Land floras: the major late phanerozoic atmospheric carbon dioxide/oxygen control.
Since at least the late Mesozoic, the abundance of terrestrial vegetation has been the major factor in atmospheric carbon dioxideloxygen fluctuations. Of modern ecosystem types occupying more than 1 percent of the earth's surface, productivity/area ratios of terrestrial ecosystems (excepting tundra and alpine meadow, desert scrub, and rock, ice, and sand) exceed those of marine ecosystems and probably have done so for much of late Phanerozoic time. Reduction of terrestrial ecosystems during marine transgression would decrease the world primary productivity, thus increasing the atmospheric carbon dioxide concentration and decreasing the oxygen concentration. Regression would produce opposite effects.


[Common action of limiting and inhibiting factors on the growth of yeasts in a continuous culture].
Candida utilis was cultivated under conditions of chemostat and continuous growth which was limited by phosphates. An excess of glucose inhibited the growth. The limiting and inhibiting factors produced simultaneous cooperative action. At a constant velocity of the medium flow, the concentration of biomass decreased, as a result of the inhibition of growth with residual glucose (0.96 and 1.36 per cent), by 5.5 and 15.6 per cent of the absolute value, respectively. The economic coefficient decreased in this case from 40 to 28 per cent. The inhibition of yeast growth resulted also in a decrease of phosphorus content in the cells; moreover, the cells could not utilize all oxygen dissolved in the medium.


Methods for tracing, contacting, and recruiting a cohort of survivors of childhood cancer.
Due to the use of combined modalities of multiagent chemotherapy, radiation therapy, and surgery, many children with a diagnosis of cancer are now surviving into adulthood. This pilot study sought to determine the feasibility of establishing a cohort of childhood cancer survivors and then to develop methods to trace and contact eligible participants. A retrospective cohort design was used. Four hundred and forty subjects who were treated for cancer at the University of Minnesota Hospital before the age of 21, between 1970 and 1986, had survived 5 years, and were alive at last contact were eligible. Tracing efforts were undertaken if the address was more than 2 years old or if a letter was returned by the post office. Contact procedures in this study were designed to determine whether participation rates differed according to the method of contact. In this cohort of 440 individuals, 11 had died and were not traced. Of the remaining 429 eligible individuals, 408 (95.1%) were successfully contacted. Successful tracing efforts differed by both current age and age at diagnosis. Once contacted, 370 (90.6%) agreed to participate in this study and returned a baseline health questionnaire. Each method of participation, and the combination of methods, showed similar percentages of participation. Results from this pilot study show that appropriate methods exist to establish a cohort of adults who have not been contacted since childhood.


Potential diagnostic value of P16 expression in premalignant and malignant cervical lesions.
The goal of this study was to evaluate the results of the expression of p16INK4a in normal uterine cervical epithelium, low-grade cervical intraepithelial neoplasia (CIN), high-grade CIN, squamous cell carcinoma (SCC), and adenocarcinoma of the cervix, in order to help draw a distinction between low risk and high risk patients with cervical lesions. [corrected] P16INK4a expression was evaluated by immunohistochemistry in 78 paraffin-embedded tissue samples including 39 normal cervical tissues, 11 low-grade CINs, 11 high-grade CINs, 22 cervical SCCs and 8 cervical adenocarcinomas. Two parameters in immunohistochemical p16 expression were evaluated: percentage of p16-positive cells, and reaction intensity. The p16INK4a expression rate was 81.8% in low-grade CINs, 91% in high-grade CINs, 90% in SCCs and 75% in cervical adenocarcinomas. 10% of normal cervical samples expressed p16. Moreover, there was a significant relationship between the histological diagnoses and percentage of positive cells and reaction intensity of p16 (p < 0.005). The intensity of the reaction was the best parameter to evaluate the positivity of p16. Over-expression of the p16INK4a was typical for dysplastic and neoplastic epithelia of the uterine cervix. However, p16INK4a-negative CINs and carcinomas did exist. Although negative p16INK4a expression does not definitely exclude the patient with cervical lesion from the high-risk group, immunohistochemical study for p16INK4a may be used as a supplementary test for an early diagnosis of cervical cancers.


Effect of substitution of distillers grains and glycerin for steam-flaked corn in finishing cattle diets on growth performance and carcass characteristics.
An experiment was conducted to determine the effect of substituting modified corn distillers grains with solubles (DGS) or crude soy glycerin (CG) for steam-flaked corn (SFC) in finishing diets on growth performance and carcass characteristics. Treatments were arranged as a 2 × 2 factorial with DGS (0% or 40%) and CG (0% or 10%) replacing dietary SFC in a basal diet. Growth performance and carcass traits were measured on 48 individually fed crossbred yearling cattle (21 steers and 27 heifers; 380 ± 37 kg). Cattle were randomly allotted to 48 Calan gate bunks. After the first 28 days, nine animals were removed from the study for health reasons or observed confirmation of consumption of feed from unassigned Calan gate bunk (n = 39). After the feeding period, cattle were harvested in two groups on day-124 and day-173. No DGS × CG interactions were observed (P > 0.10) for any dependent growth performance or carcass characteristic variable tested. Cattle-fed DGS as 40% of diet dry matter (DM) had greater (P< 0.01) dry matter intake (DMI), while CG inclusion at 10% of diet DM did not affect DMI (P = 0.16). Carcass-adjusted average daily gain (ADG) was not affected by DGS (P = 0.73) or CG (P = 0.28). Decreased (P = 0.03) carcass-adjusted gain-to-feed (G:F) was observed as the main effect of DGS. Greater DMI resulting from feeding DGS as 40% of diet DM appears to have driven the tendency for reduced G:F. Hot carcass weight, longissimus muscle area, 12th rib fat depth, yield grade, and marbling score were not (P> 0.10) influenced by DGS or CG. However, kidney, pelvic, fat (KPH) was increased (P = 0.01) when cattle were fed DGS as 40% of diet DM. Based on the findings presented, it is concluded that CG can substitute up to 10% of SFC in the diet without negatively affecting cattle growth performance or carcass characteristics, regardless of DGS inclusion as 40% of the diet DM.


Nitration of the mitochondrial complex I subunit NDUFB8 elicits RIP1- and RIP3-mediated necrosis.
Nitric oxide (NO) and other reactive nitrogen species target multiple sites in the mitochondria to influence cellular bioenergetics and survival. Kinetic imaging studies revealed that NO from either activated macrophages or donor compounds rapidly diffuses to the mitochondria, causing a dose-dependent progressive increase in NO-dependent DAF fluorescence, which corresponded to mitochondrial membrane potential loss and initiated alterations in cellular bioenergetics that ultimately led to necrotic cell death. Cellular dysfunction is mediated by an elevated 3-nitrotyrosine signature of the mitochondrial complex I subunit NDUFB8, which is vital for normal mitochondrial function as evidenced by selective knockdown via siRNA. Overexpression of mitochondrial superoxide dismutase substantially decreased NDUFB8 nitration and restored mitochondrial homeostasis. Further, treatment of cells with either necrostatin-1 or siRNA knockdown of RIP1 and RIP3 prevented NO-mediated necrosis. This work demonstrates that the interaction between NO and mitochondrially derived superoxide alters mitochondrial bioenergetics and cell function, thus providing a molecular mechanism for reactive oxygen and nitrogen species-mediated alterations in mitochondrial homeostasis.


Zebrafish ( Danio rerio) as a model for investigating the safety of GM feed ingredients (soya and maize); performance, stress response and uptake of dietary DNA sequences.
A 20-d zebrafish (Danio rerio) feeding trial, in which a near doubling of fish weight was achieved, was conducted with GM feed ingredients to evaluate feed intake, growth, stress response and uptake of dietary DNA. A partial aim of the study was to assess zebrafish as a model organism in GM safety assessments. Roundup Ready soya (RRS), YieldGard Bt maize (MON810) and their non-modified, maternal, near-isogenic lines were used in a 2 x 2 factorial design. Soya variety and maize variety were the main factors, both with two levels; non-GM and GM. Compared with fish fed non-GM maize, those fed GM maize exhibited significantly better growth, had lower mRNA transcription levels of superoxide dismutase (SOD)-1 and a tendency (non-significant) towards lower transcription of heat shock protein 70 in liver. Sex of the fish and soya variety had significant interaction effects on total RNA yield from the whole liver and transcription of SOD-1, suggesting that some diet component affecting males and females differently was present in different levels in the GM and the non-GM soya used in the present study. Dietary DNA sequences were detected in all of the organs analysed, but not all of the samples. Soya and maize rubisco (non-transgenic, multicopy genes) were most frequently detected, while MON810 transgenic DNA fragments were detected in some samples and RRS fragments were not detected. In conclusion, zebrafish shows promise as a model for this application.


Sheep mast-cell proteinases-1 and -3: cDNA cloning, primary structure and molecular modelling of the enzymes and further studies on substrate specificity.
Sheep mast-cell proteinase-1 (sMCP-1) is a serine proteinase expressed predominantly by mucosal mast cells, with specificity for cleavage C-terminal to basic and hydrophobic amino acid residues. A cDNA encoding sMCP-1 has been cloned using reverse transcriptase (RT)-PCR. It appears to be translated as a pre-proenzyme with a 17-amino-acid signal peptide, a basic 2-amino-acid propeptide and a 226-amino-acid catalytic domain. A second cDNA, encoding a serine proteinase 90% identical with sMCP-1, was also cloned and named sMCP-3. Molecular models were constructed for both enzymes using coordinates for the refined X-ray structures of human cathepsin G, chymase and rat mast-cell proteinase-2. The model for sMCP-1 suggests that the acidic Asp-226 side chain extends into the substrate-binding pocket, hydrogen-bonding with Ser-190 on the opposite side and bisecting the pocket. The location of an acidic moiety in this position would favour interaction with basic substrate residues and binding of aromatic residues is rationalized by interaction of the positively charged equatorial plane with Asp-226. The balance between chymotryptic and tryptic activities of sMCP-1 was found to be sensitive to salt concentration, with increasing univalent cation concentration favouring chymotryptic activity relative to the tryptic. Using a peptide substrate representing residues 36-59 of the human thrombin receptor, increasing salt concentration favoured cleavage at Phe-43 rather than at Arg-41.


