Psychosocial Outcomes in Adult Survivors of Retinoblastoma.
Survival rates for individuals diagnosed with retinoblastoma (RB) exceed 95% in the United States; however, little is known about the long-term psychosocial outcomes of these survivors. Adult RB survivors, diagnosed from 1932 to 1994 and treated in New York, completed a comprehensive questionnaire adapted from the Childhood Cancer Survivor Study (CCSS), by mail or telephone. Psychosocial outcomes included psychological distress, anxiety, depression, somatization, fear of cancer recurrence, satisfaction with facial appearance, post-traumatic growth, and post-traumatic stress symptoms; noncancer CCSS siblings served as a comparison group. A total of 470 RB survivors (53.6% with bilateral RB; 52.1% female) and 2,820 CCSS siblings were 43.3 (standard deviation [SD], 11) years and 33.2 (SD, 8.4) years old at the time of study, respectively. After adjusting for sociodemographic factors, RB survivors did not have significantly higher rates of depression, somatization, distress, or anxiety compared with CCSS siblings. Although RB survivors were more likely to report post-traumatic stress symptoms of avoidance and/or hyperarousal (both P < .01), only five (1.1%) of 470 met criteria for post-traumatic stress disorder. Among survivors, having a chronic medical condition did not increase the likelihood of psychological problems. Bilateral RB survivors were more likely than unilateral RB survivors to experience fears of cancer recurrence (P < .01) and worry about their children being diagnosed with RB (P < .01). However, bilateral RB survivors were no more likely to report depression, anxiety, or somatic complaints than unilateral survivors. Most RB survivors do not have poorer psychosocial functioning compared with a noncancer sample. In addition, bilateral and unilateral RB survivors seem similar with respect to their psychological symptoms.


Do visually impaired children and their parents agree on the child's vision-related quality of life and functional vision?
To investigate agreement between children with visual impairment (VI) and their parents on their ratings of the child's vision-related quality of life (VQoL) and functional vision (FV) using two novel self-report patient-reported outcome measures developed for this population. 99 children aged 10-15 years (mean age=12.2, SD=1.9) with VI (best corrected acuity (logarithm of the minimum angle of resolution) 0.50 or worse in better eye) and their parents participated in a national postal survey, completing the child and proxy versions of our novel instruments assessing VQoL and FV of children with VI-the vision-related quality of life instrument for children and young people (VQoL_CYP) and the functional vision questionnaire for children and young people (FVQ_CYP), respectively. Parent-child agreement was investigated using the Bland-Altman (BA) method. Variation across key sociodemographic and clinical characteristics was examined using the Intraclass Correlation Coefficient. Average parental ratings of their child's VQoL and FV were significantly lower than the children's own ratings, but the range of disagreement was wide, with parents both overestimating and underestimating their child's VQoL (mean score difference=5.7, BA limits of agreement (LOA): lower -22.10 (CI 95% -24.61 to 19.59) and upper 33.50 (CI 95% 30.99 to 36.01)), but more consistently underestimating the child's FV (mean score difference=-11.8, BA LOA: lower -39.60 (CI 95% -42.12 to 37.08) and upper 16 (CI 95% 13.48 to 18.52)). There was variation in agreement by some child characteristics, including vision level, time of onset and course of VI progression. Visually impaired children and their parents perceive the broader impact of living with VI very differently. There is value in routine capture of information independently from children and their parents for comprehensively gauging the impact of childhood VI and tailoring appropriate interventions.


Causes of blindness in northwest Cambodia.
A hospital-based study in the northwest of Cambodia identified 453 blind adults and 30 blind children seen consecutively at the provincial ophthalmic department between January and September 1994. Blindness was defined as a visual acuity of less than 3/60 in the better eye. Cataract was the cause of blindness in 266 (59%) adults, of which 15 cases (3.3%) were surgical complications. Sixty-three cases (14%) were due to glaucoma and 53 (11.5%) patients had corneal scars, of which 12 (2.5%) were due to trachoma. Bilateral trauma, usually due to landmine injuries, accounted for 17 patients (4%). Of the 30 blind children, corneal scarring accounted for 12 cases (40%), congenital causes for 14 (47%) and optic atrophy secondary to meningitis for 4 (13%). There is at present an inadequate ophthalmological service for the vast majority of people living outside the capital Phnom Penh. These hospital-based data suggest that there is a need to train general doctors to surgically manage patients with visual loss from cataract and glaucoma, which together account for 70% of all cases of blindness, and highlight the need for a large population-based survey.


[The antinociceptive effect of intrathecal somatostatin in monkeys].
The distribution of somatostatin (SST) throughout the nervous system suggests that this tetradecapeptide may play a physiological role in CNS in the mediation of analgesia. The present study was undertaken to evaluate the antinociceptive properties of intrathecal (IT) injection of SST in the comparison of morphine sulfate (MS) in a primate model. The study was conducted after institutional approval and adhered to the regulations of the animal research committee. Seven adult monkeys (Maccaca cyclopis Swinhoe) weighing 4-6 kg were used. In each animal a L5 laminectomy window was created to facilitate IT injection. No neurological damage from surgery was noted. With the monkey standing in a specially constructed cage, all animals randomly received the following agents at one-week interval: (1) MS 1 mg, IT; (2) SST 50 micrograms, IT; (3) SST 250 micrograms, IT; and (4) SST 250 micrograms, IT + intramuscular (IM) naloxone 400 micrograms. The measured withdrawal latency (HPWL) was converted to the maximal percentage effect (MPE %) for comparison. The HPWL was measured at predrug and 5, 15, 30, 45, 60, 90 and 120 min after injection. Venous blood sample was obtained every 15 min to determine the plasma SST level by radioimmunoassay (RIA) technique in group 3 only. The results showed that MS (1 mg, IT) produced potent antinociception (MPE 100%) for more than 2 h. Intrathecal SST 50 micrograms, however, induced mild antinociception (MPE 43%) for only a short period and a 5-fold larger dose (250 micrograms) did not significantly change the nociceptive threshold with MPE only up to 47%.(ABSTRACT TRUNCATED AT 250 WORDS)


Predictors of adherence to home rehabilitation exercises following anterior cruciate ligament reconstruction.
Although home exercises are commonly prescribed following anterior cruciate ligament (ACL) reconstruction and are considered important in obtaining successful rehabilitation outcomes, little is known about factors associated with the completion of such exercises. Consequently, this study was designed to identify predictors of adherence to home rehabilitation exercises after ACL surgery. Participants (33 women, 58 men) completed indices of athletic identity, neuroticism, optimism, and pessimism before ACL surgery and measures of daily pain, negative mood, stress, and home exercise completion for 42 days postoperatively. Participants reported a high level of adherence to the prescribed regimen. Home exercise completion increased significantly over time as the number of sets of prescribed home exercises declined. Personal factors were not predictive of home exercise completion. Participants completed fewer home exercises on days when they experienced more stress or negative mood. Day-to-day variations in negative mood and stress may contribute to adherence to prescribed home exercises.


Pure Chiral Polar Vortex Phase in PbTiO3/SrTiO3 Superlattices with Tunable Circular Dichroism.
Nontrivial polarization textures have been demonstrated in ferroelectric/dielectric superlattices, where the electrostatic, elastic, and different gradient energies compete in a delicate balance. When PbTiO3/SrTiO3 superlattices are grown on DyScO3, the coexistence of ferroelectric domains and vortex structure is observed for n = 12-20 unit cells. Here, we report an approach to achieve single-phase vortex structures in superlattices by controlling the epitaxial strain using Sr1.04Al0.12Ga0.35Ta0.50O3 substrates. The domain width follows Kittel's law with the thickness of the ferroelectric PbTiO3 layers. A phase transition from vortex to a disordered phase with temperature is characterized by the correlation length. Resonant soft X-ray diffraction circular dichroism at the titanium L-edge reveals enhanced chirality with the thickness of the ferroelectric layer. These results are supported by second-principles simulations, which demonstrate that the integrated helicity increases with n. The stabilization of chiral single-phase polar vortices in ferroelectric/dielectric superlattices can enable novel optoelectronic devices with enhanced ferroelectric-light interaction.


Pulmonary pleomorphic carcinoma with multiple metastases to the right posterior knee complicated by paraneoplastic hypercalcemia.
In this report, we describe the case of a 46-year-old male who presented with a three-month history of progressive intermittent pain over the right posterior knee. Magnetic resonance imaging showed soft tissue masses over the right popliteal fossa. Surgery was performed, and histological examination revealed the mass to be a sarcomatoid carcinoma of poor differentiation. Fluorodeoxyglucose (FDG)-positron emission tomography showed FDG uptake in the lungs and in the right para-aortic and popliteal regions. On the basis of the morphological and immunohistochemical features of the specimens, the patient's condition was diagnosed as a pulmonary pleomorphic carcinoma with multiple metastases. Systemic chemotherapy was initiated with paclitaxel and cisplatin. The patient then developed paraneoplastic hypercalcemia and ultimately succumbed to healthcare-acquired pneumonia. The results of this rare case indicate that pulmonary pleomorphic carcinomas respond poorly to combination chemotherapy with paclitaxel and cisplatin. The firm mass in the popliteal fossa that was situated behind the knee was considered to be a Baker cyst; however, the possibility of malignant metastatic sarcomas, such as pulmonary sarcomatoid carcinoma, should be considered in the differential diagnosis. In conclusion, we emphasize that pretherapeutic examinations should be the basis for the diagnosis of a mass lesion at either an unusual or usual site.


Ten-minute chat.
Alastair Porter became secretary and Registrar of the Royal College of Veterinary Surgeons in 1966. Here, he recalls the first of his 25 years in office.


