Budaya Ilmiah

• Mendorong berpikir ilmiah• Perlu suatu keterampilan• Banyak akal dan kreatif mencari ilmu• Keterampilan bisa fisik, bisa kreatifitas, banyak akal dan

berpikir kritis• Keterampilan mengakses teknologi seperti komputer dan

internet• Mendorong mencari sumber belajar (perpustakaan,

internet)• Dapat membedakan sumber informasi ilmiah dan populer• Memotivasi belajar sepanjang hidup• Learn how to learn• Menanamkan belajar mandiri

Menilai informasi

Akses pustaka tekstular & elektronik

Learn how to learn

Searching for evidence

Evidence-based

Life-long learning

Mawas diri

Skeptisisme

Ilmuwan, profesional

Modul LatihanConcept Mapping Modul Pelatihan

Standart Kompetensi

1. Memberikan kemampuan berkomunikasi lisan dengan sejawat.

2. Memberikan kemampuan bekerjasama dalam kelompok.3. Memberikan kemampuan belajar secara mandiri (self

directed learning).4. Memberikan dasar berfikir ilmiah.

Dalam berkomunikasi dengan sejawat:

Mampu untuk mengungkapkan dan bertukar informasi verbal dengan anggota kelompok

Mendengarkan dengan perhatian dan memberi waktu yang cukup kepada lawan bicara.

Mengkonfirmasikan pemahaman yang telah diperolehnya.memberikan penjelasan yang jelas akan ide/gagasannya.

Dalam bekerjasama:

Memberikan waktu yang cukup pada anggota kelompok yang lain untuk refleksi dan konsultasi sebelum mengambil keputusan bersama.

Menetapkan tindak-lanjut yang tepat terhadap apa yang telah disetujui bersama.

Dalam hal pengembangan-diri dan pembelajaran seumur hidup:

Menunjukkan kemampuan menguasai informasi baru yang di-terimanya.

Berpatisipasi aktif dalam proses pembelajaran.

Mampu untuk secara aktif mencari pustaka ilmiah, baik tekstular maupun elektronik

Mampu untuk merencanakan, mengimplementasikan, dan me-mantau pengembangan-diri-nya.

Mampu untuk mengenali kelebihan dan kekurangannya.

Dalam hal berfikir ilmiah:

Menunjukkan sikap skeptis yang sehat dan keingintahuan akan bukti ilmiah terhadap informasi yang diperolehnya.

Menerapkan evidence-based medicine dalam membuat kepu-tusan untuk memecahkan masalah kedokteran yang diha-dapinya.

Paradigma Tentang Orang Lain

Paradigma kita tentang orang lain

sering tidak lengkap, tidak tepat,

bahkan keliru. Oleh karena itu

jangan cepat menilai atau

memberi label pada diri orang lain.

DEMOKRASI

MENGHARGAI PERBEDAAN PENDAPAT

1 BENDA/KEJADIAN, DILIHAT 2 ORANG DARI SUDUT PANDANG BERBEDA, HASILNYA AKAN BERBEDA

DI DUNIA ADA FENOMENA RESEPTOROLOGI(teori

dan fakta kecocokan itu ada) , SEPERTI PADA HIV, ENZIM, LOCK AND KEY, TUMBU DAN TUTUPNYA,

