Hereditary Spastic Paraplegia Type 43 (SPG43) is Caused by Mutation in C19orf12

We report here the genetic basis for a form of progressive hereditary spastic paraplegia (SPG43) previously described in two Malian sisters. Exome sequencing revealed a homozygous missense variant (c.187G>C; p.Ala63Pro) in C19orf12, a gene recently implicated in neurodegeneration with brain iron accumulation (NBIA). The same mutation was subsequently also found in a Brazilian family with features of NBIA, and we identified another NBIA patient with a three‐nucleotide deletion (c.197_199del; p.Gly66del). Haplotype analysis revealed that the p.Ala63Pro mutations have a common origin, but MRI scans showed no brain iron deposition in the Malian SPG43 subjects. Heterologous expression of these SPG43 and NBIA variants resulted in similar alterations in the subcellular distribution of C19orf12. The SPG43 and NBIA variants reported here as well as the most common C19orf12 missense mutation reported in NBIA patients are found within a highly conserved, extended hydrophobic domain in C19orf12, underscoring the functional importance of this domain.     

Short-term course and outcome of treatments of pleural empyema in pediatric patients: repeated ultrasound-guided needle thoracocentesis vs chest tube drainage

BACKGROUND: Several reports have suggested that early chest tube drainage (CTD) may not be necessary in the treatment of severe pleural empyema (PE) in pediatric patients if appropriate antibiotic therapy and supportive care are provided. OBJECTIVES: A prospective open study to compare the short-term course of two treatment protocols of severe PE in pediatric patients. STUDY DESIGN: One group of 32 patients was treated with early insertion of a chest tube for CTD, and a second group of 35 patients was treated by a repeated ultrasound-guided needle thoracocentesis (RUSGT). The severity of the empyema was assessed by chest radiograph, the amount of fluid drained, the number of days the patient had experienced a fever, and the duration of antibiotic treatment. RESULTS: No significant differences were found between the two groups (RUSGT vs CTD) in all of the following measurements: mean (plus minus SD) duration of a temperature > or = 39 degreesC, 6.2 +/- 2.4 vs 6.5 +/- 1.8 days, respectively; mean duration of a temperature > or = 38 degreesC, 9 +/- 3.9 vs 8.2 +/- 4.5 days, respectively; fluid drained, 35.1 + 23.8 vs 30 +/- 28.2 mL/kg, respectively; duration of antibiotic treatment, 30 +/- 13.2 vs 30.2 +/- 7.3 days, respectively; and length of hospitalization and home IV treatment, 22 +/- 7.6 vs 24.2 +/- 7.5 days, respectively. A failure to respond to treatment occurred in three patients in the RUSGT-treated group and in five patients in the CTD-treated group. The failure to respond occurred in the RUSGT-treated group only in those patients with very large empyemas that caused mediastinal deviation. CONCLUSION: The treatment of PE by RUSGT is as efficacious as CTD, unless PE causes mediastinal deviation.     

Functional neuroimaging of the interference between working memory and the control of periodic ankle movement timing

Background

Limited information processing capacity in the brain necessitates task prioritisation and subsequent adaptive behavioural strategies for the dual-task coordination of locomotion with severe concurrent cognitive loading. Commonly observed strategies include prioritisation of gait at the cost of reduced performance in the cognitive task. Alternatively alterations of gait parameters such as gait velocity have been reported presumably to free processing capacity for the benefit of performance in the cognitive task. The aim of this study was to describe the neuroanatomical correlates of adaptive behavioural strategies in cognitive-motor dual-tasking when the competition for information processing capacity is severe and may exceed individuals’ capacity limitations.

Methods

During an fMRI experiment, 12 young adults performed slow continuous, auditorily paced bilateral anti-phase ankle dorsi-plantarflexion movements as an element of normal gait at .5 Hz in single and dual task modes. The secondary task involved a visual, alphabetic N-back task with presentation rate jittered around .7 Hz. The N-back task, which randomly occurred in 0-back or 2-back form, was modified into a silent counting task to avoid confounding motor responses at the cost of slightly increasing the task′s general coordinative complexity. Participants’ ankle movements were recorded using an optoelectronic motion capture system to derive kinematic parameters representing the stability of the movement timing and synchronization. Participants were instructed to perform both tasks as accurately as possible.

