Using sensitivity

analysis of the network parameters and comparing the results with cancer gene mutation spectra, we found that parameters that significantly affect the bifurcation point correspond to high-frequency oncogenic mutations. This result shows that the position of the bifurcation point is a better measure of the functionality of a biological network than gene expression levels of certain key proteins. It further demonstrates the suitability of applying systems-level analysis to biological networks as opposed to studying genes or proteins in isolation.”
“In the present study, we aimed to evaluate the possible effects of methylphenidate on rat testes. Forty-two Wistar rats were randomly distributed into three experimental SCH727965 groups of 14 rats each. For 90 days, each group via gavage received the following: group I = tap water (control group), group 2 = 5 mg/kg/day of ritalin (methylphenidate, MPH), and group 3 = CA3 inhibitor 10 mg/kg/day of ritalin. After sacrificing the animals, the body weights as well as the absolute and relative testicular weights were measured. Testes were sampled, fixed, and processed and, by histopathological examination, quantitative morphometric analysis of Sertoli cells, spermatocytes, and spermatids was performed in stages II, V, and XII. Immunohistochemistry was performed for transforming growth factor (TGF)-beta 1 and p53, and the apoptotic index was assessed through the TUNEL method. Group 2 had a reduction

of round spermatids in stage II. Group 3 had reduction in both stage 11 and stage V spermatids, as well as lower testicular weight. The p53 expression was increased in group 3. In groups 2 and 3, the TGF-beta 1 expression was reduced and the apoptotic index by TUNEL was increased. Body weights remained stable on either group. Our NVP-LDE225 research buy results showed that methylphenidate might negatively affect spermatogenesis not only by reducing testicular weight and amount of round

spermatids but also by increasing apoptotic death and p53 activation. The findings of the study, however, must be cautiously interpreted.”
“In the nitrate-responsive, homodimeric NarX sensor, two cytoplasmic membrane alpha-helices delimit the periplasmic ligand-binding domain. The HAMP domain, a four-helix parallel coiled-coil built from two alpha-helices (HD1 and HD2), immediately follows the second transmembrane helix. Previous computational studies identified a likely coiled-coil-forming alpha-helix, the signaling helix (S helix), in a range of signaling proteins, including eucaryal receptor guanylyl cyclases, but its function remains obscure. In NarX, the HAMP HD2 and S-helix regions overlap and apparently form a continuous coiled-coil marked by a heptad repeat stutter discontinuity at the distal boundary of HD2. Similar composite HD2-S-helix elements are present in other sensors, such as Sln1p from Saccharomyces cerevisiae. We constructed deletions and missense substitutions in the NarX S helix.

Additionally, it was shown that, despite maintaining a general type of insulin-like packing structure, the secondary structures were somewhat different when SPC/E and TIP4P were used. These differences could affect the overall dynamics of molecules, as well as their ability to adopt the conformation required to bind with conjugate receptors. We conclude that several, not one, water models should be used to investigate the conformational EPZ5676 supplier mobility of peptides.”
“The protein kinase C (PKC) family of proteins is an attractive drug target. Dysregulation

of PKC-dependent signalling pathways is related to several human diseases like cancer, immunological and other diseases. We approached the problem of altering PKC activities by developing C1 domain-based PKC ligands. In this report gamma-hydroxymethyl-gamma-butyrolactone (HGL) substituents were investigated in an effort to develop small

molecule-based PKC regulators with higher specificity for C1 domain than the endogenous diacylglycerols (DAGs). Extensive analysis of membrane-ligands interaction measurements revealed that the membrane-active Crenolanib purchase compounds strongly interact with the lipid bilayers and the hydrophilic parts of compounds localize at the bilayer/water interface. The pharmacophores like hydroxymethyl, carbonyl groups and acyl-chain length of the compounds are crucial for their interaction with the C1 domain proteins. The potent compounds showed more than 17-fold stronger binding affinity for the C1 domains than DAG under similar experimental conditions. Nonradioactive kinase assay confirmed that these potent compounds have similar or better PKC dependent phosphorylation capabilities than DAG under similar experimental conditions. Hence, our findings reveal that these HGL analogues represent an attractive group of structurally MI-503 nmr simple C1 domain ligands that can be further structurally