Status of Dental Caries and Its Association with Oral Hygiene Practices among School-going Children of Rural and Urban Areas in Kamrup District of Assam.
The study aimed to assess and compare the prevalence of dental caries with its association with oral hygiene practices among 13-14 years old schoolchildren in urban and rural areas in Kamrup Metropolitan (M) District, Assam. A total of 1,501 schoolchildren in the age group of 13-14 years were included in the study and dental caries was recorded from decayed missing filled teeth (DMFT)/deft index as described by World Health Organization (WHO) (1997). The children were asked to fill in the basic information in the proforma by themselves. The statistical tests used in this study were unpaired t-test, Chi-square test, and one-way ANOVA test to compare the DMFT among the different age groups, gender, and location. A statistically significant difference was found in the prevalence of the decayed (D) component between the 14 years old (33.9%) and the 13 years old (28.5%) age groups and a highly statistical difference was found between the male (27.9%) and the female (35.7%) population. However, the prevalence of decayed components for the rural (30.1%) and the urban (33.1%) population was not statistically significant. The overall prevalence of dental caries among schoolchildren of Kamrup (Metropolitan) District was 33.6%. Dental caries is a major public dental health problem; hence, an active and effective preventive program for dental care is needed for the child population in the area. Doley S, Srivastava M, Piplani A, et al. Status of Dental Caries and Its Association with Oral Hygiene Practices among School-going Children of Rural and Urban Areas in Kamrup District of Assam. Int J Clin Pediatr Dent 2022;15(2):182-186.


Dynamic intensity-weighted region of interest imaging for conebeam CT.
Patient dose from image guidance in radiotherapy is small compared to the treatment dose. However, the imaging beam is untargeted and deposits dose equally in tumor and healthy tissues. It is desirable to minimize imaging dose while maintaining efficacy. Image guidance typically does not require full image quality throughout the patient. Dynamic filtration of the kV beam allows local control of CT image noise for high quality around the target volume and lower quality elsewhere, with substantial dose sparing and reduced scatter fluence on the detector. The dynamic Intensity-Weighted Region of Interest (dIWROI) technique spatially varies beam intensity during acquisition with copper filter collimation. Fluence is reduced by 95% under the filters with the aperture conformed dynamically to the ROI during cone-beam CT scanning. Preprocessing to account for physical effects of the collimator before reconstruction is described. Reconstructions show image quality comparable to a standard scan in the ROI, with higher noise and streak artifacts in the outer region but still adequate quality for patient localization. Monte Carlo modeling shows dose reduction by 10-15% in the ROI due to reduced scatter, and up to 75% outside. The presented technique offers a method to reduce imaging dose by accepting increased image noise outside the ROI, while maintaining full image quality inside the ROI.


Hepatitis C advances in antiviral therapy: what is accepted treatment now?
The vast number of patients with hepatitis C represent a huge medical and economic burden. While 20-30% of these patients progress and develop advanced liver disease, the majority do not. Thus, it is crucial to identify patients suitable for treatment and those who may benefit most from therapy. Anti-viral therapy is recommended for those patients with chronic hepatitis C who also have elevated liver tests, detectable hepatitis C virus ribonucleic acid and significant inflammation and/or fibrosis on liver biopsy. Currently, the most effective initial therapy is the combination of interferon plus ribavirin. The sustained viral response rate (SVR) is 36-41% following a 24- or 48-week course of therapy. In general, patients with the genotype 1 infection should receive 48 weeks of therapy, and those with genotypes 2 or 3 infection only 24 weeks. Viral load estimations are problematic because of normal fluctuations (up to 0.5-10 log), assay variability and lack of a universally accepted standard; thus, viral load testing is not recommended routinely at present. The sustained viral response rate produces improvements in quality of life and liver histology (including reversal of bridging fibrosis and cirrhosis is some), and durable responses lasting 5-11 years in 95-97% of cases. While the optimal dose of ribavirin is currently unknown, available data suggest that higher doses increase efficacy (albeit with a greater degree of anemia). The dose of 800 mg/day may be the most appropriate lower dose for those patients who require dosage modification for anemia or other side-effects. Patients who have relapsed after interferon monotherapy can be successfully retreated with higher doses of interferon for 1 year or the combination of interferon and ribavarin for 24-48 weeks. Preliminary data suggest that patients with an unfavorable profile, including those with genotype 1 infection, should probably be retreated with interferon and ribavirin for 48 rather than 24 weeks. With our current best therapies, the majority of patients still do not achieve the benefits of a sustained response. Re-treatment with interferon and ribavirin may achieve a sustained response in approximately 10-25% of these patients. In the immediate future, once-weekly pegylated interferons will replace standard interferons. Initial data suggest that SVR achieved with these drugs in combination with ribavirin is increased to 54-61%, but dose modifications and side-effects are more frequent. They will thus provide an incremental benefit in terms of efficacy, particularly for genotype 1-infected patients.


Tribological and mechanical investigation of multi-directional forged nickel.
Tailoring material properties to specific application requirements is one of the major challenges in materials engineering. Grain size is a key factor affecting physical and mechanical properties of polycrystals materials, the presented work enables insight into how the pure nickel properties are affected by application of multi-directional forging (MDF) as a well-known severe plastic deformation method. It is demonstrated that the hardness and wear rate are improved by imposing MDF process. The rate of enhancement is reduced at the higher pass numbers. It is also shown that the application of MDF process changed the mechanism of wear. Non-MDF sample's surface shows spalling and delamination, while the dominated wear mechanism of final pass sample is peeling with a slight of adhesion. The change of wear mechanism can be associated with the reduction of friction coefficient of the deformed sample. By considering the linear correlation between the hardness and wear rate, a simple and fast procedure is proposed to estimate the wear rate of sample after the different MDF pass numbers using the corresponding hardness magnitude. Additionally, the attained microstructure of the final pass sample shows a combination of ultrafine grains and micro shear bands.


Nest ornamentation by female spotless starlings in response to a male display: an experimental study.
1. The use of behavioural traits by females in signalling condition has been practically ignored in evolutionary theory. However, females may also exhibit ornaments and behavioural displays, although less elaborated than those of males. 2. In this study we suggest that the carrying of feathers by spotless starlings Sturnus unicolor Temminck females to decorate the nest represents an elaborated and costly behaviour that is displayed in response to a courtship male behaviour: the carrying of nest green plants. 3. By experimentally increasing the amount of green plants in the nests, to give the appearance that highly attractive males defended them, we induced females to increase their feather carrying rates. 4. The amount of feathers carried to the nest was correlated to female reproductive experience and laying date, two variables correlated with female body condition. These results suggests that this behaviour may work as an honest indicator of female quality. 5. We conclude that male carrying plants and female carrying feathers can be viewed as two sex-specific functionally related signalling behaviours involved in mutual courtship or status signalling.


Mapping of biodiversity hubs and key ecosystem services as a tool for shaping optimal areas for conservation.
Most National Parks (NP) and nature reserves in Rwanda have been established opportunistically in the early 1900s, without clear consideration of ensuring the protection to all threatened different taxonomical or functional groups, such as vegetation, invertebrates, fish, and birds. With the increasing conservation objectives, raised expectations into Protected Areas (PA), and within a more challenging environmental context, it is important to identify biodiversity hubs and key areas for Ecosystem Services (ES) to maximize the efficiency of conservation efforts by assisting priority areas under threats. To date, no comprehensive analysis, to the best of our knowledge has been done to assess both biodiversity and ES in Rwanda. This is a notable gap, considering that global-scale research suggests that the spatial overlap between biodiversity targets and ES is low. This study reports a nationwide assessment, mapping the richness of threatened species and three key ES Carbon Storage, Water Quantity, and Water Quality. Our analysis has shown that PAs are neither perfectly delineated to protect biodiversity nor key ES. The state of PAs offers a taxonomic protection bias in favor of mammals and birds but leaves many endangered species in other taxonomic groups in collapsing and unprotected small ecosystems scattered around the country. Rwanda's PAs cover important carbon stock but can do better at securing higher water balance regions and clean water sources. We propose an improvement of the NP system in Rwanda to help guide the economic development along a path of green growth and ensures the well-being of both people and nature. Locating biodiversity hubs and key ES can help to connect conservationists, local people, and governments in order to better guide conservation actions.


The Hiroshima thermal-neutron discrepancy for (36)Cl at large distances. Part II: Natural in situ production as a source.
For Hiroshima, a large discrepancy between calculated and measured thermal-neutron fluences had been reported in the past, for distances to the epicenter larger than about 1,000 m. To be more specific, measured (36)Cl concentrations in environmental samples from Hiroshima were too large at these distances, and the ratio of measured to calculated values reached about 70, at a distance of 1,800 m. In an attempt to identify other sources that might also produce (36)Cl in Hiroshima samples, the role of cosmic rays and of neutrons from natural terrestrial sources was investigated. Four reaction mechanisms were taken into account: spallation reactions of the nucleonic (hadronic) component of the cosmic rays on potassium (K) and calcium (Ca) in the sample material, particle emission after nuclear capture of negative muons by K and Ca, reactions of fast-muon induced electromagnetic, and hadronic showers with K and Ca, and neutron capture reactions with (35)Cl in the sample where the neutrons originate from the above three reaction mechanisms and from uranium and thorium decay. These mechanisms are physically described and mathematically quantified. It is shown that among those parameters important for the production of (36)Cl in granite, the chemical composition of the sample, the depth in the quarry where the sample had initially been taken, and the erosion rate at the site of the quarry are most important. Based on these physical, chemical, and geological parameters, (36)Cl concentrations were calculated for different types of granite that are typical for the Hiroshima area. In samples that were of these granite types and that had not been exposed to atomic bomb(A-bomb) neutrons, the (36)Cl concentration was also determined experimentally by means of accelerator mass spectrometry, and good agreement was found with the calculated values. The (36)Cl signal due to natural in situ production was also calculated in granite samples that had been exposed to A-bomb neutrons at distances up to 1,500 m from the hypocenter. It is demonstrated that, for granite samples from Hiroshima exposed to A-bomb neutrons beyond distances of about 1,300 m from the hypocenter, the (36)Cl signal is dominated by natural in situ production.


