Knowledge, awareness and practices of dental care waste management among private dental practitioners in Tricity (Chandigarh, Panchkula and Mohali).
The objective of this study is to assess the awareness and practices of dental care waste management among private dental practitioners in Tricity (Chandigarh, Panchkula and Mohali). A cross-sectional study was conducted in 100 private dental practitioners selected by simple random sampling using a close-ended questionnaire. Amongst the total respondents 52% were males and 48% were females. Nearly 14% of the dental practitioners were not aware of the different categories of the waste generated in their clinics and 12% of the practitioners were not aware of the color coding used to dispose the waste. About 26% of them practiced wrong measures to dispose sharps and extracted tooth respectively. A majority 32% of Dentists did not disposed outdated and expired medicines properly. Majority of the dental practitioners was aware of categories and color coding used for disposal of different types of wastes yet they do not follow the same in their practice. Hence, strict prosecution laws should also be imposed under biomedical waste management act for the Dentists so that it should be implemented in daily practice.


5-(2-Oxo-3-indolinylidene)thiazolidine-2,4-dione-1,3-di-Mannich base derivatives: synthesis and evaluation for antileukemic activity.
A novel series of 5-(2-oxo-3-indolinylidene)thiazolidine-2,4-dione, having the 1- and 3-positions of the isatin and thiazolidine rings respectively, substituted by various Mannich bases, was prepared. Five compounds were evaluated for antileukemic activity against P388 lymphocytic leukemia in the mouse. The di-Mannich base with a dimethylamino component exhibited the highest activity of the tested compounds. Introduction of bromine into the aromatic moiety of isatin ring (position 5) increased the activity of the parent molecule to a smaller extent.


State-Specific Rates of Primary and Secondary Syphilis Among Men Who Have Sex with Men - United States, 2015.
In 2015, the rate of reported primary and secondary syphilis in the United States was 7.5 cases per 100,000 population, nearly four times the previous lowest documented rate of 2.1 in 2000 (1). In 2015, 81.7% of male primary and secondary syphilis cases with information on the sex of the sex partner were among gay, bisexual, and other men who have sex with men (collectively referred to as MSM) (1). These data suggest a disproportionate incidence of disease among MSM. However, attempts to quantify this disparity have been hindered by limited data on the size of the MSM population at the state level. To produce the first estimates of state-specific rates of primary and secondary syphilis among MSM, CDC used MSM population estimates based on a new methodology (2) and primary and secondary syphilis case counts reported in 2015 to the National Notifiable Diseases Surveillance System. Among 44 states reporting information on the sex of sex partners for ≥70% of male cases, the overall rate of primary and secondary syphilis among all men (aged ≥18 years) in the United States in 2015 was 17.5 per 100,000, compared with 309.0 among MSM and 2.9 among men who reported sex with women only. The overall rate of primary and secondary syphilis among MSM was 106.0 times the rate among men who have sex with women only and 167.5 times the rate among women.* These data highlight the disproportionate impact of syphilis among MSM and underscore the need for innovative and targeted syphilis prevention measures at the state and local level, especially among MSM. It is important that health care providers recognize the signs and symptoms of syphilis, screen sexually active MSM for syphilis at least annually, and provide timely treatment according to national sexually transmitted diseases treatment guidelines (3).


Lymphocyte subsets and Langerhans' cells in toxic epidermal necrolysis. Report of a case.
Toxic epidermal necrolysis is a life-threatening disease, the pathogenesis of which remains largely unknown. Histologically, in addition to the characteristic epidermal alterations, there is a sparse mononuclear cell infiltrate in the dermis. The immunologic characteristics of this infiltrate are not well known. In a case of drug-induced toxic epidermal necrolysis with fatal outcome in a 48-year-old man, we demonstrated that the majority of the inflammatory cells were of helper/inducer T-lymphocyte subsets, having only a minority of cytotoxic/suppressor T-lymphocytes and rare cells with natural killer cell phenotype. The significance of these observations is discussed, with reference to the occurrence of lesions at epithelial sites bearing local networks of antigen-presenting cells (Langerhans' cells).


Influence of hearing loss on children's identification of spondee words in a speech-shaped noise or a two-talker masker.
This study evaluated the influence of hearing loss on children's speech-perception abilities in a speech-shaped noise or a two-talker masker. For both masker conditions, it was predicted that children with hearing loss would require a more advantageous signal to noise ratio (SNR) than children with normal hearing to achieve the same criterion level of performance. However, it was hypothesized that the performance gap between children with hearing loss and children with normal hearing would be larger in the two-talker than in the speech-shaped noise masker. A repeated-measures design compared the spondee identification performance of two age groups of children with hearing loss (9-11 and 13-17 years of age) and a group of children with normal hearing (9-11 years of age) in continuous speech-shaped noise or a two-talker masker. Estimates of the SNR required for 70.7% correct spondee identification were obtained using an adaptive, four-alternative, forced-choice procedure. Children were tested in the sound field. Children with hearing loss wore their personal hearing aids at their regular settings during testing. Both groups of children with hearing loss performed more poorly than children with normal hearing in the speech-shaped noise masker. Younger children required an additional 2.7 dB SNR and older children required an additional 4.7 dB SNR to achieve the same level of performance as children with normal hearing. This disadvantage decreased to 8.1 dB for both age groups of children with hearing loss in the two-talker masker. For children with hearing loss, degree of hearing loss was significantly correlated with performance in the speech-shaped noise masker, but not in the two-talker masker. A larger performance gap was observed between children with hearing loss and children with normal hearing in competing speech than in steady state noise. These results are consistent with the hypothesis that hearing loss influenced children's perceptual processing abilities.


2010 ACVIM small animal consensus statement on leptospirosis: diagnosis, epidemiology, treatment, and prevention.
This report offers a consensus opinion on the diagnosis, epidemiology, treatment, and prevention of leptospirosis in dogs, an important zoonosis. Clinical signs of leptospirosis in dogs relate to development of renal disease, hepatic disease, uveitis, and pulmonary hemorrhage. Disease may follow periods of high rainfall, and can occur in dogs roaming in proximity to water sources, farm animals, or wildlife, or dogs residing in suburban environments. Diagnosis is based on acute and convalescent phase antibody titers by the microscopic agglutination test (MAT), with or without use of polymerase chain reaction assays. There is considerable interlaboratory variation in MAT results, and the MAT does not accurately predict the infecting serogroup. The recommended treatment for optimal clearance of the organism from renal tubules is doxycycline, 5 mg/kg p.o. q12h, for 14 days. Annual vaccination can prevent leptospirosis caused by serovars included in the vaccine and is recommended for dogs at risk of infection.


Tick-borne illnesses: identification and management in the emergency department
Tick-borne illnesses are increasing in prevalence and geographic reach. Because the presentation of these illnesses is sometimes nonspecific, they can often be misdiagnosed, especially in the early stages of illness. A detailed history with questions involving recent activities and travel and a thorough physical examination will help narrow the diagnosis. While some illnesses can be diagnosed on clinical findings alone, others require confirmatory testing, which may take days to weeks to result. This issue reviews the emergency department presentation of 9 common tick-borne illnesses and evidence-based recommendations for identification, testing, and treatment.


Generalised versus Regional Odontodysplasia: Diagnosis, Transitional Management, and Long-Term Followup-A Report of 2 Cases.
Background. Odontodysplasia is an uncommon condition. It can be localised or generalised, isolated or part of a syndrome. Case Report. We first report the case of an 8.5-year-old boy who presented with abnormally shaped teeth and multiple intraoral abscesses. Findings of clinical and radiographic examinations were consistent with those of generalised odontodysplasia. A 2-step, conservative treatment plan was executed with a 10-year followup. Step 1 was root canal treatment of nonvital teeth. Step 2 was crowning without preparation of new vital, erupted, and malformed teeth. The second case is that of a 12-year-old girl who presented with lack of teeth in the upper-left quadrant. The impacted teeth were exposed surgically, and fixed restoration was performed for temporary aesthetic improvement. Conclusion. Instead of tooth extraction, an approach previously used in similar cases, conservative management is feasible and offers better prosthetic treatment options for the future.


IL-11 contribution to tumorigenesis in an NRF2 addiction cancer model.
The interaction between cancer cells and their microenvironment is an important determinant of the pathological nature of cancers, particularly their tumorigenic abilities. The KEAP1-NRF2 system, originally identified as a critical defense mechanism against oxidative stress, is often dysregulated in various human cancers forming solid tumors, resulting in the aberrant activation of NRF2. Increased accumulation of NRF2 in cancers is strongly associated with the poor prognoses of cancer patients, including those with lung and breast cancers. Multiple lines of evidence suggest that aberrantly activated NRF2 in cancer cells drives their malignant progression and that the cancer cells consequently develop 'NRF2 addiction.' Although the downstream effectors of NRF2 that are responsible for cancer malignancy have been extensively studied, mechanisms of how NRF2 activation contributes to the aggressive tumorigenesis remains to be elucidated. In this study, we found a significant correlation between NRF2 and IL-11 status in breast cancer patients. Based on a recent report demonstrating that IL-11 is induced downstream of NRF2, we examined the significance of IL-11 in NRF2-driven tumorigenesis with a newly established NRF2 addiction cancer model. Expression of Il11 was elevated during the tumorigenesis of the NRF2 addiction cancer model, but intriguingly, it was hardly detected when the cancer model cells were cultured in vitro. These results imply that a signal originating from the microenvironment cooperates with NRF2 to activate Il11. To the best of our knowledge, this is the first report showing the influence of the microenvironment on the NRF2 pathway in cancer cells and the contribution of NRF2 to the secretory phenotypes of cancers. Disruption of Il11 in the NRF2 addiction cancer model remarkably inhibited the tumorigenesis, suggesting an essential role of IL-11 in NRF2-driven tumorigenesis. Thus, this study suggests that IL-11 is a potential therapeutic target for NRF2-addicted breast cancers.


Transcriptional control of cellular metabolism by mTOR signaling.
Tumor cells are characterized by adaptations in cellular metabolism that afford growth and proliferative advantages over normal cells and, thus, contribute to cancer pathophysiology. There is an increasing appreciation of the fact that oncogenic signaling controls the metabolic reprogramming of cancer cells; however, the mechanisms and critical players are only beginning to be elucidated. Recent studies have revealed that mTOR complex 1 (mTORC1), a master regulator of cell growth and proliferation downstream of oncogenic signaling pathways, controls specific aspects of cellular metabolism through the induction of metabolic gene expression. mTORC1 activation is sufficient to promote flux through glycolysis and the oxidative branch of the pentose phosphate pathway, as well as to stimulate de novo lipogenesis, all processes that are important in tumor biology. As mTORC1 signaling is aberrantly elevated in the majority of genetic tumor syndromes and sporadic cancers, this pathway is poised to be a major driver of the metabolic conversion of tumor cells.