altered to improve their potencies.”
“We examined whether zinc transporter 8 autoantibodies (ZnT8A; arginine ZnT8-RA, tryptophan ZnT8-WA, and glutamine ZnT8-QA variants) differed between immigrant and Swedish patients due to different polymorphisms of SLC30A8, HLA-DQ, or both. Newly diagnosed autoimmune (>= 1 islet autoantibody) type 1 diabetic patients (n = 2,964, <18 years, 55% male) were ascertained in the Better Diabetes Diagnosis study. Two subgroups were identified: Swedes (n = 2,160, 73%) and immigrants (non-Swedes; n = 212, 7%). Non-Swedes had less frequent ZnT8-WA (38%) than Swedes (50%), consistent with a lower frequency in the non-Swedes (37%) of SLC30A8 CT+TT (RW+WW) genotypes than in the Swedes (54%). ZnT8-RA (57 and 58%, respectively) did not differ despite a higher frequency of CC (RR) genotypes in non-Swedes (63%) than Swedes (46%). We tested whether this inconsistency was due to HLA-DQ as 2/X (2/2; 2/y; y is anything but 2 or 8), which was a major genotype in non-Swedes (40%) compared with Swedes (14%).

Here we first review published computer-aided structural predictions of HIV-1 integrase in complex with its interactors. These include DNA and the human HAT protein. Next, we present a prediction of the complex between HIV-1 integrase with the human prolyl-isomerase-1 (hPin1) enzyme. Interaction with hPin1 is crucial for efficient HIV-1 infection and it increases integrase stability (Manganaro et. al 2010, Nat. Med. 16, 329). The modeling presented here, which is validated against experimental data, provides a rationale for a variety of viral protein’s mutations which impair protein function and

HIV-1 virus replication in vivo without significantly affecting enzymatic activity.”
“Pink-footed geese Anser brachyrhynchus nest in two contrasting but commonly found habitats: steep cliffs and open tundra slopes. In Svalbard, we compared nest densities Chk inhibitor and nesting success in these two environments over ten breeding seasons to assess the impact of spring snow cover, food availability to nesting adults and arctic fox Vulpes lagopus (main terrestrial predator) abundance. In years with extensive spring snow cover, fewer geese at both colonies attempted to breed, possibly because snow cover limited pre-nesting feeding

opportunities, leaving adults in poor breeding condition. Nesting success at the steep cliff colony was lower with extensive spring snow cover; such conditions force birds to commit to repeated and prolonged recess periods at far distant feeding areas, leaving nests open to predation. By contrast, nesting success at the open tundra slope was learn more not affected by spring snow cover; even if birds were apparently in poor condition they could feed immediately adjacent to their nests and defend them from predators. Foxes were the main nest predator in the open tundra slopes but avian predators JNJ-26481585 manufacturer likely had a larger impact at the steep cliffs colony. Thus, the relative inaccessibility

of the cliffs habitat may bring protection from foxes but also deprives geese from readily accessing feeding areas, with the best prospects for successful nesting in low spring snow cover years. Our findings indicate that spring snow cover, predator abundance and food proximity did not uniformly influence nesting success of this herbivore, and their effects were dependent on nesting habitat choice.”
“As an important enzyme in the conjugation phase of drug clearance, UGT2B4 helps metabolize various endogenous and exogenous substances, and polymorphisms in the corresponding gene can influence enzyme activity. This study investigated the association between polymorphisms in UGT2B4 and the risk of developing pancreatic cancer in Han Chinese individuals. A hospital-based case-control study was conducted with 1579 healthy controls and 406 pancreatic cancer patients from China. Genomic DNA was obtained from peripheral blood lymphocytes.

We used this approach to investigate the biochemical effects of a-tocopherol in the liver using a rat model. Rats (21-day-old) were fed either an a-tocopherol-sufficient control (n = 10) or an a-tocopherol-deficient (n 10) diet for 2 months before sacrifice. Livers were homogenized in methanol-chloroform-water (3 : 1 : 1, v/v/v), and the polar phase extracts of the liver samples were analyzed using H-1 NMR. Multivariate statistical analysis of the data was performed using

