The Distribution of Toxoplasma gondii Cysts in the Brain of a Mouse with Latent Toxoplasmosis: Implications for the Behavioral Manipulation Hypothesis

reportedly manipulates rodent behavior to enhance the likelihood of transmission to its definitive cat host. The proximate mechanisms underlying this adaptive manipulation remain largely unclear, though a growing body of evidence suggests that the parasite-entrained dysregulation of dopamine metabolism plays a central role. Paradoxically, the distribution of the parasite in the brain has received only scant attention. at six months of age and examined 18 weeks later. The cysts were distributed throughout the brain and selective tropism of the parasite toward a particular functional system was not observed. Importantly, the cysts were not preferentially associated with the dopaminergic system and absent from the hypothalamic defensive system. The striking interindividual differences in the total parasite load and cyst distribution indicate a probabilistic nature of brain infestation. Still, some brain regions were consistently more infected than others. These included the olfactory bulb, the entorhinal, somatosensory, motor and orbital, frontal association and visual cortices, and, importantly, the hippocampus and the amygdala. By contrast, a consistently low incidence of tissue cysts was recorded in the cerebellum, the pontine nuclei, the caudate putamen and virtually all compact masses of myelinated axons. Numerous perivascular and leptomeningeal infiltrations of inflammatory cells were observed, but they were not associated with intracellular cysts. distribution stems from uneven brain colonization during acute infection and explains numerous behavioral abnormalities observed in the chronically infected rodents. Thus, the parasite can effectively change behavioral phenotype of infected hosts despite the absence of well targeted tropism

The relationship between pain with walking and self-rated health 12 months following total knee arthroplasty: a longitudinal study

Background A subgroup of patients continue to report pain with walking 12 months after total knee arthroplasty (TKA). The association between walking pain and self-rated health (SRH) after TKA is not known. This prospective longitudinal study aimed to investigate the association between a comprehensive list of preoperative factors, postoperative pain with walking, and SRH 12 months after TKA. Methods Patients (N = 156) scheduled for TKA completed questionnaires that evaluated demographic and clinical characteristics, symptoms, psychological factors, and SRH. SRH was re-assessed 12 months after TKA. Clinical variables were retrieved from medical records. Pain with walking was assessed before surgery, at 6 weeks, 3, and 12 months after TKA. Subgroups with distinct trajectories of pain with walking over time were identified using growth mixture modeling. Multiple linear regression was used to investigate the relationships between pain with walking and other factors on SRH. Results Higher body mass index, a higher number of painful sites at 12 months, recurrent pain with walking group membership, ketamine use, higher depression scores, and poorer preoperative self-rated health were associated with poorer SRH 12 months after TKA. The final model was statistically significant (p = 0.005) and explained 56.1% of the variance in SRH 12 months after surgery. SRH improved significantly over time. Higher C-reactive protein levels, higher number of painful sites before surgery, higher fatigue severity, and more illness concern was associated with poorer preoperative SRH. Conclusions In patients whose walking ability decreases over time, clinicians need to assess for unreleaved pain and decreases in SRH. Additional research is needed on interventions to improve walking ability and SRH

Preoperative risk factors associated with chronic pain profiles following total knee arthroplasty.

BackgroundOne in five patients experience chronic pain 12 months following total knee arthroplasty (TKA). This longitudinal study used a person-centred approach to identify subgroups of patients with distinct chronic pain profiles following TKA and identified preoperative characteristics associated with these profiles.MethodsOn the day before surgery, 202 patients completed questionnaires that assessed pain, interference with functioning, fatigue, anxiety, depression and illness perceptions. Average and worst pain were assessed prior to surgery, on postoperative day 4, at 6 week and at 3 and 12 months following surgery. Using growth mixture modelling, two subgroups with distinct average and worst pain profiles were identified.ResultsPatients in the "lower average" and "lower worst" pain classes had moderate preoperative pain scores that decreased over the remaining 9 months following TKA. Patients in the "higher average" and "higher worst" pain classes had relatively higher preoperative pain scores that increased during the first three months and then decreased slightly over the remaining 9 months. Patients in the higher pain classes had higher interference with function scores; used opioids prior to surgery more often, were more likely to receive a continuous nerve block and ketamine; had higher preoperative fatigue severity and interference scores; and had worse perceptions of illness than patients in the lower pain classes.ConclusionsThese risk factors may be used to identify subgroups of patients at higher risk for more severe pain after TKA. Future studies should test whether modifying these risk factors can improve patients' outcomes after TKA.Significance statementThe present study provides a novel and original analysis of pain profiles following total knee arthroplasty that may contribute to our understanding of the transition from acute to chronic pain. Our results may be used to identify patients at higher risk for poorer outcomes based on preoperative risk factors

Efektivitas Berbagai Konsentrasi Kacang Kedelai (Glycine max (L.) Merill) Sebagai Media Alternatif Terhadap Pertumbuhan Jamur Candida albicans