How I treat primary CNS lymphoma.
Primary CNS lymphoma (PCNSL) is a rare malignancy with peculiar clinical and biologic features, aggressive course, and unsatisfactory outcome. It represents a challenge for multidisciplinary clinicians and scientists as therapeutic progress is inhibited by several issues. Molecular and biologic knowledge is incomplete, limiting the identification of new therapeutic targets, and the particular microenvironment of this malignancy, and sanctuary sites where tumor cells grow undisturbed, strongly affects treatment efficacy. Moreover, active treatments are known to be associated with disabling neurotoxicity, posing the dilemma of whether to intensify therapy to improve the cure rate or to de-escalate treatment to avoid sequels. The execution of prospective trials is also difficult because of the rarity of the tumor and the impaired general condition and poor performance status of patients. Thus, level of evidence is low, with consequent uncertainties in therapeutic decisions and lack of consensus on primary endpoints for future trials. Despite this unfavorable background, laboratory and clinical researchers are coordinating efforts to develop new ideas, resulting in the recent publication of studies on PCNSL's biology and molecular mechanisms and of the first international randomized trials. Herein, these important contributions are analyzed to provide recommendations for everyday practice and the rationale for future trials.


Growth of the nuclear envelope in the vegetative phase of the green alga Acetabularia. Evidence for assembly from membrane components synthesized in the cytoplasm.
The primary nucleus of the green alga Acetabularia grows about 25,000-fold in volume while it is separated from the endoplasmic reticulum and the whole cytoplasm by a special paranuclear cisterna of a vacuolar labyrinthum system which shows only very few (two to six per square micrometer) and small (ca. 40-120 nm in diamter) fenestrations. The nuclear envelope does not bear polyribosomes, nor do they occur in the entire zone intermediate between the nuclear envelope and the paranuclear cisterna. It is suggested that this special form of nuclear envelope growth takes place by assembly from cytoplasmically synthesized proteins that are translocated across the paranuclear cisterna in a nonmembrane-structured form.


Atmospheric ethanol in London and the potential impacts of future fuel formulations.
There is growing global consumption of non-fossil fuels such as ethanol made from renewable biomass. Previous studies have shown that one of the main air quality disadvantages of using ethanol blended fuels is a significant increase in the production of acetaldehyde, an unregulated and toxic pollutant. Most studies on the impacts of ethanol blended gasoline have been carried out in the US and Brazil, with much less focus on the UK and Europe. We report time resolved measurements of ethanol in London during the winter and summer of 2012. In both seasons the mean mixing ratio of ethanol was around 5 ppb, with maximum values over 30 ppb, making ethanol currently the most abundant VOC in London air. We identify a road transport related source, with 'rush-hour' peaks observed. Ethanol is strongly correlated with other road transport-related emissions, such as small aromatics and light alkanes, and has no relationship to summer biogenic emissions. To determine the impact of road transport-related ethanol emission on secondary species (i.e. acetaldehyde and ozone), we use both a chemically detailed box model (incorporating the Master Chemical Mechanism, MCM) and a global and nested regional scale chemical transport model (GEOS-Chem), on various processing time scales. Using the MCM model, only 16% of the modelled acetaldehyde was formed from ethanol oxidation. However, the model significantly underpredicts the total levels of acetaldehyde, indicating a missing primary emission source, that appears to be traffic-related. Further support for a primary emission source comes from the regional scale model simulations, where the observed concentrations of ethanol and acetaldehyde can only be reconciled with the inclusion of large primary emissions. Although only constrained by one set of observations, the regional modelling suggests a European ethanol source similar in magnitude to that of ethane (∼60 Gg per year) and greater than that of acetaldehyde (∼10 Gg per year). The increased concentrations of ethanol and acetaldehyde from primary emissions impacts both radical and NOx cycling over Europe, resulting in significant regional impacts on NOy speciation and O3 concentrations, with potential changes to human exposure to air pollutants.


Structural analysis of the microglia-interneuron interactions in the CA1 hippocampal area of the APP/PS1 mouse model of Alzheimer's disease.
Microglia can interact with glutamatergic neurons and, through control of synaptic elements, regulate their physiological function. Much less is known about the partnership between microglia and GABAergic inhibitory interneurons. Here, we compared the interactions between microglia and parvalbumin (PV+) and somatostatin (SOM+) expressing interneurons in the CA1 hippocampal area of APP/PS1 transgenic mice that mimic certain aspects of the Alzheimer's disease (AD). We first uncovered a high level of interactions between microglia and two types of interneurons, with 98% of SOM+ and 90% of PV+ cells receiving different types of putative microglial contacts. The latter included the microglia soma to the interneuron soma (SomaMG -to-SomaIN ), the microglia process to the interneuron soma (ProcessMG -to-SomaIN ) and the microglia process to the interneuron dendrite (ProcessMG -to-DendIN ) interactions. Moreover, we found significantly larger areas of interaction for the SomaMG -to-SomaIN and the ProcessMG -to-DendIN type of contacts between microglia and SOM+ cells. In contrast, PV+ cells exhibited larger areas for the ProcessMG -to-SomaIN interactions. Second, in APP/PS1 mice, although the overall microglia interactions with interneurons remained preserved, the fraction of interneurons receiving putative microglia contacts on their dendrites was reduced, and larger areas of interactions were observed for somatic contacts, suggesting a stronger modulation of the interneuron output by microglia in AD. In summary, these results reveal microglia as important partners of hippocampal PV+ and SOM+ GABAergic cells, with interneuron type-specific pattern of interactions. Thus, microglia may play an essential role in the operation of interneurons under normal conditions and their dysfunction in disease.


Fragile X-associated tremor/ataxia syndrome: pathophysiology and management.
The purpose of this paper is to review the prevalence, pathophysiology, and management of fragile X-associated tremor/ataxia syndrome (FXTAS). The pathophysiology of FXTAS involves ribonucleic acid (RNA) toxicity due to elevated levels of the premutation-expanded CGG (eoxycytidylate-deoxyguanylate-deoxyguanylate)-repeat FMR1 mRNA, which can sequester a variety of proteins important for neuronal function. A recent analysis of the inclusions in FXTAS demonstrates elevated levels of several proteins, including small ubiquitin-related modifiers 1/2 (SUMO1/2), that target molecules for the proteasome, suggesting that some aspect(s) of proteasomal function may be altered in FXTAS. Recent neuropathological studies show that Parkinson disease and Alzheimer disease can sometimes co-occur with FXTAS. Lewy bodies can be found in 10% of the brains of patients with FXTAS. Microbleeds and iron deposition are also common in the neuropathology, in addition to white matter disease (WMD) and atrophy. The premutation occurs in 1:200 females and 1:400 males. Penetrance for FXTAS increases with age, though lower in females (16%) compared to over 60% of males by age 70. To diagnose FXTAS, an MRI is essential to document the presence of WMD, a primary component of the diagnostic criteria. Pain can be a significant feature of FXTAS and is seen in approximately 50% of patients.


maresin2 fine-tunes ULK1 O-GlcNAcylation to improve post myocardial infarction remodeling.
Myocardial infarction (MI) is one of the common causes of hospitalization and death all over the world. Maresin2 (MaR2), a specialized pro-solving mediator of inflammation, has been consolidated to be a novel cytokine fine-tuning inflammatory cascade. However, the precise mechanism is still unknown. Here, we demonstrated that maresin2 relieved myocardial damage via ULK1 O-GlcNAc modification during MI. The myocardial infarction model was established by ligating the left anterior descending artery (LAD). Echocardiography, histopathology, transmission electron microscope, and Western blot were used to evaluate cardiac function and remodeling. Furthermore, primary neonatal rat cardiomyocytes (NRCMs) were cultivated, and immunoprecipitation (IP) assays were performed to explore the specific mechanism. As suggested, maresin2 treatment protected cardiac function and ameliorated adverse cardiac remodeling. Furthermore, we found that maresin2 facilitated autophagy and inhibited apoptosis under the modulation of O-GlcNAcylation-dependent ULK1 activation. Meanwhile, we discovered that maresin2 treatment ameliorated the inflammation of myocardial cells by inhibiting the interaction of TAK1 and TAB1. Maresin2 is likely to promote autophagy while relieving apoptosis and inflammation of myocardial cells, thereby exerting a protective effect on the heart after MI.


Opposing actions of Bay K 8644 enantiomers on calcium current, prolactin secretion, and synthesis in pituitary cells.
Dihydropyridine (DHP) Ca2+ channel modulators were used to explore the relationship between voltage-gated Ca2+ channels and PRL secretion, synthesis, and mRNA in PRL-secreting pituitary cells. Optical isomers of the Ca2+ channel agonist Bay K 8644 produced stereospecific and opposing effects on L-type Ca2+ current, PRL release, and synthesis in GH3 and GH4C1 cells. (-)-Bay K 8644 (R5417) behaved as a pure agonist, enhancing Ca2+ current several-fold while shifting the current-voltage curve 10-15 mV in the hyperpolarizing direction. The agonist effect was independent of holding potential, but decreased during prolonged Ba2+ or Ca2+ entry. R5417 produced a concentration-dependent increase in acute PRL release and enhanced PRL production by GH cells several-fold during a 72-h period. (+)-Bay K 8644 (R4407) behaved as a weak Ca2+ channel antagonist, inhibiting L-type Ca2+ current, KCl-stimulated PRL secretion, and PRL production at concentrations of 0.5-5 microM. These two isomers produced similar effects on PRL production by normal rat pituitary cells in dispersed culture. R5417 (500 nM) increased PRL produced in 72 h to 233 +/- 8% of the control value. R4407 reduced this quantity by 36 +/- 9%. The effects of the DHPs on PRL mRNA levels were consistent with the effects observed for acute secretion and hormone production. The agonist R5417 increased PRL mRNA 147 +/- 5% over a 30-h period, and the potent DHP Ca2+ channel blocker nimodipine inhibited PRL mRNA production 2-fold. These results demonstrate that racemic Bay K 8644 interacts with L-type Ca2+ channels in normal and transformed pituitary cells as a mixed agonist-antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)


High expression of hTERT and stemness genes in BORIS/CTCFL positive cells isolated from embryonic cancer cells.
BORIS/CTCFL is a member of cancer testis antigen family normally expressed in germ cells. In tumors, it is aberrantly expressed although its functions are not completely well-defined. To better understand the functions of BORIS in cancer, we selected the embryonic cancer cells as a model. Using a molecular beacon, which specifically targets BORIS mRNA, we demonstrated that BORIS positive cells are a small subpopulation of tumor cells (3-5% of total). The BORIS-positive cells isolated using BORIS-molecular beacon, expressed higher telomerase hTERT, stem cell (NANOG, OCT4, SOX2) and cancer stem cell marker genes (CD44 and ALDH1) compared to the BORIS-negative tumor cells. In order to define the functional role of BORIS, stable BORIS-depleted embryonic cancer cells were generated. BORIS silencing strongly down-regulated the expression of hTERT, stem cell and cancer stem cell marker genes. Moreover, the BORIS knockdown increased cellular senescence in embryonic cancer cells, revealing a putative role of BORIS in the senescence biological program. Our data indicate an association of BORIS expressing cells subpopulation with the expression of stemness genes, highlighting the critical role played by BORIS in embryonic neoplastic disease.