Results

Increased processing complexity in the dual-task 2-back condition led to significant changes in movement parameters such as the average inter-response interval, the coefficient of variation of absolute asynchrony and the standard deviation of peak angular velocity. A regions-of-interest analysis indicated correlations between these parameters and local activations within the left inferior frontal gyrus (IFG) such that lower IFG activations coincided with performance decrements.

Conclusions

Dual-task interference effects show that the production of periodically timed ankle movements, taken as modelling elements of the normal gait cycle, draws on higher-level cognitive resources involved in working memory. The interference effect predominantly concerns the timing accuracy of the ankle movements. Reduced activations within regions of the left IFG, and in some respect also within the superior parietal lobule, were identified as one factor affecting the timing of periodic ankle movements resulting in involuntary ‘hastening’ during severe dual-task working memory load. This ‘hastening’ phenomenon may be an expression of re-automated locomotor control when higher-order cognitive processing capacity can no longer be allocated to the movements due to the demands of the cognitive task. The results of our study also propose the left IFG as a target region to improve performance during dual-task walking by techniques for non-invasive brain stimulation.     

First detection of Theileria parva in cattle from Cameroon in the absence of the main tick vector Rhipicephalus appendiculatus

A major risk factor for the spread of livestock diseases and their vectors is the uncontrolled transboundary movement of live animals for trade and grazing. Such movements constrain effective control of tick‐transmitted pathogens, including Theileria parva. Only limited studies have been undertaken to identify ticks and tick‐borne diseases (TTBDs) affecting cattle in central African countries, including Cameroon. We hereby report the collection of baseline data on the prevalence of T. parva in Cameroon through a countrywide cross‐sectional survey, conducted in 2016, involving collection of blood samples from cattle from 63 sites across the five agro‐ecological zones (AEZs) of the country. ELISA‐based surveillance of infected cattle was performed on 479 randomly selected samples and revealed specific antibodies to T. parva in 22.7% and T. mutans in 41.1% of cattle. Screening of 1,340 representative DNA samples for the presence of T. parva identified 25 (1.86%) positives using a p104 antigen gene‐based nested PCR assay. The positives were distributed across agro‐ecological zones I, II, III and V. None of the p104 positive cattle exhibited clinical symptoms of East Coast fever (ECF). Using reverse line blot (RLB), 58 (4.3%) and 1,139 (85%) of the samples reacted with the T. parva and T. mutans oligonucleotide probes, respectively. This represents the first report of T. parva from Cameroon. Surprisingly, no Rhipicephalus appendiculatus ticks, the main vector of T. parva, were identified in a parallel study involving comprehensive morphological and molecular survey of tick species present in the country. Only two of the 25 p104 positive cattle were PCR‐positive for the CD8+ T‐cell target schizont‐expressed antigen gene Tp1. Cloning and sequencing of Tp1 amplicons revealed sequence identity with the reference T. parva Muguga. This new finding raises serious concerns of a potential spread of ECF into the central African region.     

Organization and stability of a polytopic membrane protein: deletion analysis of the lactose permease of Escherichia coli.

The overall topology of polytopic membrane proteins is thought to result from either the oriented insertion of the N-terminal alpha-helical domain followed by passive insertion of subsequent helices or from the function of independent topogenic determinants dispersed throughout the molecules. By using the lactose permease of Escherichia coli, a well-characterized membrane protein with 12 transmembrane domains and the N and C termini on the cytoplasmic surface of the membrane, we have studied the insertion and stability of in-frame deletion mutants. So long as the first N-terminal and the last four C-terminal putative alpha-helical domains are retained, stable polypeptides are inserted into the membrane, even when an odd number of helical domains is deleted. Moreover, even when an odd number of helices is deleted, the C terminus remains on the cytoplasmic surface of the membrane, as judged by lacY-phoA fusion analysis. In addition, permease molecules devoid of even or odd numbers of putative transmembrane helices retain a specific pathway for downhill lactose translocation. The findings imply that relatively short C-terminal domains of the permease contain topological information sufficient for insertion in the native orientation regardless of the orientation of the N terminus.     

Do patients with chronic rhinosinusitis benefit from consultation with an ENT-doctor?