Socioeconomic and Familial Factors Associated with Gross Motor Skills among US Children Aged 3-5 Years: The 2012 NHANES National Youth Fitness Survey.
The first aim of this study was to examine the prevalence of below average gross motor skills in a representative sample of US children aged 3 to 5 years. The second aim was to identify socioeconomic and familial characteristics that are associated with below average gross motor skills. Secondary analysis was conducted using the datasets from the 2012 National Health and Examination Survey National Youth Fitness Survey (NNYFS). The NNYFS assessed gross motor skills among 329 children aged 3-5 years, using the Test of Gross Motor Development-Second Edition (TGMD-2). Socioeconomic and familial characteristics of interest, such as family income and family structure, were asked in an in-person interview. This study estimated that one in three US children age 3 to 5 years old (33.9%) scored below average for gross motor quotient. In the gross motor subsets, one in four (24.4%) scored below average for locomotion and two in five (39.9%) scored below average for object control. Children living below the poverty threshold were more likely to have a higher gross motor quotient (odds ratio, OR = 2.76; 95% confidence interval, CI = 1.09-7.00). Girls were more likely to have a higher locomotor score (OR = 2.17; 95% CI = 1.10-4.25). Those living with other child(ren) aged ≤5 years were more likely to have a higher locomotor score (OR = 2.36; 95% CI = 1.01-5.54), while those living with child(ren) aged 6-17 years were more likely to have a higher object control score (OR = 1.83; 95% CI = 1.24-2.69). This study revealed risk factors associated with poor gross motor development, furthering our understanding of gross motor development in early childhood.


Potentiation of doxorubicin-induced apoptosis and differentiation by indomethacin in K-562 leukemia cells.
In this study we have examined the antitumor effect of combined administrations of indomethacin (IND) with doxorubicin (DOX) on growth of K-562 leukemia cells. Although, as single drug treatment, only high concentrations of IND reduced growth (>200 microM) and induced apoptosis (>800 microM) of the K-562 cells, a synergistic effects on DOX-induced cell growth inhibition, apoptosis and differentiation were observed during the co-administration of DOX with 10 microM IND. Cells treated with this combination had elevated GSHt level compare to DOX-treated cells. Modulation of GSHt level of DOX-treated cells with Cd2+ ions or BSO confirmed its important role in processes of DOX-induced differentiation. Results of this study showed that IND has a positive effect on therapeutic efficacy of DOX, and could be a perspective modulator in cancer chemotherapy.


Temporal disorder as a mechanism for spatially heterogeneous diffusion.
A fundamental issue in analyzing diffusion in heterogeneous media is interpreting the space dependence of the associated diffusion coefficient. This reflects the well-known Ito-Stratonovich dilemma for continuous stochastic processes with multiplicative noise. In order to resolve this dilemma it is necessary to introduce additional constraints regarding the underlying physical system. Here we introduce a mechanism for generating nonlinear Brownian motion based on a form of temporal disorder. Motivated by switching processes in molecular biology, we consider a Brownian particle that randomly switches between two distinct conformational states with different diffusivities. In each state the particle undergoes normal diffusion (additive noise) so there is no ambiguity in the interpretation of the noise. However, if the switching rates depend on position, then in the fast-switching limit one obtains Brownian motion with a space-dependent diffusivity. We show that the resulting multiplicative noise process is of the Ito form. In particular, we solve a first-passage time problem for finite switching rates and show that the mean first-passage time reduces to the Ito version in the fast-switching limit.


Development of a rational nomenclature for naming peptide and protein toxins from sea anemones.
Sea anemone toxins are predominantly peptide and proteins that act mainly on sodium and potassium channels, as well as in a variety of target cells causing lysis. Over recent years, the number of sea anemone peptide toxins as well as cytolytic pore-forming proteins and phospholipase A(2) sequences submitted to databases has been rapidly increasing due to the developments in DNA sequencing technology and proteomic approaches. However, the lack of a systematic nomenclature has resulted in multiple names being assigned to the same toxins, toxins from unrelated species being designated by the same name, and ambiguous name designations. Therefore, in this work we propose a systematic nomenclature in which we adopted specific criteria, based on order of discovery and phylogenetic analysis, in order to avoid redundant sea anemone toxin names. Implementation of the nomenclature proposed here not only allowed us to rename the already published 191 anemone toxins without ambiguities, but it can be used to unambiguously name newly discovered toxins whether or not they are related to previously published sea anemone sequences. In the new nomenclature each toxin name contains information about the toxin's biological activity, origin and relationship to known isoforms. Ongoing increases in the speed of DNA sequencing will raise significantly the number of sea anemone toxin sequences in the literature. This will represent a constant challenge in their clear identification and logical classification, which could be solved using the proposed nomenclature.


Lysolipids regulate raft size distribution.
The lipid matrix of cellular membranes, directly and indirectly, regulates many vital functions of the cell. The diversity of lipids in membranes leads to the formation of ordered domains called rafts, which play a crucial role in signal transduction, protein sorting and other cellular processes. Rafts are believed to impact the development of different neurodegenerative diseases, such as Alzheimer's, Parkinson's, Huntington's ones, amyotrophic lateral sclerosis, some types of cancer, etc. These diseases correlate with the change in the membrane lipid composition resulting from an oxidative stress, age-related processes, dysfunction of proteins, and many others. In particular, a lot of studies report a significant rise in the level of lysolipids. Physicochemical properties of rafts are determined by membrane composition, in particular, by the content of lysolipids. Lysolipids may thus regulate raft-involving processes. However, the exact mechanism of such regulation is unknown. Although studying rafts in vivo still seems to be rather complicated, liquid-ordered domains are well observed in model systems. In the present study, we used atomic force microscopy (AFM) to examine how lysophospholipids influence the liquid-ordered domains in model ternary membranes. We demonstrated that even a small amount of lysolipids in a membrane significantly impacts domain size depending on the saturation of the lysolipid hydrocarbon tails and the amount of cholesterol. The mixture with the bigger relative fraction of cholesterol was more susceptible to the action of lysolipids. This data helped us to generalize our previous theoretical model of the domain size regulation by lipids with particular molecular shape expanding it to the case of lysolipids and dioleoylglycerol.


High expression of CEACAM6 and CEACAM8 mRNA in acute lymphoblastic leukemias.
CEACAM family members are a set of widely expressed proteins involved in several biological functions, including cell adhesion, migration, signal transduction, and the regulation of gene expression. Abnormal overexpression and downregulation of some CEACAMs have been described in tumor cells. Monoclonal antibodies grouped in the CD66 cluster recognize CEACAM members. Ectopic CD66 expression is commonly detected in B-cell lineage acute lymphoblastic leukemia (ALL). To investigate the CEACAM messenger RNA (RNA) expression in leukemic blasts, we performed a quantitative polymerase chain reaction (RQ-PCR) analysis in purified RNA samples from a consecutive series of acute leukemias (135 patients). Most B-cell lineage ALL expressed CD66 (79.5%), whereas no single case of T-cell lineage ALL disclosed CD66 reactivity (0%). All the BCR-ABL+ ALL cases showed CD66 expression. CD66 was positive even in cases without CD10 expression (72.7%) and/or with MLL rearrangements. Despite the sharp contrast between T-ALL and B-ALL in CD66 reactivity, CEACAM patterns were comparable, and only minor differences for CEACAM1 and CEACAM8 were detected. All the leukemic samples showed overexpression of CEACAM6 and 8 when compared with normal granulocytes. These results were confirmed by dilutional experiments. The leukemic pattern paralleled the normal regenerating bone marrow with lower values for CEACAM1. In line with the results for CD66 reactivity, neoplastic cell lines had a uniform low expression of CEACAM family members. It remains to be investigated whether these CEACAM disturbances provide growth advantages to tumoral cells by inhibiting the anoikis process.


Clinical studies of the vibration syndrome using a cold stress test measuring finger temperature.
Since nine years multicentre, transversal and longitudinal clinical studies on hand-arm, vibration-exposed patients are being performed in cooperation with French occupational medicine centers and social security institutions. These studies are based upon current clinical assessment and standardized, temperature-measuring cooling tests. Data acquisition uses a portable, 10-channel, micro-processor-based temperature recorder and miniature thermal sensors. Temperature is monitored at the ten finger tips continuously, before, during and after a cold stress performed in strictly controlled conditions. Data from examinations performed at outlying sites are transferred through the telephonic network to a central processing unit. Data analysis uses a specific, expert-type software procedure based upon previous clinical studies on (i) 238 "normal" subjects, and (ii) 3,046 patients with vascular disturbances of the upper extremities of various etiologies. This procedure includes a staging process which assigns each finger a class representing the degree of severity of the abnormalities of response to cold ("dysthermia") related to vascular disorders. All data processing is fully automatic and results in a printed examination report. To date, over 1,623 vibration-exposed forestry, building and mechanical workers were examined. Sixty-three per cent of patients had received high dose of vibration (daily use of chain saws, air hammers, ballast tampers over many years). Typical white finger attacks or only neurological symptoms were found in 36% and 23% of patients respectively. The rate of sever dysthermia was much higher in patients with white finger attacks (83%) than in patients without (32%). In 90% of the vibration-exposed patients, the severity of dysthermia has differed greatly from one finger to another and between hands, while in non-exposed patients with primary Raynaud syndrome the dysthermia are generally similar for all fingers but the thumbs. Of 208 forestry workers who were asymptomatic but had dysthermia on a first examination, 31% have developed vascular or neural symptoms within subsequent follow-up. Of 223 symptomatic patients with more or less severe dysthermia at a first examination performed in winter, 17% had the same abnormalities in summer and microvascular lesions at capillaroscopy, while the other 83% had reversible dysthermia and only functional capillaroscopic abnormalities. These studies suggest that temperature-measuring cooling tests performed under well-defined, standard conditions provide significant data for grading the severity and assessing the reversibility of Raynaud phenomena, and for detecting subclinical vasomotor disorders in asymptomatic patients.


Nursing management of hearing impairment in nursing facility residents.
This article has described the key points in the evidence-based practice guideline entitled Nursing Management of Hearing Impairment in Nursing Facility Residents. The guideline outlining the nursing management of nursing facility residents with hearing impairment is supported by 175 articles: 94 research articles (both experimental and descriptive) and 81 nonresearch articles (expert opinion). The full guideline includes the significance of hearing impairment, key definitions, individuals at risk, assessment criteria and tools, description of practice, and steps for evaluation and outcomes. We believe the implementation of this evidence-based practice guideline will improve the quality of life and quality of care of nursing facility residents.