Role of ICAM1 in invasion of human breast cancer cells.
We identified previously a region on chromosome 19p13.2 spanning the genes encoding the intercellular adhesion molecules (ICAM), ICAM1, ICAM4 and ICAM5 as a breast cancer susceptibility locus. Genetic variants in this region were also associated with indicators of disease severity, including higher rates of metastases to other organs. Based on this association, we set out to explore the role of ICAM1 in proliferation and invasion of human breast cancer cells. We observed that ICAM1 downregulation at the mRNA and protein levels led to a strong suppression of human breast cell invasion through a matrigel matrix. Under the same conditions, no significant effect on cell proliferation in vitro was seen. Incubation of cells with an antibody against ICAM1 blocked invasion of the highly metastatic MDA-MB-435 cell line in a dose-dependent manner without affecting cell migration. We also demonstrated that the level of ICAM1 protein expression on the cell surface positively correlated with metastatic potential of five human breast cancer cell lines and that ICAM1 mRNA levels were elevated in breast tumor compared with adjacent normal tissue. These results corroborate our previous genetic finding that variations in the ICAM region are associated with the occurrence of metastases and establish a causal role of ICAM1 in invasion of metastatic human breast carcinoma cell lines.


Penetration of Lead by the Wood Piddock Martesia striata.
An attack by Martesia striata Linnaeus on the lead sheathing of a power cable is described. This is the third such attack recorded and all have occurred in Florida waters. A guide for describing future attacks is recommended with the hope that the specific conditions under which attacks occur can be learned.


Constraining binding hot spots: NMR and molecular dynamics simulations provide a structural explanation for enthalpy-entropy compensation in SH2-ligand binding.
NMR spectroscopy and molecular dynamics (MD) simulations were used to probe the structure and dynamics of complexes of three phosphotyrosine-derived peptides with the Src SH2 domain in an effort to uncover a structural explanation for enthalpy-entropy compensation observed in the binding thermodynamics. The series of phosphotyrosine peptide derivatives comprises the natural pYEEI Src SH2 ligand, a constrained mimic, in which the phosphotyrosine (pY) residue is preorganized in the bound conformation for the purpose of gaining an entropic advantage to binding, and a flexible analogue of the constrained mimic. The expected gain in binding entropy of the constrained mimic was realized; however, a balancing loss in binding enthalpy was also observed that could not be rationalized from the crystallographic structures. We examined protein dynamics to evaluate whether the observed enthalpic penalty might be the result of effects arising from altered motions in the complex. (15)N-relaxation studies and positional fluctuations from molecular dynamics indicate that the main-chain dynamics of the protein show little variation among the three complexes. Root mean squared (rms) coordinate deviations vary by less than 1.5 A for all non-hydrogen atoms for the crystal structures and in the ensemble average structures calculated from the simulations. In contrast to this striking similarity in the structures and dynamics, there are a number of large chemical shift differences from residues across the binding interface, but particularly from key Src SH2 residues that interact with pY, the "hot spot" residue, which contributes about one-half of the binding free energy. Rank-order correlations between chemical shifts and ligand binding enthalpy for several pY-binding residues, coupled with available mutagenesis and calorimetric data, suggest that subtle structural perturbations (<1 A) from the conformational constraint of the pY residue sufficiently alter the geometry of enthalpically critical interactions in the binding pocket to cause the loss of binding enthalpy, leading to the observed enthalpy-entropy compensation. We find no evidence to support the premise that enthalpy-entropy compensation is an inherent property and conclude that preorganization of Src SH2 ligand residues involved in binding hot spots may eventuate in suboptimal interactions with the domain. We propose that introducing constraints elsewhere in the ligand could minimize enthalpy-entropy compensation effects. The results illustrate the utility of the NMR chemical shift to highlight small, but energetically significant, perturbations in structure that might otherwise go unnoticed in an apparently rigid protein.


Unusual Deformation and Fracture in Gallium Telluride Multilayers.
The deformation and fracture mechanism of two-dimensional (2D) materials are still unclear and not thoroughly investigated. Given this, mechanical properties and mechanisms are explored on example of gallium telluride (GaTe), a promising 2D semiconductor with an ultrahigh photoresponsivity and a high flexibility. Hereby, the mechanical properties of both substrate-supported and suspended GaTe multilayers were investigated through Berkovich-tip nanoindentation instead of the commonly used AFM-based nanoindentation method. An unusual concurrence of multiple pop-in and load-drop events in loading curve was observed. Theoretical calculations unveiled this concurrence originating from the interlayer-sliding mediated layers-by-layers fracture mechanism in GaTe multilayers. The van der Waals force dominated interlayer interactions between GaTe and substrates was revealed much stronger than that between GaTe interlayers, resulting in the easy sliding and fracture of multilayers within GaTe. This work introduces new insights into the deformation and fracture of GaTe and other 2D materials in flexible electronics applications.


Does ethnicity affect survival following colorectal cancer? A prospective, cohort study using Iranian cancer registry.
The present study compared the differences between survivals of patients with colorectal cancer according to their ethnicity adjusted for other predictors of survival. In this prospective cohort study patients were followed up from definite diagnosis of colorectal cancer to death. Totally, 2431 person-year follow-ups were undertaken for 1127 colorectal cancer patients once every six months. The data were analyzed by stata software using bivariate analysis, multivariate analysis, and Cox regression. The age at diagnosis was significantly different between men and women (p<0.03). 61.2% were male and the rest were female. Most patients were Fars (51.2%), followed by Turciks (21.5%), Kurds (8.2%), and 7.5% Lurs. Of the patients, 75% had a survival of more than 2.72 years, 50% a survival of 5.83 years, and 25% longer than 13.1 years after diagnosis. Risk ratio was significantly different among ethnics (p<0.05). The variables of ethnicity, being non married, tumor grade, family history of cancer, and smoking were considered as determinants of the patients' survival in Cox regression model. The median survival time in Fars, Kurds, Lurs, Turks and other ethnics was 5.83, 2.44, 5.49, and 8.52 years, respectively. Ethnicity and access to healthcare are predictors of survival of patients with colorectal cancer which may define priorities in controlling cancer and implementing interventional and prevention plans.


Tumorigenicity of simian virus 40-transformed rat hepatocytes.
Simian virus 40 (SV40)-transformed F344 rat hepatocytes were transplanted into newborn and normal and irradiated adult syngeneic F344 hosts. Three independently isolated SV40-transformed hepatocyte cell lines were inoculated s.c. into newborn syngeneic animals. One cell line, SV40hpl, produced tumors in two of 12 animals. Fixed tissue sections indicated that the tumors were relatively undifferentiated but had some epithelial cells and contained a peripheral mononuclear leukocyte infiltrate. Serum from a tumor-bearing animal tested by immunoprecipitation demonstrated antibodies to SV40 large-T- but not to small-t-antigen. A portion of one of the tumors was used to prepare the tumor cell line SV40hpl-1, which was 100% positive by immunofluorescence for SV40 nuclear T-antigen. In adult F344 rats subjected previously to whole-body irradiation, inoculation of SV40hpl-1 cells produced tumors in 83% of the animals. Continued passage of the tumor cell line in irradiated rats produced a tumor in one animal which paralyzed its host. The cell line derived from this tumor (SV40hpl-1-T1-2) was tumorigenic in nonirradiated adult hosts. The tumor cell lines were morphologically similar to each other but different from the SV40hpl-transformed cell line; the tumor cells contained less cytoplasm and grew to high densities in strings or multilayered foci without covering the dish surface. All tumor cells retained SV40 antigen expression, and at least one complete copy of the virus genome was retained through two passages in animals. We concluded that SV40 transformation of rat hepatocytes can produce a tumorigenic cell line. We have shown previously that SV40-transformed hepatocytes retain the ability to express proteins characteristic of adult differentiated liver. Development of this model system will enable us to examine expression of these proteins not only in transformed cells with tumorigenic potential but also in tumor tissue and transplantable tumor cell lines.


Quality and Usability of Arthritic Pain Self-Management Apps for Older Adults: A Systematic Review.
To appraise the quality and usability of currently available pain applications that could be used by community-dwelling older adults to self-manage their arthritic pain. A systematic review. Searches were conducted in App Store and Google Play to identify pain self-management apps relevant to arthritic pain management. English language pain management apps providing pain assessment and documentation function and pain management education were considered for inclusion. A quality evaluation audit tool based on the Stanford Arthritis Self-Management Program was developed a priori to evaluate app content quality. The usability of included apps was assessed using an established usability evaluation tool. Out of the 373 apps that were identified, four met the inclusion criteria. The included apps all included a pain assessment and documentation function and instructions on medication use, communication with health professionals, cognitive behavioral therapy-based pain management, and physical exercise. Management of mood, depression, anxiety, and sleep were featured in most apps (N = 3). Three-quarters (N = 3) of the apps fell below the acceptable moderate usability score (≥3), while one app obtained a moderate score (3.2). Few of the currently available pain apps offer a comprehensive pain self-management approach incorporating evidence-based strategies in accordance with the Stanford Arthritis Self-Management Program. The moderate-level usability across the included apps indicates a need to consider the usability needs of the older population in future pain self-management app development endeavors.