principal component analysis and orthogonal partial least squares-discriminant analysis. Identification of H-1 NMR signals was performed primarily using the Human Metabolome Database, Biological Magnetic Resonance Data Bank Selleckchem GDC-0994 and previous literature, and confirmed by spiking with metabolites and applying two-dimensional NMR. The statistical analysis revealed that alpha-tocopherol deficiency caused an www.selleckchem.com/products/Staurosporine.html increase in carnitine, choline, L-valine, L-lysine, tyrosine and inosine content and a reduction in glucose and uridine 5′-monophosphate content. Changes in carnitine and glucose suggest a possible shift in energy metabolism. Copyright (C) 2010 John Wiley & Sons, Ltd.”
“A 71-year-old man presented with disfiguring skin

changes of the nose and cheek. The patient had undergone a surgery of a malignant melanoma of the right paranasal sinus and then 5 months later received radiation therapy with 60 Gy total dose to the endonasal area. Physical examination revealed elastosis, open and closed comedones, and cysts check details in the field of radiation exposure. Taking in account the exclusive affection of the irradiated skin, we diagnosed a radiation-induced Favre-Racouchot disease. We recommended topical treatment with vitamin A derivatives in combination with physical comedo extraction.”
“For tissue engineering

applications, scaffolds should be porous to enable rapid nutrient and oxygen transfer while providing a three-dimensional (3D) microenvironment for the encapsulated cells. This dual characteristic can be achieved by fabrication of porous hydrogels that contain encapsulated cells. In this work, we developed a simple method that allows cell encapsulation and pore generation inside alginate hydrogels simultaneously. Gelatin beads of 150-300 mu m diameter were used as a sacrificial porogen for generating pores within cell-laden hydrogels. Gelation of gelatin at low temperature (4 degrees C) was used to form beads without chemical crosslinking and their subsequent dissolution after cell encapsulation led to generation of pores within cell-laden hydrogels. The pore size and porosity of the scaffolds were controlled by the gelatin bead size and their volume ratio, respectively. Fabricated hydrogels were characterized for their internal microarchitecture, mechanical properties and permeability.

Immature (L(4)) O. equi were present in two horses and removals were 0% in one horse and 39% in the other. Eyeworms (Thelazia lacrymalis) were found in one horse at necropsy. Even though a small number of horses were used in the present research, the commonality of their background made them ideal candidates as a group for this study. This aspect helps strengthen the validity of the interpretation of the findings.”
“Curcumin (Cur), one of the most widely used natural active constituents with a great variety of beneficial biological

and pharmacological activities, is a practically water-insoluble substance with a short biologic half-life. The aim of this study was to develop a sustained-release solid dispersion by employing water-insoluble carrier cellulose Metabolism inhibitor acetate for solubility enhancement, release control, and oral bioavailability improvement of Cur. Solid dispersions were characterized by solubility, in vitro drug release, Fourier transform infrared spectroscopy, X-ray diffractometry, and differential scanning calorimetry studies. The in vivo performance was assessed by a pharmacokinetic study. Solid-state characterization techniques revealed the amorphous nature of Cur in solid

dispersions. Solubility/dissolution of Cur was enhanced in the formulations in comparison with pure drug. Sustained-release see more profiles of Cur from the solid dispersions were ideally controlled in vitro up to 12 h. The optimized formulation provided an improved pharmacokinetic parameter (C (max) = 187.03 ng/ml, t (max) = 1.95 h) in rats as compared with pure drug (C (max) = 87.06 ng/ml, t (max) = 0.66 h). The information from this study suggests that the developed solid dispersions successfully enhanced the solubility and sustained release of poorly water-soluble drug Cur, thus improving its oral bioavailability effectively.”
“In

this study, PHA biosynthesis operon of Comamonas sp. EB172, an acid-tolerant strain, consisting of three genes encoding acetyl-CoA acetyltransferase (phaA(Co) gene, 1182 bp), acetoacetyl-CoA reductase (phaB(Co) gene, 738 bp) and PHA synthase, class I (phaC(Co) gene, 1694 bp) were identified. Sequence analysis of the phaA(Co), phaB(Co) and phaC(Co) genes selleck inhibitor revealed that they shared more than 85%, 89% and 69% identity, respectively, with orthologues from Delftia acidovorans SPH-1 and Acidovorax ebreus TPSY. The PHA biosynthesis genes (phaC(Co) and phaAB(Co))were successfully cloned in a heterologous host, Escherichia coil JM109. E. coli JM109 transformants harbouring pGEM’-phaC(Co)AB(Re) and pGEM’-phaC(Re)AB(Co) were shown to be functionally active synthesising 33 wt.% and 17 wt.% of poly(3-hydroxybutyrate) [P(3HB)]. E. coil JM109 transformant harbouring the three genes from the acid-tolerant Comamonas sp.

