Effective psychological therapies to improve lifestyle behaviors in (pre)pregnant women: A systematic review.

Poor lifestyle behaviors impact (pre)pregnant women by affecting pregnancy outcomes and offspring health. This systematic review provides an overview of psychological therapies to support lifestyle behavior changes among (pre)pregnant women. Scientific databases were searched from their inception to 20 December 2020 for studies investigating the effects of psychological therapies on improvements in lifestyle behaviors. Studies were eligible if they included (pre)pregnant women, examined the effects of a psychological therapy on at least one lifestyle behavior and used a control group receiving usual pregnancy care or a non-psychological intervention. Lifestyle behaviors of interest were dietary intake, physical activity, smoking, alcohol consumption, drug use, body weight loss and body weight gain during pregnancy. Pregnancy complications were included as outcome measures. Motivational interviewing (MI) (n = 21), cognitive behavioral therapy (CBT) (n = 8), incentive-based contingency management (IBCM) (n = 9), mindfulness (n = 1) and hypnosis (n = 1) were investigated as lifestyle behavior interventions. The findings revealed that MI was effective in reducing (self-reported) smoking and alcohol consumption and restricting gestational weight gain (GWG). CBT was only studied as an intervention to restrict GWG and the results predominantly confirmed its effectiveness. IBCM showed the strongest effect on reducing smoking and substance use. The studies using hypnosis or mindfulness to reduce smoking or restrict GWG, respectively, showed no associations. The use of psychological therapies to improve lifestyle behaviors among (pre)pregnant women is new and the scientific proof is promising. Before wide implementation is legitimated, more evidence is needed on the consequences of lifestyle change for pregnancy outcomes.

The clinical feasibility of deep hyperthermia treatment in the head and neck: new challenges for positioning and temperature measurement.

To apply high-quality hyperthermia treatment to tumours at deep locations in the head and neck (H&N), we have designed and built a site-specific phased-array applicator. Earlier, we demonstrated its features in parameter studies, validated those by phantom measurements and clinically introduced the system. In this paper we will critically review our first clinical experiences and demonstrate the pivotal role of hyperthermia treatment planning (HTP). Three representative patient cases (thyroid, oropharynx and nasal cavity) are selected and discussed. Treatment planning, the treatment, interstitially measured temperatures and their interrelation are analysed from a physics point of view. Treatments lasting 1 h were feasible and well tolerated and no acute treatment-related toxicity has been observed. Maximum temperatures measured are in the range of those obtained during deep hyperthermia treatments in the pelvic region but mean temperatures are still to be improved. Further, we found that simulated power absorption correlated well with measured temperatures illustrating the validity of our treatment approach of using energy profile optimizations to arrive at higher temperatures. This is the first data proving that focussed heating of tumours in the H&N is feasible. Further, HTP proved a valuable tool in treatment optimization. Items to improve are (1) the transfer of HTP settings into the clinic and (2) the registration of the thermal dose, i.e. dosimetry.

New developments in the antiviral treatment of hepatitis C.

Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. HCV is endemic in most parts of the world, with an estimated 170 million people infected worldwide and 3-4 million new cases each year. HCV-related end-stage liver disease is now the main indication for liver transplantation in the USA and Western Europe. Unfortunately, no vaccine or immunoglobulin is available to prevent HCV infection. Currently, HCV treatment consists of the combined administration of pegylated interferon and ribavirin for a period of 24-48 weeks, resulting in complete viral eradication in 40-80% of patients, depending on genotype, viral load and patient characteristics. This therapy is often accompanied with side-effects that affect compliance and reduce treatment outcomes. Recently, reliable in vitro culture systems have been developed which accelerated antiviral therapy research. Many new specifically targeted antiviral therapies for hepatitis C (STAT-C) and treatment strategies are evaluated in clinical trials. These new antiviral agents are expected to improve treatment significantly with potentially shorter treatment duration. The most promising antiviral agents will be reviewed.

Winner of the "New Investigator Award" at the European Society of Hyperthermia Oncology Meeting 2007. The HYPERcollar: a novel applicator for hyperthermia in the head and neck.