Human neutrophil clearance of bacterial pathogens triggers anti-microbial γδ T cell responses in early infection.
Human blood Vγ9/Vδ2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vγ9/Vδ2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vγ9/Vδ2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-γ and tumor necrosis factor (TNF)-α. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vγ9/Vδ2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-α dependent proliferation of Vγ9/Vδ2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting γδ T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis--characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity--show a selective activation of local Vγ9/Vδ2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The γδ T cell-driven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of γδ T cells and TNF-α and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive γδ T cells in early infection and suggest novel diagnostic and therapeutic approaches.


Glutamine-β-cyclodextrin for targeted doxorubicin delivery to triple-negative breast cancer tumors via the transporter ASCT2.
Chemotherapy is the primary therapy for triple-negative breast cancer (TNBC) and the tumor-targeted delivery of chemotherapeutic drugs is necessary to minimize their side effects on normal tissues. TNBC cells display addictions to glutamine in culture, and the levels of the glutamine transporter, alanine-serine-cysteine transporter 2 (ASCT2), are elevated in many types of cancer. However, glutamine- or ASCT2-based carriers have not been used in tumor-targeted drug delivery. In this study, a novel derivative of β-cyclodextrin (β-CD), glutamine-β-cyclodextrin (GLN-CD), was developed by conjugating glutamine with the 6-hydroxy of β-CD, and GLN-CD was then used to prepare doxorubicin (DOX) inclusion complexes (DOX@GLN-CD) for TNBC treatment. GLN-CD and glutamine have similar ASCT2-binding sites, and GLN-CD has the potential to enter cells through ASCT2-dependent facilitated diffusion. An increase in the degree of substitution did not promote binding between GLN-CD and ASCT2. GLN-CD and DOX formed inclusion complexes at a molar ratio of 1 : 1. DOX@GLN-CD specifically accumulated in TNBC cells, including MDA-MB-231 and BT549 cells, where it subsequently induced G2/M blockade and apoptosis, but hardly affected nontumorigenic MCF10A cells. l-γ-Glutamyl-p-nitroanilide (GPNA), which is a specific inhibitor of ASCT2, antagonistically decreased the cellular uptake of DOX@GLN-CD by TNBC cells, which further confirmed the role of ASCT2 in DOX@GLN-CD transport. In vivo, DOX@GLN-CD accumulated specifically in tumors, achieved improved outcomes and minimized the toxic effects on main organs at the same dose as DOX. As a novel derivative of β-CD, GLN-CD is an effective carrier that can specifically deliver DOX to TNBC cells via targeting ASCT2 and minimize its uptake by normal cells.


Aromatase and sex steroid receptors in human vena cava.
Among sex steroids, especially estrogen metabolism has been considered to play a role in the function and pathology of human veins. We investigated the expression and activity of the estrogen-producing enzyme aromatase and estrogen receptor (ER) in human vena cava to assess possible in situ biosynthesis of estrogens and their modes of action. We first examined aromatase expression by immunohistochemistry in human inferior vena cava obtained from 29 autopsy cases (11 males, 18 females, 63.6 +/- 3.0 years old). We then semiquantitated the level of aromatase mRNA by reverse transcriptase-polymerase chain reaction in 24 cases and aromatase activity by 3H-water assay in 15 cases to examine whether or not and in which cell types aromatase was expressed. We also studied alternative use of multiple exon 1s of its gene and immunolocalization of 17beta-hydroxysteroid dehydrogenase type I (17beta-HSD I), which converts estrone produced by aromatase to estradiol, a biologically active estrogen and ER. Aromatase and 17beta-HSD I immunoreactivity were both detected in smooth muscle cells (SMC) of the media in all the cases and in endothelial cells (EC) in 20 and 22 cases, respectively. ER immunoreactivity was detected in SMC of vena cava in 21 cases. The amount of aromatase mRNA was significantly greater in the cases utilizing 1c (I.3) or 1d (P.II) of exon 1 (9 cases, 191.1 +/- 26.3 attomol/ng total RNA) than those utilizing 1b (I.4) as the promoter (14 cases, 50.6 +/- 13.0 attomol/ng total RNA) (p < 0.01). Significant correlation (p < 0.05) was observed between the amount of aromatase mRNA and aromatase activity in 15 cases examined. No significant correlation was detected between the amount of aromatase mRNA or aromatase labeling index and the ER status. These results suggest that estrone and estradiol are produced in the human vena cava and that their production is mediated by aromatase and 17beta-HSD I, respectively but not all of these locally synthesized estrogens may not work directly in situ.


Time-dependent changes in striatal monoamine levels and gene expression following single and repeated amphetamine administration in rats.
As drug addiction may result from pathological usurpations of learning and memory's neural mechanisms, we focused on the amphetamine-induced time-dependent neurochemical changes associated with neural plasticity. We used juvenile rats as the risk for drug abuse is higher during adolescence. Experiment 1 served to define the appropriate amphetamine dose and the neurochemical effects of a single administration. In experiment 2, rats received seven amphetamine or saline injections in the open-field test throughout a twelve-day period. We measured the mRNA levels of the brain-derived neurotrophic factor (BDNF), its tropomyosin receptor kinase B (TrkB), the cAMP response element-binding protein (CREB), the microRNA-132, the Rho GTPase-activating protein 32 (p250GAP), the corticotropin-releasing factor (CRF), and monoamines and amino-acids contents in the nucleus accumbens and the dorsal striatum 45, 90, and 180 min after the last injection. We found that amphetamine changed gene expression only at certain time points and in a dose and region-dependent manner. Repeated but not single administrations upregulated accumbal and striatal BDNF (180 min) and striatal pri-miR-132 (90 min) expression, while downregulated accumbal CREB levels (90 min). As only some drug users develop addiction, we compared brain parameters between low and high amphetamine responders. Prone subjects characterized by having reduced striatal 5-HT metabolism, higher accumbal BDNF and TrkB expression, and lower levels of CREB in the dorsal striatum and p250GAP in both regions. Thus, individual differences in drug-induced changes in neurotransmission and gene expression in nigrostriatal and mesolimbic dopaminergic pathways may underlie the plasticity adaptations associated with behavioral sensitization to amphetamine.


Optimum recursive filtering of noisy two-dimensional data with sequential parameter identification.
A two-dimensional recursive estimation algorithm based on the asymmetric half-plane model is described for the problem of MMSE (minimum mean-square error) filtering. The optimum filtering problem is solved by formulating the asymmetric half-plane ARMA (autoregressive moving average) model for two-dimensional data. The sequential parameter identification from the noisy two-dimensional data is also discussed, utilizing the stochastic approximation. Experiments were performed for real image data, combining the proposed parameter identification and estimation algorithms. The results show that this method gives considerable improvement in SNR.


Music expertise shapes audiovisual temporal integration windows for speech, sinewave speech, and music.
This psychophysics study used musicians as a model to investigate whether musical expertise shapes the temporal integration window for audiovisual speech, sinewave speech, or music. Musicians and non-musicians judged the audiovisual synchrony of speech, sinewave analogs of speech, and music stimuli at 13 audiovisual stimulus onset asynchronies (±360, ±300 ±240, ±180, ±120, ±60, and 0 ms). Further, we manipulated the duration of the stimuli by presenting sentences/melodies or syllables/tones. Critically, musicians relative to non-musicians exhibited significantly narrower temporal integration windows for both music and sinewave speech. Further, the temporal integration window for music decreased with the amount of music practice, but not with age of acquisition. In other words, the more musicians practiced piano in the past 3 years, the more sensitive they became to the temporal misalignment of visual and auditory signals. Collectively, our findings demonstrate that music practicing fine-tunes the audiovisual temporal integration window to various extents depending on the stimulus class. While the effect of piano practicing was most pronounced for music, it also generalized to other stimulus classes such as sinewave speech and to a marginally significant degree to natural speech.


[Severe anaphylactoid complications in anesthesia. Apropos of 35 cases].
35 cases of severe anaphylactoid accidents during anesthesia are reported. Clinical symptomatology is dominated by cardiovascular collapse and/or bronchospasm and/or cutaneous and mucous manifestations. The course is always favourable. The usual risk factors (drug allergy, atopic background, spasmophilia, multiple anesthesia) are found. Pentothal alone or added to succinylcholine is most incriminated, followed by C-T 1341, curare-like agents, propanidid and macromolecular solutions. The immunoallergic investigation is incomplete, founded on the inhibition of leukocyte migration test TIML. The principal mechanisms responsible for these accidents and the most frequent causal products are recalled. Laboratory tests are reviewed. In conclusion, the authors propose a curative and preventive action to be taken when faced with this severe and non-exceptional accident of anesthesia.


New methods of estimating the number of motor units in a muscle.
Two electrophysiological methods have been described for estimating the number of motor units (MU) in a muscle. The methods are based on the original methods of Mc Comas and others, which involve dividing the maximum compound potential (MCP) of muscle evoked by supramaximal electrical stimulation of nerve by a mean motor unit potential (MMUP). The important modifications in the methods are the incorporation of the fluctuations in the response of MU to electrical excitation and a possible correction for the overlap in the firing levels of motor axons. The methods have been used in the estimation of the number of motor units in the first dorsal interosseous, thenar, hypothenar, and extensor digitorum brevis muscles of normal subjects and patients with various neuromuscular disorders. The results indicate that previous motor unit estimates were in general erroneously high.


Socioeconomic inequalities in access to specialized psychotropic prescribing among older Swedes: a register-based study.
Mental disorders among older adults are mainly treated with psychotropic drugs. Few of these drugs are, however, prescribed by specialized geriatricians or psychiatrists, but rather from general practitioners (GPs). Socioeconomic inequalities in access to specialist prescribing have been found in younger age groups. Hence, we aimed to investigate whether there are socioeconomic differences in access to geriatrician and psychiatrist prescribing of psychotropic drugs among older adults. By record-linkage of The Swedish Prescribed Drug Register and The Swedish Education Register, we obtained information for persons aged 75-89 years who had filled a prescription for psychotropic drugs (antipsychotics, anxiolytics, hypnotic/sedatives or antidepressants) with information on prescriber specialty from July to October 2005 (n = 221 579). Multinomial regression analysis was used to investigate whether education was associated with geriatrician and psychiatrist prescribing of psychotropic drugs. The vast majority of the psychotropic drugs were prescribed by 'GPs and other specialists' (∼95% GPs). Older adults with higher educational level were more likely to be prescribed psychotropic drugs from psychiatrists and geriatricians. However, after adjustment for place of residence, the association between patient's education and prescription by a geriatrician disappeared, whereas the association with seeing a psychiatrist was only attenuated. Access to specialized prescribing of psychotropics is unequally distributed between socioeconomic groups of older adults in Sweden. This finding was partially confounded by place of residence for geriatrician but not for psychiatrist prescribing. Further research should examine if inequalities in specialized psychotropic prescribing translate into worse outcomes for socioeconomically deprived and non-metropolitan-living older individuals.


