Day: 02/03/2011

Three-dimensional atomic imaging of crystalline nanoparticles

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Determining the three-dimensional (3D) arrangement of atoms in crystalline nanoparticles is important for nanometre-scale device engineering and also for applications involving nanoparticles, such as optoelectronics or catalysis. A nanoparticle’s physical and chemical properties are controlled by its exact 3D morphology, structure and composition1. Electron tomography enables the recovery of the shape of a nanoparticle from a series of projection images2, 3, 4. Although atomic-resolution electron microscopy has been feasible for nearly four decades, neither electron tomography nor any other experimental technique has yet demonstrated atomic resolution in three dimensions. Here we report the 3D reconstruction of a complex crystalline nanoparticle at atomic resolution. To achieve this, we combined aberration-corrected scanning transmission electron microscopy5, 6, 7, statistical parameter estimation theory8, 9 and discrete tomography10, 11. Unlike conventional electron tomography, only two images of the target—a silver nanoparticle embedded in an aluminium matrix—are sufficient for the reconstruction when combined with available knowledge about the particle’s crystallographic structure. Additional projections confirm the reliability of the result. The results we present help close the gap between the atomic resolution achievable in two-dimensional electron micrographs and the coarser resolution that has hitherto been obtained by conventional electron tomography.

source: nature

Femtosecond X-ray protein nanocrystallography

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X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded1, 2, 3. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction ‘snapshots’ are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source4. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes5. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (~200 nm to 2 μm in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes6. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.

source: nature

Is testicular microlithiasis associated with testicular cancer?

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Testicular microlithiasis (tes-TIK-u-lur mi-kro-lih-THI-uh-sis) refers to small clusters of calcium seen on an ultrasound examination of the testicles. A growing number of studies have shown a relationship between testicular microlithiasis and testicular cancer. However, it remains uncertain whether having testicular microlithiasis is an independent risk factor for testicular cancer.

Testicular microlithiasis is uncommon and has many possible causes, such as infection and injury. Most studies of testicular microlithiasis have evaluated men who have had testicular ultrasounds done for some other reason, such as swelling, pain or infertility. In these studies, there appears to be a small association between microlithiasis and testicular cancer. But there’s not enough evidence to be certain that the microlithiasis caused cancer.

Few studies of healthy men with no symptoms have been conducted. But results indicate that testicular microlithiasis is much more common than is testicular cancer. This has led researchers to believe that microlithiasis is unlikely to increase an otherwise healthy man’s risk of testicular cancer.

If testicular microlithiasis is noted on an ultrasound done for some other reason, your doctor may recommend that you do regular testicular self-exams and make an appointment if you find any unusual lumps. If you have other risk factors for testicular cancer, your doctor may recommend close follow-up with annual testicular ultrasound scans.

source: mayo clinic

What is a Baker cyst?

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A Baker cyst is swelling caused by fluid from the knee joint protruding to the back of the knee. The back of the knee is also referred to as the popliteal area of the knee. A Baker cyst is sometimes called a popliteal cyst. When an excess of knee joint fluid is compressed by the body weight between the bones of the knee joint, it can become trapped and separate from the joint to form the fluid-filled sac of a Baker cyst. The name of the cyst is in memory of the physician who originally described the condition, the British surgeon William Morrant Baker (1839-1896).

What causes a Baker cyst?

Baker cysts are not uncommon and can be caused by virtually any cause of joint swelling (arthritis). The excess joint fluid (synovial fluid) bulges to the back of the knee to form the Baker cyst. The most common type of arthritis associated with Baker cysts is osteoarthritis, also called degenerative arthritis. Baker cysts can occur in children with juvenile arthritis of the knee. Baker cysts also can result from cartilage tears (such as a torn meniscus), rheumatoid arthritis, and other knee problems.

What are symptoms of a Baker cyst?

A Baker cyst may cause no symptoms or be associated with knee pain and/or tightness behind the knee, especially when the knee is extended or fully flexed. Baker cysts are usually visible as a bulge behind the knee that is particularly noticeable on standing and when compared to the opposite uninvolved knee. They are generally soft and minimally tender.

Baker cysts can become complicated by protrusion of fluid down the leg between the muscles of the calf (dissection). The cyst can rupture, leaking fluid down the inner leg to sometimes cause the appearance of a painless bruise on the inner ankle. Baker cyst dissection and rupture are frequently associated with swelling of the leg and can mimic phlebitis of the leg. A ruptured Baker cyst typically causes rapid-onset swelling of the leg.

How is a Baker cyst diagnosed?

Baker cysts can be diagnosed by the doctor’s examination and confirmed by radiological testing (either ultrasound, injection of contrast dye into the knee followed by imaging, called an arthrogram, or MRI scan) if necessary.

How is a Baker cyst treated?