Role of intracellular calcium in volume regulation by rabbit medullary thick ascending limb cells.
Previous studies demonstrated that Ca2(+)-activated K+ channels in luminal membrane of rabbit medullary thick ascending limb cells (MTAL) are activated on exposure of the cells to hyposmotic solutions [J. Taniguchi and W. B. Guggino. Am. J. Physiol. 257 (Renal Fluid Electrolyte Physiol. 26): F347-F352, 1989]. In this study, we investigated the mechanism of activation of Ca2(+)-activated K+ channels in MTAL cells exposed to hyposmotic solutions. MTAL cells swell in hyposmotic medium and regulate volume back toward the starting volume. This regulatory volume decrease (RVD) is inhibited at high medium K+ concentrations or by presence of quinine or Ba2+ in extracellular medium, suggesting involvement of K+ channels. Measurements of intracellular Ca2+ concentrations with fura-2 show that intracellular Ca2+ rises in hyposmotic solutions and that this rise does not occur in absence of extracellular Ca2+. Nifedipine and verapamil also inhibit rise in intracellular Ca2+. Decreasing intracellular Ca2+ by removal of external Ca2+ in presence of EDTA or by chelation of intracellular Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) inhibits RVD. We conclude that hypotonic solutions activate K+ efflux probably via K+ channels and Ca2+ influx via a nifedipine- and verapamil-sensitive pathway. Lowering intracellular Ca2+ removes the ability of MTAL cells to regulate volume in hyposmotic solutions.


ERCP licence in the context of medical practices, legal regulations, medical ethics and patient's rights in our country.
Endoscopic Retrograde Cholangiopancreatography (ERCP) is an invasive endoscopic procedure mainly used for hepatobiliary and pancreatic disorders. Although it was first developed by a surgeon, McCune, there is still debate on who can perform this procedure. This problem, which actually needs to be solved within medical ethics, has been brought to the courts, and lawsuits have been filed against general surgeons to prevent them from performing ERCP. The current situation in our country demonstrates that 50-70% of ERCP procedures are performed by general surgeons. In regions where there are not enough gastroenterology specialists, only general surgeons perform this procedure. Today, general surgeons have hundreds of articles on ERCP procedures and studies accepted as international guideline. ERCP procedure -which is in fact a surgical procedure- is included in hepatobiliary surgical procedures in the general surgery core training schedule. General surgeons receive ERCP education in a 6-month challenging program at centers accredited by the Turkish Surgical Society. The problem of ERCP license cannot be solved by legal authorities but by medical, ethical and deontological discussions. Our recommendation here is that the Ministry of Health should associate this procedure with a specific legislation, just like in endoscopy, and establish a specific ERCP training program accepted for license. In this article, the problem of who should perform ERCP was discussed within the framework of legal legislation, medical doctrine and realities of our country.


Impact of the COVID-19 pandemic on routine immunization services in Yerevan and vaccinations against COVID-19 in Armenia.
The coronavirus disease (COVID-19) has led to millions of deaths around the world. The indirect effects of the pandemic, include disruption of routine immunization services. We conducted a retrospective review to assess the impact of the pandemic on routine immunization in Yerevan and the vaccinations against COVID-19 in Armenia. We compared the number of administered doses of DPT/VHB/HIB/IPV1,2,3, Pneumococcal1,2,3, Rotarix1,2, and MMR1 vaccines in target groups in 2020 and 2021 and the total vaccination coverage in 2019, 2020, and 2021. We also analyzed the number of COVID-19 vaccines administered in Armenia from 17 May 2021 to 6 February 2022. There was a decline in the number of administered doses of vaccines at the beginning of the pandemic due to restrictive quarantine measures: 16 ± 4.5 (95% CI, 11.8-20.2), p < 0.05, during the second wave 18 ± 2.6 (95% CI, 15.6-20.4), p < 0.05 and during the interruption due to COVID-19 vaccine delivery 16 ± 7.4 (95% CI, 9.1-22.9), p < 0.05. There was no significant decrease in the number of vaccinations during the first, third, and fourth pandemic waves (p > 0.05) Overall, the COVID-19 vaccination process was slow and only 30% of the population were vaccinated. The COVID-19 pandemic led to disruptions in the routine immunization process, but there was no significant decrease in the total vaccine coverage due to rapid scaling up of the vaccination services and catch-up vaccinations. Thus, the restrictions imposed during the pandemic did not affect the overall progress of vaccination.


Holographic characterization and tracking of colloidal dimers in the effective-sphere approximation.
An in-line hologram of a colloidal sphere can be analyzed with the Lorenz-Mie theory of light scattering to measure the sphere's three-dimensional position with nanometer-scale precision while also measuring its diameter and refractive index with part-per-thousand precision. Applying the same technique to aspherical or inhomogeneous particles yields measurements of the position, diameter and refractive index of an effective sphere that represents an average over the particle's geometry and composition. This effective-sphere interpretation has been applied successfully to porous, dimpled and coated spheres, as well as to fractal clusters of nanoparticles, all of whose inhomogeneities appear on length scales smaller than the wavelength of light. Here, we combine numerical and experimental studies to investigate effective-sphere characterization of symmetric dimers of micrometer-scale spheres, a class of aspherical objects that appear commonly in real-world dispersions. Our studies demonstrate that the effective-sphere interpretation usefully distinguishes small colloidal clusters in holographic characterization studies of monodisperse colloidal spheres. The effective-sphere estimate for a dimer's axial position closely follows the ground truth for its center of mass. Trends in the effective-sphere diameter and refractive index, furthermore, can be used to measure a dimer's three-dimensional orientation. When applied to colloidal dimers transported in a Poiseuille flow, the estimated orientation distribution is consistent with expectations for Brownian particles undergoing Jeffery orbits.


Dietary cholesterol induced changes in lipid profile in patients with nephrotic syndrome and chronic renal failure.
Fifteen patients with nephrotic syndrome (9 aged below 30 years), 6 patients with chronic renal failure and 26 healthy males (14 below 30 years) were studied. After estimating the basal serum levels of total cholesterol (STC), triglycerides (STG), high density lipoprotein (HDL) and low density lipoprotein (LDL), the patients were given a high cholesterol and high fat breakfast (containing 32 g fat and 527 mg cholesterol) for 7 days. Lipoprotein levels were again estimated on days 8 and 16. In the basal state, all patients with nephrotic syndrome had markedly elevated levels of STC and LDL. In patients aged below 30 years, STG and VLDL levels were also elevated, while HDL levels were similar in both the groups in comparison to their respective age group controls. In patients with renal failure, basal levels of all lipoproteins were similar to levels in controls. After the high cholesterol fat diet, there was an insignificant rise in all lipoprotein values in patients with nephrotic syndrome and renal failure. However, HDL levels rose significantly in patients with nephrotic syndrome aged below 30 years. Patients with nephrotic syndrome and chronic renal failure can safely be given high cholesterol and high fat diet despite abnormalities in lipid lipoprotein metabolism.


Down-regulation and CpG island hypermethylation of CRYAA in age-related nuclear cataract.
Age-related cataract (ARC) is the leading cause of blindness among older adults, and the chaperone-like activity of αA-crystallin (CRYAA) is considered to be critical for the maintenance of eye lens transparency. To assess the potential contribution of epigenetic regulation of CRYAA genes relevant to ARC pathogenesis, we evaluated DNA methylation, a tissue-specific genetic modulation that affects gene expression. Reverse-transcription PCR and Western blot were used to analyze the expression of CRYAA. Methylation status was analyzed by bisulfite genomic sequencing of the CpG islands in 15 eyes with age-related nuclear cataracts and 15 control eyes. The demethylating agent zebularine was used to investigate the relationship between hypermethylation of the CpG islands and down-expression of CRYAA. The mRNA and protein levels of CRYAA were significantly reduced in the lens epithelia of age-related nuclear cataract cases vs. age-matched controls, which corresponded to hypermethylation of the CpG island of CRYAA promoter. Treatment with a DNA-demethylating agent was associated with restoration of CRYAA expression. Comparing DNA methylation and mRNA and protein levels revealed significant differences between age-related nuclear cataract and control lenses. The evidence presented suggests that CRYAA undergoes epigenetic repression in the lens epithelia in age-related nuclear cataract.


Isoflurane and sodium nitroprusside reduce the depressant effects of protamine sulfate on isolated ischemic rat hearts.
The administration of protamine sulfate (protamine) to reverse the action of heparin is associated with adverse reactions. We studied the effects of protamine and isoflurane on isolated, perfused rat hearts previously subjected to cardioplegic ischemia. Hearts were perfused with oxygenated Krebs-Henseleit (KH) solution for 30 min, then subjected to cardioplegic ischemia for 30 min (KCl 16 mEq/L at 31 degrees C) and 5 min reperfusion. Drug exposure lasted 15 min, and the recovery period was 60 min. Test groups were control, protamine (10 microg/mL), isoflurane (1.5%), protamine +/- isoflurane, sodium nitroprusside (SNP) (2.5 ng/mL), and SNP +/- protamine. Left ventricular developed pressure (LVP), coronary flow, and myocardial oxygen consumption were depressed by protamine to 30% +/- 4%, 47% +/- 4%, and 39% +/- 4% of baseline (P < 0.001 versus control), respectively. Isoflurane and SNP afforded partial protection from the effects of protamine: LVP was 57% +/- 5% and 51% +/- 3% of baseline, respectively (P < 0.05 versus protamine alone and control); coronary flow was 70% +/- 6% and 97% +/- 12% of baseline, respectively (P < 0.05 versus protamine alone; P < 0.05 for isoflurane versus control); and O2 consumption was 69% +/- 6% and 88% +/- 15% of baseline, respectively (P < 0.05 versus protamine; P < 0.05 for isoflurane versus control). In this model, protamine-induced myocardial depression and coronary vasoconstriction were less pronounced in the presence of either isoflurane or SNP. We examined the interactions of isoflurane, sodium nitroprusside, and protamine in a rat heart model and found that both isoflurane and sodium nitroprusside partially protect the heart from the depressant effects of protamine. This finding is significant, as these drugs are often used in heart surgery.


