Comparison of expectorated sputum after manual chest physical therapy and high-frequency chest compression

This study is a quantitative comparison of the sputum produced by 12 subjects with cystic fibrosis (CF) who received high-frequency chest compression (HFCC) and standard chest physical therapy (CPT) in randomized order. Six subjects routinely used manual CPT and six routinely used the HFCC. None had acute infections or hospitalization in the six weeks before the study. Two certified respiratory therapists alternated subjects and CPT vs HFCC order during the two weeks of the matched study. For all sessions, the expectorated sputum was collected in preweighed cups, which were reweighed immediately after collection and again after evaporation to dryness. The wet and dry weights of the sputum produced as a result of the two techniques were significantly different, with HFCC having greater weight. Regardless of the mode of therapy, the sputum produced by the subjects who regularly received HFCC had greater water content than did the sputum produced by those subjects who regularly received CPT. No significant difference was found between the two therapists regarding sputum expectorated by the subjects during CPT. These results show that sputum production by subjects with CF who receive CPT by certified respiratory therapists can be as great as the sputum produced by the same subjects who receive HFCC. The results also suggest that unknown factors attributed to the therapists may produce different levels of effort from time to time that may decrease the respiratory therapists' effectiveness, whereas the HFCC therapy may be more consistently effective because it is entirely machine based.     

Increasing peptide identifications and decreasing search times for ETD spectra by pre-processing and calculation of parent precursor charge

Background

Early diagnosis and treatment of Mycobacterium tuberculosis infection can prevent most deaths resulting from this pathogen; however, multidrug-resistant strains present serious threats to global tuberculosis control and prevention efforts. In this study, we identified antigens that could be used for the serodiagnosis of drug-resistant M. tuberculosis strains, using a proteomics-based analysis.

Results

Serum from patients infected with drug-resistant or drug-susceptible M. tuberculosis strains and healthy controls was subjected to two-dimensional gel electrophoresis using a western blot approach. This procedure identified nine immunoreactive proteins, which were subjected to MALDI-TOF-MS analysis. Six recombinant proteins, namely rRv2031c, rRv0444c, rRv2145c, rRv3692, rRv0859c, and rRv3040, were expressed and used to determine the immuno-reactivity of 100 serum samples. Antibody reactivity against rRv2031c, rRv3692, and rRv0444c was consistently observed. Among them, the best sensitivity and specificity of rRv3692 were 37% and 95% respectively. Furthermore, when rRv2031c and rRv3692 or rRv2031c, rRv3692, and rRv0444c were combined in 2:1 or equal amounts, the assay sensitivity and specificity were improved to 56.7% and 100% respectively.

Conclusions

These results suggest that Rv2031c, Rv3692, and Rv0444c are possible candidate biomarkers for effective use in the serodiagnosis of drug-resistant tuberculosis infections, and a combined formula of these antigens should be considered when designing a subunit assay kit.     

Increasing and decreasing functional area of the dentition (FAD) of Mammuthus primigenius

The occlusal morphology and continuous molar replacement in elephants provide a very effective functional area for grinding the biomass that is more or less abrasive. Parts of two subsequent molars contribute to the “functional area of the dentition” (FAD). The FAD size, measured in cm², is associated with age and body size. The FAD stage is indicated by the specific teeth contributing to the FAD and represents the individual age. This study concentrates on Mammuthus primigenius and compares the FAD stages, as derived from growth series, with the fossil Elephas antiquus, as well as the extant Elephas maximus and Loxodonta africana. During the life history of the taxa studied, the functional area increases simultaneously with an increase in body size, but decreases severely in senile age stages. In some senile individuals, the FAD is only about 20–50 % of the mean area of an adult animal. The reduction of the FAD beyond a specific size does not mean an immediate starvation of the animal. The general constitution of the individual and the resources of fat accumulation earlier may support the animal for some time but certainly not over a longer period. Nevertheless, the highly reduced functional area was sufficient to keep the animal alive despite its full adult body mass. A much larger FAD in all adult stages provides the energy requirements needed for all additional life functions including competition and reproduction.     

