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

As a result of the efficacy of highly active antiretroviral therapy (HAART), patients with human immunodeficiency virus (HIV) can survive longer and are thus naturally prone to ageing-related degenerative disorders such as Parkinson’s disease (PD). Managing PD and HIV in the same patient may be challenging, as HAART and levodopa interact and may cause intolerable side effects. Concerns about the increased risk of hardware infection in immunocompromised patients submitted to deep brain stimulation of the subthalamic nucleus (STN-DBS) still persist. We report a PD patient with HIV infection who suffered peak-dose dyskinesias and intolerable gastrointestinal side effects while on HAART, prompting its suspension. STN-DBS allowed complete postoperative levodopa withdrawal and HAART restart, without infectious complications after 12 months of follow-up. STN-DBS seems to be a safe procedure in selected patients with both medically refractory PD and HIV infection, and may result in clinical optimization of both conditions.

/pdf/deep-brain-stimulation-of-the-subthalamic-nucleus-for-2ik2lgq9q9.pdf

Deep Brain Stimulation of the Subthalamic Nucleus for Parkinson's Disease in a Patient with HIV Infection: Dual Clinical Benefit.

A previously healthy 40-year-old man presented to our movement disorders clinic in 2000 with a mild right akinetic-rigid syndrome; the symptoms had started 1 year before. The neurological examination was otherwise normal. There was no previous exposure to dopamine antagonists and no history of cerebral vascular events. The family history was also unremarkable. PD was diagnosed after careful examination and testing, including blood tests, brain MRI, and I-FP-CIT SPECT. Parkin mutation search was negative. One year later, a dull nuchal pain and subsequent dropped head (DH) emerged (Fig. 1), which progressed for a few weeks and then stabilized; no other new neurological manifestations appeared. At this time the patient was on no medication. Laboratory investigations were normal, including complete blood count, electrolytes, liver enzymes, glucose, creatinine, blood urea nitrogen, thyroid function tests, serum CK and inflammation markers; acetylcholine receptor antibodies were negative. IBZM SPECT was compatible with PD. EMG was conducted at that time and repeated 1 year later, showing no changes regarding the trapezius, sternocleidomastoid or scapular muscles; repetitive stimulation was normal. Cervical MRI showed mild disk bulging, but no other changes were apparent. Levodopa/carbidopa (100/25 mg) was introduced tid, with mild improvement of head drop. Cervical MRI was repeated in 2007 but no new relevant findings were observed, and cervical muscles were apparently intact. Repeat EMG examination disclosed normal muscle activity in the trapezius and sternocleidomastoid muscles, but a myopathic pattern was seen in the cervical paraspinal muscles bilaterally. Paraspinal muscle biopsy was then performed, and read by a muscle disorders expert neuropathologist, but only mild nonspecific changes were apparent (Fig. 2). The clinical course has been otherwise quite as expected, with akinesia and rigidity predominantly involving right sided limbs, and the emergence of motor fluctuations and disabling dyskinesias. Using the Unified Parkinson’s Disease Rating Scale part III, the patient scored a total of 40 while off medication for 12 h, and 9 during the best on state after the acute levodopa challenge. Formal cognitive tests revealed MMSE 30/30, Frontal Assessment Battery 16/18 and the total score of Mattis Dementia Rating Scale was 138/144; all these are normal scores as compared to an ageand education-matched normative population. The patient did not have any behavioural disturbances, as assessed by the clinical interview and using the Beck Depression Inventory and the Brief Symptom Inventory. He denied any clinically significant dysautonomic features, such as erectile dysfunction, bladder problems, constipation or symptomatic orthostatic hypotension, and there were no symptoms suggestive of REM sleep behaviour disorder, although no formal autonomic or sleep studies have been conducted. The patient underwent bilateral deep brain stimulation (DBS) of the subthalamic nucleus in 2010, with significant improvement of the parkinsonian symptoms and fluctuations but no effect on the dropped head. Very similar results had been achieved from a previous acute levodopa A. Oliveira J. Massano M. J. Rosas Movement Disorders and Functional Surgery Unit, Centro Hospitalar de Sao Joao, Porto, Portugal

Dropped head syndrome in early-onset Parkinson disease treated with bilateral subthalamic stimulation: clinical, imaging, EMG, and biopsy findings