Enhancing Benzene Combustion Activity through Preferential Platinum Atom Exposure via Strategic Pt-Cu Alloying.
Volatile organic compounds such as benzene are hazardous air pollutants that require effective elimination. Noble metal-based catalysts exhibit high benzene combustion activity, but their prohibitive cost necessitates strategies to enhance utilization efficiency. This study investigates a Pt-Cu alloy catalyst for improved benzene combustion by preferentially exposing Pt active sites through Cu alloying. Aberration-corrected scanning transmission electron microscopy and X-ray spectroscopy characterize the nanoscale distribution and enrichment of Pt on the alloy surface. Kinetic measurements demonstrate substantially enhanced activity compared with Pt catalysts, attributed to increased Pt metallic site exposure rather than alteration of the reaction mechanism. In situ Fourier transform infrared (FTIR) spectroscopy reveals a higher abundance of terrace-like Pt sites in the alloy, beneficial for benzene adsorption. Partial pressure dependence analyses indicate competitive adsorption of benzene and O2, following Langmuir-Hinshelwood kinetics. These findings provide conceptual insights into tuning surface composition in bimetallic catalysts to optimize noble metal efficiency, with broad applicability for sustainable catalytic process advancement.


Challenges of Diabetes Management in Toddlers.
Toddlers with type 1 diabetes have distinctive combination of challenges to their families and healthcare providers. A major factor is the difficulty in achieving metabolic control without risking hypoglycemia. The rising incidence of type 1 diabetes in toddlers increases the magnitude of the problem and creates a greater need for providing specialized service to cater for this age group's unique need. Type 1 has a specific disease nature in younger children and its clinical presentation mimics common childhood diseases. Symptoms and signs in the newly presented toddler with diabetes might be unspecific causing diagnosis to be missed or delayed. With the low cognitive ability and immature communication, toddlers might not be able to express their ill-feeling resulting from hypoglycemia or hyperglycemia. Hypoglycemia fear is common, which aggravates stress and reduces adherence to strict metabolic control. Nocturnal hypoglycemia is more common in toddlers and can be undiagnosed unless continuous glucose monitoring is used. Insulin administration and adjustment can be challenging due to pain, fear, refusal, and frequent intercurrent illness. Glucose monitoring is crucial. However, it can be distressing to the child and difficult to adhere to due to commitment or financial reasons. Insulin pump therapy is proven to be an effective and a safe method of treatment for toddlers, but it requires intensive training, resources, and long-term support. Provision of multidisciplinary team with special expertise in managing toddlers with diabetes is essential. Providing more physiological insulin regimes and customized technology is required to improve treatment compliance and diabetes control.


Use of monoclonal antibody HMB-45 in the cytologic diagnosis of melanoma.
The value of mouse monoclonal antibody (MAb) HMB-45 for the diagnosis of melanoma was retrospectively evaluated in cytologic preparations. Twenty-two (68.7%) of the 32 melanoma cases studied reacted with MAb HMB-45 while none of the 36 nonmelanoma tumors stained with this antibody. These results indicate that MAb HMB-45 can be helpful in the diagnosis of melanoma, especially in those patients who have no clinical indications of having a metastatic melanoma or in some cases in which the presence of melanin cannot be demonstrated by special histochemical stains.


Levels and trends of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (PCBs) in Spanish commercial fish and shellfish products, 1995-2003.
The polychlorinated dibenzo-p-dioxin (PCDD), dibenzofuran (PCDF), and polychlorinated biphenyl (PCB) contents of 123 Spanish commercial salmon, tuna fish, sardine, oyster, mussel, and clam samples from 1995 to 2003 were investigated. A significant decrease of dioxin and non-ortho PCB concentrations in the studied species was found over the years. The decrease was greater in the case of dioxins than in that of non-ortho PCBs, especially during the early years of the study. PCB and PCDD/F concentrations in the years 2001-2003 were comparable to those reported in the literature for similar species collected after 1999. Mean PCB concentrations ranged from 3.46 ng/g of fresh weight (fw) in clams to 100 ng/g of fw in tuna fish. PCDD/F mean current levels ranged from 0.62 pg/g of fw in clams to 2.89 pg/g of fw in oysters. Toxic equivalent quantities (WHO-TEQ) ranged from 0.05 pg of WHO-TEQ(PCDD/Fs)/g of fw in clams to 0.5 pg of WHO-TEQ(PCDD/Fs)/g of fw in salmon (in the upper bound determination levels). When coplanar PCBs were included, the WHO-TEQ(PCDD/Fs+cop) (PCBs) values increased by a range of 1.7 times in oysters to 14.1 times in tuna fish. The decrease in dioxin concentrations suggests that efforts to control dioxin emissions and to reduce human exposure through foodstuffs are succeeding. The high contribution of PCBs to total WHO-TEQs in the fish and shellfish species investigated suggests that it is important to determine PCBs in foodstuffs, and especially in fish products, and they should be included in further research and future legislation.


Dissolution rate studies of cholesterol monohydrate in bile acid-lecithin solutions using the rotatingdisk method.
A physical model approach was used to investigate cholesterol gallstone dissolution kinetics in simulated bile. Critical experimental and theoretical investigations simulating in vivo conditions showed that, in the bile acid-lecithin solutions, there is a significant interfacial barrier for both cholesterol gallstone and cholesterol monohydrate pellet dissolution. In the present study, the rotating-disk dissolution method and the accompanying Levich theory were applied to assess the contributions of the diffusion convection mass transfer resistance and of the interfacial barrier to the overall kinetics. Cholesterol dissolution rates in bile acid solutions were about 2-20 times slower than diffusion-controlled rates depending upon the degree of agitation. As found in previous studies, these rates in the presence of sufficient concentrations of dissolution accelerators approached the theoretical diffusion-convection-controlled rates. To account for the much slower dissolution rates in bile acid-lecithin solutions, two possible kinetic interpretations were investigated. The first is based upon slow crystal-micellar solution interfacial kinetics, and the second is based upon a slow rate of cholesterol solubilization in the aqueous diffusion layer. For the latter, an analytical mathematical solution was obtained.


Dual Application of Patient-Specific Occlusion-Based Positioning Guide and Fibular Cutting Guide for Accurate Reconstruction of Segmental Mandibular Defect.
In this study, the authors introduced a dual application of patient-specific occlusion-based positioning guide and fibular cutting guide to obtain ideal occlusal relationship and mandibular contour in patients undergoing mandibular reconstruction. A retrospective review was performed in 21 patients who underwent mandibular reconstruction with a fibular osteocutaneous free flap. Using computed tomography and intraoral scanning data, fibular cutting guide and occlusion-based positioning guide were simulated in a modeling software and 3-dimensionally printed. Both guides were applied in 9 patients, defined as dual guide group, while the fibular cutting guide was solely used in the remaining patients, defined as single guide group. Functional outcomes including occlusion status, trismus, presence of osseointegrated implant were assessed at 1-year postoperative period. To evaluate the accuracy of the reconstruction, the discrepancy between the planned simulation and actual surgical result was quantified by measuring mandibular deviation angle and volume conformity. Regarding the functional outcomes, all patients in dual guide group showed satisfactory occlusion and intact oral capacity at postoperative 1-year assessment, while 3 patients in single guide group had prolonged malocclusion. The dual guide group showed significantly decreased deviation angle in coronal (right side, 2.93°±1.98° vs. 7.02°±2.81°, P =0.003) and axial plane (right side, 3.20°±2.04° vs. 7.63°±3.40°, P =0.006). The mean volume conformity between the simulation and actual fibular object was significantly higher in the dual guide group (75.27%±6.12% vs. 59.06%±8.57%, P =0.001). In conclusion, the use of occlusion-based positioning guide combined with the fibular cutting guide can enhance the accuracy of mandible reconstruction and functional outcomes.


A large and massive abdominal venous thrombosis associated with the presence of a big axillary mass, lupus-like syndrome and antiphospholipid antibodies.
This case report concerns a 40-year-old patient with an unspecific abdominal pain, diarrhoea, a big axillary mass and a previous pulmonary infection. After biopsy of the axillary mass the diagnosis of lymphoma was excluded based on the presence of cells expressing polyclonal antibodies. Abdominal CT scans and angionuclear magnetic resonance showed an extensive intestinal venous thrombosis. The patient also presented positive results for C and S proteins, lupic anticoagulant factor and antiphospholipid antibodies (anticardiolipin antibodies - IgM and IgG). Treatment started with administration of recombinant tissue plasminogen activator and heparin which decreased the degree of thrombosis. Antibiotics were also administrated to treat pulmonary and abdominal infections. After 25 days, he was discharged with no signs of infection, no abdominal pain and reduction of the thrombosis. He was medicated with warfarin, hydroxichloroquine and clopidogrel. Forty-five days after discharge, abdominal CT scan showed a significant regression of thrombosis.


X/XO or H2O2 induced IPEC-J2 cell as a new in vitro model for studying apoptosis in post-weaning piglets.
We previously demonstrated that intestinal epithelial cell apoptosis in weaned piglets is much more serious than that observed in sucking piglets and is related to oxidative stress during weaning. It is difficult to study the apoptosis mechanisms only using in vivo methods because of the limit of existing research technology. An in vitro cellular system is required for piglet intestinal epithelial cell apoptosis research. In this study, a non-tumorigenic epithelial cell line, IPEC-J2 cells, was employed as a cell model. Hydrogen peroxide and xanthine/xanthine oxidase (X/XO) were both used and compared for apoptosis modeling. The concentrations of hydrogen peroxide and XO were selected and verified using cell viability analysis, the comet assay and flow cytometry. Intracellular ROS were measured using fluorescent probes. Additionally, the expression levels of the apoptosis-related genes Fas, Bcl-2, P53, Caspase 3, Caspase 8, and Caspase 9 were analyzed using quantitative RT-PCR. The results indicated the optimal modeling method is a final concentration of 0.5 mM H2O2 incubated with IPEC-J2 cells for 1 h at 37 °C in 5 % CO2 for hydrogen peroxide-induced apoptosis modeling, and a final concentration of 250 μM X/50 U/L XO incubated with IPEC-J2 cells for 6 h at 37 °C in 5 % CO2 for X/XO-induced apoptosis modeling. For the apoptotic pathway, the X/XO modeling method is more similar to 21 days weaning piglets. Therefore, we suggest that X/XO modeling with IPEC-J2 cells be used as an in vitro cell culture model for weaning piglet intestinal epithelial cell apoptosis.