Prediction of maximum exposure in poor metabolizers following inhibition of nonpolymorphic pathways.
Marked increases in exposure of some substrates have been noted in poor metabolizers given inhibitors of nonpolymorphic enzymes. Among the small number of clinical trials conducted to investigate this problem, a wide variation in the degree of maximum exposure ratios (area under the curve in poor metabolizers in the presence of inhibitor/area under the curve in extensive metabolizers) among the different substrates has been reported, with some trials reporting profound increases (> tenfold), and others demonstrating less remarkable changes (< twofold). The conduct of such trials raises safety concerns for the trial participants, in addition to other ethical and logistic concerns; therefore, the possibility was investigated that maximum exposure (area under the curve in poor metabolizers in the presence of an inhibitor) could be predicted, and that substrates susceptible to large increases in exposure could be identified. Existing clinical trials were identified by data mining the literature. A theoretical approach was developed to predict maximum exposure in poor metabolizers from studies in extensive metabolizers treated with an inhibitor of the nonpolymorphic pathway. Maximum exposure was predicted in eleven instances and the mean percentage difference between predicted and observed was 11.9%. Substrates with a fraction of substrate dose metabolized by the polymorphic enzyme (fm(POLY)) higher than 75% are at greater risk of exhibiting maximum exposure ratios of more than tenfold.


Optimization of small molecule degraders and antagonists for targeting estrogen receptor based on breast cancer: current status and future.
The estrogen receptor (ER) is a classical receptor protein that plays a crucial role in mediating multiple signaling pathways in various target organs. It has been shown that ER-targeting therapies inhibit breast cancer cell proliferation, enhance neuronal protection, and promote osteoclast formation. Several drugs have been designed to specifically target ER in ER-positive (ER+) breast cancer, including selective estrogen receptor modulators (SERM) such as Tamoxifen. However, the emergence of drug resistance in ER+ breast cancer and the potential side effects on the endometrium which has high ER expression has posed significant challenges in clinical practice. Recently, novel ER-targeted drugs, namely, selective estrogen receptor degrader (SERD) and selective estrogen receptor covalent antagonist (SERCA) have shown promise in addressing these concerns. This paper provides a comprehensive review of the structural functions of ER and highlights recent advancements in SERD and SERCA-related small molecule drugs, especially focusing on their structural optimization strategies and future optimization directions. Additionally, the therapeutic potential and challenges of novel SERDs and SERCAs in breast cancer and other ER-related diseases have been discussed.


Combining PCI-24781, a novel histone deacetylase inhibitor, with chemotherapy for the treatment of soft tissue sarcoma.
Histone deactylase inhibitors (HDACi) are a promising new class of anticancer therapeutics; however, little is known about HDACi activity in soft tissue sarcoma (STS), a heterogeneous cohort of mesenchymal origin malignancies. Consequently, we investigated the novel HDACi PCI-24781, alone/in combination with conventional chemotherapy, to determine its potential anti-STS-related effects and the underlying mechanisms involved. Immunoblotting was used to evaluate the effects of PCI-24781 on histone and nonhistone protein acetylation and expression of potential downstream targets. Cell culture-based assays were utilized to assess the effects of PCI-24781 on STS cell growth, cell cycle progression, apoptosis, and chemosensitivity. Quantitative reverse transcription-PCR, chromatin immunoprecipitation, and reporter assays helped elucidate molecular mechanisms resulting in PCI-24781-induced Rad51 repression. The effect of PCI-24781, alone or with chemotherapy, on tumor and metastatic growth was tested in vivo using human STS xenograft models. PCI-24781 exhibited significant anti-STS proliferative activity in vitro, inducing S phase depletion, G(2)/M cell cycle arrest, and increasing apoptosis. Superior effects were seen when combined with chemotherapy. A PCI-24781-induced reduction in Rad51, a major mediator of DNA double-strand break homologous recombination repair, was shown and may be a mechanism underlying PCI-24781 chemosensitization. We showed that PCI-24781 transcriptionally represses Rad51 through an E2F binding-site on the Rad51 proximal promoter. Although single-agent PCI-24781 had modest effects on STS growth and metastasis, marked inhibition was observed when combined with chemotherapy. In light of these findings, this novel molecular-based combination may be applicable to multiple STS histologic subtypes, and potentially merits rigorous evaluation in human STS clinical trials.


Trans-ethnic genomic informed risk assessment for Alzheimer's disease: An International Hundred K+ Cohorts Consortium study.
As a collaboration model between the International HundredK+ Cohorts Consortium (IHCC) and the Davos Alzheimer's Collaborative (DAC), our aim was to develop a trans-ethnic genomic informed risk assessment (GIRA) algorithm for Alzheimer's disease (AD). The GIRA model was created to include polygenic risk score calculated from the AD genome-wide association study loci, the apolipoprotein E haplotypes, and non-genetic covariates including age, sex, and the first three principal components of population substructure. We validated the performance of the GIRA model in different populations. The proteomic study in the participant sites identified proteins related to female infertility and autoimmune thyroiditis and associated with the risk scores of AD. As the initial effort by the IHCC to leverage existing large-scale datasets in a collaborative setting with DAC, we developed a trans-ethnic GIRA for AD with the potential of identifying individuals at high risk of developing AD for future clinical applications.


Special Characteristics of the Resilience of Russian Families in the Face of Modern Challenges (A Preliminary Study).
A challenge is considered a "wake-up call" for family resilience, requiring a proper response (willingness to evaluate, understand an event and its signals, and also give an adequate response). Family resilience is defined as an adequate response to challenges, that is, the ability to cope with them based on the cultural-historical context and family resources, such as clear and open family communication and connectedness, the use of social resources, a broad system of values and senses, the ability to derive meaning from adversity, acceptance, and flexibility. This article reports on a study which aimed to analyze components of the resilience of Russian families in response to life circumstances that have become challenges for them. The study was conducted from March 20 to May 7, 2022. Participants took an online survey on Yandex-forms; the link to the survey was distributed through social networks on public pages and in private messages. Two hundred seventy-four (274) representatives of Russian families responded, including 234 women and 40 men (14.6%) ranging from age 17 to 65 (cf. 34.1+12.5). After removing the data of 15 participants who did not report a negative event in their families, the final sample consisted of 259 people. Challenges for modern Russian families can be categorized as loss challenges, relationship challenges, global challenges, challenges of illness, and challenges of financial well-being. The challenges of loss stimulate flexibility of response, acceptance, and overcoming suffering through mutual understanding. Global challenges and the challenges of illness awaken family spirituality. The ability to discuss problems together and share decision making becomes a resource to meet the challenge of families' financial well-being. Confidence in solving problems and a positive outlook become resources to face relationship challenges. The intensity of events is a signal for a family to evoke communication and connectedness, acceptance, and flexibility, as well as family resilience as a whole. There is a connection between the difficulties that respondents regard as challenges and the characteristics of their family resilience; the most adequate response to challenges is to increase family resilience.


EEG correlates of math anxiety during arithmetic problem solving: Implication for attention deficits.
Anxiety about math can lead to long-term negative consequences related to academic achievement and professional success. However, it remains unclear how elevated math-anxiety modulates brain activity while solving arithmetic problems. In the current study, we recorded electrophysiological responses throughout arithmetic problem solving, both at the period of anticipating an upcoming arithmetic problem and solving an arithmetic problem. Results showed that, after controlling for mathematical performance, people with higher math anxiety tended to show stronger beta band oscillation and P300 amplitude while expecting the arithmetic problems, as well as stronger gamma band activity while solving the arithmetic problems. These results suggest that individuals highly anxious about math might use more attentional resources during the course of anticipating the upcoming arithmetic problems, and showed greater attentional bias toward arithmetic problems during solving arithmetic problems.


Improving Patient Outcomes in the Dual Crises of Climate Change and COVID-19: Proceedings of the Third Annual Clinical Climate Change Meeting, January 8, 2021.
The tremendous global toll of the COVID-19 pandemic does not fall equally on all populations. Indeed, this crisis has exerted more severe impacts on the most vulnerable communities, spotlighting the continued consequences of longstanding structural, social, and healthcare inequities. This disparity in COVID-19 parallels the unequal health consequences of climate change, whereby underlying inequities perpetuate adverse health outcomes disproportionately among vulnerable populations. As these two crises continue to unfold, there is an urgent need for healthcare practitioners to identify and implement solutions to mitigate adverse health outcomes, especially in the face of global crises. To support this need, the 2021 Clinical Climate Change Conference held a virtual meeting to discuss the implications of the convergence of the climate crisis and COVID-19, particularly for vulnerable patient populations and the clinicians who care for them. Presenters and panelists provided evidence-based solutions to help health professionals improve and adapt their practice to these evolving scenarios. Together, participants explored the community health system and national solutions to reduce the impacts of COVID-19 and the climate crisis, to promote community advocacy, and foster new partnerships between community and healthcare leaders to combat systemic racism and achieve a more just and equitable society.


Photophysical properties of benzanthrone derivatives: effect of substituent, solvent polarity and hydrogen bonding.
Benzanthrone derivatives are potential fluorescent probes for various chemical and biological environments. A mechanistic understanding of their photophysical properties is pivotal for designing an efficient fluorescence sensor based on the benzanthrone framework. In this study, we report on the effect of chemical substitution on the photophysical properties of two benzanthrone derivatives, namely, 3-(N'-methyl)-piperazino-7H-benzo[de]anthracen-7-one [Me-PBA] and 3-(N'-phenyl)-piperazino-7H-benzo[de]anthracen-7-one [Ph-PBA] in different solvents and solvent mixtures of varying polarities and proticities. Both benzanthrone derivatives show interesting solvent-dependent photophysical properties. Although both derivatives exhibit strong intramolecular charge transfer (ICT) characteristics in the excited state, the extent of the charge transfer is significantly influenced by the nature of the chemical substitution. Modulation of photophysical parameters as a function of solvent properties led us to propose that ICT is affected by solvent polarity and hydrogen bonding. From the viscosity effect, it is revealed that the weaker emission of Ph-PBA compared to Me-PBA in polar solvents is primarily due to the non-radiative torsional motion of the phenyl group in the former derivative. In protic solvents, intermolecular hydrogen bonding imparts strong non-radiative deactivation to both derivatives, thus rendering a weak fluorescence yield.