Can Proprioceptive Training Reduce Muscle Fatigue in Patients With Motor Neuron Diseases? A New Direction of Treatment.
Muscle fatigue is a serious problem in patients with motor neuron diseases (MNDs). It commonly disturbs both daily life activity and rehabilitation tolerance. A particular concern should be taken when MNDs occur in older ages. Older patients with MNDs usually have a worse clinical presentation and a lower survival rate. This could increase the occurrence of muscle fatigue. Muscle fatigue occurs due to a dysfunction in either motor or sensory systems. Current exercise interventions performed to decrease the occurrence of muscle fatigue focused only on treating motor causes of muscle fatigue. It has been demonstrated that these interventions have a high debate in their effectiveness on decreasing the occurrence of muscle fatigue. Also, these exercise interventions ignored training the affected sensory part of muscle fatigue, however, the important role of the sensory system in driving the motor system. Thus, this review aimed to develop a novel exercise intervention by using proprioceptive training as an intervention to decrease the occurrence of muscle fatigue in patients with MNDs particularly, older ones. The physiological effects of proprioceptive training to decrease the occurrence of muscle fatigue could include two effects. The first effect includes the ability of the proprioceptive training to increase the sensitivity of muscle spindles as an attempt to normalize the firing rate of α-motoneurons, which their abnormalities have major roles in the occurrence of muscle fatigue. The second effect includes its ability to correct the abnormal movement-compensations, which develop due to the biomechanical constraints imposed on patients with MNDs.


Morphine aggravates inflammatory, behavioral, and hippocampal structural deficits in septic rats.
Although pain and sepsis are comorbidities of intensive care units, reported data on whether pain control by opioid analgesics could alter inflammatory and end-organ damage caused by sepsis remain inconclusive. Here, we tested the hypothesis that morphine, the gold standard narcotic analgesic, modifies behavioral and hippocampal structural defects induced by sepsis in male rats. Sepsis was induced with cecal ligation and puncture (CLP) and behavioral studies were undertaken 24 h later in septic and/or morphine-treated animals. The induction of sepsis or exposure to morphine (7 mg/kg) elicited similar: (i) falls in systolic blood pressure, (ii) alterations in spatial memory and learning tested by the Morris water maze, and (iii) depression of exploratory behavior measured by the new object recognition test. These hemodynamic and cognitive defects were significantly exaggerated in septic rats treated with morphine compared with individual interventions. Similar patterns of amplified inflammatory (IL-1β) and histopathological signs of hippocampal damage were noted in morphine-treated septic rats. Additionally, the presence of intact opioid receptors is mandatory for the induction of behavioral and hemodynamic effects of morphine because no such effects were observed when the receptors were blocked by naloxone. That said, our findings suggest that morphine provokes sepsis manifestations of inflammation and interrelated hemodynamic, behavioral, and hippocampal deficits.


Transcriptional Patterns of Biogeochemically Relevant Marker Genes by Temperate Marine Bacteria.
Environmental microbial gene expression patterns remain largely unexplored, particularly at interannual time scales. We analyzed the variability in the expression of marker genes involved in ecologically relevant biogeochemical processes at a temperate Atlantic site over two consecutive years. Most of nifH transcripts, involved in nitrogen (N) fixation, were affiliated with the symbiotic cyanobacterium Candidatus Atelocyanobacterium thalassa, suggesting a key role as N providers in this system. The expression of nifH and amoA (i.e., marker for ammonia oxidation) showed consistent maxima in summer and autumn, respectively, suggesting a temporal succession of these important N cycling processes. The patterns of expression of genes related to the oxidation of carbon monoxide (coxL) and reduced sulfur (soxB) were different from that of amoA, indicating alternate timings for these energy conservation strategies. We detected expression of alkaline phosphatases, induced under phosphorus limitation, in agreement with the reported co-limitation by this nutrient at the study site. In contrast, low-affinity phosphate membrane transporters (pit) typically expressed under phosphorus luxury conditions, were mainly detected in post-bloom conditions. Rhodobacteraceae dominated the expression of soxB, coxL and ureases, while Pelagibacteraceae dominated the expression of proteorhodopsins. Bacteroidetes and Gammaproteobacteria were major contributors to the uptake of inorganic nutrients (pit and amt transporters). Yet, in autumn, Thauma- and Euryarchaeota unexpectedly contributed importantly to the uptake of ammonia and phosphate, respectively. We provide new hints on the active players and potential dynamics of ecologically relevant functions in situ, highlighting the potential of metatranscriptomics to provide significant input to future omics-driven marine ecosystem assessment.


Mammographic breast density and breast cancer risk by menopausal status, postmenopausal hormone use and a family history of breast cancer.
Few studies have investigated the association between breast density and breast cancer by a family history of breast cancer, menopausal status, and postmenopausal hormone use (PMH). We investigated if associations of breast density and breast cancer differ according to the status of these risk factors. This study included 1,481 incident breast cancer cases diagnosed within the Nurses' Health Study I and II cohorts and 2,779 matched controls. Breast density was measured from digitized film images with computerized techniques. Information on breast cancer risk factors was obtained prospectively from the biennial questionnaires before the date of the cancer diagnosis for cancer cases and their matched controls. The data were analyzed with logistic regression. Breast cancer risk increased with increasing percent breast density in all strata (p for trend in all subsets <0.0001). The density-related risk of breast cancer was similar in women with and without a family history (OR = 4.00 [95 % CI 2.01-7.94] vs. 3.71 [95 % CI 2.79-4.94] for density ≥50 % vs. <10 %, p for interaction = 0.53). The magnitude of the association between density and breast cancer risk, however, appeared to be stronger in premenopausal women than in postmenopausal women without PMH history (OR = 5.49 [95 % CI 2.44-12.39] vs. 3.02 [95 % CI 1.62-5.63] for density ≥50 % vs. <10 %, p-heterogeneity = 0.17) and appeared to be stronger in postmenopausal women currently using hormones compared with postmenopausal women who never used PMH (OR = 4.50 [95 % CI 2.99-6.78] vs. 3.02, p-heterogeneity = 0.20) or with past hormone use (OR = 4.50 vs. 3.71 [95 % CI 1.90-7.23], p-heterogeneity = 0.23). Findings on associations by menopausal status/hormone use are suggestive and should be examined in additional larger studies.


Dairy Consumption at Snack Meal Occasions and the Overall Quality of Diet during Childhood. Prospective and Cross-Sectional Analyses from the IDEFICS/I.Family Cohort.
There is scarce information on the influence of dairy consumption between main meals on the overall diet quality through childhood, constituting the main aim of this research. From the Identification and prevention of Dietary- and lifestyle induced health EFfects In Children and infantS (IDEFICS) study, and based on the data availability in each period due to drop outs, 8807 children aged 2 to 9.9 years from eight European countries at baseline (T0: 2007-2008); 5085 children after two years (T1); and 1991 after four years (T3), were included in these analyses. Dietary intake and the Diet Quality Index (DQI) were assessed by two 24 hours dietary recalls (24-HDR) and food frequency questionnaire. Consumption of milk and yogurt (p = 0.04) and cheese (p < 0.001) at snack meal occasions was associated with higher DQI scores in T0; milk and yogurt (p < 0.001), and cheese (p < 0.001) in T1; and cheese (p = 0.05) in T3. Consumers of milk (p = 0.02), yogurt (p < 0.001), or cheese (p < 0.001) throughout T0 and T1 at all snack moments had significantly higher scores of DQI compared to non-consumers. This was also observed with the consumption of cheese between T1 and T3 (p = 0.03). Consumption of dairy products at snack moments through childhood is associated with a better overall diet quality, being a good strategy to improve it in this period.


Expression of adenylyl cyclase isoforms in neutrophils.
In the present study, we have identified the expression of adenylyl cyclase (AC) isoforms in rat neutrophils according to the mRNA analysis and the distinct mode of regulation of isoform activity. Agarose gel electrophoresis of reverse transcription-polymerase chain reaction (RT-PCR)-amplified products resulted in a single band of the expected size for each product with nucleotide sequences corresponding to AC1 to AC9. AC1 was abundant, while AC2, 6 and 9 were of moderate expression among the AC isoforms in neutrophils based on the quantitative real-time RT-PCR analysis. Exposure of neutrophils to Ca(2+) ionophore A23187, isoproterenol and forskolin stimulated cellular cyclic AMP accumulation. EDTA and the calmodulin (CaM) antagonist, trifluoperazine, prevented the A23187-induced response. Pretreatment with pertussis toxin (PTX) inhibited the alpha(2)-adrenergic agonist, UK14304-induced cellular cyclic AMP elevation. In addition, UK14304 augmented the cyclic AMP elevation when cells were stimulated by isoproterenol. Phorbol 12-myristate 13-acetate (PMA) attenuated the augmentation response of UK14304 and isoproterenol. Treatment of the membrane preparations from rat neutrophils with Ca(2+)/CaM, forskolin, isoproterenol, GTPgammaS or Gbetagamma all increased cyclic AMP production. The addition of protein kinase C (PKC) catalytic fragment and Gbetagamma augmented the Ca(2+)/CaM- and isoproterenol-stimulated AC activity, respectively. However, forskolin and the activated protein kinase A (PKA) attenuated the GTPgammaS- and isoproterenol-stimulated AC activity, respectively. KT5720, a PKA inhibitor, reversed the inhibition by PKA. Taken together, these data suggest the presence of four groups of AC isoforms in rat neutrophils.