The purpose of this work was to define all features, and show the potential, of the novel HYPERcollar applicator system for hyperthermia treatments in the head and neck region. The HYPERcollar applicator consists of (1) an antenna ring, (2) a waterbolus system and (3) a positioning system. The specific absorption rate (SAR) profile of this applicator was investigated by performing infra-red measurements in a cylindrical phantom. Mandatory patient-specific treatment planning was performed as an object lesson to a patient with a laryngeal tumour and an artificial lymph node metastasis. Comfort tests with healthy volunteers have revealed that the applicator provides sufficient comfort to maintain in treatment position for an hour: the standard hyperthermia treatment duration in our centre. By phantom measurements, we established that a central focus in the neck can be obtained, with 50% iso-SAR lengths of 3.5 cm in transversal directions (x/y) and 9-11 cm in the axial direction (z). Using treatment planning by detailed electromagnetic simulations, we showed that the SAR pattern can be optimised to enable simultaneous encompassing of a primary laryngeal tumour and a lymph node metastasis at the 25% iso-SAR level. This study shows that the applicator enables a good control, and sufficient possibilities for optimisation, of the SAR pattern. In an ongoing clinical feasibility study, we will investigate the possibilities of heating various target regions in the neck with this apparatus.

Altered hepatobiliary disposition of acetaminophen glucuronide in isolated perfused livers from multidrug resistance-associated protein 2-deficient TR(-) rats.

Previous studies have demonstrated that phenobarbital treatment impairs the biliary excretion of acetaminophen glucuronide (AG), although the transport system(s) responsible for AG excretion into bile has not been identified. Initial studies in rat canalicular liver plasma membrane vesicles indicated that AG uptake was stimulated modestly by ATP, but not by membrane potential, HCO(3)(-), or pH gradients. To examine the role of the ATP-dependent canalicular transporter multidrug resistance-associated protein 2 (Mrp2)/canalicular multispecific organic anion transporter (cMOAT) in the biliary excretion of AG, the hepatobiliary disposition of acetaminophen, AG, and acetaminophen sulfate (AS) was examined in isolated perfused livers from control and TR(-) (Mrp2-deficient) Wistar rats. Mean bile flow in TR(-) livers was approximately 0.3 microl/min/g of liver ( approximately 4-fold lower than control). AG biliary excretion was decreased (>300-fold) to negligible levels in TR(-) rat livers, indicating that AG is an Mrp2 substrate. Similarly, AS biliary excretion in TR(-) livers was decreased ( approximately 5-fold); however, concentrations were still measurable, suggesting that multiple mechanisms, including Mrp2-mediated active transport, may be involved in AS biliary excretion. AG and AS perfusate concentrations were significantly higher in livers from TR(-) compared with control rats. Pharmacokinetic modeling of the data revealed that the rate constant for basolateral egress of AG increased significantly from 0.028 to 0.206 min(-1), consistent with up-regulation of a basolateral organic anion transporter in Mrp2-deficient rat livers. In conclusion, these data indicate that AG biliary excretion is mediated by Mrp2, and clearly demonstrate that substrate disposition may be influenced by alterations in complementary transport systems in transport-deficient animals.

Screening the foods of an endangered parrot, the kakapo (Strigops habroptilus), for oestrogenic activity using a recombinant yeast bioassay.

In recent years the possibility of environmental oestrogens affecting the reproduction of vertebrates has become an issue of both public and scientific interest. Although the significance of such chemicals remains controversial there is clear evidence that, in some contexts, environmental oestrogens can influence the fertility of vertebrates. Highly endangered species represent a situation in which even modest reductions in the fertility of key individuals may have implications for the survival of the entire species. This paper reports the screening of both natural and supplementary foods of the kakapo (Strigops habroptilus), a critically endangered New Zealand nocturnal parrot, for oestrogenic activity using a recombinant yeast based bioassay. Low levels of oestrogenic activity were detected in one of the 'chick-raising' foods, but no oestrogenic activity was detected in the adult supplementary foods. The oestrogenicity of a range of phytochemicals possibly associated with the kakapo natural diet was also examined. Two such phytochemicals, podocarpic acid and its reduced derivative podocarpinol, showed weak oestrogenic activity (approximately 10(-6) and 10(-4) of the activity of 17-beta-oestradiol, respectively).