A double-blind, randomized, placebo-controlled trial of pindolol augmentation in depressive patients resistant to serotonin reuptake inhibitors. Grup de Recerca en Trastorns Afectius.
Pindolol has been reported to hasten the antidepressant action of selective serotonin reuptake inhibitors in open-label and placebo-controlled trials. Pilot studies also suggested that pindolol could augment the antidepressant response in unresponsive patients. We investigated whether the addition of pindolol can induce a rapid response in treatment-resistant patients. After a single-blind lead-in placebo phase of 5 days to exclude placebo responders, 80 outpatients with major depression who did not respond to a minimum of 6 weeks of treatment with clomipramine hydrochloride, 150 mg/d; fluoxetine hydrochloride, 40 mg/d; fluvoxamine maleate, 200 mg/d; or paroxetine hydrochloride, 40 mg/d, were randomly assigned to additionally receive placebo (3 times daily) or pindolol (2.5 mg 3 times daily) for 10 days. The median number of ineffective treatments in the current episode was 2 (range, 1-4). Hamilton Rating Scale for Depression and Montgomery-Asberg Scale for Depression scores were used as primary measures of efficacy. At end point, the Hamilton and Montgomery-Asberg scores and change from baseline in Hamilton score were not significantly different in patients taking placebo or pindolol. The response rate was equal in both groups (12.5%). No differences in the clinical outcome were found when the various pretreatment subgroups were considered. At end point, the plasma concentration of pindolol was 9.9+/-5.1 ng/mL (mean +/- SD; n = 40). Although pindolol can accelerate the antidepressant action of selective serotonin reuptake inhibitors in previously untreated patients, it does not elicit a rapid clinical response in treatment-resistant patients within a 10-day period.


Investigating the ability of Pseudomonas fluorescens UW4 to reduce cadmium stress in Lactuca sativa via an intervention in the ethylene biosynthetic pathway.
A typical plant response to any biotic or abiotic stress, including cadmium (Cd), involves increased ethylene synthesis, which causes senescence of the affected plant part. Stressed plants can experience reduced ethylene and improved growth if they are inoculated with bacteria that have the enzyme ACC deaminase, which metabolizes the ethylene precursor ACC (1-aminocyclopropane-1-carboxylate). We investigated whether one such bacterium, Pseudomonas fluorescens UW4, reduces the production of ethylene and improves the growth of lettuce (Lactuca sativa) sown in Cd-contaminated potting material (PRO-MIX® BX). Plants were inoculated with the wild-type P. fluorescens UW4 or a mutant strain that cannot produce ACC deaminase. Cadmium-treated plants contained up to 50 times more Cd than did control plants. In noninoculated plants, Cd induced a 5-fold increase in ethylene concentration. The wild-type bacterium prevented Cd-induced reductions in root biomass but there was no relationship between Cd treatment and ethylene production in inoculated plants. In contrast, when the concentration of ethylene was plotted against the extent of bacterial colonization of the roots, increased colonization with wild-type P. fluorescens UW4 was associated with 20% less ethylene production. Ours is the first study to show that the protective effect of this bacterium is proportional to the quantity of bacteria on the root surface.


Patellofemoral arthroplasty with a custom-fit femoral prosthesis.
We reviewed the outcomes of a series of patellar arthroplasty operations with custom-fit femoral prostheses to examine the effectiveness of this procedure in relieving pain and restoring function in the knee. Twenty-two patellofemoral arthroplasty operations were performed in 21 patients (mean age, 48.6 years) at 2 institutions between 1994 and 2002. All patients had advanced patellofemoral arthritis and had undergone an average of 2.5 previous patellofemoral operations. The prosthesis, consisting of a custom-fit chrome cobalt trochlear component and an all-polyethylene patellar button, was implanted in a procedure designed to minimize bone resection. Patients later underwent three-view radiography of the knee to confirm that the prosthesis was positioned correctly. One patient required revision of an undersized patellar button 18 months postoperatively, and 2 other patients had postoperative arthrofibrosis necessitating arthroscopic debridement. No patient required revision of the trochlear component, and no loosening or migration of any component has been found since the first procedure was performed. However, the polyethylene patellar button has worn in 3 patients, and the patella broke in 1 patient. An average of 60 months postoperatively, patients used the Western Ontario and McMaster Universities Osteoarthritis Index to rate their preoperative and present joint pain, stiffness, and function. Patients' mean overall ratings (potential range, 24-96) were significantly lower for their present symptoms (28.4) than for their preoperative symptoms (63.4). Mean scores on each subscale also decreased: from 13.0 to 5.5 for pain, from 5.4 to 2.4 for stiffness, and from 45.0 to 20.6 for function. We conclude that, in carefully selected patients, patellofemoral arthroplasty with a custom-fit prosthesis is a viable surgical treatment for isolated patellofemoral arthritis.


National Trends and Disparities in the Diffusion of Laparoscopic Surgery for Children in the United States.
Background: Laparoscopic surgery has become the standard of care for many surgical treatments. The diffusion of laparoscopy has been investigated for adult patient populations but is still unknown for pediatric populations. This study sought to describe national trends in diffusion of laparoscopic surgery for common pediatric conditions and identify disparities in use of laparoscopic surgery. Study Design: A retrospective analysis of serial cross-sectional data was performed using the Healthcare Cost and Utilization Project's Kids' Inpatient Database from 1997 to 2016. Pediatric patients (ages ≤18) undergoing appendectomy, cholecystectomy, fundoplication, or inguinal hernia repair were identified. The diffusion of laparoscopy for each procedure was measured using the proportion of laparoscopic surgeries over years. Results: National trends demonstrate increases in the use of laparoscopy for children over the past two decades from 13.4% to 88.7% for appendectomy, from 82.6% to 94.9% for cholecystectomy, from 7.4% to 77.4% for fundoplication, and from 1.5% to 23.5% for repair of inguinal hernia (P < .001). Disparities in diffusion of laparoscopy were found from various pediatric populations, and the disparities varied by specific procedures and years. In particular, the proportion of laparoscopic appendectomy in 1997 was 11.3% at urban teaching hospitals and was 13.9% at rural hospitals (P = .01), while the proportions in 2016 increased to 90.8% at urban teaching hospitals versus 71.3% at rural hospitals (P < .001). Conclusions: Laparoscopy has become the standard surgical care for common pediatric surgical conditions. Widening disparities in use of laparoscopic surgery for pediatric populations appear between urban teaching hospitals and rural hospitals.


The effect of hospital volume on patient outcomes in severe acute pancreatitis.
We investigated the relation between hospital volume and outcome in patients with severe acute pancreatitis (SAP). The determination is important because patient outcome may be improved through volume-based selective referral. In this cohort study, we analyzed 22,551 SAP patients in 2,208 hospital-years (between 2000 and 2009) from Taiwan's National Health Insurance Research Database. Primary outcome was hospital mortality. Secondary outcomes were hospital length of stay and charges. Hospital SAP volume was measured both as categorical and as continuous variables (per one case increase each hospital-year). The effect was assessed using multivariable logistic regression models with generalized estimating equations accounting for hospital clustering effect. Adjusted covariates included patient and hospital characteristics (model 1), and additional treatment variables (model 2). Irrespective of the measurements, increasing hospital volume was associated with reduced risk of hospital mortality after adjusting the patient and hospital characteristics (adjusted odds ratio [OR] 0.995, 95% confidence interval [CI] 0.993-0.998 for per one case increase). The patients treated in the highest volume quartile (≥14 cases per hospital-year) had 42% lower risk of hospital mortality than those in the lowest volume quartile (1 case per hospital-year) after adjusting the patient and hospital characteristics (adjusted OR 0.58, 95% CI 0.40-0.83). However, an inverse relation between volume and hospital stay or hospital charges was observed only when the volume was analyzed as a categorical variable. After adjusting the treatment covariates, the volume effect on hospital mortality disappeared regardless of the volume measures. These findings support the use of volume-based selective referral for patients with SAP and suggest that differences in levels or processes of care among hospitals may have contributed to the volume effect.


Elucidating the structural and functional prophecy of the Rv2326c gene, an ABC transporter of Mycobacterium tuberculosis H37Rv through computational approach.
Tuberculosis is a fatal disease caused by Mycobacterium tuberculosis. M. tuberculosis becoming drug-resistant day by day, necessitating to know the mechanism behind the drug resistance and how to overcome this deadly malady. Drug resistance and reduced drug bioavailability are caused by a class of transporter proteins called the ATP-binding cassette (ABC) transporters, which pump a range of medicines out of cells at the price of ATP hydrolysis. By using computational approaches, we tried to elaborate the probable function of the Rv2326c gene of M. tuberculosis, perhaps involved in drug resistance mechanism. The presence of the signature motif of ABC transporters (LSGGELQRLALAAAL and LSGGQMRRVVLAGLL) and ATP binding motif (GXXXXGKT and GXXXXGKS) in the protein sequence signifying its importance in the ATP binding and transportation of molecules. Further, this manuscript elaborated about tertiary structure and validation, functional category, localization, phosphorylation site prediction, mutational analysis of conserved motifs. Ligand docking study shows the highest affinity with ATP than GTP justified its function as an ATP binding protein. The Rv2326c protein is present in the inner membrane and working as an ATP binding protein and might be playing a dynamic role in transportation. In this study, we found that Rv2326c protein might be working as an ABC transporter by which the drugs and other molecules are imported or exported into the bacterium. As a result, the current study provides a means to better understand its normal functioning and basic biology, which can help in the development of novel therapeutic targeting approaches for Rv2326c protein.


Non--cloth-covered caged-ball prostheses. The second decade.
The Starr-Edwards Models 6120 mitral and 1200/60 aortic valves are caged-ball prostheses with cloth-covered sewing rings and bare-metal struts. Introduced in 1965, they have been in continuous clinical use longer than any other currently available heart valve prostheses. Late results with this valve are analyzed and compared with recent series employing other current valve prostheses. One hundred thirty-four mitral 6120 prostheses were inserted at the University of Oregon Health Sciences Center from 1965 through 1977, with 118 operative survivors followed for a mean of 5.4 years. Twelve-year survival rate (+/- standard error) was 50 (+/-8) percent. Twelve percent of late deaths were valve related. Eighty-eight (+/-5) percent of valves were still in place at 12 years. The embolic rate was 5.8 (+/-1.0) percent per patient-year for all emboli and 2.2(+/-0.6) percent per patient-year for serious emboli. Two hundred forty-nine operative survivors among 282 patients undergoing aortic valve replacement during the same period of time were followed for a mean of 4.3 years. Twelve-year survival was 61 (+/-6) percent and the removal-free rate was 92(+/-5) percent. Six percent of late deaths were valve related. Embolic rates were 5.0 (+/-.7) percent and 1.8 (+/-.4) percent per patient-year for all emboli and serius emboli, respectively. Structural failure, specifically ball variance, was not encountered with this prosthesis. Ninety percent of 10 year survivors are in N.Y.H.A. Functional Class I or II. There was one anticoagulant-related death in 1,698 patient-years of follow-up. The current non--cloth-covered caged-ball valves provide unquestionable durability and well-documented results into their second decade of use. They provide a base line for comparison with newer prostheses and offer a valid, current choice for both aortic and mitral valve replacement.