Hepatocyte nuclear factor 4alpha is a central regulator of bile acid conjugation.
Hepatocyte nuclear factor 4alpha (HNF4alpha) has an important role in regulating the expression of liver-specific genes. Because bile acids are produced from cholesterol in liver and many enzymes involved in their biosynthesis are preferentially expressed in liver, the role of HNF4alpha in the regulation of bile acid production was examined. In mice, unconjugated bile acids are conjugated with taurine by the liver-specific enzymes, bile acid-CoA ligase and bile acid-CoA:amino acid N-acyltransferase (BAT). Mice lacking hepatic HNF4alpha expression exhibited markedly decreased expression of the very long chain acyl-CoA synthase-related gene (VLACSR), a mouse candidate for bile acid-CoA ligase, and BAT. This was associated with markedly elevated levels of unconjugated and glycine-conjugated bile acids in gallbladder. HNF4alpha was found to bind directly to the mouse VLACSR and BAT gene promoters, and the promoter activities were dependent on HNF4alpha-binding sites and HNF4alpha expression. In conclusion, HNF4alpha plays a central role in bile acid conjugation by direct regulation of VLACSR and BAT in vivo.


Circadian rhythms in a nutshell.
Living organisms on this planet have adapted to the daily rotation of the earth on its axis. By means of endogenous circadian clocks that can be synchronized to the daily and seasonal changes in external time cues, most notably light and temperature, life forms anticipate environmental transitions, perform activities at biologically advantageous times during the day, and undergo characteristic seasonal responses. The effects of transmeridian flight and shift work are stark reminders that although modern technologies can create "cities that never sleep" we cannot escape the recalcitrance of endogenous clocks that regulate much of our physiology and behavior. Moreover, malfunctions in the human circadian timing system are implicated in several disorders, including chronic sleep disorders in the elderly, manic-depression, and seasonal affective disorders (SAD or winter depression). Recent progress in understanding the molecular mechanisms underlying circadian rhythms has been remarkable. In its most basic form, circadian clocks are comprised of a set of proteins that, by virtue of the design principles involved, generate a self-sustaining transcriptional-translational feedback loop with a free-running period of about 24 h. One or more of the clock components is acutely sensitive to light, resulting in an oscillator that can be synchronized to local time. This review provides an overview of the roles circadian clocks play in nature, how they might have arisen, human health concerns related to clock dysfunction, and mainly focuses on the clockworks found in Drosophila and mice, the two best studied animal model systems for understanding the biochemical and cellular bases of circadian rhythms.


Efficacy and Safety of Pembrolizumab for Heavily Pretreated Patients With Advanced, Metastatic Adenocarcinoma or Squamous Cell Carcinoma of the Esophagus: The Phase 2 KEYNOTE-180 Study.
Effective treatment options are limited for patients with advanced, metastatic esophageal cancer progressing after 2 or more lines of systemic therapy. To evaluate the efficacy and safety of pembrolizumab for patients with advanced, metastatic esophageal squamous cell carcinoma (ESCC) or advanced, metastatic adenocarcinoma of the esophagus and gastroesophageal junction that progressed after 2 or more lines of systemic therapy. This phase 2, open-label, interventional, single-arm study, KEYNOTE-180, enrolled 121 patients from January 12, 2016, to March 21, 2017, from 57 sites in 10 countries. Patients had advanced, metastatic esophageal cancer that progressed after 2 or more lines of therapy and had evaluable tumor samples for biomarkers. Pembrolizumab, 200 mg, was administered intravenously every 3 weeks until disease progression, unacceptable toxic effects, or study withdrawal, for up to 2 years. Primary end point was objective response rate per the Response Evaluation Criteria in Solid Tumors by central imaging review for all patients. As of September 18, 2017, of 121 enrolled patients (100 men and 21 women; median age, 65 years [range, 33-87 years]), 18 (14.9%) had undergone 3 or more prior therapies, 63 (52.1%) had ESCC, and 58 (47.9%) had tumors positive for programmed death ligand-1 (PD-L1), defined as a combined positive score of 10 or higher assessed by immunohistochemistry. Median duration of follow-up was 5.8 months (range, 0.2-18.3 months). Objective response rate was 9.9% (95% CI, 5.2%-16.7%) among all patients (12 of 121), and median duration of response was not reached (range, 1.9-14.4 months). Objective response rate was 14.3% (95% CI, 6.7%-25.4%) among patients with ESCC (9 of 63), 5.2% (95% CI, 1.1%-14.4%) among patients with adenocarcinoma (3 of 58), 13.8% (95% CI, 6.1%-25.4%) among patients with PD-L1-positive tumors (8 of 58), and 6.3% (95% CI, 1.8%-15.5%) among patients with PD-L1-negative tumors (4 of 63). Overall, 15 patients (12.4%) had treatment-related grade 3 to 5 adverse events. Only 5 patients (4.1%) discontinued treatment because of adverse events. There was 1 treatment-related death from pneumonitis. Where effective treatment options are an unmet need, pembrolizumab provided durable antitumor activity with manageable safety in patients with heavily pretreated esophageal cancer. Phase 3 studies evaluating pembrolizumab vs standard therapy for patients with esophageal cancer progressing after first-line therapy or in combination with chemotherapy as first-line therapy for patients with locally advanced unresectable or metastatic esophageal cancer are ongoing. ClinicalTrials.gov identifier: NCT02559687.


Spider Chitin: An Ultrafast Microwave-Assisted Method for Chitin Isolation from Caribena versicolor Spider Molt Cuticle.
Chitin, as a fundamental polysaccharide in invertebrate skeletons, continues to be actively investigated, especially with respect to new sources and the development of effective methods for its extraction. Recent attention has been focused on marine crustaceans and sponges; however, the potential of spiders (order Araneae) as an alternative source of tubular chitin has been overlooked. In this work, we focused our attention on chitin from up to 12 cm-large Theraphosidae spiders, popularly known as tarantulas or bird-eating spiders. These organisms "lose" large quantities of cuticles during their molting cycle. Here, we present for the first time a highly effective method for the isolation of chitin from Caribena versicolor spider molt cuticle, as well as its identification and characterization using modern analytical methods. We suggest that the tube-like molt cuticle of this spider can serve as a naturally prefabricated and renewable source of tubular chitin with high potential for application in technology and biomedicine.


Optimization of functional MRI for detection, decoding and high-resolution imaging of the response patterns of cortical columns.
The capacity of functional MRI (fMRI) to resolve cortical columns depends on several factors. These include the spatial scale of the columnar pattern, the point-spread of the fMRI response, the voxel size, and the signal-to-noise ratio (SNR) considering thermal and physiological noise. However, it remains unknown how these factors combine, and what is the voxel size that optimizes fMRI of cortical columns. Here we combine current knowledge into a quantitative model of fMRI of realistic patterns of cortical columns with different spatial scales and degrees of irregularity. We compare different approaches for identifying patterns of cortical columns, including univariate and multivariate based detection, multi-voxel pattern analysis (MVPA) based decoding, and high-resolution imaging and reconstruction of the pattern of cortical columns. We present the dependence of the performance of each approach on the parameters of the imaged pattern as well as those of the data acquisition. In addition, we predict voxel sizes that optimize fMRI of cortical columns under various scenarios. We found that all measures associated with multivariate detection and decoding could be approximately calculated from a measure we termed "multivariate contrast-to-noise ratio" (mv-CNR), which is a function of the contrast-to-noise ratio (CNR) and number of voxels. Furthermore, mv-CNR implied that the optimal voxel width for detection and decoding is independent of changes in response amplitude, SNR and imaged volume that are not caused by changes in voxel size. For regular patterns, optimal voxel widths for detection, decoding and imaging/reconstructing the pattern of cortical columns were approximately half the main cycle length of the organization. Optimal voxel widths for irregular patterns were less dependent on the main cycle length, and differed between univariate detection, multivariate detection and decoding, and reconstruction. We compared the effects of different factors of Gradient Echo fMRI at 3 Tesla (T), Gradient Echo fMRI at 7T, and Spin-Echo fMRI at 7T on the detection, decoding, and reconstruction measures considered and found that in all cases the width of the fMRI point-spread had the most significant effect. In contrast, different response amplitudes and noise characteristics played a relatively minor role. We recommend specific voxel widths for optimal univariate detection, for multivariate detection and decoding, and for high-resolution imaging of cortical columns under these three data-acquisition scenarios. Our study supports the planning, optimization, and interpretation of high-resolution fMRI of cortical columns and the decoding of information conveyed by these columns.


Clinical applications of cardiovascular angiogenesis.
Angiogenesis is fundamental to both normal physiologic (wound healing) and pathologic (cancer) processes. Manipulation of divergent angiogenic signals promises effective therapy of atherosclerotic cardiovascular disease. Positive proangiogenic strategies promise collateral circulation to ischemic territories, while negative antiangiogenic strategies starve the fibromuscular proliferation within the atherosclerotic lesion. Indeed, recent phase 1 trials suggest that delivering DNA or recombinant protein to the site of vascular occlusion may stimulate physiologically significant collateral circulation in chronically ischemic myocardium. While symptomatic and functional improvement has been documented, toxicity profiles and effects on long-term patient survival are still unclear. The purposes of this article are as follows: (1) to review the pathophysiologic basis for pro- and antiangiogenic strategies in the treatment of cardiovascular disease, (2) to examine the clinical trials of proangiogenic gene or recombinant protein delivery into ischemic beds, and conversely, (3) to explore antiangiogenic strategies in the prevention and treatment of intimal neovascularization and smooth muscle proliferation within the vessel wall.


Defect-Induced Band-Edge Reconstruction of a Bismuth-Halide Double Perovskite for Visible-Light Absorption.
Halide double perovskites have recently been developed as less toxic analogs of the lead perovskite solar-cell absorbers APbX3 (A = monovalent cation; X = Br or I). However, all known halide double perovskites have large bandgaps that afford weak visible-light absorption. The first halide double perovskite evaluated as an absorber, Cs2AgBiBr6 (1), has a bandgap of 1.95 eV. Here, we show that dilute alloying decreases 1's bandgap by ca. 0.5 eV. Importantly, time-resolved photoconductivity measurements reveal long-lived carriers with microsecond lifetimes in the alloyed material, which is very promising for photovoltaic applications. The alloyed perovskite described herein is the first double perovskite to show comparable bandgap energy and carrier lifetime to those of (CH3NH3)PbI3. By describing how energy- and symmetry-matched impurity orbitals, at low concentrations, dramatically alter 1's band edges, we open a potential pathway for the large and diverse family of halide double perovskites to compete with APbX3 absorbers.


