Induction of neutralizing antibodies specific to dengue virus serotypes 2 and 4 by a bivalent antigen composed of linked envelope domains III of these two serotypes

There is no vaccine to prevent dengue fever, a mosquito-borne viral disease, caused by four serotypes of dengue viruses. In this study, which has been prompted by the emergence of dengue virus envelope domain III as a promising sub-unit vaccine candidate, we have examined the possibility of developing a chimeric bivalent antigen with the potential to elicit neutralizing antibodies against two serotypes simultaneously. We created a chimeric dengue antigen by splicing envelope domain IIIs of serotypes 2 and 4. It was expressed in Escherichia coli and purified to near homogeneity. This protein retains the antigenic identities of both its precursors. It elicited antibodies that could efficiently block host cell binding of both serotypes 2 and 4 of dengue virus and neutralize their infectivity (neutralizing antibody titers approximately 1:40 and ~1:80 for dengue virus serotypes 2 and 4, respectively). This work could be a forerunner to the development of a single envelope domain III-based tetravalent antigen.     

Intracystic invasive papillary carcinoma of the male breast with analyses of loss of heterozygosity on chromosome 16q

A 64-year-old man noticed a right subareolar mass in May 2005. On physical examination, an oval-shaped, well-circumscribedthe tumor (6.0 × 5.5 cm in size) was located just beneath the right nipple. The tumor was elastic, firm and freely movable. Neither axillary nor supraclavicular lymph nodes were palpable. Mammography demonstrated a 5 × 5-cm, relatively distinct and dense mass without microcalcifications or spiculations. There were no findings of concurrent gynecomastia. Ultrasonography revealed a large multilocular cyst with a mural hypoechoic protruding lesion exhibiting wide-based morphology with an irregular margin. On contrast-enhanced computed tomography, the inner lesion enhanced, but direct invasion of the tumor to the major pectoral muscle was not found. An intracystic papillary lesion, possibly papillary carcinoma, was suspected. In December 2007, wide excision of the tumor was performed. On histopathological examination, the tumor had a papillary pattern with a small cribriform component in the cystic wall with microinvasion of the stroma. Marginal status was negative. The final diagnosis of the disease was a microinvasive intracystic papillary carcinoma of low grade without axillary lymph node metastases. Immunohistochemically, estrogen receptor and progesterone receptor were both positive, but negative for HER-2 protein. No LOH on 16q could be detected. The prognosis of the disease was unclear; however, the malignant potential of this condition may be more clearly determined by studying the LOH on chromosome 16q.     

Long-term outcome of hepatocellular carcinoma patients who underwent liver resection using microwave tissue coagulation

Background/Aims. Our policy for the surgical treatment of hepatocellular carcinoma (HCC) has been to minimize the extent of liver resection using a microwave tissue coagulator (MTC) and to not perform Pringle''s maneuver for the prevention of ischemic injury to the liver routinely. We verify the safety of liver resection using MTC in HCC patients with poor liver functional reserve, and clarify the long-term outcome of HCC patients who underwent curative resection using MTC. Methodology. One hundred sixty-eight patients who underwent curative resection using MTC between 1992 and 2001 were divided into two groups according each patient''s score in the Indocyanin Green Retension 15 Test (ICG-R15 test). The high (ICG-R15 values>20) and low ICG-R15 groups (ICG-R15 values<20) included 100 and 68 HCC patients, respectively. Clinical characteristics of each group were evaluated, and operative mortality and morbidity, as well as overall and disease-free survival rates, were compared between the two groups to determine risk factors for overall and disease-free survival. Results. Although there were significant differences in liver function-related parameters between the low and high ICG-R15 groups, no differences in surgical or tumor factors were found. No patients in this study developed post-operative liver failure, and there was no significant difference in morbidity between the low and high ICG-R15 groups. The overall survival rate of the low ICG-R15 group was significantly longer than the high ICG-R15 group (p=0.0003). Cox''s multivariate analysis showed that an ICG-R15 value less than 20 was the only significant independent factor for overall survival. Disease-free survival rates in the low ICG-R15 group were significantly longer than in the high ICG-R15 group (p=0.0007). Multivariate analysis showed that serum albumin level and number of tumors were significant independent factors for disease-free survival. Conclusion. The long-term outcome of HCC patients with low ICG-R15 following curative resection using MTC was acceptable. This procedure was safe even for patients with high ICG-R15.     

Successful ceftriaxone therapy of endocarditis due to penicillin non-susceptible viridans streptococci

Viridans streptococci are a major cause of infective endocarditis, and penicillin non-susceptibility is increasing in these organisms. We present the initial reported case of infective endocarditis due to penicillin non-susceptible viridans streptococci successfully treated with ceftriaxone monotherapy. The lack of evidence supporting the recommendations for treatment of endocarditis due to penicillin non-susceptible viridans streptococci is discussed.     

