Changes in odor quality discrimination following recovery from olfactory nerve transection

Following recovery from olfactory nerve transection, animals regain their ability to discriminate between odors. Odor discrimination is restored after new neurons establish connections with the olfactory bulb. However, it is not known if the new connections alter odor quality perception. To address this question, 20 adult hamsters were first trained to discriminate between cinnamon and strawberry odors. After reaching criterion (> or = 90% correct response), half of the animals received a bilateral nerve transection (BTX) and half a surgical sham procedure. Animals were not tested again until day 40, a point in recovery when connections are re-established with the bulb. When BTX animals were tested without food reinforcement, they could not perform the odor discrimination task. Sham animals, however, could discriminate, demonstrating that the behavioral response had not been extinguished during the 40 day period. When reinforcement was resumed, BTX animals were able to discriminate between cinnamon and strawberry after four test sessions. In addition, their ability to discriminate between these two familiar odors was no different than that of BTX and sham animals tested with two novel odors, baby powder and coffee. These findings suggest that, after recovery from nerve transection, there are alterations in sensory perception and that restoration of odor quality discrimination requires that the animal must again learn to associate individual odor sensations with a behavioral response.      

The accuracy of several multiple sequence alignment programs for proteins

Background  

There have been many algorithms and software programs implemented for the inference of multiple sequence alignments of protein and DNA sequences. The "true" alignment is usually unknown due to the incomplete knowledge of the evolutionary history of the sequences, making it difficult to gauge the relative accuracy of the programs.     

Plasma proteome analysis in HTLV-1-associated myelopathy/tropical spastic paraparesis

Background

A new subgroup of HIV-1, designated Group P, was recently detected in two unrelated patients of Cameroonian origin. HIV-1 Group P phylogenetically clusters with SIVgor suggesting that it is the result of a cross-species transmission from gorillas. Until today, HIV-1 Group P has only been detected in two patients, and its degree of adaptation to the human host is largely unknown. Previous data have shown that pandemic HIV-1 Group M, but not non-pandemic Group O or rare Group N viruses, efficiently antagonize the human orthologue of the restriction factor tetherin (BST-2, HM1.24, CD317) suggesting that primate lentiviruses may have to gain anti-tetherin activity for efficient spread in the human population. Thus far, three SIV/HIV gene products (vpu, nef and env) are known to have the potential to counteract primate tetherin proteins, often in a species-specific manner. Here, we examined how long Group P may have been circulating in humans and determined its capability to antagonize human tetherin as an indicator of adaptation to humans.

Results

Our data suggest that HIV-1 Group P entered the human population between 1845 and 1989. Vpu, Env and Nef proteins from both Group P viruses failed to counteract human or gorilla tetherin to promote efficient release of HIV-1 virions, although both Group P Nef proteins moderately downmodulated gorilla tetherin from the cell surface. Notably, Vpu, Env and Nef alleles from the two HIV-1 P strains were all able to reduce CD4 cell surface expression.

Conclusions

Our analyses of the two reported HIV-1 Group P viruses suggest that zoonosis occurred in the last 170 years and further support that pandemic HIV-1 Group M strains are better adapted to humans than non-pandemic or rare Group O, N and P viruses. The inability to antagonize human tetherin may potentially explain the limited spread of HIV-1 Group P in the human population.     

Factors associated with physician agreement and coding choices of cause of death using verbal autopsies for 1130 maternal deaths in India

Background

The Indian Sample Registration System (SRS) with verbal autopsy methods provides estimations of cause specific mortality for maternal deaths, where the majority of deaths occur at home, unregistered. We aim to examine factors that influence physician agreement and coding choices in assigning causes of death from verbal autopsies.

Methodology/Principal Findings

Among adult deaths identified in the SRS, pregnancy-related deaths recorded in 2001–2003 were assigned ICD-10 codes by two independent physicians. Inter-rater reliability was estimated using Landis Koch Kappa classification – poor to fair agreement; > – moderate agreement; > – substantial agreement; >– high agreement. We identified factors associated with physician agreement using multivariate logistic regression. A central consensus panel reviewed cases for errors and reclassified as needed based on 2011 ICD-10 coding guidelines. Of 1130 pregnancy-related deaths, 1040 were assigned ICD-10 codes by two physicians. We found substantial agreement regardless of the woman''s residence, whether the death was registered, religion, respondent''s or deceased''s education, age, hospital admission or gestational age. Physician agreement was not influenced by the above variables, with the exception of greater agreement in cases where the respondent did not live with the deceased, or early gestational age at the time of death. A central consensus panel reviewed all cases and recoded 10% of cases due to insufficient use of information in the verbal autopsy by the coding physicians and rationale for this reclassification are discussed.

Conclusion

In the absence of complete vital registration and universal healthcare services, physician coded verbal autopsies continues to be heavily relied upon to ascertain pregnancy-related death. From this study, two independent physicians had good inter-rater reliability for assigning pregnancy-related causes of death in a nationally-represented sample, and physician coding does not appear to be heavily influenced by case characteristics or demographics.     