Diagnosis and management of Crigler-Najjar syndrome.

Crigler-Najjar syndrome (CNS) results from a mutation in one of the five exons of the gene coding for the enzyme bilirubin-UDP-glucuronosyltransferase by exon 1*1 and exons 2-5 of the UDP-glucuronosyltransferase 1 locus, the bilirubin glucuronidating isoform of UDP-glucuronosyltransferase. CNS type 2 is caused by a single base pair mutation leading to a decreased but not totally absent enzyme activity. In these patients the enzyme remains responsive to phenobarbital induction therapy and their bile contains low amounts of bilirubin mono- and diglucuronides. In CNS type 1 the enzyme activity is completely absent. CNS type 1 patients do not respond to phenobarbital and their bile does not contain more than traces of bilirubin conjugates. In 1997 we reported a World Registry on the treatment of patients with CNS type 1. Data were collected on 57 patients, of whom 21 (37%) had been transplanted at the time of data collection. Some 15 patients (26%) had brain damage, in 7 of whom the brain damage was mild and they received a liver transplant. Patients with brain damage at transplantation were significantly older than those without brain damage (14.3 vs 5.9 years). Before transplantation the serum bilirubin level of CNS type 1 patients should be kept below 350 micromol/l with daily phototherapy. Oral calcium supplementation makes phototherapy more efficient. Gene therapy has been performed successfully in the Gunn rat, an animal model for this disease. Liver cell transplantation has recently been done in a child with CNS type 1.

Oral calcium phosphate: a new therapy for Crigler-Najjar disease?

BACKGROUND & AIMS: Calcium phosphate binds unconjugated bilirubin in vitro, and dietary calcium phosphate supplementation reduces the serum bilirubin level in rats with hereditary unconjugated hyperbilirubinemia (Gunn rats). The aim of this study was to evaluate the effect of oral calcium phosphate supplementation on plasma bilirubin levels in patients with Crigler-Najjar disease. METHODS: A placebo-controlled, double-blind, crossover design was used. Eleven patients, 2-42 years of age, participated. The group included 5 patients with type I disease who were all treated with phototherapy and 6 patients with type II disease who were primarily treated with phenobarbital. In addition to plasma bilirubin levels, dietary intake and urinary and fecal excretion of calcium and phosphate were evaluated. RESULTS: A modest but significant decrease in serum bilirubin was observed in patients with type I disease (18% +/- 6%, P = 0.03) but not in patients with type II disease during treatment with calcium phosphate. Urinary output of calcium and phosphate did not change during the treatment period. CONCLUSIONS: Oral calcium phosphate may be a useful adjuvant to photo-therapy in Crigler-Najjar type I disease.

Influence of dietary calcium phosphate on the disposition of bilirubin in rats with unconjugated hyperbilirubinemia.

The aim of this study was to test a possible form of therapy that could be used in the management of unconjugated hyperbilirubinemia. We hypothesized that unconjugated bilirubin (UCB) can permeate the intestinal wall and can thus be secreted with the feces. We have previously observed that UCB binds to amorphous calcium phosphate in vitro. Orally ingested amorphous calcium phosphate may act as a trapping agent for bilirubin in the intestine, thereby preventing back-diffusion across the intestinal wall. In this study, we tested whether feeding calcium phosphate leads to enhanced excretion of unconjugated bilirubin in Gunn rats. When a purified control diet was substituted by a high calcium phosphate diet, a decrease in bilirubin levels of 30% to 50% in male Gunn rats and of 23% in female rats was observed. The fecal output of bilirubin was more than doubled in Gunn rats in the first 3 days after the normal diet had been replaced by the high calcium-phosphate diet. The biological half-life of 3 H-labeled bilirubin in blood was 89.8 +/- 17.2 hours in rats fed the purified control diet and 50.9 +/- 1.4 hours in rats fed the high calcium phosphate diet (P = .004). After 30 weeks, plasma bilirubin levels were still significantly lower in Gunn rats fed a high calcium phosphate diet. No differences were found in plasma concentrations of calcium, magnesium, phosphate, urea, and creatinine in both Gunn rats and Wistar rats on control or high calcium phosphate diets. This therapy might be useful in the management of Crigler-Najjar patients, for example, as an adjunct to phototherapy.