Antagonistic effects of indoloquinazoline alkaloids on antimycobacterial activity of evocarpine.
The interaction of quinolone and indoloquinazoline alkaloids concerning their antimycobacterial activity was studied. The antimycobacterial and modulating activity of evodiamine (1), rutaecarpine (2) and evocarpine (3) was tested on mycobacteria including three multidrug-resistant (MDR) clinical isolates of Mycobacterium tuberculosis. Antagonistic effects were concluded from fractional inhibitory concentration (FICI) values. Interaction energies of the compounds were calculated using GLUE docking module implemented in GRID. 1 and 2 exhibited weak inhibition of rapidly growing mycobacteria, however, 1 was active against Myco. tuberculosis H37Rv (MIC = 10 mg l(-1) ) while 2 was inactive. Both 1 and 2 showed a marked antagonistic effect on the susceptibility of different mycobacterial strains to 3 giving FICI values between 5 and 9. The interaction energies between compounds 1 and 2 with compound 3 suggested the possibility of complex formation in solution. Indoloquinazoline alkaloids markedly reduce the antimycobacterial effect of the quinolone alkaloid evocarpine. Complex formation may play a role in the attenuation of its antimycobacterial activity. This study gives a striking example of antagonism between compounds present in the same plant extract which should be considered in natural product based screening projects.


Atom arrangement strategy for designing a turn-on 1H magnetic resonance probe: a dual activatable probe for multimodal detection of hypochlorite.
The first dual activatable hypochlorite ((-)OCl)-sensing probe was developed, based on a new proof-of-concept design involving signal-activatable (1)H chemical probes using the triple-resonance NMR technique. The probe enabled fluorescence-(1)H MR dual turn-on detection of (-)OCl in solution and in crude tissue extracts.


Posterior longitudinal ligament resection or preservation in anterior cervical decompression surgery.
We reviewed the literature to determine differences in clinical outcomes for the removal or preservation of the posterior longitudinal ligament (PLL) in anterior cervical discectomy and fusion (ACDF). The outcomes are surgeon and case-dependent for both practices. A literature review was performed in PubMed from the years 1960 to 2014 to identify studies describing surgeries where the PLL was removed or preserved during ACDF. Searches were performed using Medical Subject Headings (MeSH) and references included in the reviewed articles were also considered. Additionally we searched recent articles that cited those from the original search. The search yielded 79 articles and 115 pertinent citations. These 194 articles were reviewed for specific discussions of PLL resection or preservation. Four articles containing 122 patients were included in the final analysis. In 69 patients the PLL was removed and in 53 the PLL was preserved. Both groups improved in clinical scores during follow up. One patient in the PLL removal group had a cerebrospinal fluid leak. MRI and correlative outcome data suggest that a non-ossified PLL itself does not contribute to significant cord compression. Postoperative MRI of patients with the PLL removed showed a larger spinal cord diameter. Resection of the PLL is safe and common in ACDF surgery but there does not appear to be a demonstrable clinical difference in patients where it is resected. The ultimate decision is likely surgeon and case-dependent. Randomized trials could further determine the importance of PLL removal in ACDF treated patients.


Omalizumab, a novel anti-IgE therapy in allergic disorders.
The incidence of allergic diseases is increasing to epidemic proportions both in the developed and developing world with increasing medical costs and lost productivity. The discovery of immunoglobulin (Ig) E heralded a new era in pathophysiological understanding of allergic disorders. Twenty-five years later, a humanised, non-anaphylactogenic antibody was developed against IgE that could provide a therapeutic alternative to the existing medications. RhuMAb-E25 (omalizumab, Xolair, Genetech, Inc.) is a novel anti-IgE antibody that is directed against the receptor-binding domain of IgE. This binding is specific towards free IgE thereby preventing it from attaching to the mast cell and its subsequent activation. Initial studies demonstrated attenuation of the early and late asthmatic responses when anti-IgE was administered to asthmatic subjects. Later this novel molecule was found to improve symptom scores, rescue medication use, quality of life scores and peak expiratory flows in patients with allergic asthma. Most importantly, omalizumab treatment reduced the corticosteroid use in asthmatic individuals. In patients with seasonal allergic rhinitis, there was a significant reduction in the nasal and ocular symptoms as well as the use of rescue medications. Omalizumab also demonstrated a high level of safety in adults, adolescents and children with a side effect profile no different from the placebo. Its development is an exciting milestone in the treatment of allergic diseases.


[Maintenance of the efficacy of the oxybutynin patch for the treatment of overactive bladder syndrome despite the change in the area of application: study of four cases.]
The transdermal route for administration of anticholinergic drugs can provide efficacy with less systemic adverse effects. The transdermal oxybutynin patch (OXYTDS) offers advantages over oral administration for patients treated for Overactive bladder (OAB) syndrome. The limited evidence on the OXY-TDS patch application areas of the skin, makes difficult counseling patients who require a change to skin zones other than those recommended by the manufacturer. The preliminary experience of four patients included in this case report suggests that changing the application area for the OXY-TDS patch outside those skin areas recommended by the manufacturer, seems effective and safe in the treatment of OAB syndrome, regardless of the characteristics of the patients.


Patient expectations of minor injury care: a cross-sectional survey.
Little is known about the expectations of patients attending the emergency department (ED) with minor injuries. Failure to address expectations may lead to dissatisfaction and poor compliance. We aimed to describe patient expectations of minor injury care and explore the association between unmet expectations and patient satisfaction. We undertook a cross-sectional questionnaire survey of 300 patients attending the ED with minor injuries on weekdays between 9:00 and 17:00. Participants completed a questionnaire asking which tests and treatments they expected, which they consequently received, whether explanations were given for tests and treatments, and how they rated satisfaction with care. The most frequently expected interventions were x-ray, analgesia and bandage/strapping. In each case the proportion expecting intervention was significantly higher than the proportion receiving intervention: x-ray (58% vs 47%, p<0.001); analgesia (40% vs 20%, p<0.001); bandage/strapping (39% vs 22%, p<0.001). There were no significant differences between the proportions expecting and receiving other interventions. At least one unmet expectation was reported by 208/300 patients (69%) but an explanation was received in 151/208 cases (73%). Conversely, 106 (35%) received an unexpected intervention, of whom 79/106 (74%) received an explanation. Patients with unmet expectations tended to rate the satisfaction lower, but the difference was not statistically significant (p=0.187). Patients often expect interventions for minor injuries that they do not receive, but in most cases an explanation was given. We were unable to demonstrate an association between unmet expectations and reduced satisfaction with care.


Immune response to fowl cholera antigens.
Experimentally prepared and commercially manufactured bacterins were evaluated by a 2-stage bird protection bioassay. Ninety percent of the commercial bacterins gave acceptable protection levels to Pasteurella multocida type 1. Sixty-seven percent of the commercial bacterins produced acceptable protection to P. multocida type 3. Survival of 75 percent was considered acceptable protection.


Nature inspired structured surfaces for biomedical applications.
Nature has created an array of superhydrophobic surfaces that possess water-repellent, self-cleaning and anti-icing properties. These surfaces have a number of potential applications in the biomedical industry, as they have the potential to control protein adsorption and cell adhesion. Natural superhydrophobic surfaces are typically composed of materials with a low intrinsic surface free-energy (e.g the cuticular waxes of lotus leaves and insect wings) with a hierarchical structural configuration. This hierarchical surface topography acts to decrease the contact area of water droplets in contact with the surface, thereby increasing the extent of the air/water interface, resulting in water contact angles greater than 150º. In order to employ these surfaces in biotechnological applications, fabrication techniques must be developed so that these multi-scale surface roughness characteristics can be reproduced. Additionally, these fabrication techniques must also be able to be applied to the material required for the intended application. An overview of some of the superhydrophobic surfaces that exist in nature is presented, together with an explanation of the theories of their wettability. Also included is a description of some of the biomedical applications of superhydrophobic surfaces and fabrication techniques that can be used to mimic superhydrophobic surfaces found in nature.


Laser acupuncture as an adjunctive therapy for spastic cerebral palsy in children.
Laser acupuncture is widely used as an alternative line of treatment in several chronic pediatric diseases. To investigate whether biostimulation by low-level laser on acupuncture points adds a clinical benefit to conventional physiotherapy in hemiplegic spastic cerebral palsy (CP) children. Forty spastic hemiplegic cerebral palsy children by age 1-4 years were chosen from the pediatric outpatient clinic of the National Institute of Laser Enhanced Sciences (NILES), Cairo University, and Menofyia University hospitals. They were randomly divided into control and study groups; 20 children each. Both groups received physiotherapy for 3 months, while only the study group also received laser acupuncture (low-level laser 650 nm with 50 mW power was applied at each acupoint for 30 s giving an energy density of 1.8 J/cm(2)). Preassessment and postassessment of muscle tone, the range of motion (ROM), and gross motor function measurements (GMFMs) were obtained, and the results were statistically analyzed. Comparison between posttreatment measures for the control vs. study groups showed significant difference in muscle tone (wrist flexors and plantar flexors) in favor of the study group, while range of motion showed no significant differences. GMFM showed no significant difference in total score while there was a significant difference in goal total score (sum of % scores for each dimension identified as goal area divided by number of goal areas) in favor of the study group. Laser acupuncture has a beneficial effect on reducing spasticity in spastic cerebral palsy and may be helpful in improving their movement.


Nanocomposite bone scaffolds based on biodegradable polymers and hydroxyapatite.
In tissue engineering, development of an osteoconductive construct that integrates with host tissue remains a challenge. In this work, the effect of bone-like minerals on maturation of pre-osteoblast cells was investigated using polymer-mineral scaffolds composed of poly(propylene fumarate)-co-poly(caprolactone) (PPF-co-PCL) and nano-sized hydroxyapatite (HA). The HA of varying concentrations was added to an injectable formulation of PPF-co-PCL and the change in thermal and mechanical properties of the scaffolds was evaluated. No change in onset of degradation temperature was observed due to the addition of HA, however compressive and tensile moduli of copolymer changed significantly when HA amounts were increased in composite formulation. The change in mechanical properties of copolymer was found to correlate well to HA concentration in the constructs. Electron microscopy revealed mineral nucleation and a change in surface morphology and the presence of calcium and phosphate on surfaces was confirmed using energy dispersive X-ray analysis. To characterize the effect of mineral on attachment and maturation of pre-osteoblasts, W20-17 cells were seeded on HA/copolymer composites. We demonstrated that cells attached more to the surface of HA containing copolymers and their proliferation rate was significantly increased. Thus, these findings suggest that HA/PPF-co-PCL composite scaffolds are capable of inducing maturation of pre-osteoblasts and have the potential for use as scaffold in bone tissue engineering.