Stability dynamics of neurofilament and GFAP networks and protein fragments.
Neurofilaments (NFs) and GFAP are cytoskeletal intermediate filaments (IFs) that support cellular processes unfolding within the uniquely complex environments of neurons and astrocytes, respectively. This review highlights emerging concepts on the transitions between stable and destabilized IF networks in the nervous system. While self-association between transiently structured low-complexity IF domains promotes filament assembly, the opposing destabilizing actions of phosphorylation-mediated filament severing facilitate faster intracellular transport. Cellular proteases, including caspases and calpains, produce a variety of IF fragments, which may interact with N-degron and C-degron pathways of the protein degradation machinery. The rapid adoption of NF and GFAP-based clinical biomarker tests is contrasted with the lagging understanding of the dynamics between the native IF proteins and their fragments.


Macroevolution of complex cytoskeletal systems in euglenids.
Euglenids comprise a group of single-celled eukaryotes with diverse modes of nutrition, including phagotrophy and photosynthesis. The level of morphological diversity present in this group provides an excellent system for demonstrating evolutionary transformations in morphological characters. This diversity also provides compelling evidence for major events in eukaryote evolution, such as the punctuated effects of secondary endosymbiosis and mutations in underlying developmental mechanisms. In this essay, we synthesize evidence for the origin, adaptive significance and diversification of the euglenid cytoskeleton, especially pellicle ultrastructure, pellicle surface patterns, pellicle strip number and the feeding apparatus. We also highlight holes in our knowledge that must be filled before we are able to confidently describe euglenid cell biology and infer the earliest stages in euglenid evolution. Nonetheless, by possessing combinations of characters resulting from adaptive change and morphostasis, euglenids have retained key pieces of evidence necessary for reconstructing the early evolution and diversification of eukaryotic life.


Simultaneous quantitation of five flavonoid glycosides in Herba Epimedii by high-performance liquid chromatography-tandem mass spectrometry.
A rapid and accurate reversed-phase liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed and validated for the quantitative determination of five flavonoid glycosides, icariin, epimedin A, epimedin B, epimedin C and hyperin in Herba Epimedii. Chromatographic separations were performed using a C(18) narrow-bore HPLC column; a mixture of an aqueous solution of ammonium formate (pH 4.0) and acetonitrile was used as the mobile phase, with compounds detected in the positive ion mode with multiple-reaction monitoring using a triple-quadrupole mass spectrometer equipped with an electrospray ionisation interface. This method for the determination of the reported flavonoid glycosides was accurate and reproducible, with a lower limit of quantication of 0.5 microg/mL. The standard calibration curves for the above-mentioned compounds were linear (r(2) > 0.998) over the concentration range 0.5-10.0 microg/mL. The relative standard deviations for intra- and inter-day precision over the concentration range for the flavonoid glycosides were lower than 7.8% with accuracy between 90.1 and 111.0%. The established method was successfully applied to the quality assessment of samples of Herba Epimedii collected from Korea and China.


Functional interaction of neuronal Cav1.3 L-type calcium channel with ryanodine receptor type 2 in the rat hippocampus.
Neuronal L-type Ca(2+) channels do not support synaptic transmission, but they play an essential role in synaptic activity-dependent gene expression. Ca(v)1.2 and Ca(v)1.3 are the two most widely expressed L-type Ca(2+) channels in neurons and have different biophysical and subcellular distributions. The function of the Ca(v) 1.3 L-type Ca(2+) channel and its cellular mechanisms in the central nervous system are poorly understood. In this study, using a yeast two-hybrid assay, we found that the N terminus of the rat Ca(v)1.3 alpha(1) subunit interacts with a partial N-terminal amino acid sequence of ryanodine receptor type 2 (RyR2). Reverse transcription-PCR and Western blot assays revealed high expression of both Ca(v)1.3 and RyR2 in the rat hippocampus. We also demonstrate a physical association of Ca(v)1.3 with RyR2 using co-immunoprecipitation assays. Moreover, immunocytochemistry revealed prominent co-localization between Ca(v)1.3 and RyR2 in hippocampal neurons. Depolarizing cells by an acute treatment of a high concentration of KCl (high-K, 60 mm) showed that the activation of L-type Ca(2+) channels induced RyR opening and led to RyR-dependent Ca(2+) release, even in the absence of extracellular Ca(2+). Furthermore, we found that RyR2 mRNA itself is increased by long term treatment of high-K via activation of L-type Ca(2+) channels. These acute and long term effects of high-K on RyRs were selectively blocked by small interfering RNA-mediated silencing of Ca(v)1.3. These results suggest a physical and functional interaction between Ca(v)1.3 and RyR2 and important implications of Ca(v)1.3/RyR2 clusters in translating synaptic activity into alterations in gene expression.


[Treatment of vascularized high-risk eyes with a Boston keratoprosthesis].
In severely compromised and vascularized high-risk eyes, the Boston keratoprosthesis procedure is often the last treatment option. The transparency of the optics is not impaired by endothelial immune reactions. This review article discusses relevant literature as well as our own data and experiences with the Boston keratoprosthesis in high-risk eyes. The relevant complications as well as the postoperative management are discussed. In more than 60% of the high-risk eyes a long-term increase in visual acuity can be achieved. Keratoprosthesis retention rates show a variable span with reported mean 5‑year retention rates of 75%. The most common postoperative complications include the formation of a retroprosthetic membrane and keratolysis in up to 50% each. More than 70% of the eyes already suffer from (secondary) glaucoma preoperatively, so that glaucoma surgery is performed simultaneously in at least 20% of cases and in the postoperative course further antiglaucomatous surgery is necessary in up to 31%. Vitreoretinal complications include, in particular, sterile vitritis and infectious endophthalmitis but persistent hypotonia is also described in one third of patients. The Boston keratoprosthesis is an alternative to conventional corneal replacement if the prognosis for allogeneic transplants is poor. Postoperative complications are common; therefore, postoperative management plays an important role. For vascularized high-risk eyes, however, it is often the only remaining option for visual rehabilitation.


Intramolecular C-H Amination of N-Alkylsulfamides by tert-Butyl Hypoiodite or N-Iodosuccinimide.
1,3-Diamines are an important class of compounds that are broadly found in natural products and are also widely used as building blocks in organic synthesis. Although the intramolecular C-H amination of N-alkylsulfamide derivatives is a reliable method for the construction of 1,3-diamine structures, the majority of these methods involve the use of a transition-metal catalyst. We herein report on a new transition-metal-free method using tert-butyl hypoiodite (t-BuOI) or N-iodosuccinimide (NIS), enabling secondary non-benzylic and tertiary C-H amination reactions to proceed. The cyclic sulfamide products can be easily transformed into 1,3-diamines. Mechanistic investigations revealed that amination reactions using t-BuOI or NIS each proceed via different pathways.


Cardiac effects of sodium stibogluconate: myocardial, electrophysiological and biochemical studies.
The pentavalent antimonial sodium stibogluconate is the mainstay of anti-leishmanial therapy. Sodium stibogluconate is less cardiotoxic than antimony and the trivalent derivatives, but has been associated with dose-related electrocardiographic changes. The effect of the currently-used regimen of sodium stibogluconate (20 mg/kg/day for 20 days) on cardiac function is uncertain. We studied 12 soldiers, mean age 24 years, with proven cutaneous leishmaniasis treated with this regimen. There were no significant changes in echocardiographic indices of left ventricular systolic or diastolic function during treatment. Indices of myocardial electrical stability (heart-rate variability and episodes of overt supraventricular and ventricular arrhythmias) were unchanged, but there was a reversible decrease in T-wave amplitude during treatment. Systolic and diastolic blood pressure fell and the heart rate increased during treatment. This regimen of sodium stibogluconate does not measurably impair left ventricular systolic or diastolic function. Minor T-wave changes occur during treatment, but there is no increase in arrhythmia frequency or change in heart-rate variability. In most young fit patients, this regimen has no cardiac side-effects. However, idiosyncratic reactions cannot be excluded, and patients with malnutrition, impaired renal function or pre-existing heart disease may be more sensitive to any cardiotoxic properties of sodium stibogluconate.


Host Phylogeny and Diet Shape Gut Microbial Communities Within Bamboo-Feeding Insects.
The gut microbiome plays an important role in a host's development and adaption to its dietary niche. In this study, a group of bamboo-feeding insects are used to explore the potential role of the gut microbiota in the convergent adaptation to extreme diet specialization. Specifically, using a 16S rRNA marker and an Illumina sequencing platform, we profiled the microbial communities of 76 gut samples collected from nine bamboo-feeding insects, including both hemimetabolous (Orthoptera and Hemiptera) and holometabolous (Coleoptera and Lepidoptera) species, which are specialized in three distinct dietary niches: bamboo leaf, shoot, and sap. The gut microbiota of these insects were dominated by Proteobacteria, Firmicutes, and Bacteroidetes and were clustered into solid (leaf and shoot) and liquid (sap) dietary niches. The gut bacterial communities of insects feeding on solid diet overlapped significantly, even though these insects belong to phylogenetically distant lineages representing different orders. In addition, the presence of cellulolytic bacterial communities within the gut microbiota allows bamboo-feeding insects to adapt to a highly specialized, fiber-rich diet. Although both phylogeny and diet can impact the structure and composition of gut microbiomes, phylogeny is the primary driving force underlying the convergent adaptation to a highly specialized diet, especially when the related insect species harbor similar gut microbiomes and share the same dietary niche over evolutionary timescales. These combined findings lay the foundation for future research on how convergent feeding strategies impact the interplays between hosts and their gut microbiomes and how the gut microbiota may facilitate convergent evolution in phylogenetically distant species in adaptation to the shared diet.


Reviewing primary Sjögren's syndrome: beyond the dryness - From pathophysiology to diagnosis and treatment.
Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease, characterized by lymphocytic infiltration of the secretory glands. This process leads to sicca syndrome, which is the combination of dryness of the eyes, oral cavity, pharynx, larynx and/or vagina. Extraglandular manifestations may also be prevalent in patients with pSS, including cutaneous, musculoskeletal, pulmonary, renal, hematological and neurological involvement. The pathogenesis of pSS is currently not well understood, but increased activation of B cells followed by immune complex formation and autoantibody production are thought to play important roles. pSS is diagnosed using the American-European consensus group (AECG) classification criteria which include subjective symptoms and objective tests such as histopathology and serology. The treatment of pSS warrants an organ based approach, for which local treatment (teardrops, moistures) and systemic therapy (including non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease-modifying antirheumatic drugs (DMARDS) and biologicals) can be considered. Biologicals used in the treatment of pSS mainly affect the total numbers of B cells (B cell depletion (Rituximab)) or target proteins required for B cell proliferation and/or activation (e.g. B cell activating factor (BAFF)) resulting in decreased B cell activity. The aim of this review is to provide physicians a general overview concerning the pathogenesis, diagnosis and management of pSS patients.


