抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

https://hull-repository.worktribe.com/preview/1797952/1-s2.0-S0140673618322797-main.pdf

Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

March 5, 2019 e1 WRITING GROUP MEMBERS Emelia J. Benjamin, MD, ScM, FAHA, Chair Paul Muntner, PhD, MHS, FAHA, Vice Chair Alvaro Alonso, MD, PhD, FAHA Marcio S. Bittencourt, MD, PhD, MPH Clifton W. Callaway, MD, FAHA April P. Carson, PhD, MSPH, FAHA Alanna M. Chamberlain, PhD Alexander R. Chang, MD, MS Susan Cheng, MD, MMSc, MPH, FAHA Sandeep R. Das, MD, MPH, MBA, FAHA Francesca N. Delling, MD, MPH Luc Djousse, MD, ScD, MPH Mitchell S.V. Elkind, MD, MS, FAHA Jane F. Ferguson, PhD, FAHA Myriam Fornage, PhD, FAHA Lori Chaffin Jordan, MD, PhD, FAHA Sadiya S. Khan, MD, MSc Brett M. Kissela, MD, MS Kristen L. Knutson, PhD Tak W. Kwan, MD, FAHA Daniel T. Lackland, DrPH, FAHA Tené T. Lewis, PhD Judith H. Lichtman, PhD, MPH, FAHA Chris T. Longenecker, MD Matthew Shane Loop, PhD Pamela L. Lutsey, PhD, MPH, FAHA Seth S. Martin, MD, MHS, FAHA Kunihiro Matsushita, MD, PhD, FAHA Andrew E. Moran, MD, MPH, FAHA Michael E. Mussolino, PhD, FAHA Martin O’Flaherty, MD, MSc, PhD Ambarish Pandey, MD, MSCS Amanda M. Perak, MD, MS Wayne D. Rosamond, PhD, MS, FAHA Gregory A. Roth, MD, MPH, FAHA Uchechukwu K.A. Sampson, MD, MBA, MPH, FAHA Gary M. Satou, MD, FAHA Emily B. Schroeder, MD, PhD, FAHA Svati H. Shah, MD, MHS, FAHA Nicole L. Spartano, PhD Andrew Stokes, PhD David L. Tirschwell, MD, MS, MSc, FAHA Connie W. Tsao, MD, MPH, Vice Chair Elect Mintu P. Turakhia, MD, MAS, FAHA Lisa B. VanWagner, MD, MSc, FAST John T. Wilkins, MD, MS, FAHA Sally S. Wong, PhD, RD, CDN, FAHA Salim S. Virani, MD, PhD, FAHA, Chair Elect On behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee

Heart Disease and Stroke Statistics—2019 Update: A Report From the American Heart Association

http://diposit.ub.edu/dspace/bitstream/2445/122776/1/gbd2016riskfactorscollaborators2017_3028.pdf

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: A systematic analysis for the Global Burden of Disease Study 2013

Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017

Background Mutations in the anoctamin 3 (ANO3) gene cause autosomal dominant craniocervical dystonia (DYT24), presenting from childhood to mid-life. However, in the past years, the clinical spectrum of this disorder has widened. We present a family with heterogeneous presentation, exemplifying phenotypic diversity in DYT24. Cases The index case presented with myoclonic dystonia at age 10. His family history was remarkable for cervical dystonia with myoclonus in his grandfather, cervical and upper limb dystonia along with dopa-responsive parkinsonism in his father and lower-limb dystonia in his teenage sister. Magnetic resonance imaging and blood work-ups of all the affected family members were normal. The genetic panel for inherited forms of dystonia disclosed a point mutation c.1787C > A (p.Ser596Tyr) segregated in all affected family members. Conclusions ANO3 mutations usually present with craniocervical dystonia and rarely generalized or leg dystonia. This family exemplifies the heterogeneous presentation of this disorder as well as a wide phenotypic variability within the same family.

Another Twist in the Tale: Intrafamilial Phenotypic Heterogeneity in ANO3-Related Dystonia

Tailoring therapy for the patient's individual motor state and daily life requirements is a long-standing vision in Parkinson disease (PD) treatment. This is particularly true when motor fluctuations emerge as a major impairment. Subthalamic nucleus deep brain stimulation (DBS) attenuates motor fluctuations and improves quality of life in PD.1,2 However, it is still delivered in a rather rigid way, with mostly constant stimulation parameters between patient visits and physician reprogramming sessions.

Approaching adaptive control in neurostimulation for Parkinson disease: Autopilot on

A 77-year-old woman presented with progressively worsening apathy, depression, urinary incontinence and slowness of movement for the past 1 year. Asymmetric akinetic-rigid parkinsonism and mild left-sided hyper-reflexia were seen on examination. No ocular movement impairment, cerebellar or sensory signs were noticed. Routine laboratory testing was normal. Brain imaging revealed a large frontal tumour which was subsequently excised and pathologically confirmed as a meningioma. Marked clinical improvement was documented 3 months after surgery, and persistent clinical and imaging remission have been confirmed annually for the following 3 years. There have been some reports of parkinsonism associated with intracranial tumours. Although this is probably an uncommon situation, it is potentially treatable, and symptoms might even remit completely following successful management. Parkinson's disease is a common cause of parkinsonism, but alternative aetiologies should be suspected whenever atypical findings are demonstrated by clinical history or examination.