Current therapy for Crigler-Najjar syndrome type 1: report of a world registry.

This study represents a multicenter survey on the management of patients with Crigler-Najjar syndrome (CNS) type 1. The aim of the survey was to find guiding principles for physicians in the care of these patients. Fifty-seven patients were included. At the time of inclusion, 21 patients had received a liver transplant (37%). The average age at transplantation was 9.1 +/- 6.9 years (range, 1-23 years); the age of the patients who had not been transplanted at the time of inclusion was 6.9 +/- 6.0 years (range, 0-23 years). Brain damage had developed in 15 patients (26%). Five patients died, and 10 are alive with some degree of mental or physical handicap. In 2 patients, ages 22 and 23 years, early signs of bilirubin encephalopathy could be reversed, in 1 by prompt medical intervention followed by liver transplantation and in the other by prompt liver transplantation. Seven patients underwent transplantation with some degree of brain damage at the time of the surgery; 1 of these died after retransplantation, 2 improved neurologically, and 4 remained neurologically impaired. The age of 8 patients with and 13 without brain damage at or before transplantation was 14.3 +/- 5.9 and 5.9 +/- 5.4 years (P < .01), respectively. Therapy of CNS type 1 consists of phototherapy (12 h/d), followed by liver transplantation. Phototherapy, although initially very effective, is socially inconvenient and becomes less efficient in the older age group, thus also decreasing compliance. Currently, liver transplantation is the only effective therapy. This survey shows that, in a significant number of patients, liver transplantation is performed after some form of brain damage has already occurred. From this, one must conclude that liver transplantation should be performed at a young age, particularly in situations in which reliable administration of phototherapy cannot be guaranteed.

Radiation therapy for cancer of the piriform sinus. A failure analysis.

This paper analyzes the results of 109 piriform sinus (PS) cancers treated between 1973 and 1984 by surgery and/or external beam radiation therapy (EBRT) in a large comprehensive cancer center, and in particular tries to redefine the role of EBRT in the management of these tumors. At the time the policy was to start with EBRT to a dose of 40 Gy. A good response to a first series was to be continued by EBRT (RT-1); in case of poor responding tumors, the primary and neck were to be operated upon (RT-S). Poor responders unfit for S or those refusing S were also carried to a full course of EBRT (RT-2). The RT-S, RT-1, and RT-2 actuarial 5-year locoregional relapse-free survival (LR-RFS) and overall survival (OS) were 60%, 40%, and 20% and 40%, 30%, and 20%, respectively. In a multivariate Cox regression analysis the most important prognostic factor appeared to be N-stage, with hazard ratios of 1.16 (N1), 2.2 (N2), and 3.3 (N3). The RT-S treatment group fared best (hazard ratio 0.5). The risk of relapse for T3,4 was 1.3 times as high as opposed to T1,2. For stage I/II (19/21 treated by EBRT only), a LR-RFS and OS at 5 years of 60% and 40%, respectively, was observed. This analysis supports data for stage III/IV PS cancers to be treated by surgery combined with EBRT; in stage I/II there might be a role for EBRT alone. It is speculated that with further sophistication in RT-techniques, the locoregional control rates by EBRT alone could improve.

Reduction in prime volume attenuates the hyperdynamic response after cardiopulmonary bypass.