Oral atorvastatin therapy increases nitric oxide-dependent cutaneous vasodilation in humans by decreasing ascorbate-sensitive oxidants

Elevated low-density lipoproteins (LDL) are associated with cutaneous microvascular dysfunction partially mediated by increased arginase activity, which is decreased following a systemic atorvastatin therapy. We hypothesized that increased ascorbate-sensitive oxidant stress, partially mediated through uncoupled nitric oxide synthase (NOS) induced by upregulated arginase, contributes to cutaneous microvascular dysfunction in hypercholesterolemic (HC) humans. Four microdialysis fibers were placed in the skin of nine HC (LDL = 177 ± 6 mg/dl) men and women before and after 3 mo of a systemic atorvastatin intervention and at baseline in nine normocholesterolemic (NC) (LDL = 95 ± 4 mg/dl) subjects. Sites served as control, NOS inhibited, L-ascorbate, and arginase-inhibited+L-ascorbate. Skin blood flow was measured while local skin heating (42°C) induced NO-dependent vasodilation. After the established plateau in all sites, 20 mM ?ngname? was infused to quantify NO-dependent vasodilation. Data were normalized to maximum cutaneous vascular conductance (CVC) (sodium nitroprusside + 43°C). The plateau in vasodilation during local heating (HC: 78 ± 4 vs. NC: 96 ± 2% CVC(max), P < 0.01) and NO-dependent vasodilation (HC: 40 ± 4 vs. NC: 54 ± 4% CVC(max), P < 0.01) was reduced in the HC group. Acute L-ascorbate alone (91 ± 5% CVC(max), P < 0.001) or combined with arginase inhibition (96 ± 3% CVC(max), P < 0.001) augmented the plateau in vasodilation in the HC group but not the NC group (ascorbate: 96 ± 2; combo: 93 ± 4% CVC(max), both P > 0.05). After the atorvastatin intervention NO-dependent vasodilation was augmented in the HC group (HC postatorvastatin: 64 ± 4% CVC(max), P < 0.01), and there was no further effect of ascorbate alone (58 ± 4% CVC(max,) P > 0.05) or combined with arginase inhibition (67 ± 4% CVC(max,) P > 0.05). Increased ascorbate-sensitive oxidants contribute to hypercholesteromic associated cutaneous microvascular dysfunction which is partially reversed with atorvastatin therapy.     

Responses of phytoplankton diversity to physical disturbance under manual operation in a large reservoir, China

In aquatic ecosystems, physical disturbances have been suggested to be one of the main factors influencing phytoplankton structure and diversity. To elucidate whether large-scale artificial operation of a hydroelectric reservoir has potential impacts on phytoplankton diversity, the impact on phytoplankton biodiversity of physical disturbances under artificial operation from May 2007 to April 2008 in tributaries of the Three Gorges Reservoir (TGR), China, was analysed. Two disturbance parameters, i.e. the absolute incremental rates of discharge (R _d,i ) and precipitation (R _p,i ), were created in this study for evaluating physical disturbance intensities during low and high water level periods of the TGR. Results showed that river discharge seemed to be the main factor controlling the phytoplankton diversity in low water level periods (≤151 m), and that precipitation was a potential promoter of the physical disturbance. During the 156-m impoundment process, the species diversity clearly decreased due to the high dilution effect on the phytoplankton communities. At high water level periods (>151 m), the low levels of disturbance eventually allowed the phytoplankton community to approach competitive exclusion in late February 2008. Sharply declining diversity values appeared when the Dinophyta blooms occurred in late March and late April 2008 (Peridinium and Ceratium, respectively).     