Positive effects of a physiological dose of GH on markers of atherogenesis: a placebo-controlled study in patients with adult-onset GH deficiency.
GH deficiency is associated with an increased cardiovascular mortality. Fifty-five patients with adult-onset GH deficiency (AO-GHD) (24 female, 31 male, mean age 49 years) were enrolled in a placebo-controlled double-blind crossover study to investigate the effects of GH therapy on a variety of cardiovascular risk factors representing different aspects of atherogenesis, including apolipo-proteins (Apo A-1, Apo B), markers of subclinical inflammation (high-sensitivity C-reactive protein (CRP) and interleukin-6) and markers of endothelial function (intercellular adhesion molecule-1, von Willebrand factor and sCD40L (a pro-atherogenic factor and marker for plaque destabilization)). GH therapy was individually dosed to obtain an IGF-I concentration within the normal range for age and sex. GH and placebo were administered for 9 months each, separated by a 4 month washout period. The final mean dose of GH was 50% higher for women and IGF-I increased to the same level in both sexes. Compared with placebo, substitution with GH showed a significant effect on Apo B (mean change -0.15 (-0.22 to -0.08) mg/l) and CRP (-1.8 (-3.3 to -0.3) mg/l). The baseline level of and change in IGF-I during treatment with GH contributed significantly to the improvement in both markers. No effects were found on interleukin-6 or Apo A-1, or on markers of endothelial function. No gender differences were observed for any of the markers at baseline or following intervention. GH substitution to naïve patients with AO-GHD at a low, individually titrated dose aiming at normalizing IGF-I was followed by significant reductions in Apo B and CRP, indicating a positive effect of GH on cardiovascular risk.


Surgical repair for macrostomia: significance of Z-plasty limb directions.
The objective of this study was to determine whether the direction of Z-plasty limbs incorporated into the surgical repair for macrostomia had a significant influence on the quality of the resultant scar. A total of 41 patients who underwent macrostomia repair by means of the same technique, and who had a follow up period of at least 2 years, were retrospectively reviewed through postoperative photographs and medical records. Quality of scar, lip symmetry, and commissure shape and thickness were recorded. Our results showed that a more favorable scar would be achieved in the medial limb of the Z-plasty if it was planned parallel to relaxed skin tension lines (P < 0.05). An unfavorable scar would be more likely if the medial limb of the Z-plasty was made in a horizontal direction or perpendicular to relaxed skin tension lines (P < 0.05). The quality of scar in both the central and lateral limbs of the Z-plasty was not significantly influenced by their direction.


Opt-out testing for human immunodeficiency virus in the United States: progress and challenges.
The Centers for Disease Control and Prevention (CDC) has recommended human immunodeficiency virus (HIV) testing for all persons aged 13 to 64 years in all health care settings. Signed consent would not be required and counseling with referral would be managed as it is for other serious conditions. The goal of the recommendations is to promote earlier entry into care to reduce unnecessary mortality and facilitate prevention by behavioral changes that accompany knowledge of serostatus. Concerns about the change include laws in some states that mandate signed consent and counseling, a perception that counseling is an effective prevention strategy, variability in payment coverage for the test, concerns about the stigma and discrimination that may accompany the HIV diagnosis, and the possibility that other testing policies would be more effective. Eleven of 16 states have changed legislation to reduce barriers to testing, 35 of 74 national professional societies have endorsed the new recommendations, and multiple demonstration projects have shown feasibility. Metrics to evaluate the health outcomes of the CDC's recommendations for HIV testing have been defined, but the data necessary to determine the effects on early entry into care, the actual reduction in disease incidence, and the unanticipated consequences are not yet available.


Impact of a Brief Group Intervention to Enhance Parenting and the Home Learning Environment for Children Aged 6-36 Months: a Cluster Randomised Controlled Trial.
This study evaluated the effectiveness of a group parenting intervention designed to strengthen the home learning environment of children from disadvantaged families. Two cluster randomised controlled superiority trials were conducted in parallel and delivered within existing services: a 6-week parenting group (51 locations randomised; 986 parents) for parents of infants (aged 6-12 months), and a 10-week facilitated playgroup (58 locations randomised; 1200 parents) for parents of toddlers (aged 12-36 months). Each trial had three conditions: intervention (smalltalk group-only); enhanced intervention with home coaching (smalltalk plus); and 'standard'/usual practice controls. Parent-report and observational measures were collected at baseline, 12 and 32 weeks follow-up. Primary outcomes were parent verbal responsivity and home learning activities at 32 weeks. In the infant trial, there were no differences by trial arm for the primary outcomes at 32 weeks. In the toddler trial at 32-weeks, participants in the smalltalk group-only trial showed improvement compared to the standard program for parent verbal responsivity (effect size (ES) = 0.16; 95% CI 0.01, 0.36) and home learning activities (ES = 0.17; 95% CI 0.01, 0.38) but smalltalk plus did not. For the secondary outcomes in the infant trial, several initial differences favouring smalltalk plus were evident at 12 weeks, but not maintained to 32 weeks. For the toddler trial, differences in secondary outcomes favouring smalltalk plus were evident at 12 weeks and maintained to 32 weeks. These trials provide some evidence of the benefits of a parenting intervention focused on the home learning environment for parents of toddlers but not infants. 8 September 2011; ACTRN12611000965909 .


The Role of Ultrasound in Epicutaneo-Caval Catheter Insertion in Neonates: Systematic Review, Meta-Analysis and Future Perspectives.
Chest and abdominal X-rays after the insertion of an epicutaneo-caval catheter in infants are the standard method of checking the tip location in many neonatal intensive care units. The role of ultrasound in the tip location of the epicutaneo-caval catheter in neonates has been the subject of many recent studies. This systematic review investigates the accuracy of epicutaneo-caval catheter tip location by comparing ultrasound and conventional radiology. We performed a systematic literature search in multiple databases. The selection of studies yielded nineteen articles. The systematic review and meta-analysis were performed according to PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analysis). The analyses showed that ultrasound is a better imaging technique for epicutaneo-caval catheter tip location in the neonatal intensive care unit than conventional radiology. By improving operator training and selecting a standardized echography protocol, ultrasound could become the gold standard for visualizing the epicutaneo-caval catheter tip in the neonatal intensive care unit. This would have some important benefits: (1) increased accuracy in tip location (2); a more rapid use of the central venous access (3); and a significant reduction in radiation exposure.


Frontotemporal dementia and parkinsonism linked to chromosome 17: a consensus conference. Conference Participants.
We held an international consensus conference on frontotemporal dementia, behavioral disturbances, and parkinsonism linked to chromosome 17 to determine whether these are homogeneous or heterogeneous disorders, to agree on terminology, and to develop strategies for further research. The group identified 13 kindreds with sufficient evidence for linkage, finding in common to all a critical 2 cM between markers D17S791 and D17S800. There was agreement that (1) despite previous descriptions that have emphasized one or another clinical or neuropathological feature, the kindreds share clinical and neuropathological features; (2) until more specific information about the genetic defects becomes available, this disorder is best termed frontotemporal dementia and parkinsonism linked to chromosome 17; and (3) further research will be enhanced by identifying the gene or genes responsible for this disorder, detecting additional cases within known families and, in new families, correlating mutations with phenotypes and more fully delineating the clinical, neuropsychological, and neuropathological characteristics of this disorder.


Activation of neural and pluripotent stem cell signatures correlates with increased malignancy in human glioma.
The presence of stem cell characteristics in glioma cells raises the possibility that mechanisms promoting the maintenance and self-renewal of tissue specific stem cells have a similar function in tumor cells. Here we characterized human gliomas of various malignancy grades for the expression of stem cell regulatory proteins. We show that cells in high grade glioma co-express an array of markers defining neural stem cells (NSCs) and that these proteins can fulfill similar functions in tumor cells as in NSCs. However, in contrast to NSCs glioma cells co-express neural proteins together with pluripotent stem cell markers, including the transcription factors Oct4, Sox2, Nanog and Klf4. In line with this finding, in high grade gliomas mesodermal- and endodermal-specific transcription factors were detected together with neural proteins, a combination of lineage markers not normally present in the central nervous system. Persistent presence of pluripotent stem cell traits could only be detected in solid tumors, and observations based on in vitro studies and xenograft transplantations in mice imply that this presence is dependent on the combined activity of intrinsic and extrinsic regulatory cues. Together these results demonstrate a general deregulated expression of neural and pluripotent stem cell traits in malignant human gliomas, and indicate that stem cell regulatory factors may provide significant targets for therapeutic strategies.


[Idiopathic pulmonary fibrosis: new insights].
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease of unknown cause. IPF has a poor prognosis with a mean survival of 2 to 5 years after diagnosis. The diagnostic process is often complex and demands a multidisciplinary approach. To date, the only curative therapy available is lung transplant. New insights into the pathogenesis of IPF have brought about changes in standard treatment strategies. New drugs have recently become available and have been shown to slow down the decline in pulmonary function considerably and improve survival.


Light-responsive paper strips as CO-releasing material with a colourimetric response.
Carbon monoxide (CO) is known for its multifaceted role in human physiology, and molecules that release CO in a controlled way have been proposed as therapeutic drugs. In this work, a light-responsive CO-releasing molecule (CORM-Dabsyl) showed a strong colourimetric response upon photochemical CO-release, owing to the tight conjugation of a Mn(i) tricarbonyl centre to a dabsyl chromophoric ligand (L). Whereas the complex was very stable in the dark in nitrogen-purged aqueous media, CO-release was effectively triggered using 405 nm irradiation. CORM-Dabsyl, L and the inactive product iCORM-Dabsyl have been investigated by DFT and TD-DFT calculations. Only mild toxicity of CORM-Dabsyl was observed against LX-2 and HepaRG® human cell lines (IC50 ∼ 30 μM). Finally, to develop a CO storage and release material that is readily applicable to therapeutic situations, CORM-Dabsyl was loaded on low-cost and easily disposable paper strips, from which the light triggered CO-release was conveniently visible with the naked eye.