Conclusion: By consulting an ENT-doctor, patients with chronic rhinosinusitis (CRS), in the general population, receive disease information and adjustment of treatment which can improve disease-specific Quality-of-Life and may improve objective measurements. Objectives: This study aims to follow persons with clinical diagnosed CRS from the general population, to evaluate their benefit from consultation with an ENT-doctor in terms of severity of symptoms and Quality-of-Life. Methods: As part of a trans-European study, selected respondents to a survey questionnaire were invited for a clinical visit. Based on the European Position Paper on Rhinosinusitis and Nasal Polyps, persons were diagnosed with CRS and followed for 2 years. Quality-of-Life was measured using the Sino Nasal Outcome Test 22 and European Quality-of-Life – 5 Dimensions. Clinical examination included rhinoscopy, acoustic rhinometry, peak nasal inspiratory flow, smell test, and skin prick test. Results: Out of 91 persons with CRS, only 42% had previously consulted an ENT-doctor, and 51% were in current treatment for CRS. Most patients were advised medical treatment and 20% underwent surgery. Disease-specific Quality-of-Life, peak nasal inspiratory flow, olfactory function, and the nasal volume significantly increased over the 2-year period.     

Bleeding events and associated factors in a cohort of adult patients taking warfarin in Sarawak,Malaysia

Evidence is emerging that rates of adverse events in patients taking warfarin may vary with ethnicity. This study investigated the rates of bleeds and thromboembolic events, the international normalised ratio (INR) status and the relationship between INR and bleeding events in Malaysia. Patients attending INR clinic at the Heart Centre, Sarawak General Hospital were enrolled on an ad hoc basis from May 2010 and followed up for 1 year. At each routine visit, INR was recorded and screening for bleeding or thromboembolism occurred. Variables relating to INR control were used as predictors of bleeds in logistic regression models. 125 patients contributed to 140 person-years of follow-up. The rates of major bleed, thromboembolic event and minor bleed per 100 person-years of follow-up were 1.4, 0.75 and 34.3. The median time at target range calculated using the Rosendaal method was 61.6 % (IQR 44.6–74.1 %). Of the out-of-range readings, 30.0 % were below range and 15.4 % were above. INR variability, (standard deviation of individuals’ mean INR), was the best predictor of bleeding events, with an odds ratio of 3.21 (95 % CI 1.10–9.38). Low rates of both major bleeds and thromboembolic events were recorded, in addition to a substantial number of INR readings under the recommended target range. This may suggest that the recommended INR ranges may not represent the optimal warfarin intensity for this population and that a lower intensity of therapy, as observed in this cohort, could be beneficial in preventing adverse events.     

Recent developments in the synthesis of regioregular thiophene-based conjugated polymers for electronic and optoelectronic applications using nickel and palladium-based catalytic systems

Thiophene-based conjugated polymers hold an irreplaceable position among the continuously growing plethora of conjugated polymers due to their exceptional optical and conductive properties, which has made them a centre of attention for the past few decades and many researchers have contributed tremendously by designing novel strategies to reach more efficient materials for electronic applications. This review aims to highlight the recent (2012–2019) findings in design and synthesis of novel thiophene-based conjugated polymers for optical and electronic devices using organometallic polycondensation strategies. Nickel- and palladium-based protocols are the main focus of this account. Among them nickel-catalyzed Kumada catalyst-transfer polycondensation, nickel-catalyzed deprotonative cross-coupling polycondensation, palladium-catalyzed Suzuki–Miyaura and Migita–Kosugi–Stille couplings are the most popular strategies known so far for the synthesis of functionalized regioregular polythiophenes exhibiting fascinating properties such as electronic, optoelectronic, chemosensitivity, liquid crystallinity and high conductivity. This account also presents a brief overview of direct arylation polymerization (DArP) protocol that has shown a great potential to lessen the drawbacks of conventional polymerization techniques. DArP is a cost-effective and green method as it circumvents the need for the synthesis of arylene diboronic acid/diboronic ester and distannyl arylenes using toxic precursors. DArP also puts off the need to preactivate the C–H bonds, hence, presenting a facile route to synthesize polymers with controlled molecular weight, low polydispersity index, high regioregularity and tunable optoelectronic properties using palladium-based catalytic systems.

Thiophene-based conjugated polymers are important conjugated polymers due to their exceptional optical and conductive properties, over the past few decades many researchers have designed novel strategies to reach more efficient materials for electronic applications.