Digital image analysis of AgNORs in cervical smears of women with premalignant and malignant lesions of the uterine cervix

We performed a hospital-based, unmatched case-control study to investigate the association between progressive stages of cervical neoplasia and digital analysis of cell proliferation by silver stained nucleolus organizer region associated proteins (AgNORs). We measured cell proliferation levels in the cervical epithelial cells of 10 women with low grade squamous intraepithelial lesions (LG-SIL), eight with high grade squamous intraepithelial lesions (HG-SIL), 11 with cervical cancer (CC) and eight with no cervical lesions (controls) using the AgNORs technique. Cell proliferation was measured by digital image analysis (DIA). DIA revealed increased total areas of AgNORs in HG-SIL and CC compared to LG-SIL and control patients. AgNORs with a kidney or cluster shape exhibited greater areas than those with a spherical or long shape. We propose a cut-off of 118 pixels to differentiate benign (control and LG-SIL) from malignant (HG-SIL and CC) lesions. DIA of AgNORs is a simple and inexpensive method for studying proliferation. The increased total area of AgNORs in malignant lesions provides information regarding cell behavior and may be related to cervical carcinogenesis; however, further validation studies are required to establish its usefulness in cytological analysis.     

1-Thio-beta-D-galactofuranosides: synthesis and evaluation as beta-D- galactofuranosidase inhibitors

Beta-D-galactofuranosidase is a good chemotherapeutic target for the design of inhibitors, since beta-D-galactofuranose is a constituent of important parasite glycoconjugates but is not present in the host mammals. With this aim, we have synthesized for the first time alkyl, benzyl and aryl 1-thio-beta-D-galactofuranosides by condensation of penta-O-benzoyl-alpha,beta-D-galactofuranose with the corresponding thiols, in the presence of SnCl4as catalyst. The complete chemical and spectroscopical characterization of these compounds showed that the reaction was stereoselective. Debenzoylation with sodium methoxide afforded the beta-S-galactofuranosides in high yield. The thioglycosides were tested as inhibitors of the beta-D- galactofuranosidase of Penicillium fellutanum, using for the first time 4-nitrophenyl-beta-D-galactofuranoside as chromogenic substrate. The 4- aminophenyl-1-thio-beta-D-galactofuranoside, obtained by catalytic hydrogenation of the nitrophenyl derivative, was the best inhibitor being then an adequate ligand for the preparation of an affinity phase aimed at the isolation of beta-d-galactofuranosidases from different sources. Also the inhibitory activity of d-galactono-1, 4-lactone was shown.      

Capturing the context of maternal deaths from verbal autopsies: a reliability study of the maternal data extraction tool (M-DET)

Background

The availability of quality data to inform policy is essential to reduce maternal deaths. To characterize maternal deaths in settings without complete vital registration systems, we designed and assessed the inter-rater reliability of a tool to systematically extract data and characterize the events that precede a nationally representative sample of maternal deaths in India.

Method/Principal Findings

Of 1017 nationally representative pregnancy-related deaths, which occurred between 2001 and 2003, we randomly selected 105 reports. Two independent coders used the maternal data extraction tool (questions with coding guidelines) to collect information on antenatal care access, final pregnancy outcome; planned place of birth and care provider; community consultation, transport, admission, hospital referral; and verification of cause of death assignment. Kappa estimated inter-rater agreement was calculated and classified as poor (K≤0.4), moderate (K = 0.4-≤0.6), substantial (K = 0.6-≤0.8) and high (K>0.8) using the criteria from Landis & Koch. The data extraction tool had high agreement for gestational age, pregnancy outcome, transport, death en route and admission to hospital; substantial agreement for receipt of antenatal care, planned place of birth, readmission and referral to higher level hospital, and whether or not death occurred in the intrapartum period; moderate to substantial agreement for classification of deaths as direct or indirect obstetric deaths or incidental deaths; moderate agreement for classification of community healthcare consultation and total number of healthcare contacts; and poor agreement for the classification of deaths as sudden deaths and other/unknown cause of death. The ability of the tool to identify the most-responsible-person in labour varied from moderate agreement to high agreement.

Conclusions

This data extraction tool achieved good inter-rater reliability and can be used to collect data on events surrounding maternal deaths and for verification/improvement of underlying cause of death.     

Compression or tension? The stress distribution in the proximal femur

Background  

Questions regarding the distribution of stress in the proximal human femur have never been adequately resolved. Traditionally, by considering the femur in isolation, it has been believed that the effect of body weight on the projecting neck and head places the superior aspect of the neck in tension. A minority view has proposed that this region is in compression because of muscular forces pulling the femur into the pelvis. Little has been done to study stress distributions in the proximal femur. We hypothesise that under physiological loading the majority of the proximal femur is in compression and that the internal trabecular structure functions as an arch, transferring compressive stresses to the femoral shaft.