Assessment of the aortic tunica media histological changes in relation with the cause of death.
The authors set out to evaluate the correlations between three of the main morphological aortic parameters (elastic fibers - FE, collagen fibers - FCOL, and smooth muscle fibers - FM) and the cause of death. Study groups included 25 cases died of a vascular disease (V_P), 37 cases died of a non-vascular disease (NV_P) and 28 cases died of a violent/suspect non-pathological cause of death (V_Dth), the latter group representing also the control group. Four aortic cross-sections (base, arch, thoracic, and abdominal regions) were collected during autopsy from the selected cases, fixed in 10% buffered formalin and first of all photographed together with a calibrating ruler. Then, they were embedded in paraffin, sectioned off at 4 μm and stained with Hematoxylin-Eosin (HE) and Orcein. The obtained histological slides were transformed into virtual slides. Fibrillary components amounts were using a custom-made software, developed in MATLAB (MathWorks, USA). Statistical tools used were Pearson's correlation test, t-test (two-sample assuming equal variances) and one-way analysis of variance (ANOVA) test. The amounts of the three fibrillary components of the aortic tunica media had a synchronous variation in all aortic regions in each of the three groups, excepting FCOL in the group of patients died from vascular pathology, which presented only a trend of synchronous variation along the aorta. FE had their lowest values and FCOL had their highest values in patients died from vascular pathology. FCOL had always higher levels than FE in people died from any pathological condition, vascular or non-vascular. FM had always at least two times lower level than that of the other types of fibers, regardless of whether the person died due to a pathological condition or not. The different pathological conditions causing death are influencing the fibrillary composition of aortic tunica media. Further studies are required to reveal other changes in the morphology of aortic wall in particular and vascular wall in general that could be related with different pathological conditions affecting the entire organism.


Diversity of esterase and lipase producing haloalkaliphilic bacteria from Lake Magadi in Kenya.
Lipids are hydrocarbons comprised of long-chain fatty acids and are found in all living things. In the environment, microorganisms degrade them to obtain energy using esterases and lipases. These enzymes are nowadays used in different industrial applications. We report isolation of 24 bacteria with esteresic and lipolytic activity from Lake Magadi, Kenya. The isolates were characterised using morphological, biochemical, and molecular methods. Isolates grew at an optimum salt concentration of 5-8% (w/v), pH range of 8.0-9.0, and temperature range of 35-40°C. The isolates were positive for esterase and lipase assay as well as other extracellular enzymes. Phylogenetic analysis of the 16S ribosomal RNA gene showed that the isolates were affiliated to the genus Bacillus, Alkalibacterium, Staphylococcus, Micrococcus, Halomonas, and Alkalilimnicola. None of the bacterial isolates produced antimicrobial agents, and all of them were resistant to trimethoprim and nalidixic acid but susceptible to streptomycin, amoxillin, chloramphenicol, and cefotaxime. Growth at elevated pH, salt, and temperature is an indicator that the enzymes from these organisms could function well under haloalkaline conditions. Therefore, Lake Magadi could be a good source of isolates with the potential to produce unique biocatalysts for the biotechnology industry.


Electroacupuncture Enhances Number of Mature Oocytes and Fertility Rates for In Vitro Fertilization.
Objective: The increasing prevalence of infertility every year is in line with the increasing need for in vitro fertilization (IVF) programs. Failure of oocyte maturation is an obstacle that often causes low success in IVF. According to several studies, controlled ovarian stimulation (COS) has been reported to increase the risk of granulosa-cell apoptosis associated with inhibition of oocyte maturation. This study was conducted to determine the effect of electroacupuncture (EA) on oocyte maturation; rate of fertilization; granulosa-cell apoptosis; and levels of growth-differentiation factor 9 (GDF9) and bone-morphogenetic protein 15 (BMP15) an IVF program. Materials and Methods: A randomized controlled trial was conducted with 24 subjects who were in the IVF program. Subjects were randomly allocated into verum-EA (n = 12) and sham-EA groups (n = 12). Microscopic assessment of oocyte maturation and rate of fertilization was performed by embryologists, and examinations of granulosa-cell apoptosis index (Bax/Bcl-2 ratio), GDF9, and BMP15 were performed, using real-time quantitative polymerase chain reaction and messenger-RNA techniques. Results: There were significant differences in oocyte maturation (P = 0.02) and fertilization rates (P = 0.03) between the verum-EA and sham-EA groups. There were differences in granulosa-cell apoptosis index between the verum-EA and sham-EA groups (P < 0.001). There were significant differences in Bax-protein expression (P = 0.04) and Bcl-2 (P = 0.03) granulosa cells between the verum-EA and sham-EA groups. There was no significant difference in GDF9 levels (P = 0.34) and BMP15 (p = 0.47) between the verum-EA and sham-EA groups. Conclusions: EA can enhance oocyte maturation and fertilization rate, and reduce the granulosa-cell apoptosis index in an IVF program.


Effects of indocyanine green injection on the retinal surface and into the subretinal space in rabbits.
To evaluate the effects of indocyanine green (ICG) injection on the retinal surface and into the subretinal space of rabbit eyes. Twenty-two Dutch-belted rabbits underwent two-port vitrectomy followed by injection of ICG (5 mg/mL) on the retinal surface and into the subretinal space. Balanced salt solution (BSS) was also injected subretinally. The locations where ICG was delivered (both epiretinal and subretinal) were exposed to light from an endoilluminator for 7 minutes. The animals were examined at 1, 7, and 14 days after surgery. The eyes were studied by fluorescein angiography as well as light and electron microscopy. No damage was observed after epiretinal ICG injection, but subretinal ICG injection resulted in damage to the outer nuclear layer, photoreceptor inner and outer segments, and retinal pigment epithelium. This damage was more severe with longer follow-up. Control experiments without ICG, in which balanced salt solution was injected into the subretinal space or light was delivered on the epiretinal surface, demonstrated only damage to the photoreceptor outer segments. Subretinal delivery of ICG (5 mg/mL) in rabbits induces retinal pigment epithelium, photoreceptor inner and outer segment, and outer nuclear layer damage. These mechanisms of damage may explain the retinal pigment epithelium changes that are sometimes seen after ICG-assisted internal limiting membrane peeling in humans.


Extremity exposure in nuclear medicine: preliminary results of a European study.
The Work Package 4 of the ORAMED project, a collaborative project (2008-11) supported by the European Commission within its seventh Framework Programme, is concerned with the optimisation of the extremity dosimetry of medical staff in nuclear medicine. To evaluate the extremity doses and dose distributions across the hands of medical staff working in nuclear medicine departments, an extensive measurement programme has been started in 32 nuclear medicine departments in Europe. This was done using a standard protocol recording all relevant information for radiation exposure, i.e. radiation protection devices and tools. This study shows the preliminary results obtained for this measurement campaign. For diagnostic purposes, the two most-used radionuclides were considered: (99m)Tc and (18)F. For therapeutic treatments, Zevalin(®) and DOTATOC (both labelled with (90)Y) were chosen. Large variations of doses were observed across the hands depending on different parameters. Furthermore, this study highlights the importance of the positioning of the extremity dosemeter for a correct estimate of the maximum skin doses.


Ultrastructure of chondrocytes in osteoarthritic femoral articular cartilage.
Osteoarthritis (OA) is a common problem in elderly, but it is not an inevitable feature of ageing. About 80-90% of individuals of both sexes have radiographic evidence of OA by the time they reach an age of 65. But not all of them have the symptoms like pain and decreased joint motion. The objective of the present study was conducted to find out whether the osteoarthritic changes in human articular cartilage are similar to the ageing process or not. Femoral articular cartilage specimens obtained from 13 osteoarthritic patients (52-80 years) undergoing total knee replacement and 9 cadavers of same age group (50-80 years) (control) were processed and studied under electron microscope. The ultrastructure of the cartilage from the two groups was compared with each other. Under the electron microscope, articular cartilage from control group had chondrocytes having a secretary cell characteristic with prominent nucleus and well developed organelles. In osteoarthritic cartilage, degenerating or necrotic chondrocytes were found. Nuclei of these chondrocytes appeared lobulated or indented. Chondrocytes below the fibrillated surface had dilated and irregular endoplasmic reticulum. Electron dense lipid deposits in the extracellular matrix as well as intracytoplasmic glycogen deposits were much increased in osteoarthritic cartilage as compared to the control group. Amount of perinuclear intracytoplasmic fine filaments was also increased in the chondrocytes of osteoarthritic cartilage. Ultrastructural findings of the osteoarthritic articular cartilage were much different from the ageing non-osteoarthritic cartilage. Hence, OA should be considered a specific process and not simply an inevitable feature of ageing.


Impact of sarcopenia on outcomes in surgical patients:A systematic review and meta-analysis.
Surgeons have historically used age as a preoperative predictor of postoperative outcomes. Sarcopenia, the loss of skeletal muscle mass due to disease or biological age, has been proposed as a more accurate risk predictor. The prognostic value of sarcopenia assessment in surgical patients remains poorly understood. Therefore, we aimed to synthesize the available literature and investigate the impact of sarcopenia on peri- and postoperative outcomes across all surgical specialties. We systematically assessed the prognostic value of sarcopenia on postoperative outcomes by conducting a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching the PubMed/MEDLINE and EMBASE databases from inception to 1st October 2022. Our primary outcomes were complication occurrence, mortality, length of operation and hospital stay, discharge to home, and postdischarge survival rate at one, three, and five years. Subgroup analysis was performed by stratifying complications according to the Clavien-Dindo classification system. Sensitivity analysis was performed by focusing on studies with an oncological, cardiovascular, emergency, or transplant surgery population, and on those of higher quality or prospective study design. A total of 294 studies comprising 97,643 patients, of which 33,070 had sarcopenia, were included in our analysis. Sarcopenia was associated with significantly poorer postoperative outcomes including greater mortality, complication occurrence, length of hospital stay, and lower rates of discharge to home (all P<0.00001). A significantly lower survival rate in patients with sarcopenia was noted at one, three, and five years (all P<0.00001) after surgery. Subgroup analysis confirmed higher rates of complications and mortality in oncological (both P<0.00001), cardiovascular (both P<0.00001), and emergency (P=0.03 and P=0.04, respectively) patients with sarcopenia. In the transplant surgery cohort, mortality was significantly higher in patients with sarcopenia (P<0.00001). Among all patients undergoing surgery for inflammatory bowel disease, the frequency of complications was significantly increased among sarcopenic patients (P=0.007). Sensitivity analysis based on higher-quality studies and prospective studies showed that sarcopenia remained a significant predictor of mortality and complication occurrence (all P<0.00001). Sarcopenia is a significant predictor of poorer outcomes in surgical patients. Preoperative assessment of sarcopenia can help surgeons to identify patients at risk, critically balance eligibility, and refine perioperative management. Large-scale studies are required to further validate the importance of sarcopenia as a prognostic indicator of perioperative risk, especially in surgical sub-specialties.