Baker cysts often resolve with removal of excess knee fluid in conjunction with cortisone injection. Medications are sometimes given to relieve pain and inflammation.

When cartilage tears or other internal knee problems are associated, surgery can be the best treatment option. During a surgical operation, the surgeon can remove the swollen tissue (synovium) that leads to the cyst formation. This is most commonly done with arthroscopic surgery.

Baker Cyst At A Glance
  • A Baker cyst is swelling caused by fluid from the knee joint protruding to the back of the knee.
  • Baker cysts are not uncommon and can be caused by virtually any cause of joint swelling (arthritis).
  • A Baker cyst may cause no symptoms or be associated with knee pain and/or tightness behind the knee, especially when the knee is extended or fully flexed.
  • Baker cysts can rupture and become complicated by protrusion of fluid down the leg between the muscles of the calf (dissection).
  • Baker cysts can be treated with medications, joint aspiration and cortisone injection, and surgical operation, usually arthroscopic surgery.

Factors Influencing Patient Adherence to Cardiovascular Medication Regimens

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Aspects other than the number and dosage of drugs can have substantial effects.

Patients with cardiovascular disease are often prescribed multiple medications, some of which require several daily doses. In a study sponsored by a large commercial prescription and health services provider, investigators assessed how various characteristics of medication regimens related to adherence in patients who were prescribed a statin (n=1,827,395) or either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin-receptor blocker (ARB) (n=1,480,304) during a 1-year period. Regimen characteristics included number of medications, unique drug classes, number of prescribers, number of pharmacies used, and consolidation (a measure of the number of pharmacy visits per filled prescription).

Patients’ mean age was 63, 49% were men, and all were insured. In the first 90 days after the index prescription, patients in both the statin and ACE/ARB groups were prescribed a mean of six unique medications by a mean of two prescribers and made a mean of five pharmacy visits. Patients in the highest 10th percentile were prescribed a mean of 12 unique medications. In multivariable analyses, older age, female sex, higher income, and lower copayments were associated with higher adherence. Lower adherence was associated with the use of more pharmacies (1.6%–2.0% decrease per additional pharmacy) and less-consolidated regimens (8% decrease with no consolidation vs. full consolidation).

Comment: These results suggest that ensuring patients have prescriptions for all appropriate medications is insufficient to maximize adherence, even in an insured population receiving prescriptions from a large pharmacy benefits manager. The findings support further study of specific interventions to improve medication adherence; the authors’ suggestion of a “pharmacy home” to centralize patients’ access to medications is particularly intriguing. Pending such studies, as the expanding evidence base increases the number of recommended treatments, we should consider cost and regimen complexity when prescribing multiple medications for patients, taking care to ensure that every prescription is justified.

— Frederick A. Masoudi, MD, MSPH

Published in Journal Watch Cardiology February 2, 2011

HPV Vaccine Seems Effective in Young Men

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Vaccinating young men against human papillomavirus appears to be effective in preventing external genital lesions, according to an international trial supported and conducted by the manufacturer and published in the New England Journal of Medicine.

Roughly 4000 males aged 16 to 26 years who had five or fewer lifetime sexual partners were randomized to receive either three doses of quadrivalent HPV vaccine or placebo. After a median follow-up of 2.9 years, the vaccine had an efficacy of 60% in preventing external genital lesions. The efficacy was 66% when considering only lesions related to HPV-6, 11, 16, or 18. The vaccine also reduced the incidence of persistent infection with these four HPV types and the DNA detection of related HPV types.

The authors conclude: “Although the point efficacy estimates for the boys and men in this study are numerically lower than those for girls and women in previous studies, the confidence intervals overlap, suggesting that vaccine efficacy may be similar for the two sexes.”

Source:NEJM

Fidaxomicin Lowers C. difficile Recurrence, Compared with Vancomycin

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In comparison with vancomycin, the macrocyclic antibiotic fidaxomicin lowered recurrence rates of Clostridium difficile infection, according to a New England Journal of Medicine study.

In a phase III noninferiority trial sponsored and conducted by the manufacturer, researchers randomized some 600 patients to 10 days of either fidaxomicin or vancomycin. The rate of clinical cure in those receiving at least one dose of the medication was about 85% in both groups. Recurrence rates among those with the most virulent C. difficile strains were similar for both regimens (about 25%), but for other strains, fidaxomicin conferred a much lower recurrence rate (8%) than vancomycin (26%).

Laboratory abnormalities — specifically, hyperuricemia and elevated transaminases — were significantly more common with fidaxomicin.

An editorialist says that fidaxomicin, while needing additional study, seems an “important advance.” In Journal Watch Infectious Diseases, Dr. Larry Baddour writes, “I hope that this is the case — new, more-effective treatments [for C. difficile infection] are badly needed.”

Source:NEJM