“
“OBJECTIVE-Diabetes increases the risk for microvascular disease. The retina and the brain both have intricate microvascular systems that are developmentally similar. We sought to examine whether microvascular lesions in the retina and in the brain

are associated and whether selleck chemicals this association differs among people with and without diabetes.\n\nRESEARCH DESIGN AND METHODS-The analysis included 4,218 participants of the Icelandic population-based Age, Gene/Environment Susceptibility-Reykjavik Study who were born in 1907-1935 and who were previously followed as a part of the Reykjavik Study. Retinal focal arteriolar narrowing, arteriovenous (AV) nicking, and microaneurysms/hemorrhages were evaluated on digital retinal images of both eyes. Cerebral micro-bleeds (CMBs) were evaluated from magnetic resonance images. Data were analyzed with logistic and multinomial logistic regression models controlling for demographics, major cardiovascular risk factors, cerebral infarcts, and white matter lesions.\n\nRESULTS-Evidence of brain microbleeds was found in 485 (11.5%) people, including 192 with multiple ( >= 2) microbleeds. Subjects with signs of retinal microvascular lesions were at a significantly Liproxstatin-1 supplier increased likelihood for having multiple CMBs, People with diabetes

in combination with the presence of either retinal AV nicking (odds ratio [OR] 2.47 [95% CI 1.42-4.31]) or retinal microaneurysms/hemorrhages (2.28 [1.24-4.18]) were significantly more likely to have multiple CMBs.\n\nCONCLUSIONS-Retinal microvascular abnormalities and brain microbleeds may occur together in older adults. People with both diabetes and signs of click here retinal microvascular lesions

(AV nicking and microaneurysms/hemorrhages) are more likely to have multiple microbleeds in the brain. Microvascular disease in diabetes extends to the brain.”
“The molecular mechanisms governing PEPC expression in maize remain to be fully defined. Differential methylation of a region in the PEPC promoter has been shown to correlate with transcript accumulation, however, to date, investigations into the role of DNA methylation in maize PEPC expression have relied on the use of methylation-sensitive restriction enzymes. Bisulphite sequencing was used here to provide a single-base resolution methylation map of the maize PEPC promoter. It is shown that four cytosine residues in the PEPC promoter are heavily methylated in maize root tissue. In leaves, de-methylation of these cytosines is dependent on illumination and is coincident with elevated PEPC expression. Furthermore, light-regulated de-methylation of these cytosines occurs only in mesophyll cells. No methylation was discovered in the 0.

In addition, this organism also possesses all the principal signaling cascades that modulate the cell metabolism in response to nutrient availability in higher eukaryotes, including the TOR and the PKA pathways. Therefore, yeast is an ideal system to study the regulation of autophagy by these signaling pathways. Here, we review the current state of our knowledge about the molecular events leading to the induction or inhibition of autophagy in yeast with special emphasis on the regulation of the function of Atg proteins. (C) 2009 Elsevier B.V. All rights reserved.”
“Protein

phosphatase 2B (PP2B) is one of the major brain phosphatases and can dephosphorylate tau at several phosphorylation sites in vitro. Previous studies that SB525334 manufacturer measured PP2B activity in human brain crude extracts showed that PP2B activity was either unchanged or decreased in Alzheimer’s disease (AD) brain. These results led to the speculation Compound C molecular weight that PP2B might regulate tau phosphorylation and that a down-regulation of PP2B might contribute to abnormal hyperphosphorylation of tau. In this study, we immunoprecipitated PP2B from brains of six AD subjects and seven postmortem-and age-matched controls and then measured the phosphatase activity. We found a three-fold increase in PP2B activity in AD brain as compared with control brains. The activation was due to the partial cleavage of PP2B by calpain I that was activated in AD brain. The truncation

of PP2B appeared to alter its intracellular distribution in the brain. In human brains, PP2B activity correlated positively, rather than negatively, to the levels of tau phosphorylation at several sites that can be dephosphorylated by PP2B in vitro. Truncation of PP2B in the frontal cortex was more than in the temporal cortex, and tau phosphorylation was also more in the frontal cortex. Taken together, these results indicate