Rapamycin Perfluorocarbon Nanoparticle Mitigates Cisplatin-Induced Acute Kidney Injury.
For nearly five decades, cisplatin has played an important role as a standard chemotherapeutic agent and been prescribed to 10-20% of all cancer patients. Although nephrotoxicity associated with platinum-based agents is well recognized, treatment of cisplatin-induced acute kidney injury is mainly supportive and no specific mechanism-based prophylactic approach is available to date. Here, we postulated that systemically delivered rapamycin perfluorocarbon nanoparticles (PFC NP) could reach the injured kidneys at sufficient and sustained concentrations to mitigate cisplatin-induced acute kidney injury and preserve renal function. Using fluorescence microscopic imaging and fluorine magnetic resonance imaging/spectroscopy, we illustrated that rapamycin-loaded PFC NP permeated and were retained in injured kidneys. Histologic evaluation and blood urea nitrogen (BUN) confirmed that renal structure and function were preserved 48 h after cisplatin injury. Similarly, weight loss was slowed down. Using western blotting and immunofluorescence staining, mechanistic studies revealed that rapamycin PFC NP significantly enhanced autophagy in the kidney, reduced the expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), as well as decreased the expression of the apoptotic protein Bax, all of which contributed to the suppression of apoptosis that was confirmed with TUNEL staining. In summary, the delivery of an approved agent such as rapamycin in a PFC NP format enhances local delivery and offers a novel mechanism-based prophylactic therapy for cisplatin-induced acute kidney injury.


Elemental microanalysis of organelles in proximal tubules. I. Alterations in transport and metabolism.
Oxygen deprivation to the kidney causes a multifactorial series of morphological, physiological, and biochemical alterations that occur as a function of time. One of the earliest events involves significant changes in the cellular contents of the physiologically important elements (ions) Na and K. Controversy exists as to the nature of changes in the content of the regulatory ion Ca, in either its free or bound form, and much less is known regarding in situ distribution and amounts of other elements such as Mg, P, S, and Cl during physiological or pathophysiological states. The objective of these studies was to evaluate element compartmentation in proximal renal tubules by using quantitative electron probe x-ray microanalysis, during specific conditions which are at least partially manifested during oxygen deprivation. Cells from control proximal tubule suspensions were compared with those exposed to (1) ouabain, to inhibit (Na+, K+)-ATPase; (2) mitochondrial uncouplers, to rapidly deplete ATP content; or (3) calcium ionophores, to cause a rapid elevation in cytoplasmic free calcium. In parallel with electron probe x-ray microanalysis imaging of subcellular elemental content, total cell potassium and ATP contents, enzyme release, oxygen consumption, cytoplasmic free calcium levels, and ultrastructural alterations were assessed. Results indicated that ATP depletion was, in the short term, more deleterious to renal proximal tubules than any of the tested ionic alterations. Intracellular organelles including mitochondria and nuclei appeared to be readily permeable to Na, K, and Cl, altering their concentrations of these ions in parallel with cytoplasmic concentrations. Lysosomes exhibited evidence of Cl accumulation, consistent with an inwardly directed proton ATPase with accompanying Cl transport. Whereas in the cytoplasm Na, K and Cl appeared to be mostly free, a large fraction of these ions within intracellular organelles seemed bound.


Extraordinarily Stretchable All-Carbon Collaborative Nanoarchitectures for Epidermal Sensors.
Multifunctional microelectronic components featuring large stretchability, high sensitivity, high signal-to-noise ratio (SNR), and broad sensing range have attracted a huge surge of interest with the fast developing epidermal electronic systems. Here, the epidermal sensors based on all-carbon collaborative percolation network are demonstrated, which consist 3D graphene foam and carbon nanotubes (CNTs) obtained by two-step chemical vapor deposition processes. The nanoscaled CNT networks largely enhance the stretchability and SNR of the 3D microarchitectural graphene foams, endowing the strain sensor with a gauge factor as high as 35, a wide reliable sensing range up to 85%, and excellent cyclic stability (>5000 cycles). The flexible and reversible strain sensor can be easily mounted on human skin as a wearable electronic device for real-time and high accuracy detecting of electrophysiological stimuli and even for acoustic vibration recognition. The rationally designed all-carbon nanoarchitectures are scalable, low cost, and promising in practical applications requiring extraordinary stretchability and ultrahigh SNRs.


Percutaneous mitral repair with the MitraClip system: safety and midterm durability in the initial EVEREST (Endovascular Valve Edge-to-Edge REpair Study) cohort.
We undertook a prospective multicenter single-arm study to evaluate the feasibility, safety, and efficacy of the MitraClip system (Evalve Inc., Menlo Park, California). Mitral valve repair for mitral regurgitation (MR) has been performed by the use of a surgically created double orifice. Percutaneous repair based on this surgical approach has been developed by use of the Evalve MitraClip device to secure the mitral leaflets. Patients with 3 to 4+ MR were selected in accordance with the American Heart Association/American College of Cardiology guidelines for intervention and a core echocardiographic laboratory. A total of 107 patients were treated. Ten (9%) had a major adverse event, including 1 nonprocedural death. Freedom from clip embolization was 100%. Partial clip detachment occurred in 10 (9%) patients. Overall, 79 of 107 (74%) patients achieved acute procedural success, and 51 (64%) were discharged with MR of < or =1+. Thirty-two patients (30%) had mitral valve surgery during the 3.2 years after clip procedures. When repair was planned, 84% (21 of 25) were successful. Thus, surgical options were preserved. A total of 50 of 76 (66%) successfully treated patients were free from death, mitral valve surgery, or MR >2+ at 12 months (primary efficacy end point). Kaplan-Meier freedom from death was 95.9%, 94.0%, and 90.1%, and Kaplan-Meier freedom from surgery was 88.5%, 83.2%, and 76.3% at 1, 2, and 3 years, respectively. The 23 patients with functional MR had similar acute results and durability. Percutaneous repair with the MitraClip system can be accomplished with low rates of morbidity and mortality and with acute MR reduction to < 2+ in the majority of patients, and with sustained freedom from death, surgery, or recurrent MR in a substantial proportion (EVEREST I; NCT00209339. EVEREST II; NCT00209274).


Universal stress protein-like gene from mulberry enhances abiotic stress tolerance in Escherichia coli and transgenic tobacco cells.
Universal stress proteins (USPs) are a conserved group of proteins initially identified and characterized in bacteria. USPs are induced under multiple stresses, and are important for stress acclimation. We cloned a USP-like gene designated as MaUSP1-like from mulberry and expressed in bacteria and tobacco to examine its relevance in abiotic stress tolerance. Escherichia coli and tobacco cells expressing MaUSP1-like gene were exposed to different abiotic stresses, and cell survival and growth was recorded to assess the stress effects. MaUSP1-like gene conferred tolerance to E. coli cells under NaCl-induced salt stress, PEG8000-induced desiccation stress, cadmium chloride-induced heavy metal stress, and heat stress. Overexpression of MaUSP1-like sustained cell division and growth in tobacco cells under salt stress. The results demonstrate that MaUSP1-like gene is capable of conferring cellular level tolerance in both prokaryotic and eukaryotic systems, under abiotic stress. The finding opened up an option to argue that maintenance of cellular level tolerance is crucial for sustenance of growth under stress and cellular level tolerance can be improved by overexpressing genes like USPs.


Leucocyte ascorbic acid levels and vitamin C intake in older people.
Leucocyte ascorbic acid (L.A.A.) levels and vitamin C intake were measured in a random sample of men and women aged 62-94 years. L.A.A. distributions are positively skewed but log normal. L.A.A. mean values show no age difference in men but are significantly lower in older women. The mean value for all women (23.88mug/10(8) cells) is significantly higher than that for all men (18.11 mug/10(8) cells). L.A.A. values are significantly higher in both sexes in the six months July to December. Vitamin C intake distributions are positively skewed but not improved by log transformation. No significant age or sex differences were found except that a significantly greater proportion of men over than of those under 70 years have intakes less than 30 mg daily. Mean intake is significantly higher in men but not in women in the six months April to September, though in both sexes a significantly greater proportion have intakes less than 30 mg daily in October to March compared with April to September. Fifty per cent. of men and 58% of women have intakes less than 30 mg daily, 23.6% of men and 28.1% of women have intakes less than 20 mg daily, and 4.7% of men and 3% of women have intakes less than 10 mg daily. These percentages increase during the winter. A moderate correlation is present between vitamin C intake and L.A.A. level. L.A.A. levels increase in parallel with but lag behind seasonal increases in vitamin C intake.


Rational design, synthesis, and biological activity of novel conformationally restricted vitamin D analogues, (22R)- and (22S)-22-ethyl-1,25-dihydroxy-23,24-didehydro-24a,24b-dihomo-20-epivitamin D(3).
Two new vitamin D analogues, (22R)- and (22S)-22-ethyl-1,25-dihydroxy-23,24-didehydro-24a,24b-dihomo-20-epivitamin D(3) (3 and 4), were rationally designed on the basis of the active space group concept previously proposed by us. The 22R ethyl group of 3 restricts the mobility of the side chain to active space regions, whereas the 22S ethyl group of 4 confines the side chain to an inactive region. The double bond at C(23) further restricts the side chain flexibility. These compounds (3 and 4) were synthesized using ortho ester Claisen rearrangement as the key step. As expected, the 22R isomer 3 has nearly 100 times higher efficacy than 1,25-dihydroxyvitamin D(3) (1) in cell differentiation, although its affinity for the vitamin D receptor (VDR) was one-seventh of that of 1. The 22S isomer 4 has significantly lower efficacy than 3. A docking study in combination with site-directed mutation analysis revealed that two carbon elongated side chain analogue 3 could be fitted in the ligand binding pocket of the VDR by adopting a stable conformation.