BACKGROUND: A hyperdynamic response to cardiopulmonary bypass is characteristically observed in the post-operative course. To determine the effect of prime volume on the hemodynamic response, a database study was performed on patients who underwent elective coronary artery bypass grafting with an extracorporeal circuit with either a large prime volume (2,350-mL prime, n = 20) or a small prime volume (1,400-mL prime, n = 20). METHODS: Measurements were carried out at fixed time points before and after cardiopulmonary bypass (until 18 hours postoperatively) and include hematocrit, colloid oncotic pressure, fluid balance, and hemodynamic profile (mean of three measurements). RESULTS: The lower colloid oncotic pressure in the large prime group (16.2 +/- 0.6 mm Hg versus 19.1 +/- 1.1 mm Hg, p = 0.0002) was associated with a highly positive fluid balance (5.5 +/- 0.9 L versus 2.8 +/- 0.7 L, p = 0.0001). With the on-bypass hematocrit aimed at 22% to 23%, autologous blood was predonated by 16 patients in the small prime group but by none in the large prime group. Reinfusion of autologous blood resulted in a reduction in blood bank requirements (p = 0.03). Mean arterial pressure was 83 +/- 4 mm Hg for small prime versus 76 +/- 4 mm Hg for large prime (p = 0.01). Cardiac index was 2.9 +/- 0.2 L.min-1.m-2 for small prime versus 3.8 +/- 0.3 L.min-1.m-2 for large prime (p = 0.0001). Pulmonary vascular resistance index was 281 +/- 40 dyne.s.cm5.m-2 for small prime versus 188 +/- 22 dyne.s.cm5.m-2 for large prime (p = 0.0009). Oxygen delivery was 42 +/- 5 mL.min-1.m-2 for small prime versus 51 +/- 3 mL.min-1.m-2 for large prime (p = 0.004). Vasoactive medication was not different among groups. CONCLUSIONS: Reduction in prime volume attenuates the hyperdynamic response after cardiopulmonary bypass. Furthermore, an important reduction in blood bank products can be obtained with small prime volumes.

Molecular biology of bilirubin metabolism.

As the genes encoding the glucuronidating enzymes are discovered, it is evident that glucuronidation is a magnificent example of how in evolution, man became adapted to his "intoxicating" environment. A superfamily of genes is necessary to dispose of the toxins and carcinogens that are encountered by inhalation and ingestion. The enzymes that glucuronidate endogenous compounds are members of this large family. For the clinician, it is important to remember that jaundice may sometimes be the result of interactions at the level of bilirubin glucuronidation. When jaundice results from inactivation of members of the UGT1 family, conjugation of certain phenols, such as the anesthetic propofol, or synthetic estrogens, such as ethinylestradiol, can also be impaired. In the case of severe bilirubin glucuronidation deficiencies, such as the Crigler Najjar syndrome type I, there are exciting prospects for a possible cure by gene therapy.

The influence of image resolution on the positron emission tomographic measurement of caudate glucose consumption.

The aim of this study was to investigate the influence of image resolution on (a) relative and absolute values of caudate glucose consumption (rCMRGlc) determined by positron emission tomography (PET), and (b) the detection of significant differences in these metabolic values between groups of subjects. For this purpose, raw data of cerebral accumulation of fluorine-18 fluorodeoxyglucose (FDG) obtained in 11 normal subjects and in nine patients with unilateral thalamic infarction were reconstructed using filtered backprojection with four different cut-off frequencies (CFs), yielding images with a transaxial resolution of 5.7, 7.1, 8.9 and 11 mm (full-width at half-maximum; FWHM). Absolute values of caudate rCMRGlc decreased significantly by more than 30% over the range of image resolutions studied. Bilateral ratios of caudate rCMRGlc were insensitive to variations in image resolution. Levels of significance assessing the differences in mean metabolic values between patients and controls were all below 0.01. They were, however, slightly better at image resolutions of 7.1 and 8.9 mm than at a resolution of 5.7 mm. These data indicate (a) that relative values of rCMRGlc are better suited to compare quantitative results from different PET cameras than are absolute values, and (b) that the CF used for the filtered back-projection exerts a small but not negligible influence on levels of significance assessing differences in metabolic values between groups of subjects.

Defective biliary excretion of epinephrine metabolites in mutant (TR-) rats: relation to the pathogenesis of black liver in the Dubin-Johnson syndrome and Corriedale sheep with an analogous excretory defect.