that truncation of PP2B by calpain I elevates its activity but does not counteract the abnormal hyperphosphorylation of tau in AD brain.”
“The rise in pediatric obesity since the 1970s has been well established in the United States and is becoming a major concern worldwide. selleck chemicals As a potential means to help slow the obesity epidemic, low-calorie sweeteners (LCS) have gained attention as dietary tools to assist in adherence to weight loss plans or prevention of excess weight gain. Observational studies tend to show positive correlations between LCS consumption and weight gain in children and adolescents. Although the data are intriguing, these epidemiologic studies do not establish that LCS cause weight gain, because there are likely many lifestyle and genetic differences between children and families who choose to consume LCS and those who do not. Short-term randomized controlled trials have shown LCS use to be BMI neutral or to have modest weight-reducing effects in overweight and obese adolescents.

Despite higher sulphate concentration, the microbial metabolism was greatly compromised or absent in the acidified slurry. This could be explained by the high concentration

of protonized short-chained volatile fatty acids in the acidified slurry (approximately 25 mM, compared to untreated slurry <0.1 mM), which act as an uncoupling agent of the cell membrane potential and thereby arrest microbial metabolism. In total the consequences of slurry acidification are greatly reduced production https://www.selleckchem.com/products/sbe-b-cd.html rates and loss of sulphide and methane, and eliminated loss of ammonia. On the other hand, increased volatilization and loss of smelly fatty acids is to be expected. (C) 2008 IAgrE. Published by Elsevier Ltd. All rights reserved.”
“Evaluation for endocrine function is a pivotal part of the male infertility workup. Endocrine dysfunction may result from endogenous and exogenous sources. This article describes the traditional roles that the hypothalamic-pituitary-gonadal endocrine axis plays in spermatogenesis and testicular dysfunction, as well as other insults that may contribute to hypospermatogenesis. Recent research into the role alternative hormonal axes play in spermatogenesis

and promising new technologies that may correct inborn or acquired endocrinopathies leading to impaired sperm growth and maturation are discussed.”
“Honokiol, a novel antitumor agent, could induce buy Saracatinib apoptosis and inhibit the growth of vascular endothelium in several tumor cell lines and xenograft models. It has been suggested that the antitumor effect of chemotherapy could be increased by combining

it with an antiangiogenesis agent in anticancer strategy. The present study explored the potential to increase the antitumor effect of adriamycin by combining it with honokiol in mouse 4T1 breast cancer models, and the underlining mechanism was investigated. Honokiol was encapsulated in liposomes to improve the water insolubility. In vitro, liposomal honokiol inhibited the proliferation of 4T1 cells via apoptosis and significantly enhanced the apoptosis of 4T1 cells induced by adriamycin. In vivo, the systemic administration BIIB057 cell line of liposomal honokiol and adriamycin significantly decreased tumor growth through increased tumor cell apoptosis compared with either treatment alone. Collectively, these findings suggest that liposomal honokiol may augment the induction of apoptosis in 4T1 cells ill vitro and in vivo, and this combined treatment has shown synergistic suppression in tumor progression according to the analysis of isobologram. The present study may be important in future exploration of the potential application of the combined approach in the treatment of breast cancer. Copyright (C) 2008 John Wiley & Sons, Ltd.

More importantly, BKM120 treatment significantly inhibits tumor growth in vivo and prolongs the survival of myeloma-bearing mice. In addition,

BKM120 shows synergistic cytotoxicity with dexamethasone in dexamethasone-sensitive MM cells. Low doses of BKM120 and dexamethasone, each of which alone has limited cytotoxicity, induce significant cell apoptosis in MM.1S and ARP-1. Mechanistic study shows that BKM120 exposure causes cell cycle arrest by upregulating p27 (Kip1) and downregulating cyclin D1 and induces caspase-dependent apoptosis by downregulating antiapoptotic XIAP and upregulating expression KPT-8602 of cytotoxic small isoform of Bim, BimS. In summary, our findings demonstrate the in vitro and in vivo anti-MM activity

