied by publisher]
Posted in Chemphyschem
The Effect of Co-occurring Substance Use on Gamma-hydroxybutyric Acid Withdrawal Syndrome.
J Addict Med. 2016 Jun 15;
Authors: Kamal RM, Dijkstra BA, Loonen AJ, De Jong CA
OBJECTIVES: Gamma-hydroxybutyric acid (GHB) withdrawal is a complex syndrome which can be potentially life-threatening. Additionally, GHB-dependent patients frequently report co-occurring substance use of other psychoactive drugs. We assessed the add-on effect of co-use on GHB withdrawal symptoms.
METHODS: We conducted an open-label, pretest-posttest design study with 95 patients selected from 229 inpatients admitted for detoxification, who were divided into GHB only (GO, n = 40), GHB plus sedatives (GSE, n = 38), and GHB plus stimulants (GST, n = 17) groups. GHB withdrawal was evaluated by means of the Subjective Withdrawal Scale. Co-use add-on effects on the severity of withdrawal symptoms were evaluated 2.5 hours after the last illicit GHB self-administration (T1) when withdrawal was expected and 2.5 hours later, after administration of a very low dose of pharmaceutical GHB (T2).
RESULTS: The GO group reported high scores of psychomotor retardation symptoms at both T1 and T2, and also high cravings, agitation, and restlessness at T1, and anxiety at T2. The GSE group reported the highest score in psycho-autonomic distress symptoms at both T1 and T2, whereas the GST group reported the highest score in psycho-motor stress factor at T2. There was no significant difference in withdrawal intensity in all symptom clusters between T1 and T2 for both GSE and GO groups. However, after 5 hours, the GST group reported significant decreases in intensity for all symptoms except for psycho-motor stress. At T1, GST and GSE groups reported more muscle twitches than the GO group as a significant add-on effect to the GHB withdrawal. At T2, the GST group experienced more agitation (P = 0.009), restlessness (P = 0.001), and rapid pulse (P = 0.034) than the GO group.
CONCLUSIONS: Co-use, especially of stimulants, caused an add-on effect on the GHB withdrawal symptoms within the first 5 hours.
PMID: 27310146 [PubMed – as supplied by publisher]
Posted in J Addict Med
Diagnosing viral and bacterial respiratory infections in acute COPD exacerbations by an electronic nose: a pilot study.
J Breath Res. 2016;10(3):036001
Authors: van Geffen WH, Bruins M, Kerstjens HA
Respiratory infections, viral or bacterial, are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). A rapid, point-of-care, and easy-to-use tool distinguishing viral and bacterial from other causes would be valuable in routine clinical care. An electronic nose (e-nose) could fit this profile but has never been tested in this setting before. In a single-center registered trial (NTR 4601) patients admitted with AECOPD were tested with the Aeonose(®) electronic nose, and a diagnosis of viral or bacterial infection was obtained by bacterial culture on sputa and viral PCR on nose swabs. A neural network with leave-10%-out cross-validation was used to assess the e-nose data. Forty three patients were included. In the bacterial infection model, 22 positive cases were tested versus the negatives; and similarly 18 positive cases were tested in the viral infection model. The Aeonose was able to distinguish between COPD-subjects suffering from a viral infection and COPD patients without infection, showing an area under the curve (AUC) of 0.74. Similarly, for bacterial infections, an AUC of 0.72 was obtained. The Aeonose e-nose yields promising results in ‘smelling’ the presence or absence of a viral or bacterial respiratory infection during an acute exacerbation of COPD. Validation of these results using a new and large cohort is required before introduction into clinical practice.
PMID: 27310311 [PubMed – as supplied by publisher]
Posted in J Breath Res
How peer conversations about HIV/AIDS media messages affect comprehension and beliefs of young South African women.
SAHARA J. 2016 Dec;13(1):68-80
Authors: Lubinga E, Maes AA, Jansen CJ
Most existent research on the effects of interpersonal discussions about health campaign messages is based on surveys. In this study, we analysed actual conversations about an HIV/AIDS poster to find out possible effects. Young South African women in 59 dyads (n = 118) participated in conversations about a deliberately puzzling HIV and AIDS poster that cautioned the target group to be faithful to one sexual partner. We measured their comprehension of the poster and beliefs about the message, before and after the conversations. Overall, actual comprehension (AC) was low, and we observed a large discrepancy between actual and perceived comprehension. In general, conversations did not improve AC. It proved to be even more probable that a correct interpretation before a conversation turned into an incorrect interpretation than the other way around. However, having a well-informed conversation partner increased the chance of acquiring adequate subsequent comprehension. We found, in general, that conversations did not decrease undesirable beliefs. One important undesirable belief even became reinforced after the conversations. Conversations among peers might be valuable in health campaigns, but our study shows that intended positive effects do not automatically follow.
PMID: 27310424 [PubMed – as supplied by publisher]
Posted in SAHARA J