Increasing and decreasing protein stability: effects of revertant substitutions on the thermal denaturation of phage lambda repressor

The thermal denaturations of five revertant lambda repressors containing single amino acid substitutions in their N-terminal domains have been studied by differential scanning calorimetry. Two substitutions slightly decrease stability, and the remaining three render the protein more stable than wild type. The Gly48----Asn and Gly48----Ser proteins are 4 degrees C more stable than wild type. These two substitutions replace an alpha helical residue, and in each case a poor helix forming residue, glycine, is replaced by a residue with a higher helical propensity. We also present data showing that one revertant, Tyr22----Phe, has reduced operator DNA binding affinity despite its enhanced stability.     

随机突变提高单胺氧化酶活性

前期获得了一个对底物美西律具有一定活性的单胺氧化酶突变体A-1(F210V/L213C)。为进一步提高其酶活性,利用MegaWHOP PCR构建了库容约为104的随机突变库。筛选后获得了一个最优突变酶ep-1,比活力为A-1的189%。选择性测定结果表明,酶的对映体选择性有较大提高,E值由101提高到282;动力学常数测定揭示,酶催化效率有较大提高,kcat/Km由0.001 51 mmol/(L?s)提高到0.002 89 mmol/(L?s)。和A-1酶相比,在所测定的11种胺类底物中,ep-1对其他7种底物的比活力有较明显提高,对其他4种底物的比活力变化不大。序列分析表明,ep-1的突变为T162A。分子动力学模拟结果提示,该突变主要通过修正通道氨基酸的二级结构和扩大活性口袋来发挥作用。     

Increasing breadth of the frontal lobe but decreasing height of the human brain between two Chinese samples from a Neolithic site and from living humans

Morphological observation and measurements of endocasts have played a vital role in research on the evolution of the human brain. However, endocasts have never been used to investigate how the human brain has evolved since the Neolithic period. We investigated the evolution of the human brain during the Holocene by comparing virtual endocasts from Beiqian site (a Neolithic Chinese site) and a sample of Chinese modern‐day humans. Standardized measurements and indices were taken to provide quantification of the overall endocast shape, including the length, breadth, height, frontal breadth, and the ratio of frontal breadth to breadth, as well as the cranial capacity. We found that the height of the endocasts and cranial capacity have decreased between our two samples, whereas the frontal breadth and sexual dimorphism have increased. We argue that these changes can be caused by random genetic mutation and epigenetic change in response to changes in the environment. Am J Phys Anthropol 154:94–103, 2014. © 2014 Wiley Periodicals, Inc.     

Increasing Himalayan tahr and decreasing chamois densities in the eastern Southern Alps, New Zealand: evidence for interspecific competition

There is anecdotal evidence that increasing densities of Himalayan tahr (Hemitragus jemlahicus) are associated with declining densities of chamois (Rupicapra rupicapra) in the Southern Alps, New Zealand. To examine this phenomenon, densities of tahr and chamois were measured at 53 sites within their sympatric range in the eastern Southern Alps during 1978–1979. In sites where only one species was present, tahr density was significantly higher than chamois density (P=0.032), probably reflecting species differences in sociality. Chamois density was higher in catchments without tahr than in those with tahr (P=0.012). Similarly, tahr density was significantly higher at sites without chamois than at those with chamois (P=0.033). Sites with both species present (termed sympatric) were significantly larger than those with only chamois or tahr (P<0.001). Following the prohibition of aerial hunting of tahr in 1983, 16 of the 17 sites where tahr and chamois were sympatric during 1978–1979 were recounted during 1991–1996. There was a 6-fold increase in the mean density of tahr between the two counts (P=0.001), whereas chamois density had declined significantly (P=0.006). Chamois persisted at only three sites, two of which had the highest chamois densities in 1978–1979. This is evidence that increasing densities of tahr exclude chamois from all but the `best' habitats. We conclude that intensive aerial hunting of tahr during 1967–1983 reduced tahr densities such that chamois could co-exist with tahr. Received: 20 March 1997 / Accepted: 8 September 1997     

Hereditary melanoblastoma in miniature pigs and its successful therapy by devitalization technique.