Evaluating efficacy of bacteriophage therapy against Staphylococcus aureus infections using a silkworm larval infection model.
Silkworm larva has recently been recognized as an alternative model animal for higher mammals to evaluate the effects of antibiotics. In this study, we examined the efficacy of the bacteriophage (phage) therapy, which harnesses phages as antibacterial agents, against Staphylococcus aureus infections, using the silkworm larval infection model. Two newly isolated staphylococcal phages, S25-3 and S13', were used as therapeutic phage candidates. They were assigned to two different lytic phage genera, Twort-like and AHJD-like viruses, based on their morphologies and the N-terminal amino acid sequences of the major capsid proteins. Both had a broad host range and strong lytic activity and showed preservative quality. Administration of these phages alone caused no adverse effects in the silkworm larvae. Moreover, the viruses showed life-prolonging effects in the silkworm larval infection model 10 min, 6 h, 12 h, and 24 h following infection. Such phage effects in the silkworm larval model were almost paralleled to the therapeutic efficacies in mouse models. These results suggest that phages S25-3 and S13' are eligible as therapeutic candidates and that the silkworm larval model is valid for the evaluation of phage therapy as well as mouse models.


Multiple developmental defects in Engrailed-1 mutant mice: an early mid-hindbrain deletion and patterning defects in forelimbs and sternum.
During mouse development, the homeobox-containing gene En-1 is specifically expressed across the mid-hindbrain junction, the ventral ectoderm of the limb buds, and in regions of the hindbrain, spinal cord, somites and somite-derived tissues. To address the function of En-1 during embryogenesis, we have generated mice homozygous for a targeted deletion of the En-1 homeobox. En-1 mutant mice died shortly after birth and exhibited multiple developmental defects. In the brains of newborn mutants, most of the colliculi and cerebellum were missing and the third and fourth cranial nerves were absent. A deletion of midhindbrain tissue was observed as early as 9.5 days of embryonic development and the phenotype resembles that previously reported for Wnt-1 mutant mice. In addition, patterning of the forelimb paws and sternum was disrupted, and the 13th ribs were truncated. The results of these studies suggest a cell autonomous role for En-1 in generation and/or survival of mid-hindbrain precursor cells and also a non-cell autonomous role in signalling normal development of the limbs and possibly sternum.


Prognostic factors of severe pneumonia in patients treated with rituximab in the intensive care unit.
The aim of this study was to describe the clinical characteristics and prognostic factors of patients treated with rituximab (RTX) who developed severe pneumonia in the intensive care unit (ICU). We systematically reviewed the medical records of 40 patients who received RTX and developed severe pneumonia in the ICU at our hospital from January 2009 to January 2019 to evaluate the underlying conditions, clinical course, and possible prognostic factors. Most patients had underlying hematologic malignancies (n = 21, 52.5%), followed by rheumatologic diseases (n = 17, 42.5%). The most frequent causative pathogens were fungi (n = 11, 27.5%), followed by bacteria (n = 9, 22.5%) and Pneumocystis jirovecii pneumonia (n = 8, 20%). Thirty patients (75%) died, and the other 10 patients (25%) survived. Compared with survivors, patients who died were significantly older (60.6 ± 10.6 vs 44.4 ± 18.3 years) and had chronic lung disease (40% vs 0%). Older age and chronic lung disease were significantly associated with mortality in patients treated with RTX.


Redox Regulation in the Base Excision Repair Pathway: Old and New Players as Cancer Therapeutic Targets.
Reactive Oxygen Species (ROS) are by-products of normal cellular metabolic processes, such as mitochondrial oxidative phosphorylation. While low levels of ROS are important signalling molecules, high levels of ROS can damage proteins, lipids and DNA. Indeed, oxidative DNA damage is the most frequent type of damage in the mammalian genome and is linked to human pathologies such as cancer and neurodegenerative disorders. Although oxidative DNA damage is cleared predominantly through the Base Excision Repair (BER) pathway, recent evidence suggests that additional pathways such as Nucleotide Excision Repair (NER) and Mismatch Repair (MMR) can also participate in clearance of these lesions. One of the most common forms of oxidative DNA damage is the base damage 8-oxoguanine (8-oxoG), which if left unrepaired may result in G:C to A:T transversions during replication, a common mutagenic feature that can lead to cellular transformation. Repair of oxidative DNA damage, including 8-oxoG base damage, involves the functional interplay between a number of proteins in a series of enzymatic reactions. This review describes the role and the redox regulation of key proteins involved in the initial stages of BER of 8-oxoG damage, namely Apurinic/Apyrimidinic Endonuclease 1 (APE1), human 8-oxoguanine DNA glycosylase-1 (hOGG1) and human single-stranded DNA binding protein 1 (hSSB1). Moreover, the therapeutic potential and modalities of targeting these key proteins in cancer are discussed. It is becoming increasingly apparent that some DNA repair proteins function in multiple repair pathways. Inhibiting these factors would provide attractive strategies for the development of more effective cancer therapies.


Advances in chemical pharmacotherapy for managing acute decompensated heart failure.
Acute decompensated heart failure (ADHF) contributes largely to the burden of heart failure and is associated with a poorer prognosis. Although numerous clinical trials evaluated the benefit of newer medications for ADHF, most of them were not successful. Areas covered: This review focusses on the updates on recent developments in chemical pharmacotherapy for the management of ADHF. A MEDLINE search for relevant review articles and original investigations on newer drugs for ADHF provided us with necessary literature. Expert opinion: Currently, popular therapies like diuretics, vasodilators, and inotropes offer symptomatic relief but do not provide survival benefit. Although multiple medications targeting novel pathways in ADHF were studied extensively, they failed to show either symptomatic or mortality benefit in available randomized trials. Improving our understanding of the complex pathophysiology of ADHF along with designing studies which include patients who are more representative of the real-world heart failure population, standardizing methods for endpoint assessment, and evaluating the role on novel biomarkers of organ dysfunction is important to improve ADHF research. Enhancing preventive strategies like improving baseline therapy in chronic heart failure patients and developing strategies for early identification of ADHF are important as our quest for innovative ADHF pharmacotherapy continues.


[Search for risk genes in Alzheimer's disease].
Alzheimer's disease (AD) is the most common form of neurodegenerative dementia. The susceptibility to AD is determined by a complex interaction between genetic, epigenetic, and environmental factors. Herein, the risk that can be attributed to genetic factors is high (up to 80%). While most AD patients are sporadic, in rare families Mendelian mode of inheritance can be observed. In these rare familial cases, full penetrant mutations have been identified in APP, PSEN1, and PSEN2. Mutations in these three genes are however rarely found in sporadic AD. For over 20 years, the only known genetic risk factor in sporadic AD cases was the APOE-ε4 allele, which increases susceptibility to AD by approximately threefold. Unfortunately, none of these genes explain the frequency of AD. Identification of additional genetic factors was propelled by the advent of genomic approaches such as genome-wide association studies, which has already led to the characterization of 26 novel genetic risk factors. Interestingly, several of these genetic signals cluster in biological pathways including cholesterol, lipid metabolism, immune response, and endocytic trafficking. An additional impulse in genetic research came from the development of novel sequencing technologies. For example, the whole exome sequencing approach has identified an association between the risk of AD and rare coding variants (minor allele frequency <1%) located in genes such as TREM2, SORL1, and ABCA7. Thus, progress from genetic research has significantly increased our understanding of the disease mechanisms operating in AD. However, even though our knowledge of the genetics of sporadic forms of AD has progressed markedly over the last years, it is still far from complete. Additional research is needed to complete the genetic architecture of AD.


Initial Reduction in Ulcer Size As a Prognostic Indicator for Complete Wound Healing: A Systematic Review of Diabetic Foot and Venous Leg Ulcers.
Significance: Percent area reduction (PAR) is commonly reported in trials including diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs). It is unclear how well PAR performs as a surrogate marker for complete wound closure. This review aimed to summarize all available evidence evaluating PAR as a predictor of complete DFU and VLU healing. Recent Advances: A review searching the CENTRAL, MEDLINE, EMBASE, and EMCARE databases was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Randomized-controlled trials and observational studies reporting PAR and any measure of its predictive ability were included. Outcomes included performance measures of PAR, timing of PAR, outcome measurement, and specific PAR cutoffs. Critical Issues: Meta-analysis was not possible due to high variability in wound duration at study start (2-48 weeks), PAR timing (2-8 weeks), PAR cutoff (-3% to 90%; determined post hoc in most studies), and outcome assessment (10-24 weeks). Six studies (21,430 DFU patients) report PAR as having acceptable to outstanding discriminatory ability (C-statistic 0.720-0.910). Five studies (29,775 VLU patients) report PAR as having poor to excellent discriminatory ability (C-statistic 0.680-0.830). One study (241 DFU and VLU patients) reports PAR sensitivity and specificity of 58.5% and 90.5%, respectively. All studies were determined to have high risk of bias. Future Directions: Despite promising discriminatory ability, most studies report post hoc analysis of patients in randomized trials, are highly heterogenous in study design, and have high risk of bias. There is scant evidence to support PAR in isolation as a surrogate for complete DFU or VLU healing in routine clinical practice.


Evaluation of EC-IC bypass for patients with atherosclerotic occlusive cerebrovascular disease: clinical and positron emission tomographic studies.
The authors report clinical evaluations of extracranial-intracranial (EC-IC) bypass surgery for patients presenting with misery perfusion on positron emission tomography (PET) due to atherosclerotic occlusive cerebrovascular disease. Seven patients underwent PET both before and after undergoing EC-IC bypass surgery. Three of the 7 patients had transient ischaemic attacks (TIAs) and 4 had minor strokes. Five of the 7 had unilateral superficial temporal-middle cerebral artery (STA-MCA) anastomosis, one had bilateral STA-MCA anastomoses and one had STA-MCA anastomosis on one side and carotid endarterectomy on the other side. PET showed postoperative improvement in regional cerebral blood flow and metabolism in 5 of the 7 patients. In the remaining 2 patients, one showed no remarkable changes on PET and the other showed exacerbation on PET due to postoperative cerebral infarction. All three patients who had TIAs had no further TIAs after surgery. Two of the 3 patients postoperatively showed improvement in misery perfusion on PET. In the 4 patients who had minor strokes, 2 showed clinical improvements. One of the 2 showed improvement not only in motor function but also in the higher cortical functions such as verbal and performance intelligence quotients. Changes on PET correlated to the clinical improvement in 4 of 7 patients. The EC-IC bypass is therefore effective in patients with haemodynamic hypoperfusion syndromes by improving the state of low perfusion.