Natural resistance of mice to mouse hepatitis virus type 3 infection is expressed in embryonic fibroblast cells.
Mouse hepatitis virus 3 (MHV3) infection in mice varies according to the mouse strain used; they may show resistance, semi-susceptibility (paralysis) or full susceptibility (lethal acute hepatitis). In order to study the mechanism of inborn resistance, viral infection was carried out in primary cultures of embryonic fibroblasts originating from various mouse strains exhibiting different sensitivities to MHV3 infection. Virus-induced cytopathic effects and cell membrane antigens as well as virus replication and interferon synthesis were studied. Persistent infection was induced in four out of six primary embryonic fibroblast cultures and in six of six secondary cultures. Two primary embryonic fibroblast cultures from susceptible strains underwent total lysis. A high yield of virus was obtained, as tested by viral titres and cell membrane antigen detection. No significant difference in virus production or in interferon synthesis was observed in fibroblast cultures of the various mouse strains tested. Cytopathic effects characterized by cell lysis were related, however, to phenotypes in vivo. This effect was lost after a single trypsinization of the culture. In addition, resistance to virus-induced cell lysis was inhibited by actinomycin D treatment. These results indicate that the intrinsic resistance of fibroblasts is effective not against virus replication but against virus-induced cell lysis. Such a cellular control mechanism may be an important factor for resistance in vivo.


Effect of interlayer spacing in layered perovskites on resistive switching memory.
We report here the effect of interlayer spacing in 2-dimensional (2D) perovskites of [C6H5(CH2)nNH3]2PbI4 (anilinium (An) for n = 0, benzylammonium (BzA) for n = 1 and phenylethylammonium (PEA) for n = 2) on resistive switching properties. X-ray diffraction (XRD) reveals that the interlayer spacing of layered PbI2 is increased from 6.98 Å to 13.29 Å for (An)2PbI4, 14.20 Å for (BzA)2PbI4 and 15.92 Å for (PEA)2PbI4, which leads to a monolayer of organic cations with stacked benzene rings between inorganic PbI42- layers. All the samples in the device structure of Ag/PMMA (polymethyl methacrylate)/perovskite/Pt show bipolar switching behavior, where the SET voltage is near +0.2 V and the RESET voltage is less than -0.5 V. The ratio of LRS (low resistance state) to HRS (high resistance state), also called the ON/OFF ratio, is increased from 106 to 108 as interlayer spacing is increased due to the gradual increase in resistance in the HRS. Endurance is slightly improved from 1.3 × 102 for An to 2.2 × 102 for PEA, whereas substantial improvement in retention is observed from 2 × 103 to 5.5 × 103. This indicates that the enhanced 2D structure is beneficial to the kinetics of forming and rupturing the conducting filaments. The ohmic-like conduction mechanism in the LRS and the hopping mechanism in the HRS are observed for all three samples. This work finds that the resistive switching properties and conduction mechanism in the HRS depend on interlayer spacing in 2D perovskites.


Outdoor air pollution: nitrogen dioxide, sulfur dioxide, and carbon monoxide health effects.
Nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide are important ambient air pollutants. High-intensity, confined space exposure to NO2 has caused catastrophic injury to humans, including death. Ambient NO2 exposure may increase the risk of respiratory tract infections through the pollutant's interaction with the immune system. Sulfur dioxide (SO2) contributes to respiratory symptoms in both healthy patients and those with underlying pulmonary disease. Controlled human exposure studies have demonstrated that experimental SO2 exposure causes changes in airway physiology, including increased airways resistance. Both acute and chronic exposure to carbon monoxide are associated with increased risk for adverse cardiopulmonary events, including death. However, studies have not demonstrated a clear dose-dependent health risk response to increasing amounts of these pollutants except at high concentrations. In addition, a number of studies examining the effects of ambient level exposure to NO2, SO2, and CO have failed to find associations with adverse health outcomes.


Concurrent contextual and time-distant mnemonic information co-exist as feedback in the human visual cortex.
Efficient processing of the visual environment necessitates the integration of incoming sensory evidence with concurrent contextual inputs and mnemonic content from our past experiences. To examine how this integration takes place in the brain, we isolated different types of feedback signals from the neural patterns of non-stimulated areas of the early visual cortex in humans (i.e., V1 and V2). Using multivariate pattern analysis, we showed that both contextual and time-distant information, coexist in V1 and V2 as feedback signals. In addition, we found that the extent to which mnemonic information is reinstated in V1 and V2 depends on whether the information is retrieved episodically or semantically. Critically, this reinstatement was independent on the retrieval route in the object-selective cortex. These results demonstrate that our early visual processing contains not just direct and indirect information from the visual surrounding, but also memory-based predictions.


Cerebral activation and distribution of inducible hsp110 and hsp70 mRNAs following focal ischemia in rat.
A potential function for inducible heat shock protein 70 (hsp70i) expression in the pathophysiology of ischemic brain has been well documented. The recently cloned hsp70 superfamily member, hsp110, was shown to be highly expressed in the brain and suggested to have a similar functional property as members of the hsp70 family. In this study, as an initial step to probe for its physiological significance in the ischemic brain, cerebral activation and distribution of hsp110 mRNA was comparatively evaluated with that of hsp70i mRNA by in situ hybridization. A rat focal cerebral ischemia model was employed to examine the distribution and localization of hsp110 and hsp70i mRNAs in both affected (ipsilateral) and unaffected (contralateral) hemispheres of the same animal. Our results demonstrated a significant accumulation of hsp110 as well as hsp70i mRNAs following ischemia; although the magnitude and kinetics of induction differ slightly, spatial expression profiles of hsp110 and hsp70i mRNAs were highly correlated in the affected region. In control brain, limited hybridization signal was observed with 3'-untranslated region (UTR) containing hsp110 probe, suggesting a possible existence of inducible hsp110 and a selective recognition of our 3'-UTR containing probe for the inducible hsp110 mRNA species. Subsequent 2D western analysis with Hsp110 specific Ab was consistent with our view, which resolved constitutive and inducible immunostained spots in rat ischemic brain. Considering a regulatory similarity as well as previously documented structural and functional similarities between hsp110 and hsp70i, we propose that coordinated cerebral activation of hsp110 and hsp70i is likely to be of significant relevance in the context of pathophysiology of ischemic brain. Further study is required to characterize the genetic and biochemical nature of rat inducible hsp110 identified in the current study.


The metabolic syndrome in a global perspective. The public health impact--secondary publication.
The term "metabolic syndrome" refers to the clustering of a number of cardiovascular risk factors (obesity, hypertension, dyslipidemia and hyperglycaemia) believed to be related to insulin resistance. The prevalence of each of these diseases as well as the metabolic syndrome is increasing world wide. Obesity, hypertension, dyslipidemia and diabetes are no longer diseases of the wealthy. By 2025, three out of four people with diabetes will be living in third world countries, and similar trends are likely for the other components of the syndrome. Preventive action is urgently needed, and studies in China and India have proven to be effective.


Frequency, Risk Factors, and Pregnancy Outcomes in Cases with Placenta Accreta Spectrum Disorder: A Case-Control Study.
Placenta accreta spectrum (PAS) disorder is an important life-threatening problem. The purpose of the current study was to determine the frequency, risk factors, and pregnancy outcomes of PAS in our population. This is a case-control study using the data from a main tertiary referral university hospital in Ahvaz, southwest of Iran. The sample included 187 cases diagnosed with placenta accreta spectrum from 2015 to 2019 and 552 controls without PAS. A multivariable logistic regression model was used to find independent risk factors with 95% confidence interval. Pregnancy outcomes were evaluated using chi-square, t-test, and Mann-Whitney U test and p<0.05 were considered statistically significant. The frequency of PAS during the study period was 3.7/1000 deliveries (0.37%). It was found that multiparity (≥3 deliveries, OR=2.05: 95%CI:1.21-3.47) and multigravidity (≥3 deliveries, OR=2.98: 95%CI:1.55-5.72), prior cesarean delivery (OR=52.55: 95%CI:19.73-139.96), and placenta previa (OR=27.48: 95%CI: 9.62-78.5) are the independent risk factors of PAS. Complications and morbidity associated with PAS included hysterectomy (60.4% vs. 0.7%, p<0.001), cystostomy (24.1% vs. 0.2%, p<0.001), the need for blood transfusion (73.7% vs. 1.4%, p<0.001), intensive care unit admission of mother (42.8% vs. 0.2%, p<0.001), duration of hospitalization (7.52±6.34 vs. 1.97±1.83, p<0.001), preterm birth <37 weeks (61.4% vs. 16.8%, p<0.001), and perinatal mortality (7.4% vs. 1.8%, p<0.001) which manifested statistically significant values. The frequency of PAS is similar to other populations. Prior cesarean delivery, placenta previa, multigravidity, and multiparity were independent risk factors and also perinatal hysterectomy and preterm birth were the most important complications.


Evaluation of race as a predictor of fear of falling in Black older adults.
Determine whether race predicts fear of falling (FOF) in older adults with a history of previous fall(s) while controlling for mobility performance, activity of daily living (ADL) independence, age, gender, and education. We examined predictors of FOF among community-dwelling older adults using data from two longitudinal randomized controlled trials that implemented fall prevention programs for community-dwelling older adults. Two hundred fifty-nine participants were included in the analysis; 145 reported low FOF, while 59 reported high FOF. After controlling for mobility performance, ADL independence, and sociodemographic factors, Black older adults were more likely to report FOF (OR = 2.17) compared to White older adults. Overall, older adults with lower mobility performance/functioning scores were more likely to have FOF (OR = 0.08). Older adults (aged ≥65 years) who are at higher risk, based on a prior history of fall(s), are more susceptible to developing FOF, as evidenced by the older adults within this study, due to limited mobility performance and functioning. Black older adults may be at greater risk of FOF than their White counterparts based on previous fall history and level of functional mobility. Incorporating measures of objective performance-based function along with measures of psychological factors are viable methods to identify and address FOF within Black older adult populations.


Change fatigue: The frontline nursing experience of large-scale organisational change and the influence of teamwork.
To evaluate the experience of change fatigue in frontline nursing staff following large-scale organisational change and determine whether improved teamwork perception scores can mitigate the experience of change fatigue in this population. There is limited published research pertaining to the experience of change fatigue in nursing, despite the rapid rate and volume of change within health care organisations. An online questionnaire was used to survey a cross section of frontline nurses from two distinct cohorts; those that transitioned to a new build hospital in an established team (n = 225), and those who transitioned into a newly reconfigured team (n = 521). Frontline nurses who transitioned in an established team reported higher levels of change fatigue following large-scale change, compared with those that commenced in a new, reconfigured team (p = 0.013). There is a small significant negative correlation between perception of teamwork and change fatigue scores. Regardless of team type, high levels of change fatigue are reported by frontline nursing staff following large-scale organisational change. Established teams have a higher perceived level of teamwork in all domains when compared with a new team in the same change conditions. It is unlikely that the perception of teamwork has any real-world impact upon the experience of change fatigue. Change fatigue is a real phenomena experienced by frontline nursing staff during large-scale organisational change conditions. Investing in teamwork training prior to or during large-scale organisational change does not affect the experience of change fatigue.