Applying selective breeding for 10 years we established the MeLiM (Melanoblastoma-bearing Libechov Minipigs) strain. Melanoblastoma (MB) in this strain shows a hereditary occurrence. Cutaneous tumours are usually nodular, multiple and distributed on various parts of body. They appear in darkly pigmented animals already at the birth or during two months thereafter (57% of all animals). Numerous organ metastases mainly into the spleen, lymph nodes and lungs are regularly ascertained in animals with cutaneous MB. Tumour cells were surprisingly found also in the inner organs of phenotypically healthy minipigs in which no cutaneous MBs were observed visually (27% of all animals). About 34% of all affected piglets die during the first 2 months of age. These features document a malignancy of this tumour in the MeLiM strain. Original surgical technique was applied in more than 40 affected minipigs at 1-2 months of age. It consists in a devitalization (ischemization) of one of cutaneous tumours by the mattress sutures conducted around the tumour base without any excision of tumour tissue. This simple procedure causes a total destruction of MB cells in all cutaneous tumours as well as in all organ metastases during 4-6 months. Animals treated by this technique were fully healed of tumour cells and no relapses were observed. This technique could bring similar positive results also in therapy of human MB.     

Functional and EMG responses to a physical therapy treatment in patellofemoral syndrome patients.

There are several pathologies related to the patellofemoral joint, in which the patellofemoral syndrome is one of the most common and challenging to treat. The patellofemoral syndrome results from a malalignment of the knee extensor mechanism. The purpose of our study was to describe and compare EMG responses of the vastus medialis and vastus lateralis muscles while walking up and down stairs and other clinical and functional responses in PFS subjects before and after a physical therapy intervention. Eleven subjects were studied and divided in two groups: six subjects with clinically diagnosed patellofemoral syndrome and five healthy control subjects. Subjects were evaluated by a functional and biomechanical evaluation protocol: postural evaluation, pain and knee function evaluation, and electromyographic activity of vastus medialis and lateralis muscles while walking up and down a staircase. Results showed higher efficiency of the vastus medialis muscle in carrying out eccentric exercises and increased muscle activity in both the vastus medialis and vastus lateralis muscles while climbing stairs after physical therapy treatment. We were able to identify an improvement in postural alignment of lower limb muscles and knee functionality among patellofemoral syndrome group subjects after treatment.     

Increasing the net charge and decreasing the hydrophobicity of bovine carbonic anhydrase decreases the rate of denaturation with sodium dodecyl sulfate

This study compares the rate of denaturation with sodium dodecyl sulfate (SDS) of the individual rungs of protein charge ladders generated by acylation of the lysine epsilon-NH3+ groups of bovine carbonic anhydrase II (BCA). Each acylation decreases the number of positively charged groups, increases the net negative charge, and increases the hydrophobic surface area of BCA. This study reports the kinetics of denaturation in solutions containing SDS of the protein charge ladders generated with acetic and hexanoic anhydrides; plotting these rates of denaturation as a function of the number of modifications yields a U-shaped curve. The proteins with an intermediate number of modifications are the most stable to denaturation by SDS. There are four competing interactions-two resulting from the change in electrostatics and two resulting from the change in exposed hydrophobic surface area-that determine how a modification affects the stability of a rung of a charge ladder of BCA to denaturation with SDS. A model based on assumptions about how these interactions affect the folded and transition states has been developed and fits the experimental results. Modeling indicates that for each additional acylation, the magnitude of the change in the activation energy of denaturation (DeltaDeltaG(double dagger)) due to changes in the electrostatics is much larger than the change in DeltaDeltaG(double dagger) due to changes in the hydrophobicity, but the intermolecular and intramolecular electrostatic effects are opposite in sign. At the high numbers of acylations, hydrophobic interactions cause the hexanoyl-modified BCA to denature nearly three orders of magnitude more rapidly than the acetyl-modified BCA.