PERJODOHAN, HOBI, KECOCOKAN BERTEMAN

COCOK JALAN BERSAMA, TAK COCOK TERPAKSA JALAN SENDIRI-SENDIRI, TIDAK PERLU MEMBENCI,

TETAPI TETAP SALING MENGASIHI DAN SALING MEMBANTU

YANG PENTING HIDUP BERMAKNA DAN BERARTI

POLA PIKIR KEHIDUPANMENANG-KALAH KALAH-MENANG

KALAH-KALAHMENANG-MENANG

TUTORIAL THE SEVEN JUMPS

1. CLARIFY UNFAMILIAR TERMS2. DEFINE THE PROBLEMS3. BRAINSTORM POSSIBLE HYPOTHESES OR

EXPLANATIONS4. ARRANGE EXPLANATIONS INTO A

TENTATIVE SOLUTION5. DEFINE LEARNING OBJECTIVES6. GATHER INFORMATION AND PRIVATE

STUDY7. SHARE THE RESULTS OF INFORMATION

GATHERING AND PRIVATE STUDY

1. KLARIFIKASI ISTILAH

2. PENETAPAN MASALAH / PROBLEM

3. ANALISIS MASALAH

4. JAWABAN SEMENTARA / HIPOTESIS

5. PENETAPAN LEARNING OBJEK / TUJUAN BELAJAR

6. MENCARI INFORMASI

7. PRESENTASI HASIL

Skenario

1. HIV AIDS

2. Mad Cow

3. Diare

Uji coba yang sudah dilaksanakan dengan skenario Flu Burung

ContohSkenario 2Mad Cow

Contoh Tinjauan Pustaka

• Teori Prion

• Teori Madcow

Penyakit akibat Prion pada manusia

• Kuru

• Creutjzveld Jacob Disease (CJD)

• Variant CJD

Mad Cow

• Terjadi inflamasi pada penyakit ini• Penyakit Sapi Gila• Dikenal sebagai Bovine Spongivorm

Encephalopathy (BSE)• Menyerang Otak dan bersifat fatal (fatal

neurological disease)• Penyebab infeksi pada umumnya virus, bakteri,

jamur dll• Penyebab belum begitu dikenal yaitu Prion,

Protein abnormal

Teori tentang asal timbulnya BSE

• Adanya perubahan pola pakan sapi dengan menggunakan tepung daging dan tulang (Meat and Bone Meal=MBM) yang terkontaminasi oleh agen penyebab scrapie (protein penyebab sapi gila) pada domba dan kambing.

• MBM dimakan sapimanusia memakan daging sapi terkontaminasiBSE

• Zoonosis, dapat ditularkan kepada manusia dengan mengkonsumsi hewan pengidap BSE.

• BSE tergolong klp Transmissible Spongiform Encephalopathy (TSE)

Definisi prion

• Prion adalah pembawa penyakit menular yang hanya terdiri dari protein. Prion tidak dapat dimusnahkan dengan panas, radiasi, atau formalin. Prion menyebabkan berbagai penyakit degenerasi seperti kuru, scrapie, Creutzfeldt-Jakob disease (vCJD), dan bovine spongiform encephalopathy (BSE atau sapi gila). Semua penyakit ini menyerang otak atau sistem syaraf lainnya, mematikan, dan belum dapat disembuhkan. Namun sebuah vaksin telah dikembangkan untuk tikus dan sedang dikembangkan lebih lanjut untuk manusia.

•

Penemu Prion• Stanley Ben Prusiner dilahirkan di Des Moines, Iowa, pada 28 Mei 1942 dan

dibesarkan di des Moines dan Cincinnati, Ohio. Di Cincinnati ia belajar di SMA Walnut Hills.

• Prusiner menerima gelar sarjana dalam ilmu kimia dan gelar dokter dari Universitas Pennsylvania. Kemudian ia menempuh program magang kedokteran di Universitas California, San Francisco. Setelah magang, Prusiner melanjutkan ke Institut Kesehatan Nasional (NIH). Ia belajar glutaminase dalam E. coli di laboratorium Earl Stadtman. Setelah tiga tahun di NIH ia kembali ke Universitas California, San Francisco untuk menyelesaikan residensinya dalam neurologi. Setelah menyelesaikan residensinya pada 1974, Prusiner bergabung sebagai dosen di Departemen Neurologi di UCSF. Sejak saat itu ia menjabat menjadi dosen dan dosen tamu di Universitas California, San Francisco dan Universitas California, Berkeley.

• Pada 2003 ia terpilih sebagai anggota Akademi Ilmu Pengetahuan dan Seni Serbia di Departemen Kimia dan Ilmu Biologi.

• Ia menerima Albert Lasker Award for Basic Medical Research pada 1994 dan dianugerahi Penghargaan Nobel dalam Fisiologi atau Kedokteran pada 1997 untuk penemuannya atas prion, sejenis agen menular yang bereproduksi sendiri yang terdiri atas protein.