Infeksi jamur kulit cukup banyak ditemukan di Indonesia, salah satu disebabkan oleh Candida albicans yaitu kandidiasis.Penyakit ini dapat diperiksa secara makroskopis dengan media SDA yang harganya cukup mahal, higroskopis dan tidak diperoleh sembarang tempat sehingga perlu dibuat media alternatif salah satunya yaitu menggunakan kacang kedelai. Penelitian ini bertujuan untuk mengetahui efektivitas berbagai konsentrasi kacang kedelai (Glycine max (L.) Merill) sebagai media alternatif terhadap pertumbuhan jamur Candida albicans. Jenis penelitian ini adalah penelitian eksperimen atau percobaan dengan post test with control group. Penelitian ini dilakukan pada bulan Februari 2015 di Laboratorium Mikrobiologi Jurusan Analis Kesehatan Poltekkes Kemenkes Yogyakarta. Obyek penelitian ini adalah kacang kedelai konsentrasi 2%, 4%, 6% dan 8% yang diujikan terhadap Candida albicans sebagai subyek penelitian. Media SDA (Sabouraud Dextrose Agar) digunakan sebagai kontrol terhadap pertumbuhan jamur Candida albicans. Pengolahan data yang digunakan meliputi uji deskriptif dan uji efektivitas. Hasil yang diperoleh diuji dengan uji deskriptif, didapatkan rata-rata koloni pada media kacang kedelai konsentrasi 2%, 4%, 6% dan 8% yaitu sebesar 3,67 koloni, 4,83 koloni, 5,17 kolonidan 5,33 koloni. Hasil uji efektivitas menunjukkan bahwa kacang kedelai dapat digunakan sebagai media alternative terhadap pertumbuhan jamur Candida albicans pada konsentrasi minimal 4% dengan hasil persentase sebesar 107,33%.Semakin tinggi konsentrasi kacang kedelai semakin banyak jumlah koloni yang dihasilka

Development of an internet-delivered cognitive behavioral therapy program for use in combination with exercise therapy and education by patients at increased risk of chronic pain following total knee arthroplasty

Background Approximately 20% of patients experience chronic pain after total knee arthroplasty (TKA). Due to the growing number of TKA procedures, this will affect an increasing number of people worldwide. Catastrophic thinking, dysfunctional illness perception, poor mental health, anxiety and depression characterize these non-improvers, and indicate that these patients may need individualized treatment using a treatment approach based on the bio-psycho-social health model. The present study developed an internet-delivered cognitive behavioral therapy (iCBT) program to be combined with exercise therapy and education for patients with knee osteoarthritis (OA) at increased risk of chronic pain after TKA. Methods The development process followed the first two phases of the UK Medical Research Council framework for complex interventions. In the development phase, the first prototype of the iCBT program was developed based on literature review, established iCBT programs and multidisciplinary workshops. The feasibility phase consisted of testing the program, interviewing users, condensing the program, and tailoring it to the patient group. A physiotherapist manual was developed and adapted to physiotherapists who will serve as mentors. Results The development process resulted in an iCBT program consisting of 10 modules with educational texts, videos and exercises related to relevant topics such as goalsetting, stress and pain, lifestyle, automatic thoughts, mindfulness, selective attention, worry and rumination. A physiotherapist manual was developed to guide the physiotherapists in supporting the patients through the program and to optimize adherence to the program. Conclusions The iCBT program is tailored to patients at risk of chronic pain following TKA, and may be useful as a supplement to surgery and/or exercise therapy. A multicentre RCT will evaluate the iCBT program in combination with an exercise therapy and education program. This novel intervention may be a valuable contribution to the treatment of OA patients at risk of chronic pain after TKA. Trial registration The RCT is pre-registered at ClinicalTrials.gov: NCT03771430 11/12/2018.

The effectiveness of exercise therapy and education plus cognitive behavioral therapy, alone or in combination with total knee arthroplasty in patients with knee osteoarthritis – study protocol for the MultiKnee trial

Background One in five patients report chronic pain following total knee arthroplasty (TKA) and are considered non-improvers. Psychological interventions such as cognitive behavioral therapy (CBT), combined with exercise therapy and education may contribute to reduced pain an improved function both for patients with OA or after TKA surgery, but the evidence for the effectiveness of such interventions is scarce. This randomized controlled trial with three arms will compare the clinical effectiveness of patient education and exercise therapy combined with internet-delivered CBT (iCBT), evaluated either as a non-surgical treatment choice or in combination with TKA, in comparison to usual treatment with TKA in patients with knee OA who are considered candidates for TKA surgery. Methods The study, conducted in three orthopaedic centers in Norway will include 282 patients between ages 18 and 80, eligible for TKA. Patients will be randomized to receive the exercise therapy + iCBT, either alone or in combination with TKA, or to a control group who will undergo conventional TKA and usual care physiotherapy following surgery. The exercise therapy will include 24 one hour sessions over 12 weeks led by a physiotherapist. The iCBT program will be delivered in ten modules. The physiotherapists will receive theoretical and practical training to advise and mentor the patients during the iCBT program. The primary outcome will be change from baseline to 12 months on the pain sub-scale from the Knee Injury and Osteoarthritis Outcome Score (KOOS). Secondary outcomes include the remaining 4 sub-scales from the KOOS (symptoms, function in daily living, function in sports and recreation, and knee-related quality of life), EQ-5D-5L, the Pain Catastrophizing Scale, the 30-s sit-to-stand test, 40-m walking test and ActiGraph activity measures. A cost-utility analysis will be performed using QALYs derived from the EQ-5D-5L and registry data. Discussion This is the first randomized controlled trial to investigate the effectiveness of exercise therapy and iCBT with or without TKA, to optimize outcomes for TKA patients. Findings from this trial will contribute to evidence-based personalized treatment recommendations for a large proportion of OA patients who currently lack an effective treatment option. Trial registration Clinicaltrials.gov : NCT03771430. Registered: Dec 11, 2018

Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome

OBJECTIVE: IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucrase-isomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase-isomaltase (SI) gene variants for their potential relevance in IBS. DESIGN: We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p.Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. RESULTS: CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case-control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05). CONCLUSIONS: SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients