Chlamydia pecorum-Induced Arthritis in Experimentally and Naturally Infected Sheep.

Chlamydia pecorum is an obligate intracellular pathogen with a wide host range including livestock such as sheep, cattle, goats, and pigs as well as wildlife species such as koalas. Chlamydial polyarthritis is an economically important disease resulting in swollen joints, lameness, stiffness, and weight loss in young sheep. In the present study, tissues from sheep experimentally or naturally infected with Chlamydia pecorum were assessed by histopathology and immunohistochemistry. Carpal, hock, and stifle joints as well as spleen, liver, kidney, lymph nodes, lung, and brain of 35 sheep from different inoculation groups were available. Two different C. pecorum strains (IPA and E58), different routes of administration (intraarticular or intravenous), UVA-irradiated IPA strain, and corresponding noninfected control groups were investigated. Similar investigations on tissues from 5 naturally infected sheep were performed. The most obvious inflammatory lesions were observed in synovial tissues and, notably, in the renal pelvis from the experimentally infected group and naturally infected animals. This resulted in chronic or chronic-active arthritis and pyelitis. Intralesional chlamydial inclusions could be demonstrated by immunohistochemistry in both tissues. Immunohistochemical evaluation of the presence and distribution of macrophages, T and B cells in synovial tissues revealed macrophages as the most prevalent inflammatory cell population. Previous observations indicated that C. pecorum isolates can infect circulating monocytes. Together with the finding of the histological lesions in synovial tissues and internal organs alongside the presence of C. pecorum DNA, these observations suggest chlamydial arthritis in lambs is the result of hematogeneous spread of C. pecorum.

Protocol for motor and language mapping by navigated TMS in patients and healthy volunteers; workshop report.

INTRODUCTION: Navigated transcranial magnetic stimulation (nTMS) is increasingly used for preoperative mapping of motor function, and clinical evidence for its benefit for brain tumor patients is accumulating. In respect to language mapping with repetitive nTMS, literature reports have yielded variable results, and it is currently not routinely performed for presurgical language localization. The aim of this project is to define a common protocol for nTMS motor and language mapping to standardize its neurosurgical application and increase its clinical value. METHODS: The nTMS workshop group, consisting of highly experienced nTMS users with experience of more than 1500 preoperative nTMS examinations, met in Helsinki in January 2016 for thorough discussions of current evidence and personal experiences with the goal to recommend a standardized protocol for neurosurgical applications. RESULTS: nTMS motor mapping is a reliable and clinically validated tool to identify functional areas belonging to both normal and lesioned primary motor cortex. In contrast, this is less clear for language-eloquent cortical areas identified by nTMS. The user group agreed on a core protocol, which enables comparison of results between centers and has an excellent safety profile. Recommendations for nTMS motor and language mapping protocols and their optimal clinical integration are presented here. CONCLUSION: At present, the expert panel recommends nTMS motor mapping in routine neurosurgical practice, as it has a sufficient level of evidence supporting its reliability. The panel recommends that nTMS language mapping be used in the framework of clinical studies to continue refinement of its protocol and increase reliability.

Is outcome of constraint-induced movement therapy in unilateral cerebral palsy dependent on corticomotor projection pattern and brain lesion characteristics?

AIM: The aim of the study was to explore individual variations in outcome of hand function after constraint-induced movement therapy (CIMT) in relation to the organization of corticomotor projection and brain lesion characteristics in participants with unilateral cerebral palsy (CP). METHOD: Sixteen participants (eight males, eight females; mean age 13 y, [SD 2 y] range 10-16 y) with unilateral CP (nine right-sided; Manual Ability Classification System [MACS] level I, n=1; level II, n=15) who participated in a 2-week CIMT day camp (63 h) were included in the study. Various aspects of hand function were measured by the Jebsen-Taylor Hand Function Test (JTHFT), the Assisting Hand Assessment (AHA), and the Melbourne Assessment, both before and after the day camp. Transcranial magnetic stimulation was used to explore the corticomotor organization, and brain lesion characteristics were described by visual assessment of conventional structural magnetic resonance images. RESULTS: At a group level, the training was associated with significant improvements in JTHFT (p=0.003) and AHA (p=0.046), but not in Melbourne Assessment scores. Improvements were found in all types of corticomotor projection patterns, i.e. contralateral, mixed, and ipsilateral. There was no relationship between functional improvement and brain lesion characteristics. INTERPRETATION: Individuals with CP experience improved motor outcomes after CIMT, independent of corticomotor projection pattern and lesion characteristics.

CosSIF: Cosine similarity-based image filtering to overcome low inter-class variation in synthetic medical image datasets.

Crafting effective deep learning models for medical image analysis is a complex task, particularly in cases where the medical image dataset lacks significant inter-class variation. This challenge is further aggravated when employing such datasets to generate synthetic images using generative adversarial networks (GANs), as the output of GANs heavily relies on the input data. In this research, we propose a novel filtering algorithm called Cosine Similarity-based Image Filtering (CosSIF). We leverage CosSIF to develop two distinct filtering methods: Filtering Before GAN Training (FBGT) and Filtering After GAN Training (FAGT). FBGT involves the removal of real images that exhibit similarities to images of other classes before utilizing them as the training dataset for a GAN. On the other hand, FAGT focuses on eliminating synthetic images with less discriminative features compared to real images used for training the GAN. The experimental results reveal that the utilization of either the FAGT or FBGT method reduces low inter-class variation in clinical image classification datasets and enables GANs to generate synthetic images with greater discriminative features. Moreover, modern transformer and convolutional-based models, trained with datasets that utilize these filtering methods, lead to less bias toward the majority class, more accurate predictions of samples in the minority class, and overall better generalization capabilities. Code and implementation details are available at: https://github.com/mominul-ssv/cossif.

Grip force coordination during bimanual tasks in unilateral cerebral palsy.

AIM: The aim of the study was to investigate coordination of fingertip forces during an asymmetrical bimanual task in children with unilateral cerebral palsy (CP). METHOD: Twelve participants (six males, six females; mean age 14y 4mo, SD 3.3y; range 9-20y;) with unilateral CP (eight right-sided, four left-sided) and 15 age-matched typically developing participants (five males, 10 females; mean age 14y 3mo, SD 2.9y; range 9-18y,) were included. Participants were instructed to hold custom-made grip devices in each hand and place one device on top of the other. The grip force and load force were recorded simultaneously in both hands. RESULTS: Temporal coordination between the two hands was impaired in the participants with CP (compared with that in typically developing participants), that is they initiated the task by decreasing grip force in the releasing hand before increasing the force in the holding hand. The grip force increase in the holding hand was also smaller in participants with CP (involved hand/non-dominant hand releasing, p<0.001; non-involved hand/dominant hand releasing, p=0.007), indicating deficient scaling of force amplitude. The impairment was greater when participants with CP used their non-involved hand as the holding hand. INTERPRETATION: Temporal coordination and scaling of fingertip forces were impaired in both hands in participants with CP. The non-involved hand was strongly affected by activity in the involved hand, which may explain why children with unilateral CP prefer to use only one hand during tasks that are typically performed with both hands.

Hand function in relation to brain lesions and corticomotor-projection pattern in children with unilateral cerebral palsy.

AIM: To investigate relationships between hand function, brain lesions, and corticomotor projections in children with unilateral cerebral palsy (CP). METHOD: The study included 17 children (nine males, eight females; mean age 11.4 [SD 2.4] range 7-16 y), with unilateral CP at Gross Motor Function Classification System level I and Manual Ability Classification System level I or II. Hand function was assessed with the Box and Blocks test and Assisting Hand Assessment (AHA). Conventional structural magnetic resonance images were assessed visually for type, location, and extent of brain lesions. Single-pulse transcranial magnetic stimulation (TMS) provided information on organization of corticomotor projections. RESULTS: The most favourable hand function was seen in children who had white-matter damage of immaturity with mild white-matter loss and contralateral motor projections. Children with ipsilateral projections had the most impaired function. Nevertheless, in this subgroup a range of ability was seen (AHA 29-59%). Motor-projection patterns appeared to be influenced by lesion extent and location, but not by lesion type. INTERPRETATION: Combining information from structural magnetic resonance images and TMS can improve prediction of hand function. A wide variation in hand function was seen within all motor-projection patterns. Although the most impaired hand function was seen in the ipsilateral motor-projection group, some children in this group had fairly good ability. Such information is important for treatment planning.

Integrating navigated transcranial magnetic stimulation motor mapping in hypofractionated and single-dose gamma knife radiosurgery: A two-patient case series and a review of literature.

BACKGROUND: The aim of the study was to demonstrate the feasibility of integrating navigated transcranial magnetic stimulation (nTMS) in preoperative gamma knife radiosurgery (GKRS) planning of motor eloquent brain tumors. CASE DESCRIPTION: The first case was a 53-year-old female patient with metastatic breast cancer who developed focal epileptic seizures and weakness of the left hand. The magnetic resonance imaging (MRI) scan demonstrated a 30 mm metastasis neighboring the right precentral gyrus and central sulcus. The lesion was treated with adaptive hypofractionated GKRS following preoperative nTMS-based motor mapping. Subsequent follow-up imaging (up to 12 months) revealed next to complete tumor ablation without toxicity. The second case involved a previously healthy 73-year-old male who similarly developed new left-handed weakness. A subsequent MRI demonstrated a 26 mm metastatic lesion, located in the right postcentral gyrus and 5 mm from the hand motor area. The extracranial screening revealed a likely primary lung adenocarcinoma. The patient underwent preoperative nTMS motor mapping prior to treatment. Perilesional edema was noted 6 months postradiosurgery; nevertheless, long- term tumor control was demonstrated. Both patients experienced motor function normalization shortly after treatment, continuing to final follow-up. CONCLUSION: Integrating preoperative nTMS motor mapping in treatment planning allowed us to reduce dose distributions to perilesional motor fibers while achieving salvage of motor function, lasting seizure freedom, and tumor control. These initial data along with our review of the available literature suggest that nTMS can be of significant assistance in brain radiosurgery. Prospective studies including larger number of patients are still warranted.

Heterozygous variants in DCC: Beyond congenital mirror movements.

OBJECTIVE: To perform a comprehensive characterization of a cohort of patients with congenital mirror movements (CMMs) in Sweden. METHODS: Clinical examination with the Woods and Teuber scale for mirror movements (MMs), neuroimaging, navigated transcranial magnetic stimulation (nTMS), and massive parallel sequencing (MPS) were applied. RESULTS: The cohort is ethnically diverse and includes a total of 7 patients distributed in 2 families and 2 sporadic cases. The degree of MMs was variable in this cohort. MPS revealed 2 novel heterozygous frameshift variants in DCC netrin 1 receptor (DCC). Two siblings harboring the pathogenic variant in c.1466_1476del display a complex syndrome featuring MMs and in 1 case receptive-expressive language disorder, chorea, epilepsy, and agenesis of the corpus callosum. The second DCC variant, c.1729delG, was associated with a typical benign CMM phenotype. No variants in DCC, NTN1, RAD51, or DNAL4 were found for the 2 sporadic CMM cases. However, one of these sporadic cases had concomitant high-risk myelodysplastic syndrome and a homozygous variant in ERCC excision repair like 2 (ERCC6L2). Reorganized corticospinal projection patterns to upper extremities were demonstrated with nTMS. CONCLUSIONS: The presence of chorea expands the clinical spectrum of syndromes associated with variants in DCC. Biallelic pathogenic variants in ERCC6L2 cause bone marrow failure, but a potential association with CMM remains to be studied in larger cohorts.

Stereotactic Brain Biopsy in Eloquent Areas Assisted by Navigated Transcranial Magnetic Stimulation: a Technical Case Report.

BACKGROUND AND IMPORTANCE: Stereotactic brain biopsy (SB) is an important part of the neurosurgical armamentarium, with the possibility of achieving histopathological diagnosis in otherwise inaccessible lesions of the brain. Nevertheless, the procedure is not without the risk of morbidity, which is especially true for lesions in eloquent parts of the brain, where even a minor adverse event can result in significant deficits. Navigated transcranial magnetic stimulation (nTMS) is widely used to chart lesions in eloquent areas, successfully guiding maximal safe resection, while its potential role in aiding with the planning of a stereotactic biopsy is so far unexplored. CLINICAL PRESENTATION: Magnetic resonance imaging of a 67-yr-old woman presenting with dysphasia revealed a noncontrast enhancing left-sided lesion in the frontal and parietal pars opercularis. Due to the location of the lesion, nTMS was used to chart both primary motor and language cortex, utilizing this information to plan a safe SB trajectory and sampling area according to the initial work-up recommendations from the multidisciplinary neuro-oncology board. The SB was uneventful, with histology revealing a ganglioglioma, WHO I. The patient was discharged the following day, having declined to proceed with tumor resection (awake surgery) due to the non-negligible risk of morbidity. Upon 1- and 3-mo follow-up, she showed no signs of any procedure-related deficits. CONCLUSION: nTMS can be implemented to aid with the planning of a stereotactic biopsy procedure in eloquent areas of the brain, and should be considered part of the neurosurgical armamentarium.

Folic acid supplementation lowers blood arsenic.

BACKGROUND: Chronic arsenic exposure currently affects >100 million persons worldwide. Methylation of ingested inorganic arsenic (InAs) to monomethylarsonic (MMAs) and dimethylarsinic (DMAs) acids relies on folate-dependent one-carbon metabolism and facilitates urinary arsenic elimination. OBJECTIVE: We hypothesized that folic acid supplementation to arsenic-exposed Bangladeshi adults would increase arsenic methylation and thereby lower total blood arsenic. DESIGN: In this randomized, double-blind, placebo-controlled trial, we evaluated blood concentrations of total arsenic, InAs, MMAs, and DMAs in 130 participants with low plasma folate (<9 nmol/L) before and after 12 wk of supplementation with folic acid (400 microg/d) or placebo. RESULTS: MMAs in blood was reduced by a mean +/- SE of 22.24 +/- 2.86% in the folic acid supplementation group and by 1.24 +/- 3.59% in the placebe group (P < 0.0001). There was no change in DMAs in blood; DMAs is rapidly excreted in urine as evidenced by an increase in urinary DMAs (P = 0.0099). Total blood arsenic was reduced by 13.62% in the folic acid supplementation group and by 2.49% in the placebo group (P = 0.0199). CONCLUSIONS: Folic acid supplementation to participants with low plasma concentrations of folate lowered blood arsenic concentrations, primarily by decreasing blood MMAs and increasing urinary DMAs. Therapeutic strategies to facilitate arsenic methylation, particularly in populations with folate deficiency or hyperhomocysteinemia or both, may lower blood arsenic concentrations and thereby contribute to the prevention of arsenic-induced illnesses.

Effect of maternal status and breastfeeding practices on infant nutritional status - a cross sectional study in the south-west region of Bangladesh.

INTRODUCTION: The aim of this study was to address the current scenario of LBW and infant nutritional and to analyze the effect of maternal status and pattern of their breast feeding practices on perinatal and postnatal infant development. METHODS: Cross-sectional study design with structured questionnaires was used among 510 mother-infant pair to collect data. Maternal anthropometric, socio-economic and demographic characteristics and breast feeding practice were used as independent variable and birth weight and infant growth status as dependent variable. Descriptive and crosstab analysis were used to analyze the effect. RESULTS: The study revealed that about 29.4% infants were born with low birth weight (LBW). Mother with no education and from low income family were more likely (OR: 3.484, 95%CI: 1.993-6.089 and OR: 2.078, 95% CI: 1.274-3.387) to have LBW infant compared with mother with higher education and from higher income family. Similarly, lower maternal height, weight and MUAC (< 150 cm, <50 kg and < 22 cm respectively) were shown to have more risk of having LBW compared with higher height, weight and MUAC (RR: 1.628, 2.375 and 2.115; 95%CI: 1.250- 2.120, 1.844- 3.059, 1.623- 2.757). The prevalence of exclusive breastfeeding was found among 45% mother. Postnatal growth and development of infant was not found significantly different (P > 0.05) among those who breast feed exclusively and non-exclusively. CONCLUSION: The study confirms that lower level of maternal education; family income and anthropometric measurement significantly increase the risk of LBW. The prevalence of exclusive breastfeeding practice was not found satisfactory.

Pemetrexed therapy in elderly patients with good performance status: analysis of two phase III trials of patients with nonsquamous non-small-cell lung cancer.

INTRODUCTION: A widely held misperception contends that all elderly patients, even those with good performance status (PS 0-1), are unable to tolerate aggressive chemotherapy. The objective of these analyses was to evaluate the survival and safety of treatment with pemetrexed in elderly patients with nonsquamous non-small-cell lung cancer (NSCLC) and PS 0-1. PATIENTS AND METHODS: Two randomized studies, 1 reporting the activity of pemetrexed in combination with cisplatin vs. cisplatin and gemcitabine in chemotherapy-naive patients (N = 1725) and another comparing single-agent pemetrexed with placebo in the maintenance setting (N = 663) were retrospectively considered. Data from patients with nonsquamous advanced NSCLC with PS 0-1 in these studies were evaluated in 2 separate dichotomous analyses (< 65 years and ≥ 65 years and < 70 years and ≥ 70). Cox proportional hazard models were used to estimate covariate-adjusted between-arm hazard ratios (HRs) with 95% confidence intervals for each age group. RESULTS: In the first-line study, 32.7% of the 1252 patients with nonsquamous NSCLC were ≥ 65 years and 12.8% were ≥ 70 years old. In the maintenance study, 33.1% of the 481 patients with nonsquamous NSCLC were ≥ 65 years and 16.0% were ≥ 70 years old. In both studies, the adjusted HRs for overall survival (range, 0.62-0.89) favored pemetrexed and were similar between the older and younger age groups. Dose intensity delivered and toxicities observed for patients treated with pemetrexed were manageable and similar between the older and younger age groups. CONCLUSIONS: For elderly patients with nonsquamous advanced NSCLC and PS 0-1, pemetrexed therapy, with its favorable toxicity profile, is a viable option, either in combination with cisplatin in the first-line setting or as maintenance therapy after initial chemotherapy.

Validation of a new biomechanical model to measure muscle tone in spastic muscles.

BACKGROUND: There is no easy and reliable method to measure spasticity, although it is a common and important symptom after a brain injury. OBJECTIVE: The aim of this study was to develop and validate a new method to measure spasticity that can be easily used in clinical practice. METHODS: A biomechanical model was created to estimate the components of the force resisting passive hand extension, namely (a) inertia (IC), (b) elasticity (EC), (c) viscosity (VC), and (d) neural components (NC). The model was validated in chronic stroke patients with varying degree of hand spasticity. Electromyography (EMG) was recorded to measure the muscle activity induced by the passive stretch. RESULTS: The model was validated in 3 ways: (a) NC was reduced after an ischemic nerve block, (b) NC correlated with the integrated EMG across subjects and in the same subject during the ischemic nerve block, and (c) NC was velocity dependent. In addition, the total resisting force and NC correlated with the modified Ashworth score. According to the model, the neural and nonneural components varied between patients. In most of the patients, but not in all, the NC dominated. CONCLUSIONS: The results suggest that the model allows valid measurement of spasticity in the upper extremity of chronic stroke patients and that it can be used to separate the neural component induced by the stretch reflex from resistance caused by altered muscle properties.