of BKM120 and suggest that BKM120 alone or together with other MM chemotherapeutics, particularly dexamethasone, may be a promising treatment for MM.”
“Background\n\nThe potential benefits and harms of different lighting in neonatal units have not been quantified.\n\nObjectives\n\nTo compare the effectiveness of cycled lighting (CL) (approximately 12 hours of light on and 12 hours of light off) with irregularly dimmed light (DL) or near darkness (ND) and with continuous bright light (CBL) on growth in preterm infants at three and six months of age.\n\nSearch methods\n\nWe conducted electronic searches of the literature (in January 2013) of the Cochrane Central Register of Controlled Trials, Issue 12, 2012 (CENTRAL), MEDLINE, EMBASE, CINAHL and abstracts from Pediatric Academic Societies’ annual meetings. We searched Controlled-trials.com https://www.selleckchem.com/products/mk-5108-vx-689.html and Clinicaltrials.gov for ongoing trials and abstracts from the Pediatric Academic Societies (PAS) Annual Meetings (2000 to 2013) using the Abstracts2view website on 10 May 2013.\n\nSelection criteria\n\nRandomized or quasi-randomised trials of CL versus ND or CBL in preterm and low birth weight infants.\n\nData collection and analysis\n\nWe AZD1208 performed data collection and analyses according

to the methods of the Cochrane Neonatal Review Group.\n\nMain results\n\nSix studies enrolling 424 infants compared CL versus ND (including one additional trial identified in this update that enrolled 37 infants). No study reported on weight at three or six months. In one study (n = 40), there was no statistically significant difference in weight at four months between the CL and ND groups. In another study (n = 62), the ratio of day-night activity prior to discharge favoured the CL group (mean difference (MD) 0.18, 95% confidence interval (CI) 0.17 to 0.19) indicating 18% more activity during the day than during the night in the CL group compared with the ND group. Two studies (n = 189) reported on retinopathy of prematurity (stage >= 3). There was no statistically significant difference between the CL and ND groups (typical risk ratio (RR) 0.53,95% CI 0.25 to 1.

Annual rates of low-density lipoprotein cholesterol testing differentially improved for beneficiaries with diabetes in the intervention group by 3.1 percentage points (95% CI, 1.4-4.8 percentage points; P < .001) and for those with cardiovascular disease by 2.5 percentage points (95% CI, 1.1-4.0 percentage points; P < .001), but performance on other quality measures did not differentially change.\n\nCONCLUSIONS AND RELEVANCE The AQC was associated with lower spending for Medicare beneficiaries but not with consistently improved quality. Savings among Medicare

beneficiaries BEZ235 and previously demonstrated savings among BCBS enrollees varied similarly across settings, services, and time, suggesting that organizational responses were associated with broad changes in patient care.”
“Background\n\nVaginismus is an involuntary contraction of the vaginal muscles which makes sexual intercourse difficult or impossible. It is one of the more common female psychosexual problems. Various therapeutic strategies for vaginismus, such as sex therapy and desensitisation, have been proposed, and uncontrolled case series appear promising.\n\nObjectives\n\nTo assess the effects of different interventions for vaginismus.\n\nSearch methods\n\nWe searched the Cochrane Depression,

Anxiety and Neurosis Group’s Specialised Register (CCDANCTR-Studies and CCDANCTR-References) to August 2012. This register contains relevant randomised controlled trials Nepicastat ic50 from: The Cochrane Library (all years), EMBASE (1974 to date), MEDLINE (1950 to date) and PsycINFO(1967 to date). We searched reference lists and conference abstracts. We contacted experts in the field regarding unpublished material.\n\nSelection criteria\n\nControlled trials comparing treatments for vaginismus with another treatment, a placebo treatment, treatment as usual or waiting list control.\n\nData collection and analysis\n\nThe review authors extracted data which we verified with the trial investigator where possible.\n\nMain results\n\nFive studies were included, of which four

with a total of 282 participants provided data. No meta-analysis was possible due to heterogeneity of comparisons within included studies as well as inadequate reporting of data. All studies were considered to be SNS-032 concentration at either moderate or high risk of bias. The results of this systematic review indicate that there is no clinical or statistical difference between systematic desensitisation and any of the control interventions (either waiting list control, systematic desensitisation combined with group therapy or in vitro (with women under instruction by the therapist) desensitisation) for the treatment of vaginismus. The dropout rates were higher in the waiting list groups.\n\nAuthors’ conclusions\n\nA clinically relevant effect of systematic desensitisation when compared with any of the control interventions cannot be ruled out. None of the included trials compared other behaviour therapies ( e.