Introduction

• Prion diseases are also known as Transmissible Spongiform Encephalopathies (TSE)

• Animal and human diseases• Uniformly fatal• Characterized by long incubation periods,

and a multifocal neuropathological picture of neuronal loss, spongiform changes, and astrogliosis

Prions - History

• Theory of infectious proteinaceous material first developed in 1960s by Alper and Griffith

• 1981 – Merz observed strange fibrils in scrapie-infected mouse brains

• 1982 – Prusiner purified the infectious material and confirmed that it consisted of a specific protein. He coined the term “prion”. The specific protein was named PrP.

• 1986 – Bovine Spongiform Encephalopathy (BSE or “Mad Cow’s Disease”) in the UK

• 1996 – Variant CJD which may be related to ingestion of contaminated meats

Prions

• PrPC - protease sensitive, PrPSc - resistant • Other distinguishing features

– Resistance to inactivation by proteolytic enzymes

– Resistance to conventional disinfectants– Resistance to standard sterilization methods

• Standard sterilization including nucleases, UV irradiation, treatment with psoralens, divalent cations, metal chelators, acids between pH 3 and 7, hydoxyamine, formalin, and boiling.

Prion protein is indestructible

by heat up to 1000° F (350° C)

Hot enough to melt lead.In 1986, 4.5 million cows were incinerated in the U.K. after

the discovery of BSE. The ashes, stored in underground

concrete containers, were retested again in 1998 and

found to still be infected with active prions.

Prion configuration

• The cellular prion protein is predominantly composed of the alpha helix structure and is almost devoid of the beta structure

• Scrapie prions are composed of about 43% beta sheets

Pathogenesis

• Prnp gene encodes for the PrP protein

• This gene resides on the short arm of chromosome 20

• PrPSc directly interacts with PrPC to cause the normal form of the protein to rearrange its structure

• “Protein X” hypothesis

Infection

• Humans might be infected by prions in 2 ways– Acquired infection– Hereditary transmission

• The lymphoreticular and nervous system are pathways for prion agent replication

• Prion diseases do not typically elicit an immune response by the host

Diseases

• All are part of a group of diseases called transmissible spongiform encephalopathies (TSE)

• Both animal and human forms exist• Animal examples include:

– Bovine Spongiform Encephalopathy (mad Cow’s disease)

– Feline Spongiform Encephalopathy (cats)– Scrapie (in sheep)– Chronic Wasting Disease (deer, elk, moose)– Transmissible Mink Encephalopathy (mink)

Scrapie

• Known to have existed for at least 200 years without being transmitted to humans, while being endemic in sheep populations all over the world.

• There are 23 variations of prion mutation possible, each with a different incubation period as well as patterns of amyloid plaque in the brain.

• Each variation is known by a unique symptom, such as “drowsy”, “hyper”, or “fat building”.

Diseases – human forms

• Sporadic Creutzfeldt-Jakob Disease

• Variant CJD

• Kuru

• Gerstmann-Straussler-Scheinker Syndrome

• Fatal Familial Insomnia (FFI)

Kuru• Cannibal culture of Papua New Guinea.

• Affected mostly women and children, with

a small amount of men. anywhere from 5

to 10 percent of the population died each

year from kuru.1

• When loved one died, men ate muscle

portions and women and children were

left with the lesser organs and brain,

where we now know prions tend to

cluster.

• The rare male cases occurred because of

the possible 20 to 30 year dormancy

period of prions where the infectious

agents were ingested as children.

Kuru (continued)

• Analyzed by New Yorker Carleton Gajdusek and Lithuanian Dr. Vincent Zigas (both in photo) in 1957.

• Initially believed to be a virus causing encephalitis (swelling of the brain), with the same symptoms as Parkinson's, Alzheimer's, and MS. However these were degenerative, not infectious diseases, and not epidemic as kuru was.

• After autopsy, Gajdusek made the connection of brain damage to recently discovered CJD.

• No treatment was ever found, and when cannibalism was eventually phased out of the culture, so too came the disappearance of kuru.