The anti-cancer property of proteins extracted from Gynura procumbens (Lour.) Merr.
Gynura procumbens (Lour.) Merr. belongs to the Asteraceae Family. The plant is a well-known traditional herb in South East Asia and it is widely used to treat inflammation, kidney discomfort, high cholesterol level, diabetic, cancer and high blood pressure. Our earlier study showed the presence of valuable plant defense proteins, such as peroxidase, thaumatin-like proteins and miraculin in the leaf of G. procumbens. However, the effects of these defense proteins on cancers have never been determined previously. In the present study, we investigated the bioactivity of gel filtration fractionated proteins of G. procumbens leaf extract. The active protein fraction, SN-F11/12, was found to inhibit the growth of a breast cancer cell line, MDA-MB-231, at an EC50 value of 3.8 µg/mL. The mRNA expressions of proliferation markers, Ki67 and PCNA, were reduced significantly in the MDA-MB-23 cells treated with SN-F11/12. The expression of invasion marker, CCL2, was also found reduced in the treated MDA-MB-231 cells. All these findings highlight the anti-cancer property of SN-F11/12, therefore, the proteins in this fraction can be a potential chemotherapeutic agent for breast cancer treatment.


Disability and HIV: What drives this relationship in Eastern and Southern Africa?
The Eastern and Southern Africa (ESA) region is the epicentre of the global HIV epidemic and also home to a large number of people with disabilities. Both HIV and Disability are significant public health issues. While they are generally viewed as distinct and unrelated phenomena data seems to suggest that they are particularly closely intertwined in ESA. For the first time in history, by using the same disability indicator consistently, the publication of the World Report on Disability in 2011 has allowed for the comparison of disability data between countries, and across regions. This has the potential to shed some light on the relationship between disability and socio-economic markers and other health conditions in a way that was not possible previously. In the absence of disability and HIV-specific population-based surveys, this paper uses global socio-economic and HIV datasets and compares them to data contained in the most recent World Report on Disability. The analysis suggests that disability prevalence may be related to HIV-prevalence in ESA (Pearson 0.87). It identifies research and policy gaps and seeks to shed light on the relationship between the two phenomena. It concludes that, more than any other region in the world, ESA needs to ensure better data collection on disability and the inclusion of disability throughout its HIV programmes in order to provide a comprehensive and appropriate response to the epidemic.


Evaluation of the effect of oral administration of collagen peptides on an experimental rat osteoarthritis model.
Collagen is an extracellular matrix protein present in the skin, tendon, cartilage and bone. Collagen peptides (CP) are produced by the hydrolysis of gelatin (heat-denatured collagen) by proteases and are utilized as a component of nutraceuticals. The current study investigated the effect of CP on the articular cartilage of OA by evaluating the serum levels of biomarkers (CTX-II for type II collagen degradation and CPII for type II collagen synthesis), histopathological changes (Mankin score, based on the toluidine blue staining of proteoglycans), and immunohistochemical staining of matrix metalloproteinase (MMP)-13 and type II collagen, using a rat experimental osteoarthritis (OA) model. Anterior cruciate ligament transection (ACLT) was performed on the right knee joint to surgically induce OA. Animals were divided into four groups: Control group (Control), sham-operated group (Sham), ACLT group without collagen peptide (ACLT group) and ACLT group with oral administration of CP (CP group). ACLT induced histological damages and significantly increased the Mankin score (P<0.05). However, CP administration markedly suppressed the Mankin score, although this difference was not significant. In addition, serum CTX-II levels were significantly decreased in CP group compared with those in the ACLT group (P<0.05). By contrast, serum CPII levels did not differ significantly among the four groups. Moreover, immunohistochemical staining of type II collagen and MMP-13 (an important type II collagen-degrading enzyme) indicated that the amount of type II collagen increased, whereas the number of MMP-13 positive chondrocytes decreased in the CP group compared with ACLT group. These observations suggest that CP has the potential to exert chondroprotective action on OA by inhibiting MMP-13 expression and type II collagen degeneration.


Quercetin Alleviates the Progression of Breast Cancer-Related Depression via Inhibiting the Pyroptosis and Promoting the Immune Response.
Breast cancer-related depression (BCRD) seriously inhibits the life quality of patients with breast cancer. The Xiaoyao Kangai Jieyu Formula is known to inhibit the progression of depression. However, the detailed function of the Xiaoyao Kangai Jieyu Formula in BCRD remains unclear. Network pharmacology was constructed to assess the downstream target of the Xiaoyao Kangai Jieyu Formula in BCRD. In addition, the tail suspension test, sucrose preference test, and forced swimming test were used to test the symptom of depression in mice. Fluoro-Jade B staining was performed to observe the structure of neurons. RT-qPCR and western blot were applied to evaluate mRNA and protein levels. Besides, ELISA was performed to test the inflammatory responses and the immune response-related cytokines. Quercetin was identified as the key component of the Xiaoyao Kangai Jieyu Formula. Quercetin significantly inhibited BCRD-induced neuron pyroptosis via downregulation of PYD and card domain containing (ASC), NLR family pyrin domain containing 3 (NLRP3), and caspase-1, and quercetin could reverse BCRD-caused inhibition of neuron viability. Quercetin significantly attenuated the symptom of BCRD in mice, and it could reverse the contents of 5-hydroxytryptamine (5-HT), dopamine (DA), and neutrophil elastase (NE) in mice. Moreover, quercetin could promote the immune responses in xenograft mice via upregulation of interleukin- (IL-) 2, interferon-γ (IFN-γ), and IL-10. Quercetin, the active ingredient of the Xiaoyao Kangai Jieyu Formula, effectively mitigated the progression of BCRD by inhibiting pyroptosis, promoting immune response, and improving serum metabolism.


Aptitude X treatment interactions: implications for patient education research.
Aptitude x treatment interaction (ATI) has been used only rarely in patient education research. This research paradigm incorporates individual differences (aptitudes) into experimental studies exploring differences in information strategies (treatments). ATI has great potential for applications to patient education research. It identifies patient characteristics and optimal instructional treatments, it is compatible with psychological theories and clinical approaches alike, and it offers a specific methodology for approaching existing problems in a new way. This article presents studies in which ATI has illuminated specific patient needs and treatments, and suggested further applications. Three studies (in addition to those reviewed) are examined in depth. One study determined general guidelines for designing instructional literature to accompany medication (drug package inserts), that would satisfy the requirements of a group of patients with varied reading ability. Another study examined the effect of patients' "prior knowledge" on their participation in a health education program. A third study explored the interaction between patients' view of self-control over their health and the use of different media for health-care instruction. Guidelines and considerations for conducting further ATI-based research are presented and discussed.


Somite chondrogenesis. A structural analysis.
Light and electron microscopy are used in this study to compare chondrogenesis in cultured somites with vertebral chondrogenesis These studies have also characterized some of the effects of inducer tissues (notochord and spinal cord), and different nutrient media, on chondrogenesis in cultured somites Somites from stage 17 (54-60 h) chick embryos were cultured, with or without inducer tissues, and were fed nutrient medium containing either horse serum (HS) and embryo extract (EE), or fetal calf serum (FCS) and F12X Amino acid analyses were also utilized to determine the collagen content of vertebral body cartilage in which the fibrils are homogeneously thin (ca. 150 A) and unbanded. These analyses provide strong evidence that the thin unbanded fibrils in embryonic cartilage matrix are collagen. These thin unbanded collagen fibrils, and prominent 200-800 A protein polysaccharide granules, constitute the structured matrix components of both developing vertebral cartilage and the cartilage formed in cultured somites Similar matrix components accumulate around the inducer tissues notochord and spinal cord. These matrix components are structurally distinct from those in embryonic fibrous tissue The synthesis of matrix by the inducer tissues is associated with the inductive interaction of these tissues with somitic mesenchyme. Due to the deleterious effects of tissue isolation and culture procedures many cells die in somitic mesenchyme during the first 24 h in culture. In spite of this cell death, chondrogenic areas are recognized after 12 h in induced cultures, and through the first 2 days in all cultures there are larger accumulations of structured matrix than are present in equivalently aged somitic mesenchyme in vivo. Surviving chondrogenic areas develop into nodules of hyaline cartilage in all induced cultures, and in most non-induced cultures fed medium containing FCS and F12X There is more cell death, less matrix accumulation, and less cartilage formed in cultures fed medium containing HS and EE. The inducer tissues, as well as nutrient medium containing FCS and F12X, facilitate cell survival, the synthesis and accumulation of cartilage matrix, and the formation of cartilage nodules in cultured somites.


Hip Muscle Strength Explains Only 11% of the Improvement in HAGOS With an Intersegmental Approach to Successful Rehabilitation of Athletic Groin Pain.
Exercise-based rehabilitation targeting intersegmental control has high success rates and fast recovery times in the management of athletic groin pain (AGP). The influence of this approach on hip strength and lower limb reactive strength and how these measures compare with uninjured athletes (CON) remain unknown. Additionally, the efficacy of this program after return to play (RTP) has not been examined. First, to examine differences in isometric hip strength, reactive strength, and the Hip and Groin Outcome Score (HAGOS) between the AGP and CON cohorts and after rehabilitation; second, to examine the relationship between the change in HAGOS and the change in strength variables after rehabilitation; last, to track HAGOS for 6 months after RTP. Cohort study; Level of evidence, 2. A total of 42 athletes diagnosed with AGP and 36 matched controls completed baseline testing: isometric hip strength, lower limb reactive strength, and HAGOS. After rehabilitation, athletes with AGP were retested, and HAGOS was collected at 3 and 6 months after RTP. In total, 36 athletes with AGP completed the program with an RTP time of 9.8 ± 3.0 weeks (mean ± SD). At baseline, these athletes had significantly lower isometric hip strength (abduction, adduction, flexion, extension, external rotation: d = -0.67 to -1.20), single-leg reactive strength (d = -0.73), and HAGOS (r = -0.74 to -0.89) as compared with the CON cohort. Hip strength (d = -0.83 to -1.15) and reactive strength (d = -0.30) improved with rehabilitation and were no longer significantly different between groups at RTP. HAGOS improvements were maintained or improved in athletes with AGP up to 6 months after RTP, although some subscales remained significantly lower than the CON group (r = -0.35 to -0.51). Two linear regression features (hip abduction and external rotation) explained 11% of the variance in the HAGOS Sports and Recreation subscale. Athletes with AGP demonstrated isometric hip strength and reactive strength deficits that resolved after an intersegmental control rehabilitation program; however, improved hip strength explained only 11% of improvement in the Sports and Recreation subscale. HAGOS improvements after pain-free RTP were maintained at 6 months.