Care plans and care planning in the management of long-term conditions in the UK: a controlled prospective cohort study.
In the UK, the use of care planning and written care plans has been proposed to improve the management of long-term conditions, yet there is limited evidence concerning their uptake and benefits. To explore the implementation of care plans and care planning in the UK and associations with the process and outcome of care. A controlled prospective cohort study among two groups of patients with long-term conditions who were similar in demographic and clinical characteristics, but who were registered with general practices varying in their implementation of care plans and care planning. Implementation of care plans and care planning in general practice was assessed using the 2009-2010 GP Patient Survey, and relationships with patient outcomes (self-management and vitality) were examined using multilevel, mixed effects linear regression modelling. The study recruited 38 practices and 2439 patients. Practices in the two groups (high and low users of written documents) were similar in structural and population characteristics. Patients in the two groups of practices were similar in demographics and baseline health. Patients did demonstrate significant differences in reported experiences of care planning, although the differences were modest. Very few patients in the cohort reported a written plan that could be confirmed. Analysis of outcomes suggested that most patients show limited change over time in vitality and self-management. Variation in the use of care plans at the practice level was very limited and not related to patient outcomes over time. The use of written care plans in patients with long-term conditions is uncommon and unlikely to explain a substantive amount of variation in the process and outcome of care. More proactive efforts at implementation may be required to provide a rigorous test of the potential of care plans and care planning.


Risk factors for cesarean delivery among Puerto Rican women.
The rate of primary cesarean delivery in Puerto Rico in 2002 was 52% higher than in 1996 and 85% higher than among Puerto Rican women delivering on the U.S. mainland. Reasons for these differences were explored using birth certificate data. Distributions of mothers' age, education, parity, level of prenatal care, pregnancy weight gain, medical risk factors, labor induction, labor or delivery complications, and infant birth weight among births in Puerto Rico in 2002 (n=40,489) were compared with births in Puerto Rico in 1996 (n=51,357) and births to Puerto Rican women delivering on the mainland in 2002 (n=47,800). Multivariable log-linear regression models were used to estimate relative risks for primary cesarean delivery by year, place of delivery, and selected risk factors. Risk for cesarean delivery was higher in Puerto Rico in 2002 than in both 1996 (relative risk 2.1, 95% confidence interval 2.0, 2.3) and on the mainland in 2002 (relative risk 2.4, 95% confidence interval 2.2, 2.6). This translates into one additional cesarean delivery in Puerto Rico in 2002 for every 4.2 live births, controlled for examined risk factors. Higher rates of cesarean delivery in Puerto Rico in 2002 could not be explained by examined risk factors. Until further research reveals ways to safely reduce the rate of cesarean delivery in Puerto Rico, physicians, public health practitioners, and other stakeholders may want to focus their efforts on reducing rates among low-risk women and those with no labor complications. II.


A modified zinc acetate gel, a potential nonantiretroviral microbicide, is safe and effective against simian-human immunodeficiency virus and herpes simplex virus 2 infection in vivo.
We previously showed that a prototype gel comprising zinc acetate (ZA) in carrageenan (CG) protected mice against vaginal and rectal herpes simplex virus 2 (HSV-2) challenge as well as macaques against vaginal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) challenge. In this work, we modified buffers and cosolvents to obtain a stable, nearly iso-osmolal formulation and evaluated its safety and efficacy against SHIV-RT and HSV-2. In vitro toxicity to lactobacilli and Candida albicans was determined. Macaques were given daily doses of ZA and CG (ZA/CG) or CG alone vaginally for 14 days and challenged with SHIV-RT 24 h later. Mice were challenged vaginally or rectally with HSV-2 immediately after a single gel treatment to measure efficacy or vaginally 12 h after daily gel treatment for 7 days to evaluate the gel's impact on susceptibility to HSV-2 infection. The modified ZA/CG neither affected the viability of lactobacilli or C. albicans nor enhanced vaginal HSV-2 infection after daily ZA/CG treatment. Vaginal SHIV-RT infection of macaques was reduced by 66% (P = 0.006) when macaques were challenged 24 h after the last dose of gel. We observed 60% to 80% uninfected mice after vaginal (P < 0.0001) and rectal (P = 0.008) high-dose HSV-2 challenge. The modified ZA/CG gel is safe and effective in animal models and represents a potential candidate to limit the transmission of HIV and HSV-2.


The effect of the gamma-subunit of the cyclic GMP phosphodiesterase of bovine and frog (Rana catesbiana) retinal rod outer segments on the kinetic parameters of the enzyme.
Rod-outer-segment cyclic GMP phosphodiesterase (PDE) (subunit composition alpha beta gamma 2) contains catalytic activity in alpha beta. The gamma-subunits are inhibitors. Removal of the gamma-subunits increases Vmax. without affecting the Km. The inhibitory effect of a single gamma-subunit (alpha beta gamma) on the Vmax. of alpha beta is much greater in bovine than in frog (Rana catesbiana) PDE. Bovine PDE in the alpha beta gamma 2 state has a Vmax. that is 2.6 +/- 0.4% of the Vmax. of alpha beta. The removal of one gamma-subunit to give alpha beta gamma results in a Vmax. 5.2 +/- 1% of that for maximal activity. Frog alpha beta gamma 2 has a Vmax. 10.8 +/- 2%, and alpha beta gamma has a Vmax. 50 +/- 18%, of the Vmax. of alpha beta. These data suggest that a single gamma-subunit can inhibit the catalytic activity of active sites on both alpha- and beta-subunits in bovine, but not in frog, rod-outer-segment PDE.


Phenological mismatch and ontogenetic diet shifts interactively affect offspring condition in a passerine.
Climate change may cause phenological asynchrony between trophic levels, which can lead to mismatched reproduction in animals. Although indirect effects of mismatch on fitness are well described, direct effects on parental prey choice are not. Moreover, direct effects of prey variation on offspring condition throughout their early development are understudied. Here, we used camera trap data collected over 2 years to study the effects of trophic mismatch and nestling age on prey choice in pied flycatchers (Ficedula hypoleuca). Furthermore, we studied the effect of mismatch and variation in nestling diet on offspring condition. Both experimentally induced and natural mismatches with the caterpillar peak negatively affected absolute and relative numbers of caterpillars and offspring condition (mass, tarsus and wing length) and positively affected absolute and relative numbers of flying insects in the nestling diet. Feeding more flying insects was negatively correlated with nestling day 12 mass. Both descriptive and experimental data showed preferential feeding of spiders when nestlings were <7 days old. Receiving more spiders during this phase was positively correlated with tarsus growth. These results highlight the need for a more inclusive framework to study phenological mismatch in nature. The general focus on only one prey type, the rarity of studies that measure environmental abundance of prey, and the lack of timing experiments in dietary studies currently hamper understanding of the actual trophic interactions that affect fitness under climate change.


[Biliary hypertension in opisthorchiasis patients].
On the basis of the over twenty years experience with the treatment of surgical complications of opisthorchiasis the authors propose a classification of causes of biliary hypertension in patients with this disease. The intra-, inter- and extracanalicular causes of the obstruction of biliary ducts, hypertension in the duodenum and associated forms are formulated. To prevent and successfully treat the biliary syndrome it is necessary to reestablish the bile outflow by surgical methods.


Mental health outcomes following COVID-19 infection: impacts of post-COVID impairments and fatigue on depression, anxiety, and insomnia - a web survey in Sweden.
The negative impact of the COVID-19 pandemic on the mental health is now clearly established. However, information on the levels of mental ill health of people infected with COVID-19 and potential correlates of poor mental health is still limited. Therefore, the current study aimed to study indicative of potential mental health problems in individuals with a history of probable or confirmed SARS CoV-2 infection/infections and address the impacts of post-COVID impairments and fatigue following COVID-19 infection/infections on depression, anxiety, and insomnia. A web-survey including demographics, questions related to COVID-19 status and post-COVID impairments, and standardized measures of depression, anxiety, insomnia, and fatigue was completed by 507 individuals with a history of probable or confirmed SARS CoV-2 infection/infections. We found significant rates of significant depression, anxiety, and insomnia in our sample, with more than 70% experiencing levels above the clinical cut offs for at least one psychological health problems. Higher levels of depression, anxiety, and insomnia were associated with the severity of COVID-19 infection in the acute phase, hospitalization because of COVID-19, and higher levels of post-COVID impairments and fatigue. Reduced motivation emerged as the strongest predictor for mental ill health. These findings highlight that individuals infected with COVID-19, especially those who still have experienced post-COVID impairments, are more likely to suffer from mental ill-health and may be more vulnerable for poor mental health outcomes. Therefore, more effective actions are needed to take in order to promote and protect mental health of individuals with a history of COVID-19 infection.


Biomechanical studies on the effect of iatrogenic dentin removal on vertical root fractures.
The aim of this study was to understand the mechanism by which iatrogenic root dentin removal influences radicular stress distribution and subsequently affects the resistance to vertical root fractures (VRF) in endodontically treated teeth. The experiments were conducted in two phases. Phase 1: freshly extracted premolar teeth maintained in phosphate-buffered saline were instrumented to simulate three different degrees of dentin removal, designated as low, medium, and extreme groups. Micro-Ct analyzes were performed to quantitatively determine: (a) the amount of dentin removed, (b) the remaining dentin volume, and (c) the moment of inertia of root dentin. The specimens were then subjected to thermomechanical cycling and continuous loading to determine (a) the mechanical load to fracture and (b) dentin microcracking (fractography) using scanning electron microscopy. Phase 2: Finite element analysis was used to evaluate the influence of dentin removal on the stress distribution pattern in root dentin. The data obtained were analyzed using one-way ANOVA and Tukey's post hoc test (P < 0.05). Phase 1: A significantly greater volume of dentin was removed from teeth in extreme group when compared to low group (P < 0.01). The mechanical analysis showed that the load to fracture was significantly lower in teeth from extreme group (P < 0.05). A linear relationship was observed between the moment of inertia and load to fracture in all experimental groups (R2 = 0.52). Fractography showed that most microcracks were initiated from the root canal walls in extreme group. Phase 2: The numerical analysis showed that the radicular stress distribution increased apically and buccolingually with greater degree of root canal dentin removal. The combined experimental/numerical analyses highlighted the influence of remaining root dentin volume on the radicular bending resistance, stress distribution pattern, and subsequent propensity to VRF.