Creutzfeldt-Jakob Disease

• 10 – 15% of CJD cases occur as familial – Associated with pathogenic mutations of the

prion protein gene

• 85% are sporadic cases with no recognizable pattern of transmission– Incidence of 1 person per million per year

• Sporadic CJD may be from de novo spontaneous generation of the self-replicating prions

Sporadic CJD

• Characterized by: – Rapidly progressive multifocal neurological

dysfunction– Myoclonic jerks– A terminal state of global severe cognitive impairment– Death in about 8 months

• Rapidly expands to include behavioral abnormalities, higher cortical dysfunction, cortical visual disturbances, cerebellar dysfunction, and both pyramidal and extrapyramidal signs

CJD Transmission:

• Humans can acquire the prion by exposure to meat that has come in contact with the brain or spinal column of the animal.

• Surgical equipment can be unknowingly infected by use on a patient with CJD, and because sterilization techniques do not kill the prion, the are transmitted to the other patients in subsequent procedures.

In common slaughtering practices, the animal is often

sliced at least once through the torso, severing the spinal

column and exposing all the the surrounding flesh to the

infectious agent.

Variant Creutzfeldt-Jakob Disease

• Strong epidemiological evidence that it is linked to BSE

• Differs from the sporadic form– Mainly young people– Duration between onset and death is longer– Behavioral and neuropsychiatric symptoms

predominate

• Prions are found in the highest concentration in the brain, spinal cord, and ocular tissue, but have been found in lymphoid tissue including tonsils, spleen, and appendix

New Variant CJD (vCJD)

• Much earlier onset but same

symptoms as classic CJD, often

with prolonged life expectancy.

• A recent test on surgical

equipment used for

tonsillectomies in the U.K.

revealed that 50% of tools were

infected with vCJD, even after

sterilization and autoclaving.

(The tonsils are one of the major

glands where the body stores

prions.)

Jonathan was diagnosed with vCJD at 17 and treated with the drug Pentosan polysulphate (PPS) , commonly used as an arthritis treatment for dogs. This extended his life by several years, but did not cure him.

vCJD

• Difficult to estimate prevalence– 237 per million in the UK

• To date all cases of vCJD have been homozygous for the M129 genotype

• Spongiform changes are more common in the cerebellum versus the cerebral cortex in Classic CJD

• Plaques are more common in vCJD than in the classic form

Year Sporadic

Iatrogenic

Familial GSS vCJD Total

1994 2 0 0 0 0 2

1995 3 0 0 0 0 3

1996 13 0 0 0 0 13

1997 16 0 1 1 0 18

1998 22 1 0 1 0 24

1999 26 2 2 1 0 31

2000 32 0 0 3 0 35

2001 27 0 2 1 0 30

2002 31 0 2 2 1 36

2003 27 1 1 0 0 29

2004 40 0 1 0 0 41

2005 22 0 0 1 0 23

Total 261 4 9 10 1 285

Canadian Statistics

Iatrogenic spread of CJD

• Iatrogenic transmission was first reported in 1974 – 55 yo patient developed autopsy confirmed CJD 18

mos after receiving a corneal graft– The donor also died of CJD

• 1977 two patients developed CJD 18 mos after having a stereotactic EEG procedure

• World wide, four CJD patients have been causally linked with exposure to contaminated neurosurgical instruments

• CJD cases have also been reported after receipt of human growth hormone, and dura mater grafts

Blood Transmission

• vCJD can be transmitted while the patient is still in the incubation period

• All procedures contacting vCJD blood potentially carry a small risk of transmission

• Blood transfusions are responsible for three cases of vCJD

Blood transmission concerns

• Prions can propagate using blood as a vector

• A single unit of infected blood is sufficient to cause transmission of the disease

• Blood from preclinically infected patients can be infectious

• The bulk of prion infectivity resides in buffy coat, plasma, and cryoprecipitate

Lab Tests• In laboratory tests, animals were

injected with active prions from cows infected with BSE.

• The infectious agent was not ingested in food as most animals and humans would be exposed to the prions. Even so, all of the test subjects contracted some form of prion disease.– monkeys– sheep (different variation of scrapie

contracted)– goats– mice/ rats– pigs

Treatment - Simvastatin

• Cholesterol lowering drugs have been reported to inhibit prion replication in infected cell cultures

• Mok S, et al. in July 2006 described their results of infected mice treated with Simvastatin

• Treatment significantly delayed disease progression and prolonged survival times in established prion infection of the CNS

TERIMA KASIH