[Comments on the Portuguese translation of the International Classification of Functioning, Disability and Health].
An analysis of the World Health Organization terminology for disability indicates the influence of the social model of disability in the International Classification of Functioning, Disability, and Health. This theoretical framework should guide any translations of the document. In Brazil, the document was translated as Classificação Internacional de Funcionalidade, Incapacidade e Saúde. We argue that more appropriate than translating disability as "incapacidade" and impairments as "deficiências" would be to use the term "deficiência" for disability and "lesão" for impairment. Considering the normative impact of a WHO document for social policy and international research, the translation should accurately reflect the concepts and their theoretical basis.


Control of respiration in newborn babies. IV. Rib cage stability and respiratory regulation.
The recordings from an earlier study regarding the respiratory depth and rate changes induced by exposure to 4% CO2 in air in 13 babies with PM age varying between 32 and 43 weeks were reexamined with regard to the pattern of thoracic abdominal breathing excursion in breathing immediately prior to the CO2 exposure and the type of response induced. The pattern was called "stable" when the thoracic breathing excursions were in phase and congruent with the abdominal ones. When the thoracic excursions in comparison with the abdominal excursions were totally inverted, or incongruous but in phase, or rapidly varying between those two, the pattern was called "unstable". "Unstable" pattern of the breathing prior to the CO2 exposures was followed in an incidence of 60% by the type of response to CO2 which is characterized by a prompt rate increase (the "Type B" response) and only in 16% by the type characterized by an increased breathing amplitude (the "Type A" response). When the excursion pattern of the breathing prior to the CO2 exposures was "stable" "Type A" responses were induced in 59% and "Type B" responses in only 14%. The excursion pattern present when a baby is exposed to 4% CO2 thus seems to affect the type of respiratory depth and rate changes achieved. With increasing postmenstrual age the excursion pattern of the spontaneous breathing is more often "stable" and respiratory depth and rate changes of the "Type B" induced by CO2 less common. The variabilities of the breathing seen preferably in the preterm baby regarding regularity, rate and tidal volumes (as they could be approximated by the registration methods used) were noted most when the excursion pattern was "unstable". The results can be hypothetically interpreted to indicate a dynamic interaction between the thoracic wall and pulmonary mechanoreceptor systems of respiratory regulation. The decreasing variability of the breathing seen with increasing maturation in the baby could be explained by an increasing maturation of the neuromuscular ability to provide stability to the rib cage which would act stabilizing on the pulmonary vagal afferent input to the respiratory center.


Clostridium ramosum Bacteremia in an Immunocompetent Patient with SARS-CoV-2 Infection: A Case Report.
We report a case of Clostridium ramosum bacteremia in a 73-year-old patient with SARS-CoV-2 infection and right lower abdominal tenderness in China. The microbiological features and genomic epidemiological characteristics of C. ramosum worldwide were investigated to identify the possible sources of infection. Whole-genome sequencing of C. ramosum WD-I2 was performed using an Illumina NovaSeq 6000 platform. Phylogenetic analysis of C. ramosum WD-I2 and other publicly available C. ramosum isolates was performed and visualized using the interactive Tree of Life (iTOL) web server. The resistome of C. ramosum WD-I2 consists of two antimicrobial resistance genes (tetM and ermB), which explains the antimicrobial resistance trait to tetracycline and macrolides. Phylogenetic analysis showed that the strain closest to our isolated strain WD-I2 was SUG1069, recovered from a pig feces sample from Canada, which differed by 589 SNPs. To our knowledge, this is the first report of C. ramosum bacteremia in China. Our findings highlight the potential risk of invasive C. ramosum infections during the COVID-19 pandemic.


[Appropriate use of anti-methicillin-resistant Staphylococcus aureus agents in a retrospective study].
The track records of the use of anti-methicillin-resistant Staphylococcus aureus agents (anti-MRSA agents) in a 5-year period (2001.4-2006.3) were collected, and cases in which anti-MRSA agents were used for >4 days were selected. In each case, the results of laboratory data and bacterial examination before and after administering the anti-MRSA agents were investigated retrospectively. In addition, it was also investigated in each case whether therapeutic drug monitoring (TDM) was carried out. It was observed that the number of patients treated with anti-MRSA agents and the total dose of anti-MRSA agents used tended to increase over time, except for arbekacin sulfate. It was, however, shown that treatment with anti-MRSA agents resulted in significant decreases in body temperature, C-reactive protein, and white blood cell counts. Bacterial examination was conducted in 75.6% of the patients treated with anti-MRSA agents, with MRSA being detected in 72.4% of the cases examined. On the other hand, TDM was also conducted in 60% of the cases, but this was at a lower percentage than that of the other examinations. Quantitative bacterial examination after treatment with anti-MRSA agents indicates that TDM can be considered important for the appropriate use of anti-MRSA agents.


Cell-specific induction of hsp72-mediated protection by glutamine against oxidant injury in IEC18 cells.
Glutamine is a major metabolic fuel and trophic agent for intestinal epithelial cells that can enhance intestinal epithelial cell survival against oxidant and thermal stress, possibly through the induction of heat shock protein 72 (hsp72). In this study, we examined the possibility of a direct causal relationship and tissue specificity of glutamine-induced hsp72. Glutamine treatment of intestinal (epithelial) IEC18 cells, but not HeLa (epidermoid) cells, induces the production of hsp72 in a concentration-dependent fashion, without affecting the expression of the constitutively expressed heat shock protein, hsc73. To determine the specific role that hsp72 induction by glutamine plays in resistance of IEC18 cells to oxidant injury, stable transfected cells expressing an hsp72 antisense construct were established. Although thermal induction of hsp72 was blocked only partially by the antisense construct, glutamine induction of hsp72 was completely inhibited. This was associated with a loss of the protective effects of glutamine against oxidant-induced stress. Thus, glutamine specifically induces hsp72 in intestinal epithelial cells, which mediates cell protection against inflammation-induced stress such as oxidants.


Energy expenditure: a critical determinant of energy balance with key hypothalamic controls.
Energy stores are regulated through complex neural controls exerted on both food intake and energy expenditure. These controls are insured by interconnected neurons that produce different peptides or classic neurotransmitters, which have been regrouped into anabolic' and catabolic' systems. While the control of energy intake has been addressed in numerous investigations, that of energy expenditure has, as yet, only received a moderate interest, even though energy expenditure represents a key determinant of energy balance. In laboratory rodents, in particular, a strong regulatory control is exerted on brown adipose tissue (BAT), which represent an efficient thermogenic effector. BAT thermogenesis is governed by the sympathetic nervous system (SNS), whose activity is controlled by neurons comprised in various brain regions, which include the paraventricular hypothalamic nucleus (PVH), the arcuate nucleus (ARC) and the lateral hypothalamus (LH). Proopiomelanocortin neurons from the ARC project to the PVH and terminate in the vicinity of the melanocortin-4 receptors, which are concentrated in the descending division of the PVH, which comprise neurons controlling the SNS outflow to BAT. The LH contains neurons producing melanin-concentrating hormone or orexins, which also are important peptides in the control of energy expenditure. These neurons are not only polysynaptically connected to BAT, but also linked to brains regions controlling motivated behaviors and locomotor activity and, consequently, their role in the control of energy expenditure could go beyond BAT thermogenesis.


Iodine status of pregnant mothers residing in a district of endemic iodine deficiency in the state of Himachal Pradesh, India.
For the last 40 years the Kullu district in Himachal Pradesh, India, has been recognised as an area of endemic iodine deficiency. The state government has adopted a policy of universal iodisation of salt since 1984. The iodine status of pregnant mothers is an indicator of the community status of iodine deficiency. This study was, therefore, undertaken on the iodine status of pregnant mothers to assess the impact of universal salt iodisation. A total of 147 pregnant mothers between 20-30 years of age in their second and third trimesters, attending the antenatal clinic at the district hospital, were selected for the study. Urine samples were collected from all the pregnant mothers and analysed using standard laboratory methods. It was found that 0.68% of the pregnant mothers had urinary iodine excretion between 2.0-4.9 mcg/dL, 8.8 % between 5.0-9.9 mcg/dL and 90.5% had 10 mcg/dL or more, where below 10 signifies iodine deficiency disorder (IDD). This indicates that there is a need to strengthen the implementation of the universal salt iodisation program in the Kullu district to combat IDD.


Obesity and the metabolic syndrome in Mediterranean countries: a hypothesis related to olive oil.
In Mediterranean countries people would previously have consumed a diet with a high proportion of MUFA. Physical activity would have been intense with a low level of stress. The stearoyl-CoA desaturase (SCD1) system selected over thousands of years of this type of behavior must have adapted to a particular capacity of self regulation. Now, this pattern, called the "Mediterranean diet", has been broken and many people living by the Mediterranean consume a high quantity of calories, mainly from saturated or n-6-rich fats and the relative intake of MUFA has decreased. Simultaneously, physical activity has decreased and the pattern of stress has changed towards what is called a western lifestyle. In this new context, if people have a favorable, genetically conditioned SCD1 activity that will let them confront the new situation or else have some other compensatory mechanism, such as being keen on sport, etc, then they can prevent the appearance of some of the complications associated with the metabolic syndrome. If, on the other hand, the SCD1 pattern is genetically unfavorable for this new situation and they have a new cultural context, then they do not have the alternative compensatory mechanisms and the probability of developing the metabolic syndrome is high.