Malignant melanomatic mass of right heel

Malignant melanoma mostly occurs in sun-exposed areas and is less common in covered areas. We report a patient, who presented with painless gradually increasing mass arising from the right heel, that was found to be a malignant melanoma. Treatment with local excision led to complete resolution of symptoms. To-date, 36 months after the diagnosis, the patient is still in complete remission. The diagnosis of melanoma should be considered in the presence of non-healing skin lesion and should be biopsied and treated according to Breslow thickness and presence or absence of metastases.     

Acute Effects of Self-Selected Regimen of Rapid Body Mass Loss in Combat Sports Athletes

The purpose of the study was to assess the acute effects of the self-selected regimen of rapid body mass loss (RBML) on muscle performance and metabolic response to exercise in combat sports athletes. Seventeen male athletes (20.8 ± 1.0 years; mean ± SD) reduced their body mass by 5.1 ± 1.1% within 3 days. The RBML was achieved by a gradual reduction of energy and fluid intake and mild sauna procedures. A battery of tests was performed before (Test 1) and immediately after (Test 2) RBML. The test battery included the measurement of the peak torque of knee extensors for three different speeds, assessment of total work (Wtot) performed during a 3-min intermittent intensity knee extension exercise and measurements of blood metabolites (ammonia, lactate, glucose and urea). Absolute peak torque was lower in Test 2 compared with Test 1 at angular velocities of 1.57 rad·s^-1 (218.6 ± 40.9 vs. 234.4 ± 42.2 N·m; p = 0.013) and 3.14 rad·s^-1 (100.3 ± 27.8 vs. 111.7 ± 26.2 N·m; p = 0.008). The peak torque in relation to body mass remained unchanged for any speed. Absolute Wtot was lower in Test 2 compared with Test 1 (6359 ± 2326 vs. 7452 ± 3080 J; p = 0.003) as well as Wtot in relation to body mass (89.1 ± 29.9 vs. 98.6 ± 36.4 J·kg^-1; p = 0.034), respectively. As a result of RBML, plasma urea concentration increased from 4.9 to 5.9 mmol·l^-1 (p = 0.003). The concentration of ammonia in a post-test sample in Test 2 tended to be higher in comparison with Test 1 (80.9 ± 29.1 vs. 67.6 ± 26.5 mmol·l^-1; p = 0.082). The plasma lactate and glucose responses to exercise were similar in Test 1 and Test 2. We conclude that the self-selected regimen of RBML impairs muscle performance in 3-min intermittent intensity exercise and induces an increase in blood urea concentration in experienced male combat sports athletes.

Key points

• Previous studies have revealed a negative effect of rapid body mass loss on performance. However, there are some performance characteristics that may not change or even improve.
• The methods used for inducing rapid body mass loss have been prescribed by researchers and not chosen by the subjects in many previous studies. The duration of tests, which have revealed a negative impact of rapid body mass loss on performance have also been rather long (5-6 min) in previous studies.
• We assessed the acute effects of the self-selected regimen of rapid body mass loss on muscle performance and metabolic response to 3-min intermittent intensity exercise in experienced male combat sports athletes.
• The results suggest that the self-selected regimen of rapid body mass loss impairs muscle performance in 3-min intermittent intensity exercise and induces an increase in blood urea concentration. Hence, the recent changes in the rules of some events (wrestling), including shortening of the duration of a match, have not reduced the likelihood of the occurrence of a negative impact of rapid body mass loss on athletes'' performance capacity.

Key words: Wrestlers, karatekas, muscular endurance, peak torque, ammonia, urea.     

Development and validation of the Montreal cognitive assessment for people with hearing impairment (MoCA-H)

Background

Hearing impairment is common among older adults and affects cognitive assessments for identification of dementia which rely on good hearing function. We developed and validated a version of the Montreal Cognitive Assessment (MoCA) for people with hearing impairment.

Methods

We adapted existing MoCA 8.1 items for people with hearing impairment by presenting instructions and stimuli in written rather than spoken format. One Attention domain and two Language domain items required substitution by alternative items. Three and four candidate items respectively were constructed and field-tested along with the items adapted to written form. We used a combination of individual item analysis and item substitution to select the set of alternative items to be included in the final form of the MoCA-H in place of the excluded original items. We then evaluated the performance and reliability of the final tool, including making any required adjustments for demographic factors.

Results

One hundred and fifty-nine hearing-impaired participants, including 76 with normal cognition and 83 with dementia, completed the adapted version of the MoCA. A further 97 participants with normal hearing completed the standard MoCA as well as the novel items developed for the MoCA-H to assess score equivalence between the existing and alternative MoCA items and for independence from hearing impairment. Twenty-eight participants were retested between 2–4 weeks after initial testing. After the selection of optimal item set, the final MoCA-H had an area under the curve of 0.973 (95% CI 0.952–0.994). At a cut-point of 24 points or less sensitivity and specificity for dementia was 92.8% and 90.8%, respectively. The intraclass correlation for test–retest reliability was 0.92 (95%CI 0.78–0.97).

Conclusion

The MoCA-H is a sensitive and reliable means of identifying dementia among adults with acquired hearing impairment.