Dubin-Johnson patients, mutant Corriedale sheep and TR- and EHBR mutant rats have recessively inherited defective bile canalicular secretion of many nonbile acid organic anions. The human and ovine mutants have black livers and lysosomal pigment accumulation. The livers in TR- and EHBR mutant rats are not black, and sparse lysosomal pigment accumulation is seen. Previously, we postulated that the unidentified pigment in the Dubin-Johnson syndrome results from the accumulation of tyrosine, phenylalanine and tryptophan metabolites, such as metanephrine, which are normally secreted in bile as organic anions. We tested this hypothesis in TR- rats. 3H-epinephrine was injected intravenously; control rats secreted 2.80% +/- 0.52% of the injected dose in bile as compared with 0.19% +/- 0.07% in TR- rats. From 82% to 90% of biliary radioactivity was due to polar conjugates in control rats and mutant rats. TR- rats retained more of the injected dose in the liver, particularly in lysosomes, and secreted more in urine than did control rats. After feeding control and TR- rats for 4 mo with a rat chow diet supplemented with 4% tyrosine, tryptophan and phenylalanine, the liver did not become grossly black; however, histological and electron microscopic study revealed dense lysosomal pigment accumulation in TR- rats. Intraportal injection of metanephrine resulted in the appearance of black liver in TR- rats that persisted for at least 2 hr and was not associated with pigment accumulation by light or electron microscopic examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Plantas medicinais: seu uso tradicional em moçambique / Medicinal plants their traditional use in Mozambique

A publicação do tomo 3 de ´´planta medicinais ­ seu uso tradicional em Moçambique´´ responde ao propósito de prosseguir a obra com prioridade regula. De um modo geral, seguiu-se na exposição, descrição e ordenação, a metodologia dos trabalhos anteriores…

Plantas medicinais seu uso tradicional em moçambique / Medicinal plants for use in Mozambique

A publicação do tomo 3 de ´´planta medicinais ­ seu uso tradicional em Moçambique´´ responde ao propósito de prosseguir a obra com prioridade regula. De um modo geral, seguiu-se na exposição, descrição e ordenação, a metodologia dos trabalhos anteriores…

Hepatobiliary excretion of organic anions in double-mutant rats with a combination of defective canalicular transport and uridine 5'-diphosphate-glucuronyltransferase deficiency.

Mutant rats with a selective defect for the hepatobiliary excretion of organic anions (GT+TR- rats) are valuable models to study hepatic transport processes. However, retained conjugates in the livers of these rats may secondarily affect hepatic uptake, metabolism, and excretion of other compounds and this may confound the interpretation of test results. We have developed double mutants (GT-TR-) rats with both a conjugation and an excretion defect by cross-breeding uridine 5'-diphosphate-glucuronyl-transferase-deficient GT-TR+ Gunn rats with transport-deficient GT+TR- rats. Phenotypically, GT-TR- rats and Gunn rats are alike in that both have unconjugated hyperbilirubinemia. Intravenous administration of tetrabromosulphthalein, bilirubin diglucuronide, and bilirubin monoglucuronide revealed a significant difference in that the clearance of these compounds was reduced to 10%, 10%, and 20%, respectively, in GT-TR- rats when compared with Gunn rats. The hepatic elimination of tetrabromosulphthalein in GT-TR- rats and in GT+TR- rats is impaired to the same extent. Thus, both have a similar hepatic excretion defect. However, bile flow and bile acid excretion in GT+TR- rats are more depressed than in GT-TR- rats: bile flow, 88 +/- 3 vs. 36 +/- 1 microliters/min.kg and bile acid excretion, 3.4 +/- 0.2 vs. 1.5 +/- 0.1 mumol/min.kg in GT-TR- and GT+TR- rats, respectively. This suggests that accumulated glucuronides in the liver inhibit bile flow and bile acid excretion. To test whether conjugated bilirubin and the photoisomers of unconjugated bilirubin are excreted via the same transport pathways, the effect of phototherapy was studied in GT-TR- rats and in Gunn rats. Photoexposure caused a 120% increase in biliary excretion of bilirubin isomers in Gunn rats and only 40% in GT-TR- rats. This shows that the biliary excretion of bilirubin photoisomers is indeed affected by the hepatic excretion defect of GT-TR- rats and suggests that hepatic excretion of bilirubin photoisomers proceeds via the same route as other organic anions such as conjugated bilirubin and tetrabromosulphthalein.