/pdf/reversible-parkinsonism-due-to-a-large-intracranial-tumour-wa23wbhdwy.pdf

Reversible parkinsonism due to a large intracranial tumour

Persons with Parkinson disease (PD) who have difficulties from side effects or dosing of medications, or both, have the option of undergoing deep brain stimulation (DBS). DBS provides electrical stimulation via electrodes implanted into one or both sides of the brain. These electrodes are connected to a programmable (adjustable) pulse generator (like a pacemaker) placed under the skin of the chest. The 2 most common targets for the brain electrodes are the subthalamic nuclei (STN) or globi pallidi (GPi). One of each of these targets is found in the left and right halves of the brain. These brain structures contain circuits important for motor functions or movement. Nearby in the brain are circuits that regulate emotion, mood, and cognition. Cognition refers to mental abilities such as memory, abstract thinking, and word finding. There is concern that the benefits of DBS for movement might be offset by negative effects of DBS on thinking and emotion. Studies have shown that DBS is safe from cognitive and emotional standpoints. Still, a minority of patients have problems with cognition and emotion after DBS. It is unclear whether stimulating the STN or GPi is safer. A few studies examining a small number of patients (and often using a limited number of tests) suggest that stimulation of the GPi might be safer than the STN for cognition and emotion.1 A large well-done study is needed to help physicians and patients make the best choices. This study by Odekerken and colleagues2 is 1 of 2 recently published that seek to address the important question of whether STN or GPi DBS is safer.

https://n.neurology.org/content/neurology/84/13/e98.full.pdf

Changes in cognitive abilities after deep brain stimulation for Parkinson disease

Introduccion. La estimulacion cerebral profunda (ECP) del nucleo subtalamico (NST) en la enfermedad de Parkinson (EP) es segura y eficaz: en la mayoria de series se describen respuestas motoras duraderas y estables. Objetivo. Informar sobre el desenlace a largo plazo de la ECP del NST en pacientes con EP avanzada atendidos en un centro hospitalario portugues. Pacientes y metodos. El estado motor se valoro con la escala unificada de valoracion de la enfermedad de Parkinson, parte III, antes de la intervencion quirurgica -en dos situaciones: sin efecto de la medicacion (off) y bajo el mejor efecto (on)-, en el postoperatorio y al cabo de cinco anos (medicacion y estimulacion en on). Se cuantificaron las puntuaciones de cada sintoma axial. La incapacidad se evaluo con la escala de Rankin modificada (mRS). La aparicion de demencia se valoro seis meses y cinco anos despues de la ECP. Resultados. Setenta y uno de los 183 pacientes sometidos a la ECP del NST concluyeron los cinco anos de seguimiento. Diez de ellos quedaron excluidos: dos por fallecimiento (cancer e infarto de miocardio), cinco por perdida de seguimiento y tres por la retirada del sistema de estimulacion. La funcion motora manifesto una mejora del 78% en el postoperatorio y del 66% a los cinco anos. En el postoperatorio se aprecio mejoria de los sintomas axiales, pero al cabo de los cinco anos habian empeorado de manera significativa (p < 0,001). Las puntuaciones de la mRS tambien mejoraron en el postoperatorio, pero a los cinco anos tambien habian disminuido, pese a que la mayoria (88,5%) conservaba la capacidad ambulatoria (mRS < 4). Un paciente (1,6%) manifesto demencia a los seis meses, mientras que otros 19 (31,2%) la manifestaron al cabo de los cinco anos. La edad de los pacientes dementes era notablemente mayor (56,5 ± 7,8 frente a 63,7 ± 5,9 anos; p < 0,001). Conclusiones. En esta serie de casos, la ECP del NST demostro su eficacia en la mejora de los sintomas motores, aunque habian transcurrido cinco anos desde la implantacion. En ese periodo hubo un deterioro de los sintomas axiales y de la incapacidad, y surgieron casos de demencia, pero el posible papel de la ECP del NST como factor causal resta pendiente de concretar.

João Massano

Papers

Another Twist in the Tale: Intrafamilial Phenotypic Heterogeneity in ANO3-Related Dystonia

Approaching adaptive control in neurostimulation for Parkinson disease: Autopilot on

Reversible parkinsonism due to a large intracranial tumour

Changes in cognitive abilities after deep brain stimulation for Parkinson disease

Estimulación cerebral profunda del núcleo subtalámico en la enfermedad de Parkinson avanzada: seguimiento de cinco años en un centro portugués