it is estimated that over 24 million people suffer from dementia worldwide; in Portugal more than 150000 people are affected, and 90000 of these have Alzheimer’s disease (AD). considering the aging of the population and increasing life expectancy, as well as the deleterious impact of the disease, it becomes essential to obtain a disease-modifying treatment or, ideally, preventive. however, this is not the current reality. The aim of this manuscript is to review the progresses achieved so far with regard to pharmacological therapies in AD, particularly those with potential disease modifying effect, as well as drugs under development. A literature search has been performed, supplemented by analysis of clinical trials registered in the website clinicaltrials.gov. Several clinical trials have been developed to determine the effectiveness of new drugs in the treatment of AD. There are different drugs with different mechanisms of action. The initial excitement, especially regarding drugs which influence the amyloidogenic pathway, has faded, since many clinical trials have shown disappointing results (such as the cases of semagacestat, tarenflurbil, tramiprosate, valproate, phenserine and dimebon). Thus, new agents are under investigation (PBT2, passive immunization, davunetide, methylene blue, huperzine A, neurotrophins, intranasal insulin, among others). The lack of agreement between results observed in animal models and those seen in clinical trials may be due to methodological shortcomings or to the still insufficient knowledge concerning the pathophysiology of the disease. KEY-WORDS: AlzhEimEr’S DiSEASE; DEmENTiA; DiSEASE-mODifyiNg ThErAPy; TrEATmENT; PhArmAcOThErAPy 1. Mestrado Integrado eM MedIcIna, Faculdade de MedIcIna da unIversIdade do Porto 2. servIço de neurologIa, centro HosPItalar são João, Porto 3. dePartaMento de neurocIêncIas clínIcas e saúde Mental, Faculdade de MedIcIna da unIversIdade do Porto inTRODUçÃO Estima-se que mais de 24 milhões de pessoas padeçam de demência a nível mundial,1 existindo em Portugal cerca de 153 000 pessoas afetadas.2 Dessas, 90 000 têm Doença de Alzheimer (DA).2 De facto, a DA constitui a principal demência neurodegenerativa, sendo responsável por 50-60% dos casos de demência.3 Na DA ocorre uma deterioração insidiosa, progressiva e persistente da cognição, capacidade funcional e comportamento,4 manifestandose inicialmente por défices da memória episódica. caracteriza-se por perda neuronal, inicialmente na região temporal medial, e associa-se histologicamente a placas senis, formadas pela acumulação extracelular da proteína beta-amilóide, e a tranças neurofibrilares, compostas pela proteína tau hiperfosforilada, lesões essas que foram documentadas pela primeira vez em 1906 por Alois Alzheimer (3). O principal fator de risco é a idade.5 Verifica-se que a incidência da doença duplica a cada cinco anos a partir dos 65 anos de idade, pelo que uma em cada três pessoas com mais de 85 anos sofre da doença.5 Nos últimos anos tem sido verificado um envelhecimento da população e um aumento da esperança média de vida, pelo que as patologias mais frequentes em idosos aumentam, das quais se destaca a demência e a DA. Assim, é expectável que a demência atinja, em 2040, cerca de 81 milhões de pessoas.3,6 Tendo em conta o impacto deletério da DA nas capacidades dos doentes, que perdem a autonomia nas atividades da vida diária e se tornam dependentes de terceiros, as repercussões sentidas no doente, família e comunidade, assim como as consequências económicas, torna-se fundamental a existência de um tratamento modificador da doença ou, idealmente, preventivo, da DA. No entanto, esta não é a realidade atual. A farmacoterapia disponível não permite retardar a perda neuronal,4 atuando de modo sintomático. interfere com a neurotransmissão colinérgica (inibidores da acetilcolinesterase: donepezilo, rivastigmina, galantamina) ou glutamatérgica (antagonistas dos recetores NmDA: memantina), melhorando principalmente os sintomas 2013;27[2]:65-86 ARTIGO DE REVISÃO 66 cognitivos. Para os sintomas comportamentais e psiquiátricos são utilizados também antidepressivos, neuroléticos, ansiolíticos, antiepiléticos. A melhoria do conhecimento sobre a fisiopatologia da doença3 possibilitou encarar novas terapêuticas, com possível intervenção no curso natural da doença, pelo que vários estudos investigacionais têm sido realizados. O objetivo deste trabalho é fazer uma revisão dos progressos alcançados até ao momento presente relativamente às intervenções terapêuticas farmacológicas na DA, em particular as que possam ter efeito modificador da doença, bem como os fármacos em desenvolvimento.

/pdf/terapeutica-farmacologica-na-doenca-de-alzheimer-progressos-855yh7ztv4.pdf

Terapêutica farmacológica na doença de Alzheimer: progressos e esperanças futuras

No abstract available
Keywords: DYT6; THAP1 gene; cervical dystonia; deep brain stimulation; generalized dystonia; globus pallidus; primary dystonia.

Pallidal Deep Brain Stimulation in DYT6: Significant Long-Term Improvement of Dystonia and Disability.

https://onlinelibrary.wiley.com/page/journal/23301619/homepage/mdc312941-sup-v001.htm.

João Massano

Papers

Deep Brain Stimulation of the Subthalamic Nucleus for Parkinson's Disease in a Patient with HIV Infection: Dual Clinical Benefit.

Dropped head syndrome in early-onset Parkinson disease treated with bilateral subthalamic stimulation: clinical, imaging, EMG, and biopsy findings

Terapêutica farmacológica na doença de Alzheimer: progressos e esperanças futuras

Pallidal Deep Brain Stimulation in DYT6: Significant Long-Term Improvement of Dystonia and Disability.

Imaging evidence of nigrostriatal degeneration in DYT‐PRKRA